ALBERT

Description: 〈p〉Animals must consider competing information before deciding to eat: internal signals indicating the desirability of food and external signals indicating the risk involved in eating within a particular environment. The behaviors driven by the former are manifestations of hunger, and the latter, anxiety. The connection between pathologic anxiety and reduced eating in conditions like typical depression and anorexia is well known. Conversely, anti-anxiety drugs such as benzodiazepines increase appetite. Here, we show that GABAergic neurons in the diagonal band of Broca (DBB〈sup〉GABA〈/sup〉) are responsive to indications of risk and receive monosynaptic inhibitory input from lateral hypothalamus GABAergic neurons (LH〈sup〉GABA〈/sup〉). Activation of this circuit reduces anxiety and causes indiscriminate feeding. We also found that diazepam rapidly reduces DBB〈sup〉GABA〈/sup〉 activity while inducing indiscriminate feeding. Our study reveals that the LH〈sup〉GABA〈/sup〉-〉DBB〈sup〉GABA〈/sup〉 neurocircuit overrides anxiogenic environmental cues to allow feeding and that this pathway may underlie the link between eating and anxiety-related disorders.〈/p〉

Description: Author(s): X. H. Niu, R. Peng, H. C. Xu, Y. J. Yan, J. Jiang, D. F. Xu, T. L. Yu, Q. Song, Z. C. Huang, Y. X. Wang, B. P. Xie, X. F. Lu, N. Z. Wang, X. H. Chen, Z. Sun, and D. L. Feng To understand the pairing symmetry and superconducting transition temperature in heavily electron-doped iron-based superconductors, it is important to study more of these materials, especially ones with decent stability in air and without phase separation. Here, angle-resolved photoemission spectroscopy probes the surface electronic structure and superconducting gap in the new superconductor (Li 0 . 8 Fe 0 . 2 )OHFeSe, which shows a T c as high as 40 K. [Phys. Rev. B 92, 060504(R)] Published Tue Aug 18, 2015

Description: Sequence alignment is a long standing problem in bioinformatics. The Basic Local Alignment Search Tool (BLAST) is one of the most popular and fundamental alignment tools. The explosive growth of biological sequences calls for speedup of sequence alignment tools such as BLAST. To this end, we develop high speed BLASTN (HS-BLASTN), a parallel and fast nucleotide database search tool that accelerates MegaBLAST—the default module of NCBI-BLASTN. HS-BLASTN builds a new lookup table using the FMD-index of the database and employs an accurate and effective seeding method to find short stretches of identities (called seeds) between the query and the database. HS-BLASTN produces the same alignment results as MegaBLAST and its computational speed is much faster than MegaBLAST. Specifically, our experiments conducted on a 12-core server show that HS-BLASTN can be 22 times faster than MegaBLAST and exhibits better parallel performance than MegaBLAST. HS-BLASTN is written in C++ and the related source code is available at https://github.com/chenying2016/queries under the GPLv3 license.

Description: Defective lysosomal acid β-glucosidase (GCase) in Gaucher disease causes accumulation of glucosylceramide (GC) and glucosylsphingosine (GS) that distress cellular functions. To study novel pathological mechanisms in neuronopathic Gaucher disease (nGD), a mouse model (4L;C*), an analogue to subacute human nGD, was investigated for global profiles of differentially expressed brain mRNAs (DEGs) and miRNAs (DEmiRs). 4L;C* mice displayed accumulation of GC and GS, activated microglial cells, reduced number of neurons and aberrant mitochondrial function in the brain followed by deterioration in motor function. DEGs and DEmiRs were characterized from sequencing of mRNA and miRNA from cerebral cortex, brain stem, midbrain and cerebellum of 4L;C* mice. Gene ontology enrichment and pathway analysis showed preferential mitochondrial dysfunction in midbrain and uniform inflammatory response and identified novel pathways, axonal guidance signaling, synaptic transmission, eIF2 and mammalian target of rapamycin (mTOR) signaling potentially involved in nGD. Similar analyses were performed with mice treated with isofagomine (IFG), a pharmacologic chaperone for GCase. IFG treatment did not alter the GS and GC accumulation significantly but attenuated the progression of the disease and altered numerous DEmiRs and target DEGs to their respective normal levels in inflammation, mitochondrial function and axonal guidance pathways, suggesting its regulation on miRNA and the associated mRNA that underlie the neurodegeneration in nGD. These analyses demonstrate that the neurodegenerative phenotype in 4L;C* mice was associated with dysregulation of brain mRNAs and miRNAs in axonal guidance, synaptic plasticity, mitochondria function, eIF2 and mTOR signaling and inflammation and provides new insights for the nGD pathological mechanism.

