ALBERT

Description: The canonical genetic code ubiquitously translates nucleotide into peptide sequence with several alterations known in viruses, bacteria, mitochondria, plastids, and single-celled eukaryotes. A new hypothesis to explain genetic code changes, termed tRNA loss driven codon reassignment , has been proposed recently when the polyphyly of the yeast codon reassignment events has been uncovered. According to this hypothesis, the driving force for genetic code changes are tRNA or translation termination factor loss-of-function mutations or loss-of-gene events. The free codon can subsequently be captured by all tRNAs that have an appropriately mutated anticodon and are efficiently charged. Thus, codon capture most likely happens by near-cognate tRNAs and tRNAs whose anticodons are not part of the recognition sites of the respective aminoacyl-tRNA-synthetases. This hypothesis comprehensively explains the CTG codon translation as alanine in Pachysolen yeast together with the long known translation of the same codon as serine in Candida albicans and related species, and can also be applied to most other known reassignments. With the recently discovered genetic code alterations, time has come to revisit the processes behind the genetic code diversity across the eukaryotic tree. The tRNA loss driven codon reassignment hypothesis, which attributes a special role to the charging of anticodon-mutated tRNAs, seems to be particularly apt at explaining these events.

Description: In animals, nervous systems regulate the ingestion of food and water in a manner that reflects internal metabolic need. While the coordination of these two ingestive behaviors is essential for homeostasis, it has been unclear how internal signals of hunger and thirst interact to effectively coordinate food and water ingestion. In the last year, work in insects and mammals has begun to elucidate some of these interactions. As reviewed here, these studies have identified novel molecular and neural mechanisms that coordinate the regulation of food and water ingestion behaviors. These mechanisms include peptide signals that modulate neural circuits for both thirst and hunger, neurons that regulate both food and water ingestion, and neurons that integrate sensory information about both food and water in the external world. These studies argue that a deeper understanding of hunger and thirst will require closer examination of how these two biological drives interact. The nervous system uses internal signals of hunger and thirst to balance food and water ingestion behaviors. While hunger and thirst have traditionally been studied independently, recent work from flies and mammals suggests that cross-talk between neural systems underlying these biological drives may be more extensive than previously appreciated.

Description: Nano-silver and nano-titanium oxide films can be coated over brackets in order to reduce bacterial aggregation and friction. However, their antimicrobial efficacy, surface roughness, and frictional resistance are not assessed before. Fifty-five stainless-steel brackets were divided into 5 groups of 11 brackets each: uncoated brackets, brackets coated with 60 µm silver, 100 µm silver, 60 µm titanium, and 100 µm titanium. Coating was performed using physical vapor deposition method. For friction test, three brackets from each group were randomly selected and tested. For scanning electron microscopy and atomic-force microscopy assessments, one and one brackets were selected from each group. For antibacterial assessment, six brackets were selected from each group. Of them, three were immediately subjected to direct contact with S. mutans . Colonies were counted 3, 6, 24, and 48 h of contact. The other three were stored in water for 3 months. Then were subjected to a similar direct contact test. Results pertaining to both subgroups were combined. Groups were compared statistically. Mean (SD) friction values of the groups 'control, silver-60, silver-100, titanium-60, and titanium-100' were 0.55 ± 0.14, 0.77 ± 0.08, 0.82 ± 0.11, 1.52 ± 0.24, and 1.57 ± 0.41 N, respectively ( p  =   .0004, Kruskal–Wallis). Titanium frictions were significantly greater than control ( p  〈   .05), but silver groups were not ( p  〉   .05, Dunn). In the uncoated group, colony count increased exponentially within 48 h. The coated groups showed significant reductions in colony count ( p  〈   .05, two-way-repeated-measures ANOVA). In conclusions, all four explained coatings reduce surface roughness and bacterial growth. Nano-titanium films are not suitable for friction reduction. Nano-silver results were not conclusive and need future larger studies.

Description: Many papers have claimed the attainment of super-resolution, i.e. resolution beyond that achieved classically, by measurement of the profile of a feature in the image. We argue that measurement of the contrast of the image of a dark bar on a bright background does not give a measure of resolution, but of detection sensitivity. The width of a bar that gives an intensity at the center of the bar of 0.735 that in the bright region (the same ratio as in the Rayleigh resolution criterion) is for the coherent case with central illumination. This figure, which compares with for the Abbe resolution limit with central illumination, holds for the classical case, and so is no indication of super-resolution. Theoretical images for two points, two lines, arrays of lines, arrays of bars, and grating objects are compared. These results can be used a reference for experimental results, to determine if super-resolution has indeed been attained. The history of the development of the theory of microscope resolution is outlined. This shows the image of a dark bar on a coherent bright background, for different bar widths. There is no sharp cutoff. There is always a dip in intensity at the center, even for a bar width of, corresponding to 0.05 Airy units.

Description: On the cover: The cover image, by Yulin Lin et al., is based on the Research Article Assessment of fracture risk in proximal tibia with tumorous bone defects by a finite element method , DOI: 10.1002/jemt.22899 .

Description: Honey is a valuable food produced by bees from sugary substances that they gather in nature. The transformation the nectar into honey, by bees, is long and complex. Except for honey, where heavy metals are absent or are found only in traces, the bees and their products have always been considered excellent biomarkers of such contaminants. We have assumed that the absence of heavy metals in honey is due to the presence of a detoxification system in the digestive system of bees, which involves metallothioneins, proteins that have a role in the homeostatic control of essential and non-essential metals. We have placed the beehives in three different zones: industrial, urban and rural. Investigations were carried out with ICP-MS method for the detection of heavy metals in the guts of honey bees and honey. The metallothioneins have been identified by Immunohistochemical and Western-blotting analisys. The investigations have shown the presence of heavy metals only in bees guts but not in honey, while the presence of metallothionein has been highlighted only in epithelium of the honey sac, demonstrating the existence of an efficient system of detoxification of heavy metals. In honey bees the detoxification system is primarily based on induction of Metallothioneins Metallothionein-immunopositive cells only in the honey sac.

Description: Site-specific accumulation of flavonoids in Apocyni Veneti Folium was determined by laser scanning confocal microscope (LSCM) and the localization of catechins also was observed via vanillin -HCl staining under the conventional optical microscope. The contents of five flavonoids in Apocyni Veneti Folium from different harvest times and growth parts were measured using HPLC method. LSCM observation showed that flavonoids are accumulated in cuticle of epidermal cells and vessel walls, especially in protoplasts and nucleolus of the collenchyma cells and the epidermal cells. Catechins are localized in the palisade parenchyma cells and vessel walls, particularly in the laticifers found in the phloem. On the basis of the difference of the maximal emission wavelength between quercetin and kaempferol derivatives which have fluorescence behavior by appropriate treatment, kaempferol and its derivatives are localized exclusively in the cuticle. Results showed that the content of astragalin in Apocyni Veneti Folium from different parts revealed the decreasing trend, while hyperin and isoquercitrin were higher in June and July analyzed by HPLC. In summary, the site-specific accumulation of flavonoids in Apocyni Veneti Folium can be determined by LSCM and vanillin -HCl staining. The contents of flavonoids in Apocyni Veneti Folium are correlated with harvest times and growth parts. Site-specific accumulation of flavonoids was determined by LSCM. Tissue localization of catechins was observed via vanillin-HCl staining. Dynamic change of flavonoids in Apocyni Veneti Folium from different harvest times and growth parts were measured.

Description: The biogenesis of RNAs and proteins is a threat to the cell. Indeed, the act of transcription and nascent RNAs challenge DNA stability. Both RNAs and nascent proteins can also initiate the formation of toxic aggregates because of their physicochemical properties. In reviewing the literature, I show that co-transcriptional and co-translational biophysical constraints can trigger DNA instability that in turn increases the likelihood that sequences that alleviate the constraints emerge over evolutionary time. These directed genetic variations rely on the biogenesis of small RNAs that are transcribed directly from challenged DNA regions or processed from the transcripts that directly or indirectly generate constraints or aggregates. These small RNAs can then target the genomic regions from which they initially originate and increase the local mutation rate of the targeted loci. This mechanism is based on molecular pathways involved in anti-parasite genome defence systems, and implies that gene expression-related biophysical constraints represent a driving force of genome evolution. Are randomly generated mutations the only source of genetic variation during evolution? This paper describes the molecular mechanisms by which co-transcriptional and co-translational biophysical constraints trigger genetic variations in targeted-genomic sequences in an RNA-depending manner. This directed-mutational process that drives genome evolution is related to antiparasite genome defence systems.

Description: Clinical trial results are often interpreted by inductive reasoning, in a trial design-limited manner, directed toward modifications of the current clinical practice. Deductive reasoning is an alternative in which results of relevant trials are combined in indisputable premises that lead to a conclusion easily testable in future trials.

Description: How epithelial tissues are able to self-renew to maintain homeostasis and regenerate in response to injury remains a persistent question. The transcriptional effectors YAP and TAZ are increasingly being recognized as central mediators of epithelial stem cell biology, and a wealth of recent studies have been directed at understanding the control and activity of these factors. Recent work by Hu et al. has added to this knowledge, as they identify an Integrin-FAK-CDC42-PP1A signaling cascade that directs nuclear YAP/TAZ activity in stem cell populations of the mouse incisor, and define convergence on mTORC1 signaling as an important mediator of the proliferation of these cells. Here, we review recent studies on YAP/TAZ function and regulation in epithelial tissue-specific stem cells, merging the Hu et al. study together with our current knowledge of YAP/TAZ. The Hippo pathway effectors YAP and TAZ broadly regulate adult stem cells, and have recently been implicated in dental epithelial stem cell proliferation and restricted differentiation via an Integrin-FAK-CDC42-PP1A cascade. Here, we discuss the extracellular cues which control YAP/TAZ activity and examine downstream pathways that direct stem cell fate.

