ALBERT

Description: by Cheng-Jui Lin, Tai-Cherng Liou, Chi-Feng Pan, Pei-Chen Wu, Fang-Ju Sun, Hsuan-Liang Liu, Han-Hsiang Chen, Chih-Jen Wu Evidence has shown that indoxyl sulfate (IS) and p-cresyl sulfate (PCS) may be alternative predictors of clinical outcomes in chronic kidney disease (CKD). Both toxins are derived from the gastrointestinal tract and metabolised in the liver. However, it is unclear whether the liver affects the production of IS and PCS. Here, we explore the association between IS and PCS levels in liver cirrhosis and a CKD-based cohort (N = 115). Liver and kidney function was assessed and classified by a Child-Pugh score (child A–C) and a modified version of the Modification of Diet in Renal Disease (MDRD) equation (Stages 1–4), respectively. An animal model was also used to confirm the two toxin levels in a case of liver fibrosis. In patients with early liver cirrhosis (child A), IS and PCS were significantly associated with CKD stages. In contrast, serum IS and PCS did not significantly change in advanced liver cirrhosis (child C). A stepwise multiple linear regression analysis also showed that T-PCS was significantly associated with stages of liver cirrhosis after adjusting for other confounding factors (B = -2.29, p = 0.012). Moreover, the serum and urine levels of T-PCS and T-IS were significantly lower in rats with liver failure than in those without ( p

Description: by Guangde Zhang, Hongbo Shi, Lin Wang, Meng Zhou, Zhenzhen Wang, Xiaoxia Liu, Liang Cheng, Weimin Li, Xueqi Li Myocardial infarction (MI) is a severe coronary artery disease and a leading cause of mortality and morbidity worldwide. However, the molecular mechanisms of MI have yet to be fully elucidated. In this study, we compiled MI-related genes, MI-related microRNAs (miRNAs) and known human transcription factors (TFs), and we then identified 1,232 feed-forward loops (FFLs) among these miRNAs, TFs and their co-regulated target genes through integrating target prediction. By merging these FFLs, the first miRNA and TF mediated regulatory network for MI was constructed, from which four regulators (SP1, ESR1, miR-21-5p and miR-155-5p) and three regulatory modules that might play crucial roles in MI were then identified. Furthermore, based on the miRNA and TF mediated regulatory network and literature survey, we proposed a pathway model for miR-21-5p, the miR-29 family and SP1 to demonstrate their potential co-regulatory mechanisms in cardiac fibrosis, apoptosis and angiogenesis. The majority of the regulatory relations in the model were confirmed by previous studies, which demonstrated the reliability and validity of this miRNA and TF mediated regulatory network. Our study will aid in deciphering the complex regulatory mechanisms involved in MI and provide putative therapeutic targets for MI.

Description: by Dominik Eichin, Juha P. Laurila, Sirpa Jalkanen, Marko Salmi The ectoenzyme CD73 catalyzes the hydrolysis of AMP, and is one of the most important producers of extracellular adenosine. On regulatory T cells, CD73 is necessary for immunosuppressive functions, and on Th17 cells CD73-generated adenosine exerts anti-inflammatory effects. However, the expression and function of CD73 in pro-inflammatory M1 and in immunosuppressive M2 macrophages is largely unknown. Here we show that CD73 expression and enzyme activity were induced in in vitro polarized pro-inflammatory human M(LPS+TNF) monocytes/macrophages, while CD73 was absent from immunosuppressive M(IL-4+M-CSF)-polarized macrophages. Inhibition of CD73 activity with the inhibitor AMPCP did not affect the polarization of human monocytes. In mice, CD73 was present on resident peritoneal macrophages. In striking contrast, elicited peritoneal macrophages remained CD73 negative regardless of their polarization towards either a pro-inflammatory M(LPS) or anti-inflammatory M(IL-4c) direction. Finally, the ability of peritoneal macrophages to polarize to pro- and anti-inflammatory cells was perfectly normal in CD73-deficient mice in vivo . These data indicate that, in contrast to other major leukocyte subpopulations, CD73 activity on macrophages does not play a major role in their polarization and that in mice host CD73 on any cell type is not required in vivo for peritoneal macrophage polarization towards either a pro- or an anti-inflammatory direction.

Description: by Hui San Ong, Mohd Syafiq Rahim, Mohd Firdaus-Raih, Effirul Ikhwan Ramlan The unique programmability of nucleic acids offers alternative in constructing excitable and functional nanostructures. This work introduces an autonomous protocol to construct DNA Tetris shapes (L-Shape, B-Shape, T-Shape and I-Shape) using modular DNA blocks. The protocol exploits the rich number of sequence combinations available from the nucleic acid alphabets, thus allowing for diversity to be applied in designing various DNA nanostructures. Instead of a deterministic set of sequences corresponding to a particular design, the protocol promotes a large pool of DNA shapes that can assemble to conform to any desired structures. By utilising evolutionary programming in the design stage, DNA blocks are subjected to processes such as sequence insertion, deletion and base shifting in order to enrich the diversity of the resulting shapes based on a set of cascading filters. The optimisation algorithm allows mutation to be exerted indefinitely on the candidate sequences until these sequences complied with all the four fitness criteria. Generated candidates from the protocol are in agreement with the filter cascades and thermodynamic simulation. Further validation using gel electrophoresis indicated the formation of the designed shapes. Thus, supporting the plausibility of constructing DNA nanostructures in a more hierarchical, modular, and interchangeable manner.

Description: by Nima Toosizadeh, Jane Mohler, David G. Armstrong, Talal K. Talal, Bijan Najafi Poor balance control and increased fall risk have been reported in people with diabetic peripheral neuropathy (DPN). Traditional body sway measures are unable to describe underlying postural control mechanism. In the current study, we used stabilogram diffusion analysis to examine the mechanism under which balance is altered in DPN patients under local-control (postural muscle control) and central-control (postural control using sensory cueing). DPN patients and healthy age-matched adults over 55 years performed two 15-second Romberg balance trials. Center of gravity sway was measured using a motion tracker system based on wearable inertial sensors, and used to derive body sway and local/central control balance parameters. Eighteen DPN patients (age = 65.4±7.6 years; BMI = 29.3±5.3 kg/m 2 ) and 18 age-matched healthy controls (age = 69.8±2.9; BMI = 27.0±4.1 kg/m 2 ) with no major mobility disorder were recruited. The rate of sway within local-control was significantly higher in the DPN group by 49% (healthy local-control slope = 1.23±1.06×10 -2 cm 2 /sec, P

Description: by Raphael H. Heiberger Today´s connected world allows people to gather information in shorter intervals than ever before, widely monitored by massive online data sources. As a dramatic economic event, recent financial crisis increased public interest for large companies considerably. In this paper, we exploit this change in information gathering behavior by utilizing Google query volumes as a "bad news" indicator for each corporation listed in the Standard and Poor´s 100 index. Our results provide not only an investment strategy that gains particularly in times of financial turmoil and extensive losses by other market participants, but reveal new sectoral patterns between mass online behavior and (bearish) stock market movements. Based on collective attention shifts in search queries for individual companies, hence, these findings can help to identify early warning signs of financial systemic risk. However, our disaggregated data also illustrate the need for further efforts to understand the influence of collective attention shifts on financial behavior in times of regular market activities with less tremendous changes in search volumes.

Description: by Sea H. Kim, Birendra Babu Adhikari, Siobanth Cruz, Michael P. Schramm, Joe A. Vinson, Vasanthy Narayanaswami The objective of this study is to transport and deliver resveratrol to intracellular sites using apolipoprotein E3 (apoE3). Reconstituted high-density lipoprotein (rHDL) bearing resveratrol (rHDL/res) was prepared using phospholipids and the low-density lipoprotein receptor (LDLr)-binding domain of apoE3. Biophysical characterization revealed that resveratrol was partitioned into the phospholipid bilayer of discoidal rHDL/res particles (~19 nm diameter). Co-immunoprecipitation studies indicated that the LDLr-binding ability of apoE3 was retained. Cellular uptake of resveratrol to intracellular sites was evaluated in glioblastoma A-172 cells by direct fluorescence using chemically synthesized NBD-labeled resveratrol (res/NBD) embedded in rHDL/res. Competition and inhibition studies indicate that the uptake is by receptor mediated endocytosis via the LDLr, with co-localization of apoE3 and res/NBD in late endosomes/lysosomes. We propose that rHDL provides an ideal hydrophobic milieu to sequester resveratrol and that rHDL containing apoE3 serves as an effective “nanovehicle” to transport and deliver resveratrol to targeted intracellular sites.

Description: by JunLi Liu, YiHu Wang, ShuJun Song, XiJie Wang, YaYa Qin, ShaoYan Si, YanChuan Guo Purpose Collagen peptides (CPs) and calcium citrate are commonly used as bone health supplements for treating osteoporosis. However, it remains unknown whether the combination of oral bovine CPs with calcium citrate is more effective than administration of either agent alone. Methods Forty 12-week-old Sprague-Dawley rats were randomly divided into five groups ( n = 8) for once-daily intragastric administration of different treatments for 3 months at 3 months after ovariectomy (OVX) as follows: sham + vehicle; OVX + vehicle; OVX + 750 mg/kg CP; OVX + CP-calcium citrate (75 mg/kg); OVX + calcium citrate (75 mg/kg). After euthanasia, the femurs were removed and analyzed by dual energy X-ray absorptiometry and micro-computed tomography, and serum samples were analyzed for bone metabolic markers. Results OVX rats supplemented with CPs or CP-calcium citrate showed osteoprotective effects, with reductions in the OVX-induced decreases in their femoral bone mineral density. Moreover, CP-calcium citrate prevented trabecular bone loss, improved the microarchitecture of the distal femur, and significantly inhibited bone loss with increased bone volume, connectivity density, and trabecular number compared with OVX control rats. CP or CP-calcium citrate administration significantly increased serum procollagen type I N-terminal propeptide levels and reduced serum bone-specific alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen levels. Conclusions Our data indicate that combined oral administration of bovine CPs with calcium citrate inhibits bone loss in OVX rats. The present findings suggest that combined oral administration of bovine CPs with calcium citrate is a promising alternative for reducing bone loss in osteopenic postmenopausal women.

Description: Article How variation in species responses to climate may influence the resilience of ecological communities to environmental change is not fully understood. Here, the authors characterize the thermal niches of insect pollinator communities and show that resilience increases along a gradient of land-use intensity. Nature Communications doi: 10.1038/ncomms8989 Authors: Sara Kühsel, Nico Blüthgen

Description: Article Sepsis, a systemic inflammatory response to bacterial infection, can lead to organ failure and death. Here, Chai et al. investigate the mechanisms behind the septic response and identify the role of oestrogen sulfotransferase in this process in mice. Nature Communications doi: 10.1038/ncomms8979 Authors: Xiaojuan Chai, Yan Guo, Mengxi Jiang, Bingfang Hu, Zhigang Li, Jie Fan, Meihong Deng, Timothy R. Billiar, Heidi R. Kucera, Nilesh W. Gaikwad, Meishu Xu, Peipei Lu, Jiong Yan, Haiyan Fu, Youhua Liu, Lushan Yu, Min Huang, Su Zeng, Wen Xie

Description: Article Antisense oligonucleotides (ASOs) can repress the expression of specific genes. Here, the authors show that a DNA/RNA heteroduplex oligonucleotide (HDO) with a structure different from ASOs is more potent in suppressing target gene expression, and causes a less adverse effect in mouse liver. Nature Communications doi: 10.1038/ncomms8969 Authors: Kazutaka Nishina, Wenying Piao, Kie Yoshida-Tanaka, Yumiko Sujino, Tomoko Nishina, Tsuyoshi Yamamoto, Keiko Nitta, Kotaro Yoshioka, Hiroya Kuwahara, Hidenori Yasuhara, Takeshi Baba, Fumiko Ono, Kanjiro Miyata, Koichi Miyake, Punit P. Seth, Audrey Low, Masayuki Yoshida, C. Frank Bennett, Kazunori Kataoka, Hidehiro Mizusawa, Satoshi Obika, Takanori Yokota

Description: Article Mycobacterium tuberculosis feeds on host fatty acids during infection, a process that requires a fructose bisphosphatase (FBPase) enzyme for gluconeogenesis. Here, Ganapathy et al. show that the bacterium has two different FBPases and that this enzymatic activity is required for full virulence. Nature Communications doi: 10.1038/ncomms8912 Authors: Uday Ganapathy, Joeli Marrero, Susannah Calhoun, Hyungjin Eoh, Luiz Pedro Sorio de Carvalho, Kyu Rhee, Sabine Ehrt

