PhylomeDB v3.0: an expanding repository of genome-wide collections of trees, alignments and phylogeny-based orthology and paralogy predictions

The growing availability of complete genomic sequences from diverse species has brought about the need to scale up phylogenomic analyses, including the reconstruction of large collections of phylogenetic trees. Here, we present the third version of PhylomeDB (http://phylomeDB.org), a public database for genome-wide collections of gene phylogenies (phylomes). Currently, PhylomeDB is the largest phylogenetic repository and hosts 17 phylomes, comprising 416 093 trees and 165 840 alignments. It is also a major source for phylogeny-based orthology and paralogy predictions, covering about 5 million proteins in 717 fully-sequenced genomes. For each protein-coding gene in a seed genome, the database provides original and processed alignments, phylogenetic trees derived from various methods and phylogeny-based predictions of orthology and paralogy relationships. The new version of phylomeDB has been extended with novel data access and visualization features, including the possibility of programmatic access. Available seed species include model organisms such as human, yeast, Escherichia coli or Arabidopsis thaliana, but also alternative model species such as the human pathogen Candida albicans, or the pea aphid Acyrtosiphon pisum. Finally, PhylomeDB is currently being used by several genome sequencing projects that couple the genome annotation process with the reconstruction of the corresponding phylome, a strategy that provides relevant evolutionary insights

ChemProt: a disease chemical biology database

Systems pharmacology is an emergent area that studies drug action across multiple scales of complexity, from molecular and cellular to tissue and organism levels. There is a critical need to develop network-based approaches to integrate the growing body of chemical biology knowledge with network biology. Here, we report ChemProt, a disease chemical biology database, which is based on a compilation of multiple chemical–protein annotation resources, as well as disease-associated protein–protein interactions (PPIs). We assembled more than 700 000 unique chemicals with biological annotation for 30 578 proteins. We gathered over 2-million chemical–protein interactions, which were integrated in a quality scored human PPI network of 428 429 interactions. The PPI network layer allows for studying disease and tissue specificity through each protein complex. ChemProt can assist in the in silico evaluation of environmental chemicals, natural products and approved drugs, as well as the selection of new compounds based on their activity profile against most known biological targets, including those related to adverse drug events. Results from the disease chemical biology database associate citalopram, an antidepressant, with osteogenesis imperfect and leukemia and bisphenol A, an endocrine disruptor, with certain types of cancer, respectively. The server can be accessed at http://www.cbs.dtu.dk/services/ChemProt/

Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro. In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research

‘Functional Connectivity’ Is a Sensitive Predictor of Epilepsy Diagnosis after the First Seizure

Background: Although epilepsy affects almost 1 % of the world population, diagnosis of this debilitating disease is still difficult. The EEG is an important tool for epilepsy diagnosis and classification, but the sensitivity of interictal epileptiform discharges (IEDs) on the first EEG is only 30–50%. Here we investigate whether using ‘functional connectivity ’ can improve the diagnostic sensitivity of the first interictal EEG in the diagnosis of epilepsy. Methodology/Principal Findings: Patients were selected from a database with 390 standard EEGs of patients after a first suspected seizure. Patients who were later diagnosed with epilepsy (i.e. $two seizures) were compared to matched nonepilepsy patients (with a minimum follow-up of one year). The synchronization likelihood (SL) was used as an index of functional connectivity of the EEG, and average SL per patient was calculated in seven frequency bands. In total, 114 patients were selected. Fifty-seven patients were diagnosed with epilepsy (20 had IEDs on their EEG) and 57 matched patients had other diagnoses. Epilepsy patients had significantly higher SL in the theta band than non-epilepsy patients. Furthermore, theta band SL proved to be a significant predictor of a diagnosis of epilepsy. When only those epilepsy patients without IEDs were considered (n = 74), theta band SL could predict diagnosis with specificity of 76 % and sensitivity of 62%. Conclusion/Significance: Theta band functional connectivity may be a useful diagnostic tool in diagnosing epilepsy

HIV's evasion of the cellular immune response

Despite a strong cytotoxic T-lymphocyte (CTL) response directed against viral antigens, untreated individuals infected with the human immunodeficiency virus (HIV-1) develop AIDS, We have found that primary T cells infected with HIV-1 downregulate surface MHC class I antigens and are resistant to lysis by HLA-A2-restricted CTL clones. In contrast, cells infected with an HIV-1 in which the nef gene is disrupted are sensitive to CTLs in an MHC and peptide-specific manner. In primary T cells HLA-A2 antigens are downmodulated more dramatically than total MHC class I antigens, suggesting that nef selectively downmodulates certain MHC class I antigens. In support of this, studies on ceils expressing individual MHC class I alietes have revealed that nef does not downmodulate HLA-C and HLA-E antigens, This selective downmodulation allows Infected cells to maintain resistance to certain natural killer cells that lyse infected cells expressing low levels of MHC class I antigens. Downmodulation of MHC class I HLA-A2 antigens occurs not only in primary T cells, but also in B and astrocytoma cell lines. No effect of other HIV-1 accessory proteins such as vpu and vpr was observed. Thus Nef is a protein that may promote escape of HIV-1 from immune surveillance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75570/1/j.1600-065X.1999.tb01283.x.pd