Description: Canine mammary gland tumors represent the second most frequent type of neoplasm in dogs, being an important problem within veterinary medical field. Canine mixed mammary tumors are the most common; the use of a transmission electron microscope (TEM) can contribute as a tool in its diagnosis by determining the characteristics of cellular components from numerous neoplasms. The aim of this study was to characterize cytologically canine mammary mixed tumor by the use of the TEM. A biopsy collected from an 11 years old bitch Shih-Tzu and analyzed by histopathology was used for ultrastructural analysis. Specimens obtained were double stained using uranyl acetate and lead citrate prior to observation in the TEM. The protocol established to transmission electron microscopy observation allowed the identification of main cellular characteristics of canine mixed mammary tumors; however, it was not possible a detailed visualization of the organelles due to the preservation of the biopsy in formaldehyde. The protocol established allowed the identification of main cellular characteristics; however, it was not possible a detailed visualization of organelles. The scratches in the sectioned tissue were reduced with speed to 1 mm/s.

Description: In the current work, irregular morphology of Staphylococcus aureus bacteria has been visualized by phase retrieval employing off-axis electron holography (EH) and 3D reconstruction electron tomography using high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM). Bacteria interacting with gold nanoparticles (AuNP) acquired a shrunken or irregular shape due to air dehydration processing. STEM imaging shows the attachment of AuNP on the surface of cells and suggests an irregular 3D morphology of the specimen. The phase reconstruction demonstrates that off-axis electron holography can reveal with a single hologram the morphology of the specimen and the distribution of the functionalized AuNPs. In addition, EH reduces significantly the acquisition time and the cumulative radiation damage (in three orders of magnitude) over biological samples in comparison with multiple tilted electron expositions intrinsic to electron tomography, as well as the processing time and the reconstruction artifacts that may arise during tomogram reconstruction. Off-axis electron holography and electron tomography have been used to show an irregular shape of S. aureus bacteria. EH reduces acquisition and processing time as well as the radiation damage inherent to the long tilting series for tomography.

Description: Present scanning electron microscope study, reports healing of excised skin wounds in Cirrhinus mrigala . Healing process of wounds, inflicted on head skin, using biopsy punch was observed at intervals—0 hour (h), 1, 2, 4, 6, 12 h, 1 day (d) 2 and 4 d. Accumulation of mucus in wound region within 1h after infliction of wound has been considered an immediate measure to provide protection to injured skin from microbial invasion and other external environmental hazards. On infliction of wound, mobilization of epithelial cells at wound edge is associated with disturbance of coaptive relationship of epithelial cells till original coaptive stability is reached. At 6–12 h appearance of epidermal ridge in region of contact of migrating fronts is due to piling up of epithelial cells. This is associated with cessation of migration of epithelial cells and their simultaneous continual arrival in the region. Speedy epithelialization of skin wounds in C. mrigala like in other fishes, compared to that of mammals and other higher vertebrates, is possibly facilitated owing to surrounding wet external environment. Microridges in initial stages of wound healing appear fragmented without particular orientation. Further, epithelial cells in epithelium in wound region and in region adjacent to wound elongate. These changes are associated with the stretching of epithelial cells indicating their streaming and migration, toward wound. Presence of superficial neuromasts, smallest functional units of lateral line system, a hydrodynamic sensory system, has been associated with important functional significance in fish. Healing of skin wounds in Cirrhinus mrigala was studied using scanning electron microscopy. Covering of wound by mucus, rapid epithelialization, and changes in pattern of microridges on the surface of epithelial cells during healing are significant.

Description: Precarious maintenance of simple DNA repeats in eukaryotes: In article number 1700077 , Sergei M. Mirkin and co-workers present a model for replication fork uncoupling at expandable (GAA) n repeats responsible for Friedreich's ataxia. Lagging strand synthesis by DNA polymerase δ (blue oval) is stalled when the repetitive 5‵-flap of an Okazaki fragment (green strand) folds forward forming a triplex with the downstream duplex. This may prompt Pol δ to switch templates to the nascent leading strand, resulting in repeat expansions.

Description: Cell size impacts cellular and organismal function through metabolism: The cover illustrates that cell size is intimately connected to mitochondrial metabolism and cellular fitness. In article 1700058 , Mikael Björklund and co-workers discuss how metabolism is often cell-size dependent due to biophysical constrains imposed by cell size and shape. As cell size defines cellular fitness, this has potential implications on organismal health as demonstrated by polyploid animal models.

Description: For the long-term success of implants, it is necessary to achieve a direct contact between the implant and the subjacent bone. To avoid bacterial penetration that could adversely affect the initial wound healing as well as the long-term behavior of the implants, an early tissue barrier must form that is able to protect the biological peri-implant structures. Given the need of an effective tissue early barrier around dental implants, the present study evaluated, in vitro, the influence of physical and chemical characteristics of two implant abutment surfaces on gingival epithelial cells (OBA-9) adhesion. To this end, titanium (Ti) and zirconia (ZrO 2 ) disk-shaped specimens were used mimicking the abutment components surfaces, while bovine enamel (BE) and glass cover slips (GCS) disks served as positive and negative controls, respectively. Roughness and surface free energy (SFE) of all materials were evaluated previously to cellular adhesion step. In sequence, the effect of each material on cells morphology and viability was analyzed after 1 and 24 hr. The results showed that roughness and SFE had no effect on the cell viability data or on their interaction ( p = .559), independent of a post-contact analysis of 1 or 24 hr. However, cells attachment and spreading increased after 24 hr on Ti and ZrO 2 than BE, corresponding to the highest SFE values. SFE appears to be an important property interfering on the quality of the soft tissue surrounding dental implants. These data can be considered a trigger point for developing new material surfaces. Titanium and zirconia substrates disclosed hydrophobic properties and admitted the highest surface free energy values when in comparison to enamel. Well-attached/spreading cells were observed on implant abutment materials.

Description: Secretion systems enable bacteria to import and secrete large macromolecules including DNA and proteins. While most components of these systems have been identified, the molecular mechanisms of macromolecular transport remain poorly understood. Recent findings suggest that various bacterial secretion systems make use of the translocation ratchet mechanism for transporting polymers across the cell envelope. Translocation ratchets are powered by chemical potential differences generated by concentration gradients of ions or molecules that are specific to the respective secretion systems. Bacteria employ these potential differences for biasing Brownian motion of the macromolecules within the conduits of the secretion systems. Candidates for this mechanism include DNA import by the type II secretion/type IV pilus system, DNA export by the type IV secretion system, and protein export by the type I secretion system. Here, we propose that these three secretion systems employ different molecular implementations of the translocation ratchet mechanism. Brownian ratchets are often discussed in the context of directed molecular movement. Bacterial secretion systems transport molecules through membranes in a directed fashion. Here, we focus on recent experiments supporting a role of translocation ratchets in the secretion and import of proteins and DNA.

Description: Bioceramics are being used in experimental bone engineering application in association with bone marrow derived mesenchymal stem cells (BM-MSCs) as a new therapeutic tool, but their effects on the ultrastructure of BM-MSCs are yet unknown. In this study we report the morphological features of ovine (o)BM-MSCs cultured with Skelite, a resorbable bioceramic based on silicon stabilized tricalcium phosphate (SiTCP), able to promote the repair of induced bone defect in sheep model. oBM-MSCs were isolated from the iliac crest, cultured until they reached near-confluence and incubated with SiTCP. After 48 hr the monolayers were highly damaged and only few cells adhered to the plastic. Thus, SiTCP was removed, and after washing the cells were cultured until they became confluent. Then, they were trypsinizated and processed for transmission electron microscopy (TEM) and RT-PCR analysis. RT-PCR displayed that oBM-MSCs express typical surface marker for MSCs. TEM revealed the presence of electron-lucent cells and electron-dense cells, both expressing the CD90 surface antigen. The prominent feature of electron-lucent cells was the concentration of cytoplasmic organelles around the nucleus as well as large surface blebs containing glycogen or profiles of endoplasmic reticulum. The dark cells had a multilocular appearance by the presence of peripheral vacuoles. Some dark cells contained endocytic vesicles, lysosomes, and glycogen aggregates. oBM-MSCs showed different types of specialized interconnections. The comparison with ultrastructural features of untreated oBM-MSCs suggests the light and dark cells are two distinct cell types which were differently affected by SiTCP bioceramic. Skelite cultured ovine BM-MSCs display electron-dense and electron-lucent cells which are differently affected by this bioceramic. This suggests that they could play a different role in bioceramic based therapy. Skelite cultured ovine bone marrow mesenchymal stem cells display electron-dense and electron-lucent cells which are differently affected by this bioceramic. This suggests that they could play a different role in bioceramic-based therapy.

Description: The objective of the present study was to compare cleaning methods for delicate insect specimens for investigations with scanning electron microscopy (SEM). As typical specimens we used aquatic larvae of mosquitoes, springtails, larvae of mayflies and caterpillars because they are very fragile and large parts of their body consist of soft tissue. Additionally their cuticle is very often covered with dirt, soil particles or other materials. Cleaning with ultrasonic sound, as the most common cleaning method used for SEM, will destroy fragile insects. Therefore we tested different procedures to remove the dirt particles. In a first approach we compared cleaning with Potassium hydroxide (KOH), Proteinase K, and Triton X in aquatic larvae of flies, which were available in numbers and kept under the same conditions. As our results showed that the treatment with KOH gives the best results we treated in a second approach springtails, larvae of mayflies and caterpillars only with KOH. The springtails and caterpillars were largely free of particles after treatment with KOH; however, the larvae of mayflies were still covered with remnants of diatoms and precipitates of calcium carbonate of the algae. KOH dissolves organic impurities, on the other hand silicon dioxide and lime crusts are not solved. With this limitation, treatment with KOH is a simple technique for routine use as cleaning method for fragile insect specimens for SEM. Cleaning of delicate insect specimens with KOH, Proteinase K, and Triton X for scanning electron microscopy (SEM) was compared. Treatment with KOH gives the best results and is a simple technique for cleaning fragile insect specimens for SEM.