Description: Article The regulatory subunits (RI) of protein kinase A (PKA) form a disulfide bond in response to cellular hydrogen peroxide. Here the authors show that disulfide-activation of PKARIa regulates VEGF-induced angiogenesis in mice and may represent a new therapeutic target in diseases with abnormal angiogenesis. Nature Communications doi: 10.1038/ncomms8920 Authors: Joseph R. Burgoyne, Olena Rudyk, Hyun-ju Cho, Oleksandra Prysyazhna, Natasha Hathaway, Amanda Weeks, Rachel Evans, Tony Ng, Katrin Schröder, Ralf P. Brandes, Ajay M. Shah, Philip Eaton

Description: Article It has been conjectured that not only states but also quantum operations can be placed in a superposition of causal order. Here, the authors use a qubit superpose the order in which two photonic gates are applied, which is shown to enable a more efficient detection of their commutation relations. Nature Communications doi: 10.1038/ncomms8913 Authors: Lorenzo M. Procopio, Amir Moqanaki, Mateus Araújo, Fabio Costa, Irati Alonso Calafell, Emma G. Dowd, Deny R. Hamel, Lee A. Rozema, Časlav Brukner, Philip Walther

Description: Article The confined surface plasmon-polariton modes in plasmonic waveguides are a promising platform for single-photon manipulation in small, coplanar architectures. Here, Bermúdez Ureña et al . demonstrate efficient coupling of a single quantum emitter to the supported modes of a V-groove plasmonic waveguide. Nature Communications doi: 10.1038/ncomms8883 Authors: Esteban Bermúdez-Ureña, Carlos Gonzalez-Ballestero, Michael Geiselmann, Renaud Marty, Ilya P. Radko, Tobias Holmgaard, Yury Alaverdyan, Esteban Moreno, Francisco J. García-Vidal, Sergey I. Bozhevolnyi, Romain Quidant

Description: Article Helical nanofilaments—composed of achiral, bent core molecules—have been shown to assemble into left- and right-handed structures. Here, the authors show diastereomeric interactions on the mesocale between chiral liquid crystal guest compounds and helical nanofilament-based pores. Nature Communications doi: 10.1038/ncomms8763 Authors: Dong Chen, Michael R. Tuchband, Balazs Horanyi, Eva Korblova, David M. Walba, Matthew A. Glaser, Joseph E. Maclennan, Noel A. Clark

Description: Article Exploring magnetic excitations and spin textures on the nanoscale may lead to new spintronic technologies and new understanding of condensed matter. Here, the authors demonstrate the potential of single-electron spins in diamond to image such excitations by characterizing spin waves in a ferromagnetic microdisc. Nature Communications doi: 10.1038/ncomms8886 Authors: Toeno van der Sar, Francesco Casola, Ronald Walsworth, Amir Yacoby

Description: Article The impact of drops on surfaces is highly relevant to our daily life and many industrial applications, such as self-cleaning and ink printing. Here, Hao et al . show the transition from superhydrophobic-like drop bouncing, due to a trapped air layer, to substrate-dependent bouncing on a liquid thin film. Nature Communications doi: 10.1038/ncomms8986 Authors: Chonglei Hao, Jing Li, Yuan Liu, Xiaofeng Zhou, Yahua Liu, Rong Liu, Lufeng Che, Wenzhong Zhou, Dong Sun, Lawrence Li, Lei Xu, Zuankai Wang

Description: by Jennifer Choe Bush, Peter Christopher Pantelis, Xavier Morin Duchesne, Sebastian Alexander Kagemann, Daniel Patrick Kennedy We present a novel “Gaze-Replay” paradigm that allows the experimenter to directly test how particular patterns of visual input—generated from people’s actual gaze patterns—influence the interpretation of the visual scene. Although this paradigm can potentially be applied across domains, here we applied it specifically to social comprehension. Participants viewed complex, dynamic scenes through a small window displaying only the foveal gaze pattern of a gaze “donor.” This was intended to simulate the donor’s visual selection, such that a participant could effectively view scenes “through the eyes” of another person. Throughout the presentation of scenes presented in this manner, participants completed a social comprehension task, assessing their abilities to recognize complex emotions. The primary aim of the study was to assess the viability of this novel approach by examining whether these Gaze-Replay windowed stimuli contain sufficient and meaningful social information for the viewer to complete this social perceptual and cognitive task. The results of the study suggested this to be the case; participants performed better in the Gaze-Replay condition compared to a temporally disrupted control condition, and compared to when they were provided with no visual input. This approach has great future potential for the exploration of experimental questions aiming to unpack the relationship between visual selection, perception, and cognition.

Description: by David G. Warnock, Daniel G. Bichet, Myrl Holida, Ozlem Goker-Alpan, Kathy Nicholls, Mark Thomas, Francois Eyskens, Suma Shankar, Mathews Adera, Sheela Sitaraman, Richie Khanna, John J. Flanagan, Brandon A. Wustman, Jay Barth, Carrolee Barlow, Kenneth J. Valenzano, David J. Lockhart, Pol Boudes, Franklin K. Johnson Trial Registration ClinicalTrials.gov NCT01196871

Description: by Clementine Menz, Mahroo K. Parsi, Julian R. J. Adams, Mohamed A. Sideek, Zlatko Kopecki, Allison J. Cowin, Mark A. Gibson Latent transforming growth factor-beta-1 binding protein-2 (LTBP-2) belongs to the fibrillin-LTBP superfamily of extracellular matrix proteins. LTBPs and fibrillins are involved in the sequestration and storage of latent growth factors, particularly transforming growth factor β (TGF-β), in tissues. Unlike other LTBPs, LTBP-2 does not covalently bind TGF-β, and its molecular functions remain unclear. We are screening LTBP-2 for binding to other growth factors and have found very strong saturable binding to fibroblast growth factor-2 (FGF-2) (Kd = 1.1 nM). Using a series of recombinant LTBP-2 fragments a single binding site for FGF-2 was identified in a central region of LTBP-2 consisting of six tandem epidermal growth factor-like (EGF-like) motifs (EGFs 9–14). This region was also shown to contain a heparin/heparan sulphate-binding site. FGF-2 stimulation of fibroblast proliferation was completely negated by the addition of 5-fold molar excess of LTBP-2 to the assay. Confocal microscopy showed strong co-localisation of LTBP-2 and FGF-2 in fibrotic keloid tissue suggesting that the two proteins may interact in vivo. Overall the study indicates that LTBP-2 is a potent inhibitor of FGF-2 that may influence FGF-2 bioactivity during wound repair particularly in fibrotic tissues.

Description: by Xinwei Shi, Hao Liu, Jing Cao, Qing Liu, Guiju Tang, Wanlu Liu, Haiyi Liu, Dongrui Deng, Fuyuan Qiao, Yuanyuan Wu Objective Extravillous trophoblast (EVT) cells invade the endometrium and the maternal spiral arterioles during the first trimester. Mammary Serine Protease Inhibitor (Maspin, SERPINB5) plays a putative role in regulating the invasive activity of cytotrophoblasts. The maspin gene is silenced in various cancers by an epigenetic mechanism that involves aberrant cytosine methylation. We investigated the effect of the methylation status of the maspin promoter on the maspin expression and the aggressiveness of EVT cells. Methods Western blotting was used to detect the maspin protein expression in EVT cells upon hypoxia. The proliferative ability, the apoptosis rate and the migration and invasiveness were measured with Cell Counting Kit-8 assay, Flow Cytometry technology and Transwell methods. Subsequently, we treated cells with recombinant maspin protein. The methylation degree of maspin promoter region upon hypoxia/ decitabine was detected by bisulfite sequencing PCR and methylation-specific PCR. Finally, we explored the effects of decitabine on maspin protein expression and the aggressiveness of EVT cells. Results Hypoxia effectively increased maspin protein expression in EVT cells and significantly inhibited their aggressiveness. The addition of recombinant maspin protein inhibited this aggressiveness. Decitabine reduced the methylation in the maspin promoter region and effectively increased the maspin protein expression, which significantly weakened the migration and invasiveness of EVT cells. Discussion The methylation status of the maspin promoter is an important factor that affects the migration and invasion of EVT cells during early pregnancy. A decrease in the methylation status can inhibit the migration and invasion of EVT cells to affect placentation and can result in the ischemia and hypoxia of placenta.

Description: by Jun-Ha Hwang, Mi Ran Byun, A. Rum Kim, Kyung Min Kim, Hang Jun Cho, Yo Han Lee, Juwon Kim, Mi Gyeong Jeong, Eun Sook Hwang, Jeong-Ho Hong Mesenchymal stem cell (MSC) differentiation is regulated by the extracellular matrix (ECM) through activation of intracellular signaling mediators. The stiffness of the ECM was shown to be an important regulatory factor for MSC differentiation, and transcriptional coactivator with PDZ-binding motif (TAZ) was identified as an effector protein for MSC differentiation. However, the detailed underlying mechanism regarding the role of ECM stiffness and TAZ in MSC differentiation is not yet fully understood. In this report, we showed that ECM stiffness regulates MSC fate through ERK or JNK activation. Specifically, a stiff hydrogel matrix stimulates osteogenic differentiation concomitant with increased nuclear localization of TAZ, but inhibits adipogenic differentiation. ERK and JNK activity was significantly increased in cells cultured on a stiff hydrogel. TAZ activation was induced by ERK or JNK activation on a stiff hydrogel because exposure to an ERK or JNK inhibitor significantly decreased the nuclear localization of TAZ, indicating that ECM stiffness-induced ERK or JNK activation is important for TAZ-driven osteogenic differentiation. Taken together, these results suggest that ECM stiffness regulates MSC differentiation through ERK or JNK activation.

Description: by Maria Cecilia P. Moura, Steven J. Smith, David B. Belzer Residential buildings are a key driver of energy consumption and also impact transportation and land-use. Energy consumption in the residential sector accounts for one-fifth of total U.S. energy consumption and energy-related CO 2 emissions, with floor space a major driver of building energy demands. In this work a consistent, vintage-disaggregated, annual long-term series of U.S. housing stock and residential floor space for 1891–2010 is presented. An attempt was made to minimize the effects of the incompleteness and inconsistencies present in the national housing survey data. Over the 1891–2010 period, floor space increased almost tenfold, from approximately 24,700 to 235,150 million square feet, corresponding to a doubling of floor space per capita from approximately 400 to 800 square feet. While population increased five times over the period, a 50% decrease in household size contributed towards a tenfold increase in the number of housing units and floor space, while average floor space per unit remains surprisingly constant, as a result of housing retirement dynamics. In the last 30 years, however, these trends appear to be changing, as household size shows signs of leveling off, or even increasing again, while average floor space per unit has been increasing. GDP and total floor space show a remarkably constant growth trend over the period and total residential sector primary energy consumption and floor space show a similar growth trend over the last 60 years, decoupling only within the last decade.

Description: by Yi-Ling Chen, Shiun Chang, Ting-Ting Chen, Chien-Kuo Lee Dendritic cells (DCs), including conventional DCs (cDCs) and plasmacytoid DCs (pDCs) are critical for initiating and controlling the immune response. However, study of DC, particularly pDC, function is hampered by their low frequency in lymphoid organs, and existing methods for in vitro DC generation preferentially favor the production of cDCs over pDCs. Here, we demonstrated that pDCs could be efficiently generated in vitro from common lymphoid progenitors (CLPs) using Flt3 ligand (FL) in three different culture systems, namely feeder-free, BM-feeder and AC-6-feeder. This was in stark contrast to common DC progenitors (CDPs), in which cDCs were prominently generated under the same conditions. Moreover, the efficiency and function of pDCs generated from these three systems varied. While AC-6 system showed the greatest ability to support pDC development from CLPs, BM-feeder system was able to develop pDCs with better functionality. pDCs could also be expanded in vivo using hydrodynamic gene transfer of FL, which was further enhanced by the combined treatment of FL and IFN-α. Interestingly, IFN-α selectively promoted the proliferation of CLPs and not CDPs, which might contribute to enhanced pDC development. Together, we have defined conditions for in vitro and in vivo generation of pDCs, which may be useful for investigating the biology of pDCs.