Description: Identification of transcription units (TUs) encoded in a bacterial genome is essential to elucidation of transcriptional regulation of the organism. To gain a detailed understanding of the dynamically composed TU structures, we have used four strand-specific RNA-seq (ssRNA-seq) datasets collected under two experimental conditions to derive the genomic TU organization of Clostridium thermocellum using a machine-learning approach. Our method accurately predicted the genomic boundaries of individual TUs based on two sets of parameters measuring the RNA-seq expression patterns across the genome: expression-level continuity and variance. A total of 2590 distinct TUs are predicted based on the four RNA-seq datasets. Among the predicted TUs, 44% have multiple genes. We assessed our prediction method on an independent set of RNA-seq data with longer reads. The evaluation confirmed the high quality of the predicted TUs. Functional enrichment analyses on a selected subset of the predicted TUs revealed interesting biology. To demonstrate the generality of the prediction method, we have also applied the method to RNA-seq data collected on Escherichia coli and achieved high prediction accuracies. The TU prediction program named SeqTU is publicly available at https://code.google.com/p/seqtu/ . We expect that the predicted TUs can serve as the baseline information for studying transcriptional and post-transcriptional regulation in C. thermocellum and other bacteria.

Description: Dicer participates in heterochromatin formation in fission yeast and plants. However, whether it has a similar role in mammals remains controversial. Here we showed that the human Dicer protein interacts with SIRT7, an NAD + -dependent H3K18Ac (acetylated lysine 18 of histone H3) deacetylase, and holds a proportion of SIRT7 in the cytoplasm. Dicer knockdown led to an increase of chromatin-associated SIRT7 and simultaneously a decrease of cytoplasmic SIRT7, while its overexpression induced SIRT7 reduction in the chromatin-associated fraction and increment in the cytoplasm. Furthermore, DNA damaging agents promoted Dicer expression, leading to decreased level of chromatin-associated SIRT7 and increased level of H3K18Ac, which can be alleviated by Dicer knockdown. Taken together with that H3K18Ac was exclusively associated with the chromatin, our findings suggest that Dicer induction by DNA damaging treatments prevents H3K18Ac deacetylation, probably by trapping more SIRT7 in the cytoplasm.

Description: Author(s): S. F. Li, X. J. Zhao, X. S. Xu, Y. F. Gao, and Zhenyu Zhang Nanoclusters with extra stability at certain cluster sizes are known as magic clusters with exotic properties. The classic Wulff construction principle, which stipulates that the preferred structure of a cluster should minimize its total surface energy, is often invoked in determining the cluster ma... [Phys. Rev. Lett. 111, 115501] Published Mon Sep 09, 2013

Description: The circular chromosome of Escherichia coli has been suggested to fold into a collection of sequentially consecutive domains, genes in each of which tend to be co-expressed. It has also been suggested that such domains, forming a partition of the genome, are dynamic with respect to the physiological conditions. However, little is known about which DNA segments of the E. coli genome form these domains and what determines the boundaries of these domain segments. We present a computational model here to partition the circular genome into consecutive segments, theoretically suggestive of the physically folded supercoiled domains, along with a method for predicting such domains under specified conditions. Our model is based on a hypothesis that the genome of E. coli is partitioned into a set of folding domains so that the total number of unfoldings of these domains in the folded chromosome is minimized, where a domain is unfolded when a biological pathway, consisting of genes encoded in this DNA segment, is being activated transcriptionally. Based on this hypothesis, we have predicted seven distinct sets of such domains along the E. coli genome for seven physiological conditions, namely exponential growth, stationary growth, anaerobiosis, heat shock, oxidative stress, nitrogen limitation and SOS responses. These predicted folding domains are highly stable statistically and are generally consistent with the experimental data of DNA binding sites of the nucleoid-associated proteins that assist the folding of these domains, as well as genome-scale protein occupancy profiles, hence supporting our proposed model. Our study established for the first time a strong link between a folded E. coli chromosomal structure and the encoded biological pathways and their activation frequencies.