Description: The Type VI secretion system (T6SS) is a multiprotein and mosaic apparatus that delivers protein effectors into prokaryotic or eukaryotic cells. Recent data on the enteroaggregative Escherichia coli (EAEC) T6SS have provided evidence that the TssA protein is a key component during T6SS biogenesis. The T6SS comprises a trans-envelope complex that docks the baseplate, a cytoplasmic complex that represents the assembly platform for the tail. The T6SS tail is structurally, evolutionarily and functionally similar to the contractile tails of bacteriophages. We have shown that TssA docks to the membrane complex, recruits the baseplate complex and initiates and coordinates the polymerization of the inner tube with that of the sheath. Here, we review these recent findings, discuss the variations within TssA-like proteins, speculate on the role of EAEC TssA in T6SS biogenesis and propose future research perspectives. In the environment, bacteria have to cope with other microbial species and therefore have evolved anti-microbial mechanisms. The bacterial Type VI secretion system (T6SS) transports toxins into bacterial and/or eukaryotic cells using a contractile mechanism. At the architectural level, the T6SS could be viewed as a nano-speargun assembled in the bacterial cytoplasm and anchored to a trans-envelope complex. We describe and speculate on recent findings demonstrating that the TssA subunit is involved in the different stages of T6SS biogenesis.

Description: This study compared several irrigation protocols and application systems for sealer penetration into dentinal tubules. Single-rooted-human teeth were divided into 5 experimental groups ( n  = 15) and a control group ( n  = 5), according to final irrigation protocols: standard needle irrigation (SNI); Vibringe; Vibringe + NaviTip FX (Vibringe NFX); Endo Spray (ES); and passive-ultrasonic-irrigation (PUI). Following obturation of the root canals, the percentage of the sealer penetration was measured at different depths using stepwise CLSM analysis. The sealer penetration in the experimental groups was significantly higher than the control group at all levels ( p  〈 .05). No significant differences were observed between Vibringe and SNI or Vibringe NFX, ES, and PUI at all depths ( p  〉 .05). The Vibringe NFX, ES, and PUI groups allowed deeper sealer penetration than SNI at 100, 250, and 500 μm levels ( p  〈 .05). The irrigant activation, the needle design, and the application form (syringe or spray) may impact the quality of the seal that is achieved with root canal filling. A stepwise approach using CLSM for quantification of sealer penetration allowed understanding of sealer penetration by irrigation methods. Irrigant activation, needle design, and irrigant application form affect the quality of sealer penetration.

Description: Intracellular bacteria were recently shown to employ eukaryotic prenylation system for modifying activity and ensuring proper intracellular localization of their own proteins. Following the same logic, the proteins of viruses may also serve as prenylation substrates. Using extensively validated high-confidence prenylation predictions by PrePS with a cut-off for experimentally confirmed farnesylation of hepatitis delta virus antigen, we compiled in silico evidence for several new prenylation candidates, including IRL9 (CMV) and few other proteins encoded by Herpesviridae, Nef (HIV-1), E1A (human adenovirus 1), NS5A (HCV), PB2 (influenza), HN (human parainfluenza virus 3), L83L (African swine fever), MC155R (molluscum contagiosum virus), other Poxviridae proteins, and some bacteriophages of human associated bacteria. If confirmed experimentally, these findings may aid in dissection of molecular functions of uncharacterized viral proteins and provide a novel rationale for statin and FT/GGT1-based inhibition of viral infections. Prenylation of bacteriophage proteins may aid in moderation of microbial infections. Many human viruses, including HCV, HIV1, ASFV, and a number of Adeno-, Pox-, and herpesviruses, including CMV, encode the substrates for mammalian prenylation enzymes. Prenylation is advantageous for viral infection; its suppression by FT/GGT and FPPS inhibitors has antiviral effects. In bacteriophages, prenylation may aid in moderation of microbial infections.

Description: The purpose of this work is to study the dependence of AFM-data reliability on scanning rate. The three-dimensional (3D) surface topography of the samples with different micro-motifs is investigated. The analysis of surface metrics for estimation of artifacts from inappropriate scanning rate is presented. Fractal analysis was done by cube counting method and evaluation of statistical metrics was carrying out on the basis of AFM-data. Combination of quantitate parameters is also presented in graphs for every measurement. The results indicate that the sensitivity to scanning rate growths with fractal dimension of the sample. This approach allows describing the distortion of the images against scanning rate and could be applied for dependences on the other measurement parameters. The article explains the relevance and comparison of fractal and statistical surface parameters for characterization of data distortion caused by inappropriate choice of scanning rate. Three samples with different topography were studied by AFM at different scanning rate. Effect of scanning rate on the result image and geometrical data of surface is investigated. Image distortion could be defined by surface statistical parameters and data of fractal analysis.

Description: The present study aimed to evaluate the effects of four endodontic chelating agents, followed by 2.5% sodium hypochlorite (NaOCl), as final irrigation regimens on organic and inorganic components of human root dentin. Sixty mandibular incisors were prepared and randomly divided into six groups ( n  = 10): QMiX, 1% peracetic acid (PA), 17% EDTA, 10% citric acid (CA), 2.5% NaOCl (solution control) and distilled water (DW-negative control). After irrigation with the chelating agents, a final flush was performed with 2.5% NaOCl. The specimens were split longitudinally in halves; one was designated for organic component analysis by polarized light microscopy (PLM) and the other for inorganic structure analysis by scanning electron microscopy (SEM). Scores data obtained in the PLM analysis were submitted to Kruskal-Wallis' test, followed by Dunn's test ( p  〈 .05). SEM findings were presented descriptively. NaOCl and DW groups showed uniformity in the fibrillar network and smear layer obliterating the dentinal tubules, while CA group presented alteration in organic and inorganic components of dentin. EDTA group did not show differences from others in the organic component, but altered the inorganic structure. QMiX and PA groups did not cause a significant morphological alteration in collagen and removed the smear layer without inorganic structure modification. As final irrigation, QMiX and PA solutions, followed by 2.5% NaOCl, showed better behavior than the other chelating agents tested, preserving organic and inorganic components of human root dentin. QMiX and PA groups removed the smear layer without inorganic structure modification. QMiX and PA groups did not cause a significant morphological alteration in collagen.

Description: Activity-dependent neuroprotective protein (ADNP), discovered in our laboratory in 1999, has been characterized as a master gene vital for mammalian brain formation. ADNP de novo mutations in humans result in a syndromic form of autism-like spectrum disorder (ASD), including cognitive and motor deficits, the ADNP syndrome ( Helsmoortel-Van Der Aa ). One of the most important cellular processes associated with ADNP is the autophagy pathway, recently discovered by us as a key player in the pathophysiology of schizophrenia. In this regard, given the link between the microtubule and autophagy systems, the ADNP microtubule end binding protein motif, namely, the neuroprotective NAP (NAPVSIPQ), was found to enhance autophagy while protecting microtubules and augmenting ADNP's association with both systems. Thus, linking autophagy and ADNP is proposed as a major target for intervention in brain diseases from autism to Alzheimer's disease (AD) and our findings introduce autophagy as a possible novel target for treating schizophrenia. Activity-dependent neuroprotective protein (ADNP) binds to microtubule-associated protein light chain 3, which forms the membrane of the autophagosome, a key organelle in the autophagy process and regulates beclin1 (BECN1) formation, an inducer of autophagy. Autophagy plays a major role in Alzheimer's disease and as recently discovered in schizophrenia and autism.

Description: Tension sensors reveal how the kinetochore shares its load: The image on the cover shows a schematic of the chromosome surface at the site of attachment to the kinetochore. Loops of pericentric chromatin (left) position the centromere, where it is coupled to microtubules (right) via the kinetochore (Ndc80 complex, blue/yellow and red/green coiled coils). In article 1600216 , Edward D. Salmon and Kerry Bloom explain that, by placing FRET biosensors in Ndc80 it is possible to study the distribution of force within the kinetochore.

Description: Over 300 years ago the father of microscopy, Antonie van Leeuwenhoek, observed dried rotifers (tiny animals) “coming back to life” upon rehydration. Since then, scientists have been fascinated by the enduring mystery of how certain organisms survive losing essentially drying out completely. Historically sugars, such as the disaccharide trehalose, have been viewed as major functional mediators of desiccation tolerance. However, some desiccation tolerant organisms do not produce this sugar, hinting that additional mediators, and potentially novel mechanisms exist. It has become apparent that a common theme among such organisms is the production and use of intrinsically disordered proteins (IDPs) to mediate survival in this dry state. However, the basic biology of these proteins – which unlike globular proteins lack persistent three-dimensional structure – is poorly understood, as are the functional mechanisms utilized by these enigmatic proteins that allow them to mediate desiccation tolerance. We purpose that probing the biochemical and biophysical nature of stress-related IDPs will provide mechanistic insights into these fascinating proteins. Remarkably, organisms from every kingdom of life can survive losing nearly all their intracellular water. A hallmark of desiccation tolerance is the use of intrinsically disordered proteins (IDPs), but how IDPs contribute to tolerance is poorly understood. Here, we discuss possible mechanisms and avenues for studying these enigmatic proteins.

Description: Nowadays, infertility is no longer considered as an unsolvable disorder due to progresses in germ cells derived from stem lineage with diverse origins. Technical and ethical challenges push researchers to investigate various tissue sources to approach more efficient gametes. The purpose of the current study is to investigate the efficacy of a combined medium, retinoic acid (RA) together with Bone Morphogenic Protein-4 (BMP4), on differentiation of Bone Marrow Mesenchymal Stem Cells (BMMSCs) and adipose-derived mesenchymal stem cells (ADMSCs) into germ cells. Murine MSCs were obtained from both Bone Marrow (BM) and Adipose Tissue (AT) samples and were analyzed for surface markers to get further verification of their nature. BMMSCs and ADMSCs were induced into osteogenic and adipogenic lineage cells respectively, to examine their multipotency. They were finally differentiated into germ cells using media enriched with BMP4 for 4 days followed by addition of RA for 7 days (11 days in total). Analyzing of differentiation potential of BMMSCs- and ADMSCs were performed via Immunofluorescence, Flowcytometry and Real time-PCR techniques for germ cell-specific markers (Mvh, Dazl, Stra8 and Scp3). Mesenchymal surface markers (CD90 and CD44) were expressed on both BMMSCs and ADMSCs, while endothelial and hematopoietic cell markers (CD31 and CD45) had no expression. Finally, all germ-specific markers were expressed in both BM and AT. Although germ cells differentiated from ADMSCs showed faster growth and proliferation as well as easy collection, they significantly expressed germ-specific markers lower than BMMSCs. This suggests stronger differentiation potential of murine BMMSCs than ADMSCs. BMMSCs and ADMSCs could differentiate in appropriate mediums to osteoblast and lipoblast respectively and could express superficial mesenchymal characteristics. ADMSCs and BMMSCs were capable of differentiation into germ cells, and BMMSCs have stronger differentiation potential than ADMSCs.