Description: by Andrew Erwin, Frank C. Sup In this paper, a novel haptic feedback scheme, used for accurately positioning a 1DOF virtual wrist prosthesis through sensory substitution, is presented. The scheme employs a three-node tactor array and discretely and selectively modulates the stimulation frequency of each tactor to relay 11 discrete haptic stimuli to the user. Able-bodied participants were able to move the virtual wrist prosthesis via a surface electromyography based controller. The participants evaluated the feedback scheme without visual or audio feedback and relied solely on the haptic feedback alone to correctly position the hand. The scheme was evaluated through both normal (perpendicular) and shear (lateral) stimulations applied on the forearm. Normal stimulations were applied through a prototype device previously developed by the authors while shear stimulations were generated using an ubiquitous coin motor vibrotactor. Trials with no feedback served as a baseline to compare results within the study and to the literature. The results indicated that using normal and shear stimulations resulted in accurately positioning the virtual wrist, but were not significantly different. Using haptic feedback was substantially better than no feedback. The results found in this study are significant since the feedback scheme allows for using relatively few tactors to relay rich haptic information to the user and can be learned easily despite a relatively short amount of training. Additionally, the results are important for the haptic community since they contradict the common conception in the literature that normal stimulation is inferior to shear. From an ergonomic perspective normal stimulation has the potential to benefit upper limb amputees since it can operate at lower frequencies than shear-based vibrotactors while also generating less noise. Through further tuning of the novel haptic feedback scheme and normal stimulation device, a compact and comfortable sensory substitution device for upper limb amputees might be created.

Description: by Aparajita Chatterjee, Daniel M. Ratner, Christopher M. Ryan, Patricia J. Johnson, Barry R. O’Keefe, W. Evan Secor, Deborah J. Anderson, Phillips W. Robbins, John Samuelson Trichomonas vaginalis causes vaginitis and increases the risk of HIV transmission by heterosexual sex, while Tritrichomonas foetus causes premature abortion in cattle. Our goals were to determine the effects, if any, of anti-retroviral lectins, which are designed to prevent heterosexual transmission of HIV, on adherence of Trichomonas to ectocervical cells and on Tritrichomonas infections in a mouse model. We show that Trichomonas Asn-linked glycans ( N -glycans), like those of HIV, bind the mannose-binding lectin (MBL) that is part of the innate immune system. N -glycans of Trichomonas and Tritrichomonas bind anti-retroviral lectins (cyanovirin-N and griffithsin) and the 2G12 monoclonal antibody, each of which binds HIV N -glycans. Binding of cyanovirin-N appears to be independent of susceptibility to metronidazole, the major drug used to treat Trichomonas . Anti-retroviral lectins, MBL, and galectin-1 cause Trichomonas to self-aggregate and precipitate. The anti-retroviral lectins also increase adherence of ricin-resistant mutants, which are less adherent than parent cells, to ectocervical cell monolayers and to organotypic EpiVaginal tissue cells. Topical application of either anti-retroviral lectins or yeast N -glycans decreases by 40 to 70% the recovery of Tritrichomonas from the mouse vagina. These results, which are explained by a few simple models, suggest that the anti-retroviral lectins have a modest potential for preventing or treating human infections with Trichomonas .

Description: by Suzan J. W. Robroek, Anne Rongen, Coos H. Arts, Ferdy W. H. Otten, Alex Burdorf, Merel Schuring Background Individuals with lower socioeconomic status are at increased risk of involuntary exit from paid employment. To give sound advice for primary prevention in the workforce, insight is needed into the role of mediating factors between socioeconomic status and labour force participation. Therefore, it is aimed to investigate the influence of health status, lifestyle-related factors and work characteristics on educational differences in exit from paid employment. Methods 14,708 Dutch employees participated in a ten-year follow-up study during 1999–2008. At baseline, education, self-perceived health, lifestyle (smoking, alcohol, sports, BMI) and psychosocial (demands, control, rewards) and physical work characteristics were measured by questionnaire. Employment status was ascertained monthly based on tax records. The relation between education, health, lifestyle, work-characteristics and exit from paid employment through disability benefits, unemployment, early retirement and economic inactivity was investigated by competing risks regression analyses. The mediating effects of these factors on educational differences in exit from paid employment were tested using a stepwise approach. Results Lower educated workers were more likely to exit paid employment through disability benefits (SHR:1.84), unemployment (SHR:1.74), and economic inactivity (SHR:1.53) but not due to early retirement (SHR:0.92). Poor or moderate health, an unhealthy lifestyle, and unfavourable work characteristics were associated with disability benefits and unemployment, and an unhealthy lifestyle with economic inactivity. Educational differences in disability benefits were explained for 40% by health, 31% by lifestyle, and 12% by work characteristics. For economic inactivity and unemployment, up to 14% and 21% of the educational differences could be explained, particularly by lifestyle-related factors. Conclusions There are educational differences in exit from paid employment, which are partly mediated by health, lifestyle and work characteristics, particularly for disability benefits. Health promotion and improving working conditions seem important measures to maintain a productive workforce, particularly among workers with a low education.

Description: by SK Hafizul Islam, Muhammad Khurram Khan, Xiong Li Over the past few years, secure and privacy-preserving user authentication scheme has become an integral part of the applications of the healthcare systems. Recently, Wen has designed an improved user authentication system over the Lee et al.’s scheme for integrated electronic patient record (EPR) information system, which has been analyzed in this study. We have found that Wen’s scheme still has the following inefficiencies: (1) the correctness of identity and password are not verified during the login and password change phases; (2) it is vulnerable to impersonation attack and privileged-insider attack; (3) it is designed without the revocation of lost/stolen smart card; (4) the explicit key confirmation and the no key control properties are absent, and (5) user cannot update his/her password without the help of server and secure channel. Then we aimed to propose an enhanced two-factor user authentication system based on the intractable assumption of the quadratic residue problem (QRP) in the multiplicative group. Our scheme bears more securities and functionalities than other schemes found in the literature.

Description: by Sherif H. Elmeligy Abdelhamid, Chris J. Kuhlman, Madhav V. Marathe, Henning S. Mortveit, S. S. Ravi Discrete dynamical systems are used to model various realistic systems in network science, from social unrest in human populations to regulation in biological networks. A common approach is to model the agents of a system as vertices of a graph, and the pairwise interactions between agents as edges. Agents are in one of a finite set of states at each discrete time step and are assigned functions that describe how their states change based on neighborhood relations. Full characterization of state transitions of one system can give insights into fundamental behaviors of other dynamical systems. In this paper, we describe a discrete graph dynamical systems (GDSs) application called GDSCalc for computing and characterizing system dynamics. It is an open access system that is used through a web interface. We provide an overview of GDS theory. This theory is the basis of the web application; i.e., an understanding of GDS provides an understanding of the software features, while abstracting away implementation details. We present a set of illustrative examples to demonstrate its use in education and research. Finally, we compare GDSCalc with other discrete dynamical system software tools. Our perspective is that no single software tool will perform all computations that may be required by all users; tools typically have particular features that are more suitable for some tasks. We situate GDSCalc within this space of software tools.

Description: by Lisa Kellman, Amy Myette, Hugo Beltrami Forest harvesting induces a step change in the climatic variables (temperature and moisture), that control carbon dioxide ( CO 2 ) production arising from soil organic matter decomposition within soils. Efforts to examine these vertically complex relationships in situ within soil profiles are lacking. In this study we examined how the climatic controls on CO 2 production change within vertically distinct layers of the soil profile in intact and clearcut forest soils of a humid temperate forest system of Atlantic Canada. We measured mineral soil temperature (0, 5, 10, 20, 50 and 100 cm depth) and moisture (0–15 cm and 30–60 cm depth), along with CO 2 surface efflux and subsurface concentrations (0, 2.5, 5, 10, 20, 35, 50, 75 and 100 cm depth) in 1 m deep soil pits at 4 sites represented by two forest-clearcut pairs over a complete annual cycle. We examined relationships between surface efflux at each site, and soil heat, moisture, and mineral soil CO 2 production. Following clearcut harvesting we observed increases in temperature through depth (1–2°C annually; often in excess of 4°C in summer and spring), alongside increases in soil moisture (30%). We observed a systematic breakdown in the expected exponential relationship between CO 2 production and heat with mineral soil depth, consistent with an increase in the role moisture plays in constraining CO 2 production. These findings should be considered in efforts to model and characterize mineral soil organic matter decomposition in harvested forest soils.

Description: by Peng Yu, Jing Zhang, Shuchun Yu, Zhenzhong Luo, Fuzhou Hua, Linhui Yuan, Zhidong Zhou, Qin Liu, Xiaohong Du, Sisi Chen, Lieliang Zhang, Guohai Xu Background and Purpose Myocardial infarction leads to heart failure. Autophagy is excessively activated in myocardial ischemia/reperfusion (I/R) in rats. The aim of this study is to investigate whether the protection of sevoflurane postconditioning (SPC) in myocardial I/R is through restored impaired autophagic flux. Methods Except for the sham control (SHAM) group, each rat underwent 30 min occlusion of the left anterior descending coronary (LAD) followed by 2 h reperfusion. Cardiac infarction was determined by 2,3,5-triphenyltetrazolium chloride triazole (TTC) staining. Cardiac function was examined by hemodynamics and echocardiography. The activation of autophagy was evaluated by autophagosome accumulation, LC3 conversion and p62 degradation. Potential molecular mechanisms were investigated by immunoblotting, real-time PCR and immunofluorescence staining. Results SPC improved the hemodynamic parameters, cardiac dysfunction, histopathological and ultrastructural damages, and decreased myocardial infarction size after myocardial I/R injury ( P 〈 0.05 vs. I/R group). Compared with the cases in I/R group, myocardial ATP and NAD + content, mitochondrial function related genes and proteins, and the expressions of SOD2 and HO-1 were increased, while the expressions of ROS and Vimentin were decreased in the SPC group ( P 〈 0.05 vs. I/R group). SPC significantly activated Akt/mTOR signaling, and inhibited the formation of Vps34/Beclin1 complex via increasing expression of Bcl2 protein ( P 〈 0.05 vs. I/R group). SPC suppressed elevated expressions of LC3 II/I ratio, Beclin1, Atg5 and Atg7 in I/R rat, which indicated that SPC inhibited over-activation of autophagy, and promoted autophagosome clearance. Meanwhile, SPC significantly suppressed the decline of Opa1 and increases of Drp1 and Parkin induced by I/R injury ( P 〈 0.05 vs. I/R group). Moreover, SPC maintained the contents of ATP by reducing impaired mitochondria. Conclusion SPC protects rat hearts against I/R injury via ameliorating mitochondrial impairment, oxidative stress and rescuing autophagic clearance.

Description: by Lisa Müller, Erich Müller, Carolin Hildebrandt, Elmar Kornexl, Christian Raschner The relative age effect (RAE), which refers to an over-representation of selected athletes born early in the selection year, was proven to be present in alpine ski racing in all age categories at both national and international levels. However, the influential factors on, or the causal mechanisms of, the RAE are still unknown. Therefore, the aim of the present study was to examine three possible influential factors on the relative age effect in alpine skiing: physical performance, anthropometric characteristics and biological maturational status. The study included the investigation of 282 elite Austrian youth ski racers and 413 non-athletes (comparison group) of the same age (10–13 years) and region. Six physical performance tests were performed, body mass and height were assessed, and the age at peak height velocity (APHV) was calculated. A significant RAE was present in the ski racers. No differences were shown in the physical performance characteristics or in the calculated APHV between the relative age quarters. These results suggest that ski racers born in the last quarter can counteract the relative age disadvantages if they already present the same level of physical performance and maturational status as those born at the beginning of the year. The height and weight of ski racers born at the beginning of the year were significantly higher compared to the non-athletes, and ski racers born in relative age quarter 1 were taller and heavier compared to the ski racers of the other quarters. This indicates that the anthropometric characteristics influence the selection process in alpine ski racing, and that relatively older athletes are more likely to be selected if they exhibit advanced anthropometric characteristics.

Description: by Andrea Pelletier-Baldelli, Jessica A. Bernard, Vijay A. Mittal Social processes are key to navigating the world, and investigating their underlying mechanisms and cognitive architecture can aid in understanding disease states such as schizophrenia, where social processes are highly impacted. Evidence suggests that social processes are impaired in individuals at ultra high-risk for the development of psychosis (UHR). Understanding these phenomena in UHR youth may clarify disease etiology and social processes in a period that is characterized by significantly fewer confounds than schizophrenia. Furthermore, understanding social processing deficits in this population will help explain these processes in healthy individuals. The current study examined resting state connectivity of the salience (SN) and default mode networks (DMN) in association with facial emotion recognition (FER), an integral aspect of social processes, as well as broader social functioning (SF) in UHR individuals and healthy controls. Consistent with the existing literature, UHR youth were impaired in FER and SF when compared with controls. In the UHR group, we found increased connectivity between the SN and the medial prefrontal cortex, an area of the DMN relative to controls. In UHR youth, the DMN exhibited both positive and negative correlations with the somatosensory cortex/cerebellum and precuneus, respectively, which was linked with better FER performance. For SF, results showed that sensory processing links with the SN might be important in allowing for better SF for both groups, but especially in controls where sensory processing is likely to be unimpaired. These findings clarify how social processing deficits may manifest in psychosis, and underscore the importance of SN and DMN connectivity for social processing more generally.