A draft genome sequence of the elusive giant squid, Architeuthis dux

Background: The giant squid (Architeuthis dux; Steenstrup, 1857) is an enigmatic giant mollusc with a circumglobal distribution in the deep ocean, except in the high Arctic and Antarctic waters. The elusiveness of the species makes it difficult to study. Thus, having a genome assembled for this deep-sea-dwelling species will allow several pending evolutionary questions to be unlocked. Findings: We present a draft genome assembly that includes 200 Gb of Illumina reads, 4 Gb of Moleculo synthetic long reads, and 108 Gb of Chicago libraries, with a final size matching the estimated genome size of 2.7 Gb, and a scaffold N50 of 4.8 Mb. We also present an alternative assembly including 27 Gb raw reads generated using the Pacific Biosciences platform. In addition, we sequenced the proteome of the same individual and RNA from 3 different tissue types from 3 other species of squid (Onychoteuthis banksii, Dosidicus gigas, and Sthenoteuthis oualaniensis) to assist genome annotation. We annotated 33,406 protein-coding genes supported by evidence, and the genome completeness estimated by BUSCO reached 92%. Repetitive regions cover 49.17% of the genome. Conclusions: This annotated draft genome of A. dux provides a critical resource to investigate the unique traits of this species, including its gigantism and key adaptations to deep-sea environments

Calpain 3 is important for muscle regeneration: Evidence from patients with limb girdle muscular dystrophies

<p>Abstract</p> <p>Background</p> <p>Limb girdle muscular dystrophy (LGMD) type 2A is caused by mutations in the CAPN3 gene and complete lack of functional calpain 3 leads to the most severe muscle wasting. Calpain 3 is suggested to be involved in maturation of contractile elements after muscle degeneration. The aim of this study was to investigate how mutations in the four functional domains of calpain 3 affect muscle regeneration.</p> <p>Methods</p> <p>We studied muscle regeneration in 22 patients with LGMD2A with calpain 3 deficiency, in five patients with LGMD2I, with a secondary reduction in calpain 3, and in five patients with Becker muscular dystrophy (BMD) with normal calpain 3 levels. Regeneration was assessed by using the developmental markers neonatal myosin heavy chain (nMHC), vimentin, MyoD and myogenin and counting internally nucleated fibers.</p> <p>Results</p> <p>We found that the recent regeneration as determined by the number of nMHC/vimentin-positive fibers was greatly diminished in severely affected LGMD2A patients compared to similarly affected patients with LGMD2I and BMD. Whorled fibers, a sign of aberrant regeneration, was highly elevated in patients with a complete lack of calpain 3 compared to patients with residual calpain 3. Regeneration is not affected by location of the mutation in the <it>CAPN3 </it>gene.</p> <p>Conclusions</p> <p>Our findings suggest that calpain 3 is needed for the regenerative process probably during sarcomere remodeling as the complete lack of functional calpain 3 leads to the most severe phenotypes.</p

Body Composition Is a Predictor for Postoperative Complications After Gastrectomy for Gastric Cancer:a Prospective Side Study of the LOGICA Trial

PURPOSE: There is a lack of prospective studies evaluating the effects of body composition on postoperative complications after gastrectomy in a Western population with predominantly advanced gastric cancer. METHODS: This is a prospective side study of the LOGICA trial, a multicenter randomized trial on laparoscopic versus open gastrectomy for gastric cancer. Trial patients who received preoperative chemotherapy followed by gastrectomy with an available preoperative restaging abdominal computed tomography (CT) scan were included. The CT scan was used to calculate the mass (M) and radiation attenuation (RA) of skeletal muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). These variables were expressed as Z-scores, depicting how many standard deviations each patient’s CT value differs from the sex-specific study sample mean. Primary outcome was the association of each Z-score with the occurrence of a major postoperative complication (Clavien-Dindo grade ≥ 3b). RESULTS: From 2015 to 2018, a total of 112 patients were included. A major postoperative complication occurred in 9 patients (8%). A high SM-M Z-score was associated with a lower risk of major postoperative complications (RR 0.47, 95% CI 0.28–0.78, p = 0.004). Furthermore, high VAT-RA Z-scores and SAT-RA Z-scores were associated with a higher risk of major postoperative complications (RR 2.82, 95% CI 1.52–5.23, p = 0.001 and RR 1.95, 95% CI 1.14–3.34, p = 0.015, respectively). VAT-M, SAT-M, and SM-RA Z-scores showed no significant associations. CONCLUSION: Preoperative low skeletal muscle mass and high visceral and subcutaneous adipose tissue radiation attenuation (indicating fat depleted of triglycerides) were associated with a higher risk of developing a major postoperative complication in patients treated with preoperative chemotherapy followed by gastrectomy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11605-022-05321-0