Description: The famous lacquer wares excavated from the Jiuliandun Tombs of the middle and late Warring States period (476–221 BC) were analyzed using scanning electron microscopy/energy as well as dispersive X-ray spectrometry (SEM/EDS), Raman spectroscopy (RS), optical microscopy (OM), and X-ray diffraction (XRD). The results showed a multilayer structure in the lacquer film, including a Qihui layer (a layer made of lacquer and various plasters), undercoat layer (or finishing coat) and colored paint layer mixed with various inorganic particles, such as quartz (SiO 2 ) and hydroxyapatite [Ca 5 (PO 4 ) 3 (OH)], as fillers in the Qihui layers or orpiment (As 2 S 3 ) and cinnabar (HgS), which were used as a yellow or red pigment, respectively. With the help of elemental mapping images, a double-layer structure of the lacquer plaster was observed, corresponding to a mixture of lacquer liquid and bone ash [Ca 5 (PO 4 ) 3 (OH)], with large-diameter particles in the ground lacquer layer near the wooden body and small quartz (SiO 2 ) particles in upper lacquer layer. Specifically, quartz particles detected in the undercoat layer as fillers could be beneficial for improving the moshardness value, cost reduction and abrasive resistance of the lacquer film. In fact, the mixed method that used urushi and inorganic particles to form lacquer plaster was an important technological innovation and deeply influenced lacquering technologies worldwide. The results of this study will not only contribute to understanding the importance of lacquer skills in the Chinese Warring States but also provide information for cultural relic conservation as well as modern lacquer manufacturing for their protection and duplication. A double-layer structure of lacquer plaster observed by elemental mapping Large hydroxyapatite particles were found in ground lacquer and small quartz particles were found in the upper lacquer layer. Quartz particles were used in the undercoat layer as fillers to improve the quality of the lacquer film. Plaster made of urushi and inorganic particles was an important ancient technological innovation.

Description: Notch is a mechanosensitive receptor that requires direct cell–cell contact for its activation. Both the strength and the range of notch signaling depend on the size and geometry of the contact sites between cells. These properties of cell–cell contacts in turn depend on cell shape and polarity. At the molecular level, the E3 ubiquitin ligase Neuralized (Neur) links receptor activation with epithelial cell remodeling. Neur regulates the endocytosis of the Notch ligand Delta (Dl), hence Notch activation. It also targets the apical polarity protein Stardust (Sdt) to promote the endocytosis of the Crumbs complex, thereby contributing to epithelium remodeling. Here, we review the interplay between Notch signaling and cell polarity and discuss the possible significance of linking Notch signaling with epithelial cell polarity via a common regulator. Notch receptor activation depends on direct cell–cell contacts that in turn depends on cell shape and cellular polarity. The size and geometry of cell–cell contacts have an impact on the strength and range of signaling. The E3 ubiquitin ligase Neuralized regulates the endocytosis and signaling activity of Delta. The activity of Neuralized is tightly regulated during development. Neuralized also modulates epithelial cell polarity by targeting the apical polarity protein Stardust and by promoting the endocytosis of Crumbs. Thus, the cell-specific expression of Neuralized (cell in orange) couples Notch receptor activation (high level of Notch activity in cells next to the Neur-expressing cell) with cell polarity regulation in epithelia (loss of the apical domain in the orange cell).

Description: DNA methylation can be considered a component of epigenetic memory with a critical role during embryo development, and which undergoes dramatic reprogramming after fertilization. Though it has been a focus of research for many years, the reprogramming mechanism is still not fully understood. Recent results suggest that absence of maintenance at DNA replication is a major factor, and that there is an unexpected role for TET3-mediated oxidation of 5mC to 5hmC in guarding against de novo methylation. Base-resolution and genome-wide profiling methods are enabling more comprehensive assessments of the extent to which ART might impair DNA methylation reprogramming, and which sequence elements are most vulnerable. Indeed, as we also review here, studies showing the effect of culture media, ovarian stimulation or embryo transfer on the methylation pattern of embryos emphasize the need to face ART-associated defects and search for strategies to mitigate adverse effects on the health of ART-derived children. DNA methylation, critical for embryo development, suffers significant changes after fertilization, including demethylation, remethylation and TET3-mediated oxidation of 5 mC to 5 hmC. In addition to infertility and environmental insults, ART (in vitro fertilization, in vitro culture, etc) could impact DNA methylation and ART related consequences in the offspring have been reported.

Description: Roles of PTEN in DNA replication. In article number 1700082 , Hou et al. discuss how PTEN, a tumor suppressor, guards the genome. The cover shows the multiple mechanisms by which PTEN ensures faithful genome duplication. PTEN promotes unperturbed baseline progression of DNA replication forks, enforces helicase-polymerase coupling, protects ssDNA, and facilitate stalled fork recovery.

Description: The image on this frontispiece shows a schematic of the human brain surrounded by choanoflagellates, filastereans, ichthyosporeans (the closest unicellular relatives of animals), sponges and ctenophores (early branching animals). Recent work highlights how these different, but extremely important organisms provide us with a new understanding on the evolutionary origin of synapses and neurons , as summarized in article 1700024 by Pawel Burkhardt and Simon G. Sprecher. Cover design: Davis Laundon

Description: Many strains of human viruses, including HCV, HIV1, and a number of Adeno-, Pox- and Herpesviruses, including CMV, encode the substrates for mammalian prenylation enzymes. As discussed by Marakasova et al. in article number 1700014 , prenylation suppression by FT/GGT and FPPS inhibitors as well as the statins has antiviral effects, which may be especially pronounced in case of African Swine Fever virus. [Image credits are to Alexandra Filatova and Dr. Mikhail Skoblov (Research Centre for Medical Genetics, Moscow)].

Description: Radiation beam interface contrast X-ray microscopy provides resolution of a few dozen nanometers from fixed whole muscle biopsies, allowing better reconstruction of the microstructure of the muscle than is currently possible with classic histological techniques. Fixed soleus muscle biopsies have been evaluated from the walk-in mouse model using phase-contrast X-ray microscopy, and results presented that corroborate the accuracy of the method used, and its potential for application in physiotherapy and occupational therapy studies. We believe that this method will enhance existing morphometric methods of analysis, leading to accurate reconstruction of other thick specimens that would otherwise require thin sectioning and reconstruction through deconvolution algorithms. A new method is suggested that can observe the soleus muscle by means of a radiation beam. This study suggests a remarkable method for analyzing muscle tissue that provides a simple and unified technique for obtaining stereoscopic tissue images.

Description: A bio-micromanipulation system is designed for manipulating micro-objects with a length scale of tens or hundreds of microns based on stereo light microscope. The world coordinate reconstruction of points on the surface of micro-objects is an important goal for the micromanipulation. Traditional pinhole camera model is applied widely in macrocomputer vision. However, this model will output bad data with remarkable error if it is directly used to reconstruct three-dimensional world coordinates for stereo light microscope. Therefore, a novel and improved pinhole camera model applied in bio-micromanipulation system is proposed in this article. The new model is composed of binocular-pinhole model and error-correction model. The binocular-pinhole model is used to output the basic world coordinates. The error-correction model is used to correct the errors from the basic world coordinates and outputs the final high-precision world coordinates. The results show that the new model achieves a precision of 0.01 mm in the X direction, 0.01 mm in the Y direction, and 0.015 mm in the Z direction within a maximum reconstruction distance of 4.1 mm in the X direction, 2.9 mm in the Y direction, and 2.25 mm in the Z direction, and that traditional pinhole camera model achieves a lower and unsatisfactory precision of about 0.1 mm. A stereovision model for stereo light microscope is proposed, which supplies a bio-micromanipulation system with the high-precision world coordinates. Binocular-pinhole model is obtained based on traditional pinhole camera model. Error-correction model corrects the errors from binocular-pinhole model.

Description: The egg capsules of five systellognathan stoneflies species representing the genus Isoperla (Plecoptera, Perlodidae) have been investigated using light and electron microscopes (SEM and TEM). We consider the structural modifications of egg coverings (egg capsules, eggshells) like: a shape of a capsule, presence of structures fixing an egg to the substratum under water, intrachorionic aeropylar system facilitating gas exchange as a factor adapting an egg/embryo to the environment. The structures protecting eggs against desiccation during a female flight before oviposition into water as well as against the dangers of external mechanical injury caused by turbulences in rapid water currents of mountain streams are described and discussed. The ground plan of the egg capsule in arctoperlarian stoneflies is also discussed. The egg capsules of five Isoperla species were investigated The egg capsules of Isoperla are radially and regionally differentiated The general organization of the egg capsules in all species investigated is similar

Description: The present study investigated the regenerative potential of connective tissues harvested from two palatal areas widely used as donor sites for muco-gingival surgical approaches. Connective tissue grafts (CTGs) were obtained by de-epithelialisation of a free gingival graft (deCTG) and by a split flap approach from a previous donor site (reCTG). Two types of mesenchymal stem cell (MSCs) were isolated and were named de-epithelialised MSCs (deMSCs) and re-entry MSCs (reMSCs). The cells were characterised and cellular functionality was investigated. CTGs were evaluated using immunohistochemical and ultrastructural approaches. No significant differences were observed regarding the frequency of colony-forming unit- fibroblasts, migration potential, and population doubling time between the two cell lines ( p  〉 0.05). Both cell lines showed positivity for CD105, CD73, CD90, and CD44 and negative expression for CD34/45, CD14, CD79a, and HLA-DR. MSCs from both cell lines successfully differentiated into osteogenic, adipogenic, and chondrogenic lineages. Cells expressing antigens characteristic of CD34+ stromal cells (CD34+, αSMA−, CD31−) were traced in both CTGs. Ultrastructural analysis highlighted the presence of putative progenitors, namely fibroblasts,—in the pericapillary regions and in remote regions of the lamina propria- and pericytes—surrounding the capillaries. This study provides supplementary arguments for the use of CTG grafts in clinical practice due to the presence of putative progenitor cell. However, results were inconclusive regarding clinical decision-making to determine optimal harvesting area. Prior harvesting in the donor area did not appear to alter the regenerative capabilities of the connective tissue. Palatal connective tissues harvested by two techniques foster mesenchymal stem cells. Previous harvesting from the palate does not alter the regenerative capabilities of the connective tissue.