Description: Article Individual-nucleotide resolution crosslinking and immunoprecipitation (iCLIP) can map RNA binding sites of RNA-binding proteins (RBPs). Here, the authors report an analysis tool that improves the binding site assignment for some RBPs that have length-dependent broader distribution for their iCLIP fragments. Nature Communications doi: 10.1038/ncomms8921 Authors: Christian Hauer, Tomaz Curk, Simon Anders, Thomas Schwarzl, Anne-Marie Alleaume, Jana Sieber, Ina Hollerer, Madhuri Bhuvanagiri, Wolfgang Huber, Matthias W. Hentze, Andreas E. Kulozik

Description: Article Pathological neovascularization causes blinding eye disease. Here the authors show that IL10 activates STAT3 signalling in the macrophages in the ageing eye, promoting their polarization towards a pro-angiogenic phenotype; interfering with this pathway reverses the pathology in a mouse model. Nature Communications doi: 10.1038/ncomms8847 Authors: Rei Nakamura, Abdoulaye Sene, Andrea Santeford, Abdelaziz Gdoura, Shunsuke Kubota, Nicole Zapata, Rajendra S. Apte

Description: by Marc O. Nadon, Jerald S. Ault, Ivor D. Williams, Steven G. Smith, Gerard T. DiNardo The coral reef fish community of Hawaii is composed of hundreds of species, supports a multimillion dollar fishing and tourism industry, and is of great cultural importance to the local population. However, a major stock assessment of Hawaiian coral reef fish populations has not yet been conducted. Here we used the robust indicator variable “average length in the exploited phase of the population (L¯)”, estimated from size composition data from commercial fisheries trip reports and fishery-independent diver surveys, to evaluate exploitation rates for 19 Hawaiian reef fishes. By and large, the average lengths obtained from diver surveys agreed well with those from commercial data. We used the estimated exploitation rates coupled with life history parameters synthesized from the literature to parameterize a numerical population model and generate stock sustainability metrics such as spawning potential ratios (SPR). We found good agreement between predicted average lengths in an unfished population (from our population model) and those observed from diver surveys in the largely unexploited Northwestern Hawaiian Islands. Of 19 exploited reef fish species assessed in the main Hawaiian Islands, 9 had SPRs close to or below the 30% overfishing threshold. In general, longer-lived species such as surgeonfishes, the redlip parrotfish ( Scarus rubroviolaceus ), and the gray snapper ( Aprion virescens ) had the lowest SPRs, while short-lived species such as goatfishes and jacks, as well as two invasive species ( Lutjanus kasmira and Cephalopholis argus ), had SPRs above the 30% threshold.

Description: by Leonie J. P. Steenis, Marjolein Verhoeven, Dave J. Hessen, Anneloes L. van Baar Background The Bayley Scales of Infant and Toddler Development-third edition (Bayley-III) are frequently used to assess early child development worldwide. However, the original standardization only included US children, and it is still unclear whether or not these norms are adequate for use in other populations. Recently, norms for the Dutch version of the Bayley-III (The Bayley-III-NL) were made. Scores based on Dutch and US norms were compared to study the need for population-specific norms. Methods Scaled scores based on Dutch and US norms were compared for 1912 children between 14 days and 42 months 14 days. Next, the proportions of children scoring 〈 1-SD and 〈 -2 SD based on the two norms were compared, to identify over- or under-referral for developmental delay resulting from non-population-based norms. Results Scaled scores based on Dutch norms fluctuated around values based on US norms on all subtests. The extent of the deviations differed across ages and subtests. Differences in means were significant across all five subtests (p 〈 .01) with small to large effect sizes ( η p 2 ) ranging from .03 to .26). Using the US instead of Dutch norms resulted in over-referral regarding gross motor skills, and under-referral regarding cognitive, receptive communication, expressive communication, and fine motor skills. Conclusions The Dutch norms differ from the US norms for all subtests and these differences are clinically relevant. Population specific norms are needed to identify children with low scores for referral and intervention, and to facilitate international comparisons of population data.

Description: by Xiao-Dan Wang, Hui Lu, Zhihong Shi, Li Cai, Shuai Liu, Shuling Liu, Tong Han, Ying Wang, Yuying Zhou, Xinping Wang, Shuo Gao, Yong Ji Posterior cortical atrophy (PCA) is a clinicoradiologic neurodegenerative syndrome characterized by predominant impairment of higher visual functions. Neuroimaging and neuropathological studies show that PCA is probably an atypical presentation of Alzheimer’s disease. However, in China PCA has rarely been studied and remains largely unknown. Our study therefore aimed to analyze the clinical manifestations and patterns of cerebral atrophy, amyloid beta deposition and regional glucose metabolism in Chinese PCA patients, comparing them directly with those of typical Alzheimer’s disease (TAD). Seven PCA patients, 6 TAD patients and 5 controls underwent neuropsychological assessment, MRI scan, 11 C-PIB PET scan and 18 F-FDG PET scan. Cerebral atrophy including ventricular enlargement, posterior atrophy and medial temporal lobe atrophy were evaluated with MRI. The uptake of 11 C-PIB was quantified at the voxel level using the standardized uptake value ratio. Comparisons of regional cerebral glucose metabolism were calculated with statistical parametric mapping. PCA patients showed significant impairment on visuospatial function in neuropsychological assessment. And PCA patients showed more severe posterior atrophy and less severe left medial temporal lobe atrophy compared with TAD patients. The data from 11 C-PIB PET scanning showed that amyloid beta deposition in PCA was comparable to TAD. Moreover, in PCA the results from 18 F-FDG PET scanning revealed significant hypometabolism in the temporoparietooccipital region and identified specific hypometabolism in the right occipital lobe, compared with TAD. Our study thus provides a preliminary view of PCA in Chinese patients. A further study with a larger number of subjects would be recommended to confirm these findings.

Description: by Q. Wang, M. Li, Edmond H. M. Lou, M. S. Wong Background Non-ionizing radiation imaging assessment has been advocated for the patients with adolescent idiopathic scoliosis (AIS). As one of the radiation-free methods, ultrasound imaging has gained growing attention in scoliosis assessment over the past decade. The center of laminae (COL) method has been proposed to measure the spinal curvature in the coronal plane of ultrasound image. However, the reliability and validity of this ultrasound method have not been validated in the clinical setting. Objectives To evaluate the reliability and validity of clinical ultrasound imaging on lateral curvature measurements of AIS with their corresponding magnetic resonance imaging (MRI) measurements. Methods Thirty curves (ranged 10.2°–68.2°) from sixteen patients with AIS were eligible for this study. The ultrasound scan was performed using a 3-D ultrasound unit within the same morning of MRI examination. Two researchers were involved in data collection of these two examinations. The COL method was used to measure the coronal curvature in ultrasound image, compared with the Cobb method in MRI. The intra- and inter-rater reliability of the COL method was evaluated by intra-class correlation coefficient (ICC). The validity of this method was analyzed by paired Student’s t -test, Bland–Altman statistics and Pearson correlation coefficient. The level of significance was set as 0.05. Results The COL method showed high intra- and inter-rater reliabilities (both with ICC (2, K) 〉0.9, p

Description: by Yongkang Kim, Taesung Park Genome-wide association studies (GWAS) have successfully discovered hundreds of associations between genetic variants and complex traits. Most GWAS have focused on the identification of single variants. It has been shown that most of the variants that were discovered by GWAS could only partially explain disease heritability. The explanation for this missing heritability is generally believed to be gene-gene (GG) or gene-environment (GE) interactions and other structural variants. Generalized multifactor dimensionality reduction (GMDR) has been proven to be reasonably powerful in detecting GG and GE interactions; however, its performance has been found to decline when outlying quantitative traits are present. This paper proposes a robust GMDR estimation method (based on the L-estimator and M-estimator estimation methods) in an attempt to reduce the effects caused by outlying traits. A comparison of robust GMDR with the original MDR based on simulation studies showed the former method to outperform the latter. The performance of robust GMDR is illustrated through a real GWA example consisting of 8,577 samples from the Korean population using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) level as a phenotype. Robust GMDR identified the KCNH1 gene to have strong interaction effects with other genes on the function of insulin secretion.

Description: by Min Gao, Renli Tian, Junhao Wen, Qingyu Xiong, Bin Ling, Linda Yang In recent years, recommender systems have become an effective method to process information overload. However, recommendation technology still suffers from many problems. One of the problems is shilling attacks-attackers inject spam user profiles to disturb the list of recommendation items. There are two characteristics of all types of shilling attacks: 1) Item abnormality: The rating of target items is always maximum or minimum; and 2) Attack promptness: It takes only a very short period time to inject attack profiles. Some papers have proposed item anomaly detection methods based on these two characteristics, but their detection rate, false alarm rate, and universality need to be further improved. To solve these problems, this paper proposes an item anomaly detection method based on dynamic partitioning for time series. This method first dynamically partitions item-rating time series based on important points. Then, we use chi square distribution (χ 2 ) to detect abnormal intervals. The experimental results on MovieLens 100K and 1M indicate that this approach has a high detection rate and a low false alarm rate and is stable toward different attack models and filler sizes.

Description: by Morgan Kruse, Rebecca Wildner, Gisoo Barnes, Monique Martin, Udo Mueller, Francesco Lo-Coco, Ashutosh Pathak The objective of this study was to estimate the net cost of arsenic trioxide (ATO) added to all- trans retinoic acid (ATRA) compared to ATRA plus chemotherapy when used in first-line acute promyelocytic leukemia (APL) treatment for low to intermediate risk patients from the perspective of the overall Italian healthcare systemA Markov model was developed with 3 health states: stable disease, disease event and death. Each month, patients could move from stable to disease event or die from either state. After a disease event, patients discontinued initial treatment and switched to the other regimen as second-line therapy. Treatment regimens, efficacy and adverse events were derived from published sources and expert opinion; unit costs were collected from standard Italian sources. Clinical outcomes and costs for pre-ATO and post-ATO scenarios were combined with population and product utilization information to calculate the total budgetary impact using a 3-year time horizon; one-way sensitivity analyses were conducted. Three-year cumulative pharmacy costs for ATO+ATRA were €46,700 per-patient versus €6,500 for ATRA+chemotherapy; however, medical costs for ATO+ATRA were €12,300 per-patient versus €30,200 for ATRA+chemotherapy. The total budgetary impact was estimated to be an additional €127,300, €312,500 and €477,800 in the first, second and third years, respectively. The model was most sensitive to changes in the cost of the ATO+ATRA regimen during the consolidation phase. Budgetary impact models are valuable to payers making formulary decisions regarding the access and affordability of new medicines. The cost of treatment analysis showed that pharmacy costs for ATO+ATRA were higher than for ATRA+chemotherapy, while all other evaluated costs were lower for ATO+ATRA treated patients. The average budgetary impact was €305,900 per year overall, representing a 3.5% increase. Further research is needed to determine the cost-effectiveness of ATO+ATRA compared to the current first-line standard of care in APL.

Description: by Antonella Agodi, Martina Barchitta, Annalisa Quattrocchi, Andrea Maugeri, Manlio Vinciguerra Objective The Death-Associated Protein Kinase 1 ( DAPK1 ) gene has been frequently investigated in cervical cancer (CC). The aim of the present study was to carry out a systematic review and a meta-analysis in order to evaluate DAPK1 promoter methylation as an epigenetic marker for CC risk. Methods A systematic literature search was carried out. The Cochrane software package Review Manager 5.2 was used. The fixed-effects or random-effects models, according to heterogeneity across studies, were used to calculate odds ratios (ORs) and 95% Confidence Intervals (CIs). Furthermore, subgroup analyses were conducted by histological type, assays used to evaluate DAPK1 promoter methylation, and control sample source. Results A total of 20 papers, published between 2001 and 2014, on 1929 samples, were included in the meta-analysis. DAPK1 promoter methylation was associated with an increased CC risk based on the random effects model (OR: 21.20; 95%CI = 11.14–40.35). Omitting the most heterogeneous study, the between study heterogeneity decreased and the association increased (OR: 24.13; 95% CI = 15.83–36.78). The association was also confirmed in all the subgroups analyses. Conclusions A significant strong association between DAPK1 promoter methylation and CC was shown and confirmed independently by histological tumor type, method used to evaluate methylation and source of control samples. Methylation markers may have value in early detection of CC precursor lesions, provide added reassurances of safety for women who are candidates for less frequent screens, and predict outcomes of women infected with human papilloma virus.