Description: A seismic experiment provides new insights on the crustal structure of the head area of the Three Gorges Reservoir in central China. The region is characterized by a relatively high rate of reservoir-induced seismicity that is often triggered within those areas associated with the ascending water level. Our 3-D velocity model of the Three Gorges region shows that the Huangling anticline (HLA) is characterized by a high-velocity crust, and the Zigui Basin (ZGB) has lower crustal velocities. The 3-D tomographic inversions are conducted using 11 901 P -wave and 12 032 S -wave arrival times from 1342 events recorded by the local network of seismic stations from early 2001 to late 2006. Initial models with varying velocity gradients are extracted to constrain a data-driven optimum 1-D model for 3-D iterative inversion scheme. Checkerboard tests are applied to assess model reliability, indicating a reasonable level of lateral and vertical resolutions. The P - and S -tomographic models reveal a local high-velocity anomaly from 5 to 10 km beneath SW portion of the HLA and a strong, large low-velocity anomaly between about 5–10 km depths at the south margin of the ZGB. Moreover, the southwest border of HLA underthrust the ZGB with slightly bigger angle. Also, a prominent high-velocity anomaly is located below 5 km beneath Shazhenxi, and to the west, the velocity anomaly turns out to be negative. There is no record help explaining the dramatic feature since incorporating local tectonic and topography, it suggests sharp gap in velocity near surface is primarily due to several secondary fracture zones. The surface responses of velocity discontinuity are generally aligned parallel to the trending of fault. Relatively good agreement between regional features and the velocity perturbations promotes further interpretation. Earthquake swarm activities from source relocation occur on the outer portions of high-velocity anomaly with nearly perpendicular dip angle. Thus, the seismicity pattern could be interpreted based on the velocity models, regional geostress and dynamic load of reservoir.

Description: As part of the international Pig-a validation trials, we examined the induction of Pig-a mutant reticulocytes and red blood cells (RET CD59– and RBC CD59– , respectively) in peripheral blood of male Sprague Dawley ® rats treated with urethane (25, 100 and 250mg/kg/day) or saline by oral gavage for 29 days. Additional endpoints integrated into this study were: micronucleated reticulocytes (MN-RET) in peripheral blood; chromosome aberrations (CAb) and DNA damage (%tail intensity via the comet assay) in peripheral blood lymphocytes (PBL); micronucleated polychromatic erythrocytes (MN-PCE) in bone marrow; and DNA damage (comet) in various organs at termination (the 29th dose was added for the comet endpoint at sacrifice). Ethyl methanesulfonate (EMS; 200mg/kg/day on Days 3, 4, 13, 14, 15, 27, 28 and 29) was evaluated as the concurrent positive control (PC). All animals survived to termination and none exhibited overt toxicity, but there were significant differences in body weight and body weight gain in the 250-mg/kg/day urethane group, as compared with the saline control animals. Statistically significant, dose-dependent increases were observed for urethane for: RET CD59– and RBC CD59– (on Days 15 and 29); MN-RET (on Days 4, 15 and 29); and MN-PCE (on Day 29). The comet assay yielded positive results in PBL (Day 15) and liver (Day 29), but negative results for PBL (Days 4 and 29) and brain, kidney and lung (Day 29). No significant increases in PBL CAb were observed at any sample time. Except for PBL CAb (likely due to excessive cytotoxicity), EMS-induced significant increases in all endpoints/tissues. These results compare favorably with earlier in vivo observations and demonstrate the utility and sensitivity of the Pig-a in vivo gene mutation assay, and its ability to be easily integrated, along with other standard genotoxicity endpoints, into 28-day rodent toxicity studies.