Description: The chilli thrips, Scirtothrips dorsalis Hood, is a serious pest of numerous important vegetable and ornamental crops. Various signals, especially phytochemical cues, determine the behavior of the phytophagous thrips at host selection. The sensory abilities of S. dorsalis are poorly understood although the antennae of adult are known to possess important sensory structures in orther insects. In this study, the morphology, distribution, and ultrastructure of the antennal sensilla of the S. dorsalis were examined by using scanning and transmission electron microscopy. Microscopy observations revealed that adult male and female S. dorsalis possess filiform antennae. Each antenna comprises a scape, a pedicel, and a flagellum composed of six segments without clear sexual dimorphism in the number and distribution of antennal sensilla. The scape and pedicel exhibit Böhm's bristles, sensilla chaetica, and sensilla campaniform. The external structures of these organs reveal their mechanosensory function. In the flagellum, the most represented sensilla are the multiporous sensilla basiconica, which can be divided into three types of single-walled olfactory sensilla; three types of sensilla chaetica with mechanosensory and gustatory functions; sensilla coeloconica, which possess hollow cuticular spoke channels and represent double-walled olfactory sensilla; sensilla capitula and sensilla cavity with thermo-hygrosensory functions; and aporous sensilla trichodea with smooth cuticula and mechanosensory function. The putative function of described sensilla is discussed in ralation to host plant selection behavior of S. dorsalis . TEM image of Sensilla chaetica type 3 of Scirtothrips dorsalis female antenna. The morphology, distribution, and ultrastructure of the antennal sensilla of the Scirtothrips dorsalis were examined by using scanning and transmission electron microscopy. We examind the antennal sensilla of S. dorsalis at ultrastructural level. The antennae appear rich in sensilla of different kinds and functions. This establish the theoretical foundation to characterize the host selection behavior of thrips.

Description: General theories (GT) are reductionist explications of apparently independent facts. Here, in reviewing the literature, I develop a GT to simplify the cluttered landscape of cancer therapy targets by revealing they cluster parsimoniously according to only a few underlying principles. The first principle is that targets can be only exploited by either or both of two fundamentally different approaches: causality-inhibition, and ‘acausal’ recognition of some marker or signature. Nonetheless, each approach must achieve both of two separate goals, efficacy (reduction in cancer burden) and selectivity (sparing of normal cells); if the mechanisms are known, this provides a definition of rational treatment. The second principle is target fragmentation, whereby the target may perform up to three categoric functions (cytoreduction, modulation, cytoprotection), potentially mediated by physically different target molecules, even on different cell types, or circulating freely. This GT remains incomplete until the minimal requirements for cure, or alternatively, proof that cure is impossible, become predictable. A reductionist General Theory of Cancer Targets is presented, proposing that all good targets are based either on causality-inhibition, or recognition; essential tasks (efficacy and selectivity) emerge differently in each case. Sophisticated hybrids may provide additional benefit. General theory analysis, including target fragmentation concepts, provides deeper insights into therapeutic mechanisms.

Description: This study aimed to prepare silk fibroin (SF) films loaded with honeysuckle flowers extract (HFE) for inducing apoptosis of HeLa cells. We mixed solution of SF and HFE by air-drying for preparing the honeysuckle flowers extract loaded silk fibroin (SFH) films. The physical properties including morphologies, contact angle, roughness, and Z range were characterized. MTS assay and fluorescence micrographs proved that SFH films inhibited the proliferation rate of HeLa cells due to induction of HFE into SF films. Furthermore, cell apoptosis assay and cell cycle analysis confirmed that the apoptosis of HeLa cells resulted from SFH films. Therefore, SFH films designed in our study might be a promising candidate material for cancer therapy. Silk fibroin (SF) films loaded with honeysuckle flowers extract (HFE) induced apoptosis of HeLa cells. Therefore, SFH films designed in our study might be a promising candidate material for cancer therapy.

Description: In this study, the change in the amounts the gunshot residues (GSR) collected by the “swab” method from shooter's right hand was analyzed using Scanning Electron Microscope-Energy Dispersive Spectroscopy (SEM-EDS) to test dependency on various conditions (such as skin color of the shooter, various physical properties, hair density of hands, size of the hands, sweaty or creamy (oiliness) hands). As a result of the analysis, there was no significant difference in the amount of GSR according to skin color, however, there was a change in the amount of GSR depending on the physical characteristics of the shooter. These results thought to have practical benefits for the experts performing GSR analysis using the swab technique to assess the incidence. In Microscopy Research and Technique sciences, chemical analysis has gained importance in the last decades. This result showed that the environmental conditions are very effective on the GSR. These analytic data will be beneficialabd useful in practice.

Description: The evolutionary origin of synapses and neurons is an enigmatic subject that inspires much debate. Non-bilaterian metazoans, both with and without neurons and their closest relatives already contain many components of the molecular toolkits for synapse functions. The origin of these components and their assembly into ancient synaptic signaling machineries are particularly important in light of recent findings on the phylogeny of non-bilaterian metazoans. The evolution of synapses and neurons are often discussed only from a metazoan perspective leaving a considerable gap in our understanding. By taking an integrative approach we highlight the need to consider different, but extremely relevant phyla and to include the closest unicellular relatives of metazoans, the ichthyosporeans, filastereans and choanoflagellates, to fully understand the evolutionary origin of synapses and neurons. This approach allows for a detailed understanding of when and how the first pre- and postsynaptic signaling machineries evolved. The evolutionary origin of synapses and neurons is an enigmatic subject that inspires much debate. Most of our knowledge and recent discussions are biased towards a metazoan perspective, leaving a considerable gap in our understanding. Recent work has now revealed important insights into the emergence and co-regulation of complex synaptic signaling machineries from studies in the closest unicellular relatives of metazoans (choanoflagellates, filastereans, and ichthyosporeans).

Description: Gene drives are selfish genetic elements that use a variety of mechanisms to ensure they are transmitted to subsequent generations at greater than expected frequencies. Synthetic gene drives based on the clustered regularly interspersed palindromic repeats (CRISPR) genome editing system have been proposed as a way to alter the genetic characteristics of natural populations of organisms relevant to the goals of public health, conservation, and agriculture. Here, we review the principles and potential applications of CRISPR drives, as well as means proposed to prevent their uncontrolled spread. We also focus on recent work suggesting that factors such as natural genetic variation and inbreeding may represent substantial impediments to the propagation of CRISPR drives. CRISPR-based synthetic selfish genetic elements, or gene drives, have been proposed as a means by which to genetically alter natural populations to address issues in agriculture, conservation, and public health. We describe key concepts of CRISPR gene drives and limitations that must be addressed before their use in the wild.

Description: Faithful DNA replication and accurate chromosome segregation are the key machineries of genetic transmission. Disruption of these processes represents a hallmark of cancer and often results from loss of tumor suppressors. PTEN is an important tumor suppressor that is frequently mutated or deleted in human cancer. Loss of PTEN has been associated with aneuploidy and poor prognosis in cancer patients. In mice, Pten deletion or mutation drives genomic instability and tumor development. PTEN deficiency induces DNA replication stress, confers stress tolerance, and disrupts mitotic spindle architecture, leading to accumulation of structural and numerical chromosome instability. Therefore, PTEN guards the genome by controlling multiple processes of chromosome inheritance. Here, we summarize current understanding of the PTEN function in promoting high-fidelity transmission of genetic information. We also discuss the PTEN pathways of genome maintenance and highlight potential targets for cancer treatment. PTEN is a guardian of the genome. However, the role of PTEN in guarding the genome has not been revealed until recently. PTEN controls multiple fundamental processes of genomic transmission. By physically interacting with key molecules in DNA replication, DNA repair/decatenation, and chromosome segregation during the cell cycle, PTEN maintains genomicintegrity and fitness.

Description: In most mammalian species enamel prisms are regularly arranged in layers of alternating directions forming an angle of approximately 90°. These successive layers of prisms are known as Hunter–Schreger bands (HSBs). The analysis of HSBs may provide valuable information regarding the species life history, taxon and personal identification, with evident applicability in physical anthropology and forensics. Obtaining good quality digital images of HSBs in intact specimens is not always a feasible task. The major problems are the low contrast of images; the reflection of incident light, which may create areas of intense shine in digital images; and the abrupt decrease in the degree of illumination that occurs after light crosses the vertical cracks, frequently present in enamel. We show here that the area of intense shine can be minimized by a polarizing filter coupled to the camera objective, and the filling of enamel cracks with corn oil can reduce refraction of light in enamel cracks. These procedures can significantly increase the quality and the area of HSBs that can be recorded in intact teeth.

Description: The ring-shaped ATPase machine, cohesin, regulates sister chromatid cohesion, transcription, and DNA repair by topologically entrapping DNA. Here, we propose a rigid scaffold model to explain how the cohesin regulators Pds5 and Wapl release cohesin from chromosomes. Recent studies have established the Smc3-Scc1 interface as the DNA exit gate of cohesin, revealed a requirement for ATP hydrolysis in ring opening, suggested regulation of the cohesin ATPase activity by DNA and Smc3 acetylation, and provided insights into how Pds5 and Wapl open this exit gate. We hypothesize that Pds5, Wapl, and SA1/2 form a rigid scaffold that docks on Scc1 and anchors the N-terminal domain of Scc1 (Scc1N) to the Smc1 ATPase head. Relative movements between the Smc1-3 ATPase heads driven by ATP and Wapl disrupt the Smc3-Scc1 interface. Pds5 binds the dissociated Scc1N and prolongs this open state of cohesin, releasing DNA. We review the evidence supporting this model and suggest experiments that can further test its key principles. The cohesin ring topologically entraps DNA to regulate chromosome segregation, transcription, and DNA repair. The cohesin regulators and subunits Pds5, Wapl, and SA2 are hypothesized to form a rigid scaffold that harnesses the energy of ATP binding to open the cohesin ring, releasing cohesin from DNA.