Description: by Yufeng Huang, Chuchu Wang, Yufeng Yao, Xiaoyu Zuo, Shanshan Chen, Chengqi Xu, Hongfu Zhang, Qiulun Lu, Le Chang, Fan Wang, Pengxia Wang, Rongfeng Zhang, Zhenkun Hu, Qixue Song, Xiaowei Yang, Cong Li, Sisi Li, Yuanyuan Zhao, Qin Yang, Dan Yin, Xiaojing Wang, Wenxia Si, Xiuchun Li, Xin Xiong, Dan Wang, Yuan Huang, Chunyan Luo, Jia Li, Jingjing Wang, Jing Chen, Longfei Wang, Li Wang, Meng Han, Jian Ye, Feifei Chen, Jingqiu Liu, Ying Liu, Gang Wu, Bo Yang, Xiang Cheng, Yuhua Liao, Yanxia Wu, Tie Ke, Qiuyun Chen, Xin Tu, Robert Elston, Shaoqi Rao, Yanzong Yang, Yunlong Xia, Qing K. Wang Atrial fibrillation (AF) is the most common cardiac arrhythmia at the clinic. Recent GWAS identified several variants associated with AF, but they account for

Description: by Shu-I Wu, Su-Chiu Chen, Shen-Ing Liu, Fang-Ju Sun, Jimmy J. M. Juang, Hsin-Chien Lee, Kai-Liang Kao, Michael E. Dewey, Martin Prince, Robert Stewart Objective Despite high mortality associated with serious mental illness, risk of acute myocardial infarction (AMI) remains unclear, especially for patients with bipolar disorder. The main objective was to investigate the relative risk of AMI associated with schizophrenia and bipolar disorders in a national sample. Method Using nationwide administrative data, an 11-year historic cohort study was assembled, comprised of cases aged 18 and above who had received a diagnosis of schizophrenia or bipolar disorder, compared to a random sample of all other adults excluding those with diagnoses of serious mental illness. Incident AMI as a primary diagnosis was ascertained. Hazard ratios stratified by age and gender were calculated and Cox regression models were used to adjust for other covariates. Results A total of 70,225 people with schizophrenia or bipolar disorder and 207,592 people without serious mental illness were compared. Hazard ratios in men adjusted for age, income and urbanization were 1.15 (95% CI 1.01~1.32) for schizophrenia and 1.37 (1.08~1.73)for bipolar disorder, and in women, 1.85 (1.58~2.18) and 1.88(1.47~2.41) respectively. Further adjustment for treated hypertension, diabetes and hyperlipidaemia attenuated the hazard ratio for men with schizophrenia but not the other comparison groups. Hazard ratios were significantly stronger in women than men and were stronger in younger compared to older age groups for both disorders; however, gender modification was only significant in people with schizophrenia, and age modification only significant in people with bipolar disorder. Conclusions In this large national sample, schizophrenia and bipolar disorder were associated with raised risk of AMI in women and in the younger age groups although showed differences in potential confounding and modifying factors.

Description: by Kwi Young Kang, In Je Kim, Min A Yoon, Yeon Sik Hong, Sung-Hwan Park, Ji Hyeon Ju Objective To study the relationship between inflammatory and structural lesions in the sacroiliac joints (SIJs) on MRI and spinal progression observed on conventional radiographs in patients with axial spondyloarthritis (axSpA). Methods One hundred and ten patients who fulfilled the ASAS axSpA criteria were enrolled. All underwent SIJ MRI at baseline and lumbar spine radiographs at baseline and after 2 years. Inflammatory and structural lesions on SIJ MRI were scored using the SPondyloArthritis Research Consortium of Canada (SPARCC) method. Spinal radiographs were scored using the Stoke AS Spinal Score (SASSS). Multivariate logistic regression analysis was performed to identify predictors of spinal progression. Results Among the 110 patients, 25 (23%) showed significant radiographic progression (change of SASSS≥2) over 2 years. There was no change in the SASSS over 2 years according to the type of inflammatory lesion. Patients with fat metaplasia or ankyloses on baseline MRI showed a significantly higher SASSS at 2 years than those without (p

Description: Article A hybrid incompatibility between Capsella plant species is due to an interaction between two immune regulators. Here, the authors show that highly divergent haplotypes result from balancing selection in the ancestral lineage and their sorting into derived lineages facilitated the evolution of the incompatibility. Nature Communications doi: 10.1038/ncomms8960 Authors: Adrien Sicard, Christian Kappel, Emily B. Josephs, Young Wha Lee, Cindy Marona, John R. Stinchcombe, Stephen I. Wright, Michael Lenhard

Description: Nature Reviews Microbiology 13, 526 (2015). doi:10.1038/nrmicro3538 Author: Cláudio Nunes-Alves Persisters are dormant bacterial populations that contribute to multidrug tolerance (MDT) because they are able to escape treatment with most antibiotics, which target metabolically active cells. A new study now characterizes the molecular basis for persister generation involving HipA, a kinase that inhibits protein synthesis

Description: Nature Reviews Microbiology 13, 589 (2015). doi:10.1038/nrmicro3504 Authors: Peter Liehl, Vanessa Zuzarte-Luis & Maria M. Mota Many clinically relevant pathogens, including certain bacteria and protozoan parasites, have developed an intracellular lifestyle that enables them to nestle in customized vacuoles. Although these pathogens are protected from extracellular defences, recent findings indicate that host cells have evolved multiple strategies to unmask the pathogen

Description: Article Mapping the distribution of fluorescence molecules, rather than just their emission intensity, can improve super-resolution fluorescence microscopy. Here, the authors present a general solution for rendering the number of fluorescent molecules recorded by confocal or STED microscopy. Nature Communications doi: 10.1038/ncomms8977 Authors: Haisen Ta, Jan Keller, Markus Haltmeier, Sinem K. Saka, Jürgen Schmied, Felipe Opazo, Philip Tinnefeld, Axel Munk, Stefan W. Hell

Description: Article Persistent antigen stimulation can cause exhaustion and unresponsiveness of CD8 cells, impairing the immune response. Here the authors show that increasing the number of CD8 cells, decreasing the antigen load or providing CD4 help can overcome the exhaustion and establish a memory response. Nature Communications doi: 10.1038/ncomms8994 Authors: Juhyun Kim, Su Jeong Ryu, Keunhee Oh, Ji-Min Ju, Ji Yeong Jeon, Giri Nam, Dong-Sup Lee, Hang-Rae Kim, Joo Young Kim, Jun Chang, Thomas Sproule, Kyungho Choi, Derry Roopenian, Eun Young Choi

Description: Article Plasmonic surfaces are used as two-dimensional metamaterials for light manipulation on nanoscale, and their optical properties can be further tuned by coating. Here the authors report a new absorption-induced scattering mode in a silver nanoparticle array coated with semiconducting organic absorbers. Nature Communications doi: 10.1038/ncomms8899 Authors: Christopher E. Petoukhoff, Deirdre M. O’Carroll

Description: Article U-shaped glacial valleys dominate 〉10 ka since the last major glaciation and the transitions from glacier-dominated to fluvial regimes are poorly understood. Here, the authors use digital topographic data to show that glacial topography is rapidly replaced by fluvial topography where rock uplift rates are high. Nature Communications doi: 10.1038/ncomms9028 Authors: Günther Prasicek, Isaac J. Larsen, David R. Montgomery

Description: by Andrew J. Massey High-content imaging is a powerful tool for determining cell phenotypes at the single cell level. Characterising the effect of small molecules on cell cycle distribution is important for understanding their mechanism of action especially in oncology drug discovery but also for understanding potential toxicology liabilities. Here, a high-throughput phenotypic assay utilising the PerkinElmer Operetta high-content imager and Harmony software to determine cell cycle distribution is described. PhenoLOGIC, a machine learning algorithm within Harmony software was employed to robustly separate single cells from cell clumps. DNA content, EdU incorporation and pHH3 (S10) expression levels were subsequently utilised to separate cells into the various phases of the cell cycle. The assay is amenable to multiplexing with an additional pharmacodynamic marker to assess cell cycle changes within a specific cellular sub-population. Using this approach, the cell cycle distribution of γH2AX positive nuclei was determined following treatment with DNA damaging agents. Likewise, the assay can be multiplexed with Ki67 to determine the fraction of quiescent cells and with BrdU dual labelling to determine S-phase duration. This methodology therefore provides a relatively cheap, quick and high-throughput phenotypic method for determining accurate cell cycle distribution for small molecule mechanism of action and drug toxicity studies.

Description: Article G protein-coupled receptors (GPCRs) are the largest family of transmembrane signaling proteins in humans and exhibit diverse activation mechanisms. Here, the authors combine electron microscopy, hydrogen deuterium exchange and Molecular dynamics simulations to gain insight into the activation mechanism of the glucagon receptor. Nature Communications doi: 10.1038/ncomms8859 Authors: Linlin Yang, Dehua Yang, Chris de Graaf, Arne Moeller, Graham M. West, Venkatasubramanian Dharmarajan, Chong Wang, Fai Y. Siu, Gaojie Song, Steffen Reedtz-Runge, Bruce D. Pascal, Beili Wu, Clinton S. Potter, Hu Zhou, Patrick R. Griffin, Bridget Carragher, Huaiyu Yang, Ming-Wei Wang, Raymond C. Stevens, Hualiang Jiang

Description: Article Light atoms are hardly visible through standard microscopy techniques, because of their smaller scattering power and higher knock-on probability. Here, the authors present an approach to probe light atoms by means of electron energy loss spectroscopy, relying on inelastically scattered electrons. Nature Communications doi: 10.1038/ncomms8943 Authors: Ryosuke Senga, Kazu Suenaga

Description: by Stéphane J. Montuelle, Susan H. Williams Cranial kinesis refers to movements of skeletal sub-units relative to one another at mobile sutures within the skull. The presence and functional significance of cranial kinesis has been investigated in various vertebrates, with much of our understanding coming from comparative studies and manipulation of ligamentous specimens. Drawing on these studies, cranial kinesis in lizards has been modeled as a four-bar linkage system involving streptostyly (rotation of the quadrate), hypokinesis (dorsoventral flexion and extension of the palato-maxillary sub-unit), mesokinesis (dorsoventral flexion and extension of the snout at the fronto-parietal suture) and metakinesis (sliding movements between parietal and supraocciptal bones). In vivo studies, although limited, suggest that cranial kinesis serves an important role during routine behaviors such as feeding. Here, we use X-ray Reconstruction Of Moving Morphology to further quantify mesokinesis in vivo in Gekko gecko during three routine behaviors: gape display, biting and post-ingestion feeding. During gape display, the snout rotates dorsally above rest position, with mesokinesis accounting for a 10% increase in maximum gape over that achieved solely by the depression of the lower jaw. During defensive biting, the snout rotates ventrally below rest position to participate in gape closure. Finally, ventroflexion of the snout also occurs during post-ingestion feeding, accounting for 42% of gape closure during intra-oral transport, 86% during puncture-crushing, and 61% during pharyngeal packing. Mesokinesis thus appears to facilitate prey puncturing by allowing the snout to rotate ventrally so that the upper teeth pierce the prey item, thus limiting the need for large movements of the lower jaw. This is suggested to maintain a firm grip on the prey and reduce the possibility of prey escape. More generally, this study demonstrates that mesokinesis is a key component of defensive biting and gape display behaviors, as well as post-ingestion feeding, all of which are linked to organismal fitness.

Description: by Xianqiong Gong, Jiaen Yang, Jinmo Tang, Chong Gu, Lijian Huang, Ying Zheng, Huiqing Liang, Min Wang, Chuncheng Wu, Yue Chen, Manying Zhang, Zhijian Yu, Qianguo Mao To understand the mechanisms underlying the discordance between normal serum alanine aminotransferase (ALT) levels and significant alterations in liver histology of chronic hepatitis B virus (HBV) infection with persistent normal ALT (PNALT) or minimally elevated ALT. A total of 300 treatment-naive chronic HBV-infected patients with PNALT (ALT ≤ upper limit of normal [ULN, 40 U/ml]) or minimally elevated ALT (1-2×ULN) were retrospectively enrolled. All patients underwent liver biopsy and histological changes were analyzed along with biochemical and HBV markers. Among 300 participants, 177 were HBeAg-positive and 123 HBeAg-negative. Significant histologic abnormalities were found in 42.9% (76/177) and 52.8% (65/123) of HBeAg-positive and HBeAg-negative patients, respectively. Significant fibrosis, which is a marker of prior injury, was more frequently detected than significant necroinflammation (suggesting active liver injury) in both HBeAg-positive and -negative groups, suggesting that liver injury occurred intermittently in our cohort. No significant differences were noticed in the percentage of patients with severe fibrosis between HBeAg-positive and negative phases or between ages 30 and 40 and over 40, suggesting that the fibrosis was possibly carried over from an early phase. Finally, lowering ALT ULN (30 U/L for men, 19 U/L for women) alone was not adequate to increase the sensitivity of ALT detection of liver injury. However, the study was limited to a small sample size of 13 HBeAg-positive patients with ALT in the revised normal range. We detected significant liver pathology in almost 50% of chronic HBV infected patients with PNALT (ALT ≤ 40 U/ml) or minimally elevated ALT. We postulated that small-scale intermittent liver injury was possibly responsible for the discordance between normal serum ALT and significant liver changes in our cohort.

Description: Article Unmet need exists for a vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV). Here the authors report the establishment and evaluation, in mice and primates, of a series of MERS-CoV immunogens and show that they can serve as promising leads for vaccine development. Nature Communications doi: 10.1038/ncomms8712 Authors: Lingshu Wang, Wei Shi, M. Gordon Joyce, Kayvon Modjarrad, Yi Zhang, Kwanyee Leung, Christopher R. Lees, Tongqing Zhou, Hadi M. Yassine, Masaru Kanekiyo, Zhi-yong Yang, Xuejun Chen, Michelle M. Becker, Megan Freeman, Leatrice Vogel, Joshua C. Johnson, Gene Olinger, John P. Todd, Ulas Bagci, Jeffrey Solomon, Daniel J. Mollura, Lisa Hensley, Peter Jahrling, Mark R. Denison, Srinivas S. Rao, Kanta Subbarao, Peter D. Kwong, John R. Mascola, Wing-Pui Kong, Barney S. Graham

Description: Article Noble metals typically crystallize with the face-centered cubic structure. Here, the authors report the synthesis of gold nanoribbons in the 4H hexagonal polytype, a previously unreported, metastable phase of gold, and use it to stabilize 4H hexagonal phases of silver, palladium and platinum. Nature Communications doi: 10.1038/ncomms8684 Authors: Zhanxi Fan, Michel Bosman, Xiao Huang, Ding Huang, Yi Yu, Khuong P. Ong, Yuriy A. Akimov, Lin Wu, Bing Li, Jumiati Wu, Ying Huang, Qing Liu, Ching Eng Png, Chee Lip Gan, Peidong Yang, Hua Zhang

Description: Article All quantum systems are connected to their environment, and this reduces their quantumness through decoherence. Here, the authors show that the interaction between a macroscale quantum system—a micromechanical oscillator—and its environment leads to non-Markovian Brownian motion Nature Communications doi: 10.1038/ncomms8606 Authors: S. Gröblacher, A. Trubarov, N. Prigge, G. D. Cole, M. Aspelmeyer, J. Eisert

Description: Article Sensory cortical tuning is shaped by experience to facilitate coding of features that are predictive of behaviourally relevant outcomes. Here the authors demonstrate that rapid behaviourally driven retuning of human visual cortex involves top–down projections as well as local inhibitory interactions. Nature Communications doi: 10.1038/ncomms8823 Authors: Lisa M. McTeague, L. Forest Gruss, Andreas Keil

Description: Article The MCM8-9 complex is required for repair of DNA double-strand breaks (DSBs). Here, the authors show that MCM8-9 is required for the nuclease activity of the MRE11-RAD50-NBS1 complex (MRN) and stabilizes its association with DNA damage sites, promoting resection of DSB ends. Nature Communications doi: 10.1038/ncomms8744 Authors: Kyung Yong Lee, Jun-Sub Im, Etsuko Shibata, Jonghoon Park, Naofumi Handa, Stephen C. Kowalczykowski, Anindya Dutta

Description: Article Homologous repair of DNA double strand breaks in Saccharomyces cerevisiae is dependent on several conserved Rad51 paralogs. Here the authors provide biochemical evidence that Rad55-Rad57 synergistically interacts with the Shu complex to promote Rad51 filament formation and homology directed repair. Nature Communications doi: 10.1038/ncomms8834 Authors: William A. Gaines, Stephen K. Godin, Faiz F. Kabbinavar, Timsi Rao, Andrew P. VanDemark, Patrick Sung, Kara A. Bernstein

Description: Article Phytochromes are red-light photoreceptors in plants that regulate key life cycle processes, yet their evolutionary origins are not well understood. Using transcriptomic and genomic data, Li et al. find that canonical plant phytochromes originated in a common ancestor of land plants and charophyte algae. Nature Communications doi: 10.1038/ncomms8852 Authors: Fay-Wei Li, Michael Melkonian, Carl J. Rothfels, Juan Carlos Villarreal, Dennis W. Stevenson, Sean W. Graham, Gane Ka-Shu Wong, Kathleen M. Pryer, Sarah Mathews

Description: Article Experimental studies of hydrogen at high pressure are challenging, so theory is central to understanding its phase behaviour; however, computed phase diagrams do not agree with previous measurements. Here, the authors use a quantum Monte Carlo method and present results in qualitative agreement with experiment. Nature Communications doi: 10.1038/ncomms8794 Authors: N. D. Drummond, Bartomeu Monserrat, Jonathan H. Lloyd-Williams, P. López Ríos, Chris J. Pickard, R. J. Needs

Description: Article The onset of neurodegenerative disorders is associated at the molecular level with insoluble protein aggregates, named amyloids. Here, the authors characterize by infrared nanospectroscopy and nanomechanical studies, the amyloid aggregation at the individual species scale. Nature Communications doi: 10.1038/ncomms8831 Authors: F. S. Ruggeri, G. Longo, S. Faggiano, E. Lipiec, A. Pastore, G. Dietler

Description: by Seungcheol Kang, Han-Soo Kim, Ilkyu Han Unplanned excision of extremity soft tissue sarcoma (STS) is common and has detrimental effects not only on patients’ oncologic outcomes but also on functional and economic issues. However, no study has analyzed a nationwide population-based database. To estimate the incidence and treatment pattern of unplanned excision in extremity STS in the Korean population, a nationwide epidemiologic study was performed using the Korean Health Insurance Review and Assessment Service database, a centralized nationwide healthcare claims registry of Korea that covers the entire Korean population. Among 1,517 patients with extremity STS in the 4-year study period, 553 (36.5%) underwent unplanned excision (unplanned group). About 80% of unplanned excisions were performed in tertiary or general hospitals. Of the unplanned group, 240 (43.4%) underwent re-excision with or without radiation therapy and/or chemotherapy, and 51 (9.2%) did not undergo re-excision but were treated with radiation therapy and/or chemotherapy; whereas, 262 (47.4%) did not undergo any further treatment following unplanned excision. This study is the first nationwide population-based study on the unplanned excision of extremity STS. The results may have implications in establishing preventive or therapeutic measures to reduce the burden of unplanned excision of extremity STS.

Description: by Dong-He Li, Wei Shi, Thomas A. Munroe, Li Gong, Xiao-Yu Kong Mitogenomes of flatfishes (Pleuronectiformes) exhibit the greatest diversity of gene rear-rangements in teleostean fishes. Duplicate control regions (CRs) have been found in the mito-genomes of two flatfishes, Samariscus latus (Samaridae) and Laeops lanceolata (Bothidae), which is rare in teleosts. It has been reported that duplicate CRs have evolved in a concerted fashion in fishes and other animals, however, whether concerted evo-lution exists in flatfishes remains unknown. In this study, based on five newly sequenced and six previously reported mitogenomes of lefteye flounders in the Bothidae, we explored whether duplicate CRs and concerted evolution exist in these species. Results based on the present study and previous reports show that four out of eleven bothid species examined have duplicate CRs of their mitogenomes. The core regions of the duplicate CRs of mitogenomes in the same species have identical, or nearly identical, sequences when compared to each other. This pattern fits the typical characteristics of concerted evolution. Additionally, phylogenetic and ancestral state reconstruction analysis also provided evidence to support the hypothesis that duplicate CRs evolved concertedly. The core region of concerted evolution is situated at the conserved domains of the CR of the mitogenome from the termination associated sequences (TASs) to the conserved sequence blocks (CSBs). Commonly, this region is con-sidered to regulate mitochondrial replication and transcription. Thus, we hypothesize that the cause of concerted evolution of the duplicate CRs in the mtDNAs of these four bothids may be related to some function of the conserved sequences of the CRs during mitochondrial rep-lication and transcription. We hope our results will provide fresh insight into the molecular mechanisms related to replication and evolution of mitogenomes.

Description: by David Knight, Konstantin G. Iliadi, Natalia Iliadi, Ronit Wilk, Jack Hu, Henry M. Krause, Paul Taylor, Michael F. Moran, Gabrielle L. Boulianne Synaptic transmission is highly plastic and subject to regulation by a wide variety of neuromodulators and neuropeptides. In the present study, we have examined the role of isoforms of the cytochrome b561 homologue called no extended memory ( nemy ) in regulation of synaptic strength and plasticity at the neuromuscular junction (NMJ) of third instar larvae in Drosophila . Specifically, we generated two independent excisions of nemy that differentially affect the expression of nemy isoforms. We show that the nemy 45 excision, which specifically reduces the expression of the longest splice form of nemy , leads to an increase in stimulus evoked transmitter release and altered synaptic plasticity at the NMJ. Conversely, the nemy 26.2 excision, which appears to reduce the expression of all splice forms except the longest splice isoform, shows a reduction in stimulus evoked transmitter release, and enhanced synaptic plasticity. We further show that nemy 45 mutants have reduced levels of amidated peptides similar to that observed in peptidyl-glycine hydryoxylating mono-oxygenase (PHM) mutants. In contrast, nemy 26.2 mutants show no defects in peptide amidation but rather display a decrease in Tyramine β hydroxylase activity (TβH). Taken together, these results show non-redundant roles for the different nemy isoforms and shed light on the complex regulation of neuromodulators.

Description: by Davide Bolignano, Graziella D’Arrigo, Anna Pisano, Giuseppe Coppolino Background Pentoxifylline (PTX) is a promising therapeutic approach for reducing inflammation and improving anemia associated to various systemic disorders. However, whether this agent may be helpful for anemia management also in CKD patients is still object of debate. Study Design Systematic review and meta-analysis. Population Adults with CKD (any KDOQI stage, including ESKD patients on regular dialysis) and anemia (Hb

Description: by Yukihiko Hiroshima, Ming Zhao, Yong Zhang, Nan Zhang, Ali Maawy, Takashi Murakami, Sumiyuki Mii, Fuminari Uehara, Mako Yamamoto, Shinji Miwa, Shuya Yano, Masashi Momiyama, Ryutaro Mori, Ryusei Matsuyama, Takashi Chishima, Kuniya Tanaka, Yasushi Ichikawa, Michael Bouvet, Itaru Endo, Robert M. Hoffman A patient-derived nude-mouse model of soft-tissue sarcoma has been established and treated in the following groups: (1) untreated controls; (2) gemcitabine (GEM) (80 mg/kg, ip, weekly, 3 weeks); (3) Pazopanib (100 mg/kg, orally, daily, 3 weeks) and (4) Salmonella typhimurium A1-R (5 × 10 7 CFU/body, ip, weekly, 3 weeks). The sarcoma was resistant to GEM (p = 0.879). Pazopanib tended to reduce the tumor volume compared to the untreated mice, but there was no significant difference (p = 0.115). S . typhimurium A1-R significantly inhibited tumor growth compared to the untreated mice (p = 0.001). S . typhimurium A1-R was the only effective treatment for the soft-tissue sarcoma nude mouse model among all treatments including a newly approved multiple tyrosine kinase inhibitor; Pazopanib. These results suggest tumor-targeting S . typhimurium A1-R is a promising treatment for chemo-resistant soft-tissue sarcoma.

Description: by Fangqun OuYang, Jian-Feng Mao, Junhui Wang, Shougong Zhang, Yue Li The mechanisms by which different light spectra regulate plant shoot elongation vary, and phytohormones respond differently to such spectrum-associated regulatory effects. Light supplementation can effectively control seedling growth in Norway spruce. However, knowledge of the effective spectrum for promoting growth and phytohormone metabolism in this species is lacking. In this study, 3-year-old Norway spruce clones were illuminated for 12 h after sunset under blue or red light-emitting diode (LED) light for 90 d, and stem increments and other growth traits were determined. Endogenous hormone levels and transcriptome differences in the current needles were assessed to identify genes related to the red and blue light regulatory responses. The results showed that the stem increment and gibberellin (GA) levels of the seedlings illuminated by red light were 8.6% and 29.0% higher, respectively, than those of the seedlings illuminated by blue light. The indoleacetic acid (IAA) level of the seedlings illuminated by red light was 54.6% lower than that of the seedlings illuminated by blue light, and there were no significant differences in abscisic acid (ABA) or zeatin riboside [ZR] between the two groups of seedlings. The transcriptome results revealed 58,736,166 and 60,555,192 clean reads for the blue-light- and red-light-illuminated samples, respectively. Illumina sequencing revealed 21,923 unigenes, and 2744 (approximately 93.8%) out of 2926 differentially expressed genes (DEGs) were found to be upregulated under blue light. The main KEGG classifications of the DEGs were metabolic pathway (29%), biosynthesis of secondary metabolites (20.49%) and hormone signal transduction (8.39%). With regard to hormone signal transduction, AUXIN-RESISTANT1 ( AUX1 ), AUX/IAA genes, auxin-inducible genes, and early auxin-responsive genes [( auxin response factor ( ARF ) and small auxin-up RNA ( SAUR )] were all upregulated under blue light compared with red light, which might have yielded the higher IAA level. DELLA and phytochrome-interacting factor 3 (PIF3), involved in negative GA signaling, were also upregulated under blue light, which may be related to the lower GA level. Light quality also affects endogenous hormones by influencing secondary metabolism. Blue light promoted phenylpropanoid biosynthesis, phenylalanine metabolism, flavonoid biosynthesis and flavone and flavonol biosynthesis, accompanied by upregulation of most of the genes in their pathways. In conclusion, red light may promote stem growth by regulating biosynthesis of GAs, and blue light may promote flavonoid, lignin, phenylpropanoid and some hormones (such as jasmonic acid) which were related to plant defense in Norway spruce, which might reduce the primary metabolites available for plant growth.