Description: To gain insight to underlying mechanism of the formation of calcium carbonate (CaCO 3 ) gallbladder stones, we did comparative study of stones with mud appearance and those with coralliform appearance. A total of 93 gallbladder stones with mud appearance and 50 stones with coralliform appearance were analyzed. The appearance, color, texture, and the detection of Clonorchis sinensis eggs by microscopic examination were compared between the two groups. Then, the material compositions of stones were analyzed using Fourier Transform Infrared spectroscopy and the spectrogram characteristics were compared. Moreover, microstructure characteristics of the two kinds of stones were observed and compared with Scanning Electron Microscopy. Mud-like gallbladder stones were mainly earthy yellow or brown with brittle or soft texture, while coralliform stones were mainly black with extremely hard texture, the differences between the two groups was significant ( p  〈 .05). The analytic results of FTIR spectroscopy showed that 95.7% (89/93) of the mud-like gallbladder stones were CaCO 3 stones, and mainly aragonite; while all of the coralliform stones were CaCO 3 stones, and mainly calcite ( p  〈 .05). Meanwhile, microscopic examination indicated that the detection rate of Clonorchis sinensis eggs in mud-like CaCO 3 stones was lower than that in coralliform CaCO 3 stones ( p  〈 .05), and that in aragonite CaCO 3 stones was lower than that in calcite CaCO 3 stones( p  〈 .05). Mud-like CaCO 3 stones mainly happened to patients with cystic duct obstruction. Clonorchis sinensis infection was mainly associated with coralliform (calcite) CaCO 3 stones. Cystic duct obstruction was mainly associated with mud-like (aragonite) CaCO 3 stones. Previous study showed that calcium carbonate stones were mainly mud-like or coralliform. The present study found that the appearance, color, texture, crystalline forms and the detection of C. sinensis eggs were different between the two kinds of stones. C. sinensis infection was mainly associated with coralliform (calcite) calcium carbonate stones. Cystic duct obstruction was mainly associated with mud-like (aragonite) calcium carbonate stones.

Description: Background Dentin hypersensitivity is an important clinical problem affecting a large percentage of the population, and various therapies have been suggested for its treatment—among them desensitizing agents and lasers. The aim of this study was to evaluate the in vitro effects of different in-office desensitizing agents and different type lasers, alone or in combination, on human dentinal tubules. Materials and Methods Eighty-four dentinal specimens obtained from freshly extracted impacted third molars were included and subsequently divided into seven groups: Group 1 (Control), Group 2 (Gluma desensitizer), Group 3 (Teethmate desensitizer), Group 4 (Nd:YAG laser), Group 5 (Er:YAG laser), Group 6 (Gluma desensitizer + Er:YAG laser), and Group 7 (Teethmate desensitizer + Er:YAG laser). The dentinal specimens of all groups were evaluated using SEM. A total of 12 images per sample were taken, and the numbers of open, partially occluded, and totally visible (open + partially occluded) dentinal tubules were counted. AFM was used to further substantiate the blocking mechanism. The data were analyzed by one-way ANOVA and Dunnett-C tests. Results Comparison of the number of occluded dentinal tubules per 100 µm 2 revealed that the laser and laser combined-treated groups showed the most occluded dentinal tubules. Gluma desensitizer + Er:YAG laser combination demonstrated significantly more tubule occlusion than all the other groups ( p  〈 .05). Conclusions The results of this study show that combined treatment methods were effective in the occlusion of dentinal tubules.

Description: Exaptations are adaptations that have undergone a major change in function. By recruiting genes from sources originally unrelated to vision, exaptation has allowed for sudden and critical photosensory innovations, such as lenses, photopigments, and photoreceptors. Here we review new or neglected findings, with an emphasis on unicellular eukaryotes (protists), to illustrate how exaptation has shaped photoreception across the tree of life. Protist phylogeny attests to multiple origins of photoreception, as well as the extreme creativity of evolution. By appropriating genes and even entire organelles from foreign organisms via lateral gene transfer and endosymbiosis, protists have cobbled photoreceptors and eyespots from a diverse set of ingredients. While refinement through natural selection is paramount, exaptation helps illustrate how novelties arise in the first place, and is now shedding light on the origins of photoreception itself. Visual systems abound in nature, from simple photopigments in bacteria to sophisticated eyes and eyespots in animals and protists, some bearing complex photoreceptors and lenses. How did these structures initially become photosensory? We explore how nonvisual genes have become recruited into photosensory evolution, via exaptation, endosymbiosis, and lateral gene transfer.

Description: The segregation of homologous chromosomes in meiosis depends on their ability to locate one another in the nucleus and establish a physical association through crossing over. A tightly regulated number of crossovers (COs) emerges following repair of induced DNA double-strand breaks by homologous recombination (HR), but the process of how HR intermediates transition into COs is still poorly understood. Two recent studies by Ahuja et al. and Rao et al. have revealed a role for chromosomally localized proteasomes in choreographing both homologous chromosome pairing and the evolution of HR intermediates into segregation-competent COs. Using chemical inhibition of the proteasome and mutant analysis, the collective data reveal conserved functions for both the proteasome and a family of E3 ligases that can direct or compete with its activity in ensuring CO formation. Here, we review these findings and the impact of the discovery that protein modification dynamics and proteasomal activity cooperate to regulate key meiotic processes. In this review, we discuss the recent studies of Ahuja et al. and Rao et al. which uncover an evolutionarily conserved role for chromosomally localized proteasome and a SUMO-ubiquitin relay in the regulation of key events of meiotic prophase: homologous chromosome pairing, synapsis, and the formation of crossovers.

Description: The instability of microsatellite DNA repeats is responsible for at least 40 neurodegenerative diseases. Recently, Mirkin and co-workers presented a novel mechanism for microsatellite expansions based on break-induced replication (BIR) at sites of microsatellite-induced replication stalling and fork collapse. The BIR model aims to explain single-step, large expansions of CAG/CTG trinucleotide repeats in dividing cells. BIR has been characterized extensively in Saccharomyces cerevisiae as a mechanism to repair broken DNA replication forks (single-ended DSBs) and degraded telomeric DNA. However, the structural footprints of BIR-like DSB repair have been recognized in human genomic instability and tied to the etiology of diverse developmental diseases; thus, the implications of the paper by Kim et al. (Kim JC, Harris ST, Dinter T, Shah KA, et al., Nat Struct Mol Biol 24: 55–60) extend beyond trinucleotide repeat expansion in yeast and microsatellite instability in human neurological disorders. Significantly, insight into BIR-like repair can explain certain pathways of complex genome rearrangements (CGRs) initiated at non-B form microsatellite DNA in human cancers. Break-induced replication (BIR) and genome instability. BIR initiates at sites of microsatellite replication fork collapse (arrowhead). Sister chromatid (black) microsatellite misalignment leads to expansion or contraction. BIR fork collapse allows cycles of error-prone microhomology-mediated BIR (MMBIR), and homology-directed or homeologous recombination to nonhomologous chromosomes (color segments). (Not to scale.)

Description: Chemosensation and mechanosensation cover an enormous spectrum of processes by which animals use information from the environment to adapt their behavior. For pragmatic reasons, these sensory modalities are commonly investigated independently. Recent advances, however, have revealed numerous situations in which they function together to control animals’ actions. Highlighting examples from diverse vertebrates and invertebrates, we first discuss sensory receptors and neurons that have dual roles in the detection of chemical and mechanical stimuli. Next we present cases where peripheral chemosensory and mechanosensory pathways are discrete but intimately packaged to permit coordinated reception of external cues. Finally, we consider how chemical and mechanical signals converge in central neural circuitry to enable multisensory integration. These insights demonstrate how investigation of the interplay between different sensory modalities is key to a more holistic and realistic understanding of sensory-guided behaviors. Although neuroscientists often study individual sensory modalities independently of all others, animals naturally assimilate diverse types of environmental cues to respond with an appropriate behavior. Recent work has revealed how multisensory integration of chemical and mechanical stimuli can occur through the use of common sensory receptor families, organs and circuitry.

Description: Recent analysis of genome sequences has identified individuals that are healthy despite carrying severe disease-associated mutations. A possible explanation is that these individuals carry a second genomic perturbation that can compensate for the detrimental effects of the disease allele, a phenomenon referred to as suppression. In model organisms, suppression interactions are generally divided into two classes: genomic suppressors which are secondary mutations in the genome that bypass a mutant phenotype, and dosage suppression interactions in which overexpression of a suppressor gene rescues a mutant phenotype. Here, we describe the general properties of genomic and dosage suppression, with an emphasis on the budding yeast. We propose that suppression interactions between genetic variants are likely relevant for determining the penetrance of human traits. Consequently, an understanding of suppression mechanisms may guide the discovery of protective variants in healthy individuals that carry disease alleles, which could direct the rational design of new therapeutics. Suppression interactions occur when the detrimental effects of a primary mutation are compensated for by a second mutation. Suppression is likely relevant for determining the severity of genetic traits, including disease. An understanding of suppression mechanisms may help identify suppressors among genetic variants, and direct the discovery of drug targets.

Description: In this manuscript we describe Proteogenomics Viewer, a web-based tool that collects MS peptide identification, indexes to genomic sequence and structure, assigns exon usage, reports the identified protein isoforms with genomic alignments and, most importantly, allows the inspection of MS2 information for proper peptide identification. It also provides all performed indexing to facilitate global analysis of the data. The relevance of such tool is that there has been an increase in the number of proteogenomic efforts to improve the annotation of both genomics and proteomics data, culminating with the release of the two human proteome drafts. It is now clear that mass spectrometry-based peptide identification of uncharacterized sequences, such as those resulting from unpredicted exon joints or non-coding regions, is still prone to a higher than expected false discovery rate. Therefore, proper visualization of the raw data and the corresponding genome alignments are fundamental for further data validation and interpretation. Also see the video abstract here: http://youtu.be/5NzyRvuk4Ac Proteogenomics Viewer is a web-based tool that collects MS peptide identification, indexes to genomic sequence and structure, assigns exon usage, reports the identified protein isoforms with genomic alignments and, most importantly, allows the inspection of MS2 spectra and peptide identification features in order to assist data validation.

Description: At metaphase in mitotic cells, pulling forces at the kinetochore-microtubule interface create tension by stretching the centromeric chromatin between oppositely oriented sister kinetochores. This tension is important for stabilizing the end-on kinetochore microtubule attachment required for proper bi-orientation of sister chromosomes as well as for satisfaction of the Spindle Assembly Checkpoint and entry into anaphase. How force is coupled by proteins to kinetochore microtubules and resisted by centromere stretch is becoming better understood as many of the proteins involved have been identified. Recent application of genetically encoded fluorescent tension sensors within the mechanical linkage between the centromere and kinetochore microtubules are beginning to reveal – from live cell assays – protein specific contributions that are functionally important. Tension sensors reveal how the kinetochore shares its load: the kinetochore links microtubules (right, green) to the centromere (left, yellow DNA strands wrapped around red histone octamers). By placing FRET biosensors in Ndc80 (blue/yellow and red/green coiled coils), it is possible to study the distribution of force within the kinetochore.

Description: There are four major hypotheses (H1, H2, H3, and H4) as to the source of missing heritability. We propose that estimates obtained from GWAS underestimate heritability by not taking into account non-DNA (epigenetic) sources of heritability. Taking those factors into account (H4) should result in increased heritability estimates.

Description: Interindividual variability is an inherent characteristic of biological systems. Whereas the underlying molecular sources of interindividual variability remain poorly understood, recent work by Ecker et al. (Ecker S, Chen L, Pancaldi V, Bagger FO, et al. 2017. Genome Biol 18: 18.) sheds light on the characterization of this phenomenon in a complex biological scenario. By combining data from the BLUEPRINT Epigenome Project with a novel analytical approach, these authors were able to measure the degree of transcriptional and epigenetic variability across a wide panel of samples and types of immune cell. Interestingly, neutrophils displayed increased variability compared to monocytes and T cells, which may be related to the crucial role of the former as an initial mediator of immune responses. Here we review recent literature in this area, and discuss some important issues raised by these innovative analyses. Furthermore, we summarize other potential sources of epigenetic variability, such as epigenetic drift and the epigenetic clock, as well as the current ongoing direction of the field. By analyzing data from the BLUEPRINT Epigenome Project, Ecker and co-workers have recently characterized the transcriptional and epigenetic interindividual variability in different types of peripheral blood cells. The challenge for the future will be to determine the underlying molecular mechanisms and the internal and external modulators of the process.

Description: Heterogeneity in mitochondrial content has been previously suggested as a major contributor to cellular noise, with multiple studies indicating its direct involvement in biomedically important cellular phenomena. A recently published dataset explored the connection between mitochondrial functionality and cell physiology, where a non-linearity between mitochondrial functionality and cell size was found. Using mathematical models, we suggest that a combination of metabolic scaling and a simple model of cell death may account for these observations. However, our findings also suggest the existence of alternative competing hypotheses, such as a non-linearity between cell death and cell size. While we find that the proposed non-linear coupling between mitochondrial functionality and cell size provides a compelling alternative to previous attempts to link mitochondrial heterogeneity and cell physiology, we emphasise the need to account for alternative causal variables, including cell cycle, size, mitochondrial density and death, in future studies of mitochondrial physiology. A recently published dataset explored the relationship between mitochondrial functionality and cell physiology. Using mathematical modelling, we suggest that a combination of metabolic scaling and cell death may account for these observations, in addition to the possibility of cell death non-linearity and functional non-linearity with cell size.

Description: Aged skin is reported to be associated with unattractive skin color changes and solar elastosis. However, comparative studies have not documented the possible correlation between the two factors. This study investigated the plausible relationship between the facial skin color of elderly Asians and solar elastosis. A total of 22 skin specimens were collected from 22 Korean patients who underwent cheek skin biopsies. Skin color was quantitatively measured using colorimetric photography techniques to produce CIE L * a * b * values; the degree of solar elastosis was quantifiably assessed using a histologic grading scale. These values were used to investigate a correlation between the CIE L * a * b * coordinates and solar elastosis grade. The solar elastosis grade increased according to patient age ( r  = 0.67, p  = .0006). However, the extent of solar elastosis was not statistically correlated with the CIE L * a * b * values, including L *, a *, and b * ( r  = 0.02, p = .95; r  = 0.15, p  = 0.50; r  = −0.07, p  = 0.76, respectively). The results showed that the solar elastosis grade increased, according to patient age, because of cumulative actinic damage. However, colorimetric skin color data did not correlate with the degree of solar elastosis. Therefore, cutaneous color changes and solar elastosis are separate, age-related phenomena. Physicians should be aware of the possible histologic changes in actinically damaged facial skin, regardless of the skin color. The solar elastosis grade increased, according to patient age; however, colorimetric skin color data did not correlate with the degree of solar elastosis. Elderly cutaneous color changes and solar elastosis are separate, age-related phenomena.

Description: Modern clinical studies have found that Pulsatilla radix contains a variety of active ingredients; however, its medicinal parts and microstructure have been controversial. Based on morphological observation and microscopic identification of different structures, we chose Anhui, Henan, Jilin, and Shanxi Province to study Pulsatilla chinensis (Bunge) Regel populations. We specifically addressed different diameters and anatomical structures of different parts of underground organs. We also found that P. chinensis (Bunge) Regel had a “joint point” structure in its underground organ. Above the “joint point” is the rhizome, below the “joint point” is the root. The main medicinal organ is the rhizome. The protective tissues of the endothelial layer of P. chinensis (Bunge) Regel changed in the process of its development. The protective tissues were replaced by epidermis, cortex, endodermis, and phloem. With the secondary growth, the endothelial cells have been radial division. This study showed that morphology and microscopic identification was an important mean of medicinal material identifications, and it had the characteristics of a convenient, fast, and intuitive method to identify the composition and structural characteristics of P. chinensis (Bunge) Regel medicinal parts. Joint points were found in the underground medicinal organs of P. chinensis for the first time. Through the observation of P. chinensis anatomical structure, we found that its medicinal part consisted of roots and rhizomes.

Description: The popular textbook image of viruses as noxious and selfish genetic parasites greatly underestimates the beneficial contributions of viruses to the biosphere. Given the crucial dependency of viruses to reproduce in an intracellular environment, viruses that engage in excessive killing (lysis) can drive their cellular hosts to extinction and will not survive. The lytic mode of virus propagation must, therefore, be tempered and balanced by non-lytic modes of virus latency and symbiosis. Here, we review recent bioinformatics and metagenomic studies to argue that viral endogenization and domestication may be more frequent mechanisms of virus persistence than lysis. We use a triangle diagram to explain the three major virus persistence strategies that explain the global scope of virus-cell interactions including lysis, latency and virus-cell symbiosis. This paradigm can help identify novel directions in virology research where scientists could artificially gain control over switching lytic and beneficial viral lifestyles. Also see the Video Abstract: http://youtu.be/GwXWz4N8o8 Viruses evolve with host cells. Their persistence is driven by trade-offs between propagation (lysis), dormancy (latency), and dependency (symbiosis) solutions. While the lytic mode governs viral ecological dynamics, the non-lytic modes of dormancy and dependency may be preferred outcomes in the long-term evolution of viruses.

Description: Is the spatial organization of membranes and compartments within cells subjected to any rules? Cellular compartmentation differs between prokaryotic and eukaryotic life, because it is present to a high degree only in eukaryotes. In 1964, Prof. Eberhard Schnepf formulated the compartmentation rule (Schnepf theorem), which posits that a biological membrane, the main physical structure responsible for cellular compartmentation, usually separates a plasmatic form a non-plasmatic phase. Here we review and re-investigate the Schnepf theorem by applying the theorem to different cellular structures, from bacterial cells to eukaryotes with their organelles and compartments. In conclusion, we can confirm the general correctness of the Schnepf theorem, noting explicit exceptions only in special cases such as endosymbiosis and parasitism. The compartmentation rule by Eberhard Schnepf (Schnepf theorem) was formulated more than 50 years ago. In its quintessence, it posits that a biological membrane separates a plasmatic form a non-plasmatic phase. The theorem addresses important biological questions including cellular and compartmental evolution as well as endosymbiosis and intracellular parasitism.

Description: Interindividual epigenetic variability: Sound or noise? This cover image tries to reflect the potential consequences of epigenetic “sound” (purposeful epigenetic changes) and epigenetic “noise” (stochastic epigenetic changes) in the establishment of interindividual epigenetic variability. The different DNA molecules make allusion to different individuals, where musical notes represent methylathed (minim) and unmethylated (crotchet) CpGs, introducing the concept of phenotypic variation across the population of interest. To highlight the idea of “purposeful” and “stochastic” epigenetic variation, DNA molecules are split into a clean, easy to interpret signal (left side), or a blurry, noisy pattern (right side) respectively, reflecting some of the current biological scenarios that are discussed in article 1700055 by Juan Ramón Tejedor and Mario F. Fraga.

Description: For the microvision system, a new autofocus evaluation function based on the Robert function is proposed by increasing the threshold value. Compared with the traditional evaluation function, the new focus function reduces the local extreme value and increases the steepness of the focusing curve. According to the characteristics of the focusing evaluation function, the focus curve can be divided into two stages: the gentle area and the steep area. In the gentle area, there will be set a large step-length to realize the fast search. In the steep area, the data will be fitted by Gauss method, and on the basis of the fitting results, the motor of microvision system was directly driven to achieve the focal plane and this method has been improved in real-time and accuracy. A new autofocus method is proposed by increasing the threshold value. The focus curve will be divided into two stages. Set a large step-length in gentle area to realize the fast search. The data be fitted by Gauss method in steep area.

Description: Anisopterous odonate male's secondary genitalia is a complex of several structures, among them the vesica spermalis is the most informative with important specific characters. The observation of those characters, mostly of membranous nature, is difficult in the Scanning Electron Microscope due to dehydration and metallization processes. In this contribution, we discuss a new and low cost procedure for the observation of these characters in the SEM, compatible with the most common agents used for preserving specimens. A new and low cost alternative for the study of characters from arthropod mixed membranous and hard cuticle structures in SEM is presented and discussed.