Description: by Diane I. Schroeder, Kartika Jayashankar, Kory C. Douglas, Twanda L. Thirkill, Daniel York, Pete J. Dickinson, Lawrence E. Williams, Paul B. Samollow, Pablo J. Ross, Danika L. Bannasch, Gordon C. Douglas, Janine M. LaSalle Over the last 20-80 million years the mammalian placenta has taken on a variety of morphologies through both divergent and convergent evolution. Recently we have shown that the human placenta genome has a unique epigenetic pattern of large partially methylated domains (PMDs) and highly methylated domains (HMDs) with gene body DNA methylation positively correlating with level of gene expression. In order to determine the evolutionary conservation of DNA methylation patterns and transcriptional regulatory programs in the placenta, we performed a genome-wide methylome (MethylC-seq) analysis of human, rhesus macaque, squirrel monkey, mouse, dog, horse, and cow placentas as well as opossum extraembryonic membrane. We found that, similar to human placenta, mammalian placentas and opossum extraembryonic membrane have globally lower levels of methylation compared to somatic tissues. Higher relative gene body methylation was the conserved feature across all mammalian placentas, despite differences in PMD/HMDs and absolute methylation levels. Specifically, higher methylation over the bodies of genes involved in mitosis, vesicle-mediated transport, protein phosphorylation, and chromatin modification was observed compared with the rest of the genome. As in human placenta, higher methylation is associated with higher gene expression and is predictive of genic location across species. Analysis of DNA methylation in oocytes and preimplantation embryos shows a conserved pattern of gene body methylation similar to the placenta. Intriguingly, mouse and cow oocytes and mouse early embryos have PMD/HMDs but their placentas do not, suggesting that PMD/HMDs are a feature of early preimplantation methylation patterns that become lost during placental development in some species and following implantation of the embryo.

Description: by Bin Huang, Yongkui Wang, Wenhao Wang, Juan Chen, Pinglin Lai, Zhongyu Liu, Bo Yan, Song Xu, Zhongmin Zhang, Chun Zeng, Limin Rong, Bin Liu, Daozhang Cai, Dadi Jin, Xiaochun Bai The mechanistic target of rapamycin (mTOR) integrates both intracellular and extracellular signals to regulate cell growth and metabolism. However, the role of mTOR signaling in osteoblast differentiation and bone formation is undefined, and the underlying mechanisms have not been elucidated. Here, we report that activation of mTOR complex 1 (mTORC1) is required for preosteoblast proliferation; however, inactivation of mTORC1 is essential for their differentiation and maturation. Inhibition of mTORC1 prevented preosteoblast proliferation, but enhanced their differentiation in vitro and in mice. Activation of mTORC1 by deletion of tuberous sclerosis 1 ( Tsc1 ) in preosteoblasts produced immature woven bone in mice due to excess proliferation but impaired differentiation and maturation of the cells. The mTORC1-specific inhibitor, rapamycin, restored these in vitro and in vivo phenotypic changes. Mechanistically, mTORC1 prevented osteoblast maturation through activation of the STAT3/p63/Jagged/Notch pathway and downregulation of Runx2. Preosteoblasts with hyperactive mTORC1 reacquired the capacity to fully differentiate and maturate when subjected to inhibition of the Notch pathway. Together, these findings identified the role of mTORC1 in osteoblast formation and established that mTORC1 prevents preosteoblast differentiation and maturation through activation of the Notch pathway.

Description: by David M. Truong, F. Curtis Hewitt, Joseph H. Hanson, Xiaoxia Cui, Alan M. Lambowitz Mobile bacterial group II introns are evolutionary ancestors of spliceosomal introns and retroelements in eukaryotes. They consist of an autocatalytic intron RNA (a “ribozyme”) and an intron-encoded reverse transcriptase, which function together to promote intron integration into new DNA sites by a mechanism termed “retrohoming”. Although mobile group II introns splice and retrohome efficiently in bacteria, all examined thus far function inefficiently in eukaryotes, where their ribozyme activity is limited by low Mg 2+ concentrations, and intron-containing transcripts are subject to nonsense-mediated decay (NMD) and translational repression. Here, by using RNA polymerase II to express a humanized group II intron reverse transcriptase and T7 RNA polymerase to express intron transcripts resistant to NMD, we find that simply supplementing culture medium with Mg 2+ induces the Lactococcus lactis Ll.LtrB intron to retrohome into plasmid and chromosomal sites, the latter at frequencies up to ~0.1%, in viable HEK-293 cells. Surprisingly, under these conditions, the Ll.LtrB intron reverse transcriptase is required for retrohoming but not for RNA splicing as in bacteria. By using a genetic assay for in vivo selections combined with deep sequencing, we identified intron RNA mutations that enhance retrohoming in human cells, but

Description: by María F. Organista, Mercedes Martín, Jesus M. de Celis, Rosa Barrio, Ana López-Varea, Nuria Esteban, Mar Casado, Jose F. de Celis The Drosophila genes spalt major (salm) and spalt-related (salr) encode Zn-finger transcription factors regulated by the Decapentaplegic (Dpp) signalling pathway in the wing imaginal disc. The function of these genes is required for cell survival and proliferation in the central region of the wing disc, and also for vein patterning in the lateral regions. The identification of direct Salm and Salr target genes, and the analysis of their functions, are critical steps towards understanding the genetic control of growth and patterning of the Drosophila wing imaginal disc by the Dpp pathway. To identify candidate Salm/Salr target genes, we have compared the expression profile of salm/salr knockdown wing discs with control discs in microarray experiments. We studied by in situ hybridization the expression pattern of the genes whose mRNA levels varied significantly, and uncovered a complex transcription landscape regulated by the Spalt proteins in the wing disc. Interestingly, candidate Salm/Salr targets include genes which expression is turned off and genes which expression is positively regulated by Salm/Salr. Furthermore, loss-of-function phenotypic analysis of these genes indicates, for a fraction of them, a requirement for wing growth and patterning. The identification and analysis of candidate Salm/Salr target genes opens a new avenue to reconstruct the genetic structure of the wing, linking the activity of the Dpp pathway to the development of this epithelial tissue.

Description: by Alexandra A. Erwin, Mauricio A. Galdos, Michelle L. Wickersheim, Chris C. Harrison, Kendra D. Marr, Jack M. Colicchio, Justin P. Blumenstiel Sexual reproduction allows transposable elements (TEs) to proliferate, leading to rapid divergence between populations and species. A significant outcome of divergence in the TE landscape is evident in hybrid dysgenic syndromes, a strong form of genomic incompatibility that can arise when (TE) family abundance differs between two parents. When TEs inherited from the father are absent in the mother's genome, TEs can become activated in the progeny, causing germline damage and sterility. Studies in Drosophila indicate that dysgenesis can occur when TEs inherited paternally are not matched with a pool of corresponding TE silencing PIWI-interacting RNAs (piRNAs) provisioned by the female germline. Using the D . virilis syndrome of hybrid dysgenesis as a model, we characterize the effects that divergence in TE profile between parents has on offspring. Overall, we show that divergence in the TE landscape is associated with persisting differences in germline TE expression when comparing genetically identical females of reciprocal crosses and these differences are transmitted to the next generation. Moreover, chronic and persisting TE expression coincides with increased levels of genic piRNAs associated with reduced gene expression. Combined with these effects, we further demonstrate that gene expression is idiosyncratically influenced by differences in the genic piRNA profile of the parents that arise though polymorphic TE insertions. Overall, these results support a model in which early germline events in dysgenesis establish a chronic, stable state of both TE and gene expression in the germline that is maintained through adulthood and transmitted to the next generation. This work demonstrates that divergence in the TE profile is associated with diverse piRNA-mediated transgenerational effects on gene expression within populations.

Description: by Caitlin Sedwick

Description: Article It is widely acknowledged that some form of carbon capture will be necessary to limit global warming to less than 2 °C, but to what extent remains unclear. Here, using climate-carbon models, the authors quantify the amount of negative emissions and carbon storage capacity required to meet this target. Nature Communications doi: 10.1038/ncomms8958 Authors: T. Gasser, C. Guivarch, K. Tachiiri, C. D. Jones, P. Ciais

Description: Article Despite normalization of the CA125 serum biomarker at the completion of carboplatin therapy the vast majority of patients with high grade serous ovarian cancers relapse. Here, Janzen et al ., identify a sub-population of tumor cells that are CA125 negative, cancer initiating and platinum resistant but readily eliminated with the addition of apoptosis enhancing drugs to carboplatin. Nature Communications doi: 10.1038/ncomms8956 Authors: D. M. Janzen, E. Tiourin, J. A. Salehi, D. Y. Paik, J. Lu, M. Pellegrini, S. Memarzadeh

Description: Article In metalloproteins, a metal cofactor participates in the formation of the correct fold. Here the authors demonstrate—using single molecule force spectroscopy and the native copper centre as an embedded internal reporter—that the blue-copper proteins azurin and plastocyanin unfold via two independent competing pathways under force. Nature Communications doi: 10.1038/ncomms8894 Authors: Amy E. M. Beedle, Ainhoa Lezamiz, Guillaume Stirnemann, Sergi Garcia-Manyes

Description: Article Quantum communications operate with shared multipartite entangled states, and this has to be certified in a setting where not all parties are trusted in the same way. Here the authors propose a method to certify multipartite entanglement in asymmetric scenarios and demonstrate it in an optical experiment. Nature Communications doi: 10.1038/ncomms8941 Authors: D. Cavalcanti, P. Skrzypczyk, G. H. Aguilar, R. V. Nery, P.H. Souto Ribeiro, S. P. Walborn

Description: Article The protein kinase MEKK3 interacts with CCM2, which is associated with the predominantly cerebrovascular CCM disease. Here the authors use structural, biochemical, cell biology and in vivo techniques to show that regulation of Rho signalling by the CCM2:MEKK3 complex is needed to maintain neurovascular integrity. Nature Communications doi: 10.1038/ncomms8937 Authors: Oriana S. Fisher, Hanqiang Deng, Dou Liu, Ya Zhang, Rong Wei, Yong Deng, Fan Zhang, Angeliki Louvi, Benjamin E. Turk, Titus J. Boggon, Bing Su

Description: Article Flexible energy storage systems usually have limited energy densities. Here the authors report a flexible lithium–oxygen battery with the cathode consisting of titanium dioxide nanowire arrays grown on carbon textiles, which displays high mechanical strength as well as promising electrochemical performance. Nature Communications doi: 10.1038/ncomms8892 Authors: Qing-Chao Liu, Ji-Jing Xu, Dan Xu, Xin-Bo Zhang

Description: Article Large-scale dense reconstruction of neuronal circuits (or connectomics) requires methods for large-volume dense en-bloc electron microscopy (EM) staining. Here the authors develop a protocol for staining tissue blocks from mouse neocortex sized at least 1 mm in diameter, enabling correlated functional and structural circuit analyses. Nature Communications doi: 10.1038/ncomms8923 Authors: Yunfeng Hua, Philip Laserstein, Moritz Helmstaedter

Description: Article Nanonization of battery electrode particles is a usual way to enhance their conductivity, but the decreased tap density is detrimental to battery performance. Here, the authors coat micron-sized lithium iron phosphate with a conducting polymer layer and demonstrate some excellent electrochemical properties. Nature Communications doi: 10.1038/ncomms8898 Authors: Limin Guo, Yelong Zhang, Jiawei Wang, Lipo Ma, Shunchao Ma, Yantao Zhang, Erkang Wang, Yujing Bi, Deyu Wang, William C. McKee, Ye Xu, Jitao Chen, Qinghua Zhang, Cewen Nan, Lin Gu, Peter G. Bruce, Zhangquan Peng