Description: In this review, we summarize recent work exploring a novel conceptual approach termed “synthetic essentiality” as a means for targeting specific tumor suppressor gene deficiencies in cancer. With the aid of extensive publically available cancer genome and clinical databases, “synthetic essentiality” could be utilized to identify synthetic essential genes, which might be occasionally deleted in some cancers but almost always retained in the context of a specific tumor suppressor deficiency. Synthetic essentiality expands the existing concepts for therapeutic strategies, including oncogene addiction, tumor maintenance, synthetic, and collateral lethality, to provide a framework for the discovery of cancer-specific vulnerabilities. Enabled by ever-expanding large-scale genome datasets and genome-scale functional screens, the “synthetic essentiality” framework provides an avenue for the identification of context-specific therapeutic targets and development of patient responder hypotheses for novel and existing therapies. We summarize recent work exploring a novel conceptual approach termed “synthetic essentiality” as a means for targeting tumor suppressor gene deficiencies in cancer. Synthetic essentiality expands the existing concepts for therapeutic strategies, including oncogene addiction, synthetic, and collateral lethality, to provide a framework for the discovery of cancer-specific vulnerabilities.

Description: Widespread expression of the transcription factor, nuclear factor (erythroid-derived 2)-like 2 (NRF2), which maintains redox homeostasis, has recently been identified in the hair follicle (HF). Small molecule activators of NRF2 may therefore be useful in the management of HF pathologies associated with redox imbalance, ranging from HF greying and HF ageing via androgenetic alopecia and alopecia areata to chemotherapy-induced hair loss. Indeed, NRF2 activation has been shown to prevent peroxide-induced hair growth inhibition. Multiple parameters can increase the levels of reactive oxygen species in the HF, for example melanogenesis, depilation-induced trauma, neurogenic and autoimmune inflammation, toxic drugs, environmental stressors such as UV irradiation, genetic defects and aging-associated mitochondrial dysfunction. In this review, the potential mechanisms whereby NRF2 activation could prove beneficial in treatment of redox-associated HF disorders are therefore discussed. Accumulation of reactive oxygen species (ROS) is associated with certain hair disorders and exposure to exogenous stressors, being implicated in apoptosis, hair loss, hair miniaturization and melanocytes damage leading to hair greying. NRF2 activators such as sulforaphane (SFN) may protect against the progression of hair disorders associated with elevated ROS.

Description: To clarify the toxicological effects of metal oxide nanoparticles (NPs) on microorganisms with environmental relevance, it is necessary to understand their interactions. In this work, they were studied the effects and the morphological interactions of two metal oxide NPs (ZnO and TiO 2 ) with microorganisms, during aerobic treatment of wastewater. The effects were evaluated according to nutrient removal from wastewater, while morphological interactions were determined by three different techniques such as TEM, HAADF-STEM, as well as an elemental mapping. According to results about effects of both NPs, they inhibited the removal of organic matter and ammonia nitrogen, and enhanced the orthophosphate removal. Related to morphological interactions, the electron-dense material of both NPs was mainly observed bounded to cell membrane. In tests with ZnO NPs, it was also observed electron-dense material internalized in microorganisms without physical damage in cell membrane. The elemental mapping was useful to determine that the electron-dense material corresponded to Zn and Ti. Both interactions, internalization and attachment of NPs on cell membrane of microorganisms may trigger the negative effect in the removal of organic matter and nitrogen. ZnO and TiO2 NPs inhibited the removal of organic matter and ammonia nitrogen from wastewater. TEM, HAADF-STEM and elemental mapping were useful to identify the attachment and internalization of NPs in microorganisms.

Description: The practical need for a simple and reliable tool for routine size analysis of nanoparticles with diameters down to a few nm embedded in a polymer matrix motivated the development of a new approach. The idea underlying the method proposed in this work is to combine intensity thresholding and contrast fitting procedures in the same software for particle recognition and measurements of sizes and size distributions of nanoparticles in transmission and scanning transmission electron microscopy images. Particle recognition in images is performed in an interactive process of manual setting the numerical threshold level after image preprocessing. We show that fitting the calculated gray level distribution to the real images is able to provide a maximum accuracy in measurements of the particle diameters in contrast to thresholding approaches. The fitting procedure is applied in the vicinity of nanoparticle images with the mass-thickness, diffraction, and chemical contrast. The grayscale function associated to the nanoparticle thickness is described using polynomial with degree ⩾ 2 and undetermined coefficients. The program for particle detection and size measurement— An alyzer of Na noparticles ( AnNa )—has been written and is described here. It was successfully tested on systems containing Ag nanoparticles grown and stabilized in aqueous solutions of different polymers for biomedical use and is available from the authors. A novel method for measuring nanoparticle size distributions on (S)TEM images was developed and implemented in An alyzer of Na noparticles ( AnNa ) program. It combines manual thresholding for particle recognition and original contrast fitting to derive sizes.

Description: SEM and light microscopy are of special interest for biologist to observe various features of the living bodies. In the current study we observed the foliar epidermal micro-morphological characters of 44 grass species using SEM and Light microscopy to assess their taxonomic utility for taxonomists in the identification process. The aim of this study is to use the foliar epidermal structural variations in both upper and lower surfaces for identification of grasses. Significant diversity was observed in both qualitative and quantitative characters using SEM and Light microscopy. Variations were observed in stomatal number, size, guard cells shape, silica bodies, macro-hairs, micro-hairs, epidermal cell number, subsidiary cells, prickles, hooks, papillae, and short and long cells. A taxonomic key is prepared using these variations for the identification of grass species. Based on these findings, SEM and Light microscopy of foliar epidermal features can be of special interest for taxonomists in the identification of complex grass taxa. SEM and LM foliar epidermal micro-morphological studies are important for plant taxonomists and a tool for taxonomic identification of grasses. The SEM and LM studies could be used to make taxonomic keys for fast and accurate identification of grass taxa.

Description: Alzheimer's disease (AD) is the most common form of dementia that gradually disrupts the brain network to impair memory, language and cognition. While the amyloid hypothesis remains the leading proposed mechanism to explain AD pathophysiology, anti-amyloid therapeutic strategies have yet to translate into useful therapies, suggesting that amyloid β-protein and its precursor, the amyloid precursor protein (APP) are but a part of the disease cascade. Further, risk of AD can be modulated by a number of factors, the most impactful being the ɛ4 isoform of apolipoprotein E (apoE). A recent study reported a novel isoform-dependent transcriptional regulation of APP by apoE. These interesting new results add to the myriad of mechanisms that have been proposed to explain how apoE4 enhances AD risk, highlighting the complexities of not only apoE and AD pathophysiology, but also of disease itself. Also see the video abstract here: https://youtu.be/yd14MBdPkCY APP transcription is differentially modulated by apoE and its isoforms: how does this novel mechanism fit with the existing hypotheses?

Description: On the cover: The cover image, by Chantelle Venter et al., is based on the Research Article Effects of metals cadmium and chromium alone and in combination on the liver and kidney tissue of male Spraque-Dawley rats: An ultrastructural and electron-energy-loss spectroscopy investigation , DOI 10.1002/jemt.22877 .

Description: The focus of this double-blind randomized study was on evaluating the effect of an aqueous extract of Mastruz ( Chenopodium ambrosioides L.) on the bone repair process in vivo. In total, 36 male Wistar rats were randomly selected for this study, and divided into 3 groups ( n  = 12): Group HS (Hemostatic Sponge), Group SM (Hemostatic Sponge with Mastruz) and Group BC (Blood Clot). In each animal, bone defects measuring 2 mm in diameter were performed in both tibias for placement of the substances. After 3 and 10 days, the animals were sacrificed, and the tissues were analyzed under an optical microscope relative to the following events: inflammatory infiltrate; necrosis; young fibroblasts; osteoclastic and osteoblastic activity; endosteal and periosteal bone formation; and bone repair. The results were assessed by using Kruskal–Wallis and Mann–Whitney tests ( p  〈 .05). Inflammatory infiltrate demonstrated difference between Groups SM and BC in the time interval of 3 days ( p  = .004); an event related to the presence of the fibrin sponge and liquid of the extract, which induced a foreign body initial reaction. The presence of young fibroblasts ( p  = .003), osteoclastic ( p  = .003), and osteoblastic ( p  = .020) activity was statistically significant between Groups HS and BC in the time interval of 10 days; performance was related to the presence of the sponge within bone. As regards injured bone tissue repair, Group SM demonstrated a higher level of regenerative capacity ( p  = 0.004), due to a larger quantities of endosteal and periosteal bone formation, demonstrated in Group SM. The aqueous extract of mastruz stimulated bone neoformation, presenting wound closure with bone tissue at the end of 10 days. The aqueous extract of Mastruz stimulated bone neoformation, and presented wound closure with bone tissue at the end of 10 days. The use of Mastruz extract is a highly promising method for obtaining rapid bone repair for use in clinical practice.

Description: Oxidative stress increase induces cellular damage and apoptosis activation, a mechanism believed to represent a final common pathway correlated to sarcopenia and many skeletal muscle disorders. The goal of this study is to evaluate if melatonin, a ROS scavenger molecule, is able to counteract or modulate myotube death. Here, differentiated C2C12 skeletal muscle cells have been treated with melatonin before chemicals known to induce apoptotic death and oxidative stress, and its effect has been investigated by means of morpho-functional analyses. Ultrastructural observations show melatonin protection against triggers by the reducing of membrane blebbing, chromatin condensation, myonuclei loss and in situ DNA cleavage. Moreover, melatonin is able to prevent mitochondrial dysfunctions which occur in myotubes exposed to the trigger alone. These findings demonstrate melatonin ability in preventing apoptotic cell death in skeletal muscle fibers in vitro, suggesting for this molecule a potential therapeutic role in the treatment of various muscle disorders. Chemical triggers induced skeletal muscle death Melatonin, a ROS scavenger molecule, is able to counteract mitochondrial damage Melatonin prevents apoptosis in C2C12 myotubes

Description: The image on the cover is a schematic illustration of how two mutually none exclusive theories: atavism (dating back to the pre-Cambrian period) and somatic evolution/convergent evolution can both contribute to explaining cancer evolution. In article 1700039 , Thomas et al. discuss the criteria that should be applied to discriminate between the two competing theories, and propose potential applications of this conceptual framework in developing novel cancer treatment strategies. Original artwork by Eric Pelatan.