Description: Article The behaviour of airborne fine ash during explosive volcanic eruptions is poorly understood. Here, the authors study hail formation during an eruption, proposing a mechanism of particle aggregation that leads to the fallout of fine ash and the occurrence of concentrically layered aggregates in volcanic deposits Nature Communications doi: 10.1038/ncomms8860 Authors: Alexa R. Van Eaton, Larry G. Mastin, Michael Herzog, Hans F. Schwaiger, David J. Schneider, Kristi L. Wallace, Amanda B. Clarke

Description: Article Turtles are ectothermic vertebrates that have experienced major environmental perturbations. Here the authors show that the geographical distribution of turtles was mediated by climate throughout the Mezozoic and show an increase in diversity of non-marine turtles starting in the Early Cretaceous. Nature Communications doi: 10.1038/ncomms8848 Authors: David B. Nicholson, Patricia A. Holroyd, Roger B. J. Benson, Paul M. Barrett

Description: by Xin Zhang, Shijiang Xiong, Yue Ma, Ting Han, Xinyu Chen, Fang Wan, Yating Lu, Songhe Yan, Yan Wang The purpose of this study was to conduct a cone-beam computed tomographic (CBCT) investigation on the root and canal configuration of the mandibular first molars, especially the morphology of the disto-lingual (DL) root, in a Chinese subpopulation. A total of 910 CBCT images of the mandibular first molars were collected from 455 patients who underwent CBCT examinations as a preoperative assessment for implants or orthodontic treatment. The following information was analyzed and evaluated: tooth position, gender, root and root canal number per tooth, root canal type of the mesial root(s) and distal root(s), angle of the DL root canal curvature, distance between two distal canal orifices in the teeth with DL root, and angle of disto-buccal canal orifice–disto-lingual canal orifice–mesio-lingual canal orifice (DB-DL-ML). Most of the mandibular first molars (64.9%, n = 591) had two roots with three root canals, and most of the mesial root canals (87.7%, n = 798) were type VI. The prevalence of the DL root was 22.1% (n = 201). The right side had a higher prevalence of DL root than the left side ( p

Description: by Tomer Stern, Rona Aviram, Chagai Rot, Tal Galili, Amnon Sharir, Noga Kalish Achrai, Yosi Keller, Ron Shahar, Elazar Zelzer One of the major challenges that developing organs face is scaling, that is, the adjustment of physical proportions during the massive increase in size. Although organ scaling is fundamental for development and function, little is known about the mechanisms that regulate it. Bone superstructures are projections that typically serve for tendon and ligament insertion or articulation and, therefore, their position along the bone is crucial for musculoskeletal functionality. As bones are rigid structures that elongate only from their ends, it is unclear how superstructure positions are regulated during growth to end up in the right locations. Here, we document the process of longitudinal scaling in developing mouse long bones and uncover the mechanism that regulates it. To that end, we performed a computational analysis of hundreds of three-dimensional micro-CT images, using a newly developed method for recovering the morphogenetic sequence of developing bones. Strikingly, analysis revealed that the relative position of all superstructures along the bone is highly preserved during more than a 5-fold increase in length, indicating isometric scaling. It has been suggested that during development, bone superstructures are continuously reconstructed and relocated along the shaft, a process known as drift. Surprisingly, our results showed that most superstructures did not drift at all. Instead, we identified a novel mechanism for bone scaling, whereby each bone exhibits a specific and unique balance between proximal and distal growth rates, which accurately maintains the relative position of its superstructures. Moreover, we show mathematically that this mechanism minimizes the cumulative drift of all superstructures, thereby optimizing the scaling process. Our study reveals a general mechanism for the scaling of developing bones. More broadly, these findings suggest an evolutionary mechanism that facilitates variability in bone morphology by controlling the activity of individual epiphyseal plates.

Description: by Hsin-Lun Wu, Wen-Kuei Chang, Ken-Hua Hu, Richard M. Langford, Mei-Yung Tsou, Kuang-Yi Chang Although procedure time analyses are important for operating room management, it is not easy to extract useful information from clinical procedure time data. A novel approach was proposed to analyze procedure time during anesthetic induction. A two-step regression analysis was performed to explore influential factors of anesthetic induction time (AIT). Linear regression with stepwise model selection was used to select significant correlates of AIT and then quantile regression was employed to illustrate the dynamic relationships between AIT and selected variables at distinct quantiles. A total of 1,060 patients were analyzed. The first and second-year residents (R1-R2) required longer AIT than the third and fourth-year residents and attending anesthesiologists ( p = 0.006). Factors prolonging AIT included American Society of Anesthesiologist physical status ≧ III, arterial, central venous and epidural catheterization, and use of bronchoscopy. Presence of surgeon before induction would decrease AIT ( p 〈 0.001). Types of surgery also had significant influence on AIT. Quantile regression satisfactorily estimated extra time needed to complete induction for each influential factor at distinct quantiles. Our analysis on AIT demonstrated the benefit of quantile regression analysis to provide more comprehensive view of the relationships between procedure time and related factors. This novel two-step regression approach has potential applications to procedure time analysis in operating room management.

Description: by Guifang Shao, Tiejun Li, Wangda Zuo, Shunxiang Wu, Tundong Liu Microarray technology plays an important role in drawing useful biological conclusions by analyzing thousands of gene expressions simultaneously. Especially, image analysis is a key step in microarray analysis and its accuracy strongly depends on segmentation. The pioneering works of clustering based segmentation have shown that k-means clustering algorithm and moving k-means clustering algorithm are two commonly used methods in microarray image processing. However, they usually face unsatisfactory results because the real microarray image contains noise, artifacts and spots that vary in size, shape and contrast. To improve the segmentation accuracy, in this article we present a combination clustering based segmentation approach that may be more reliable and able to segment spots automatically. First, this new method starts with a very simple but effective contrast enhancement operation to improve the image quality. Then, an automatic gridding based on the maximum between-class variance is applied to separate the spots into independent areas. Next, among each spot region, the moving k-means clustering is first conducted to separate the spot from background and then the k-means clustering algorithms are combined for those spots failing to obtain the entire boundary. Finally, a refinement step is used to replace the false segmentation and the inseparable ones of missing spots. In addition, quantitative comparisons between the improved method and the other four segmentation algorithms--edge detection, thresholding, k-means clustering and moving k-means clustering--are carried out on cDNA microarray images from six different data sets. Experiments on six different data sets, 1) Stanford Microarray Database (SMD), 2) Gene Expression Omnibus (GEO), 3) Baylor College of Medicine (BCM), 4) Swiss Institute of Bioinformatics (SIB), 5) Joe DeRisi’s individual tiff files (DeRisi), and 6) University of California, San Francisco (UCSF), indicate that the improved approach is more robust and sensitive to weak spots. More importantly, it can obtain higher segmentation accuracy in the presence of noise, artifacts and weakly expressed spots compared with the other four methods.

Description: by Prachi R. Bapat, Ashish R. Satav, Aliabbas A. Husain, Seema D. Shekhawat, Anuja P. Kawle, Justin J. Chu, Hemant J. Purohit, Hatim F. Daginawala, Girdhar M. Taori, Rajpal S. Kashyap Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis ( M . tb ) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts. Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis.

Description: by Amit Kumar Sinha, Hamada AbdElgawad, Gaurav Zinta, Antony Franklin Dasan, Rindra Rasoloniriana, Han Asard, Ronny Blust, Gudrun De Boeck Salinity fluctuation is one of the main factors affecting the overall fitness of marine fish. In addition, water borne ammonia may occur simultaneously with salinity stress. Additionally, under such stressful circumstances, fish may encounter food deprivation. The physiological and ion-osmo regulatory adaptive capacities to cope with all these stressors alone or in combination are extensively addressed in fish. To date, studies revealing the modulation of antioxidant potential as compensatory response to multiple stressors are rather lacking. Therefore, the present work evaluated the individual and combined effects of salinity challenge, ammonia toxicity and nutritional status on oxidative stress and antioxidant status in a marine teleost, European sea bass ( Dicentrarchus labrax ). Fish were acclimated to normal seawater (32 ppt), to brackish water (20 ppt and 10 ppt) and to hypo-saline water (2.5 ppt). Following acclimation to different salinities for two weeks, fish were exposed to high environmental ammonia (HEA, 20 mg/L representing 50% of 96h LC 50 value for ammonia) for 12 h, 48 h, 84 h and 180 h, and were either fed (2% body weight) or fasted (unfed for 7 days prior to HEA exposure). Results show that in response to decreasing salinities, oxidative stress indices such as xanthine oxidase activity, levels of hydrogen peroxide (H 2 O 2 ) and lipid peroxidation (malondialdehyde, MDA) increased in the hepatic tissue of fasted fish but remained unaffected in fed fish. HEA exposure at normal salinity (32 ppt) and at reduced salinities (20 ppt and 10 ppt) increased ammonia accumulation significantly (84 h–180 h) in both feeding regimes which was associated with an increment of H 2 O 2 and MDA contents. Unlike in fasted fish, H 2 O 2 and MDA levels in fed fish were restored to control levels (84 h–180 h); with a concomitant increase in superoxide dismutase (SOD), catalase (CAT), components of the glutathione redox cycle (reduced glutathione, glutathione peroxidase and glutathione reductase), ascorbate peroxidase (APX) activity and reduced ascorbate (ASC) content. On the contrary, fasted fish could not activate many of these protective systems and rely mainly on CAT and ASC dependent pathways as antioxidative sentinels. The present findings exemplify that in fed fish single factors and a combination of HEA exposure and reduced seawater salinities (upto 10 ppt) were insufficient to cause oxidative damage due to the highly competent antioxidant system compared to fasted fish. However, the impact of HEA exposure at a hypo-saline environment (2.5 ppt) also defied antioxidant defence system in fed fish, suggesting this combined factor is beyond the tolerance range for both feeding groups. Overall, our results indicate that the oxidative stress mediated by the experimental conditions were exacerbated during starvation, and also suggest that feed deprivation particularly at reduced seawater salinities can instigate fish more susceptible to ammonia toxicity.

Description: by Junjie Wu, Shuting Xiong, Jing Jing, Xin Chen, Weimin Wang, Jian-Fang Gui, Jie Mei YY super-males have rarely been detected in nature and only been artificially created in some fish species including tilapia and yellow catfish ( Pelteobagrusfulvidraco ), which provides a promising model for testis development and spermatogenesis. In our previous study, significant differences in morphology and miRNA expression were detected between XY and YY testis of yellow catfish. Here, solexa sequencing technology was further performed to compare mRNA expression between XY and YY testis. Compared with unigenes expressed in XY testis, 1146 and 1235 unigenes have significantly higher and lower expression in YY testis, respectively. 605 differentially expressed unigenes were annotated to 1604 GO terms with 319 and 286 genes having relative higher expression in XY and YY testis. KEGG analysis suggested different levels of PI3K-AKT and G protein-coupled receptor (GPCR) signaling pathways between XY and YY testis. Down-regulation of miR-141/429 in YY testis was speculated to promote testis development and maturation, and several factors in PI3K-AKT and GPCR signaling pathways were found as predicted targets of miR-141/429, several of which were confirmed by dual-luciferase reporter assays. Our study provides a comparative transcriptome analysis between XY and YY testis, and reveals interactions between miRNAs and their target genes that are possibly involved in regulating testis development and spermatogenesis.

Description: by Liu Yang, Guosheng Wang, Xinyi Zhao, Song Ye, Peng Shen, Weilin Wang, Shusen Zheng Next-generation sequencing technology allows simultaneous analysis of multiple susceptibility genes for clinical cancer genetics. In this study, multiplex genetic testing was conducted in a Chinese family with multiple cases of cancer to determine the variations in cancer predisposition genes. The family comprises a mother and her five daughters, of whom the mother and the eldest daughter have cancer and the secondary daughter died of cancer. We conducted multiplex genetic testing of 90 cancer susceptibility genes using the peripheral blood DNA of the mother and all five daughters. WRN frameshift mutation is considered a potential pathogenic variation according to the guidelines of the American College of Medical Genetics. A novel WRN frameshift mutation (p.N1370Tfs*23) was identified in the three cancer patients and in the youngest unaffected daughter. Other rare non-synonymous germline mutations were also detected in DICER and ELAC2 . Functional mutations in WRN cause Werner syndrome, a human autosomal recessive disease characterized by premature aging and associated with genetic instability and increased cancer risk. Our results suggest that the WRN frameshift mutation is important in the surveillance of other members of this family, especially the youngest daughter, but the pathogenicity of the novel WRN frameshift mutation needs to be investigated further. Given its extensive use in clinical genetic screening, multiplex genetic testing is a promising tool in clinical cancer surveillance.