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Signaling networks represent the molecular mechanisms controlling a cell’s response to various internal or external stimuli. Most currently available signaling databases contain only a part of the complex network of intertwining pathways, leaving out key interactions or processes. Hence, we have developed SignaLink3 (http//signalink.org/), a value-added knowledge-base that provides manually curated data on signaling pathways and integrated data from several types of databases (interaction, regulation, localisation, disease, etc.) for humans, and three major animal model organisms. SignaLink3 contains over 400 000 newly added human protein-protein interactions resulting in a total of 700 000 interactions for Homo sapiens, making it one of the largest integrated signaling network resources. Next to H. sapiens, SignaLink3 is the only current signaling network resource to provide regulatory information for the model species Caenorhabditis elegans and Danio rerio, and the largest resource for Drosophila melanogaster. Compared to previous versions, we have integrated gene expression data as well as subcellular localization of the interactors, therefore uniquely allowing tissue-, or compartment-specific pathway interaction analysis to create more accurate models. Data is freely available for download in widely used formats, including CSV, PSI-MI TAB or SQL.Growing evidence suggests that functional cis-regulatory elements (cis-REs) not only exist in epigenetically marked but also in unmarked sites of the human genome. While it is already difficult to identify cis-REs in the epigenetically marked sites, interrogating cis-REs residing within the unmarked sites is even more challenging. Here, we report adapting Reel-seq, an in vitro high-throughput (HTP) technique, to fine-map cis-REs at high resolution over a large region of the human genome in a systematic and continuous manner. Using Reel-seq, as a proof-of-principle, we identified 408 candidate cis-REs by mapping a 58 kb core region on the aging-related CDKN2A/B locus that harbors p16INK4a. By coupling Reel-seq with FREP-MS, a proteomics analysis technique, we characterized two cis-REs, one in an epigenetically marked site and the other in an epigenetically unmarked site. These elements are shown to regulate the p16INK4a expression over an ∼100 kb distance by recruiting the poly(A) binding protein PABPC1 and the transcription factor FOXC2. Downregulation of either PABPC1 or FOXC2 in human endothelial cells (ECs) can induce the p16INK4a-dependent cellular senescence. Thus, we confirmed the utility of Reel-seq and FREP-MS analyses for the systematic identification of cis-REs at high resolution over a large region of the human genome.In the context of stagnating global levels of physical activity (PA), this study examines the geographical segmentation of PA at the regional level (196 regions) in Europe. Cluster analysis and multinomial logistic regression are applied. Cluster analysis provides a taxonomy of four differentiated groups according to the health-related PA levels of the European regions. This taxonomy shows that there are significant regional disparities among European countries in terms of the regional PA level. The cluster profiles in terms of regional socioeconomic characteristics are described for each group, emphasizing the regional characteristics associated with PA. Regional economic variables, tertiary education and social Internet use are significant variables for characterizing the types of regions. The results emphasize the relevance of a European regional approach for reducing inter-regional PA disparities and improving health through PA in Europe. Practical implications of this research are based on regional European coordination, such as collaborative models of sport infrastructure use, co-financing of inter-regional facilities, mutual physical educational scholar programs and promotion of common inter-regional sport competitions and sporting events. Finally, formal schemes for exchanging of best regional practices to promote health-enhancing PA might increase the perception and the role of PA at the regional level in the European society.Viral infectious diseases are a devastating and continuing threat to human and animal health. Receptor binding is the key step for viral entry into host cells. see more Therefore, recognizing viral receptors is fundamental for understanding the potential tissue tropism or host range of these pathogens. The rapid advancement of single-cell RNA sequencing (scRNA-seq) technology has paved the way for studying the expression of viral receptors in different tissues of animal species at single-cell resolution, resulting in huge scRNA-seq datasets. However, effectively integrating or sharing these datasets among the research community is challenging, especially for laboratory scientists. In this study, we manually curated up-to-date datasets generated in animal scRNA-seq studies, analyzed them using a unified processing pipeline, and comprehensively annotated 107 viral receptors in 142 viruses and obtained accurate expression signatures in 2 100 962 cells from 47 animal species. Thus, the VThunter database provides a user-friendly interface for the research community to explore the expression signatures of viral receptors. VThunter offers an informative and convenient resource for scientists to better understand the interactions between viral receptors and animal viruses and to assess viral pathogenesis and transmission in species. Database URL https//db.cngb.org/VThunter/.N6-methyladenosine (m6A) and N6,2′-O-dimethyladenosine (m6Am) are two abundant modifications found in mRNAs and ncRNAs that can regulate multiple aspects of RNA biology. They function mainly by regulating interactions with specific RNA-binding proteins. Both modifications are linked to development, disease and stress response. To date, three methyltransferases and two demethylases have been identified that modify adenosines in mammalian mRNAs. Here, we present a comprehensive analysis of the interactomes of these enzymes. PCIF1 protein network comprises mostly factors involved in nascent RNA synthesis by RNA polymerase II, whereas ALKBH5 is closely linked with most aspects of pre-mRNA processing and mRNA export to the cytoplasm. METTL16 resides in subcellular compartments co-inhabited by several other RNA modifiers and processing factors. FTO interactome positions this demethylase at a crossroad between RNA transcription, RNA processing and DNA replication and repair. Altogether, these enzymes share limited spatial interactomes, pointing to specific molecular mechanisms of their regulation.

Appropriate thrombus-device interaction is critical for recanalization. Histology can serve as a proxy for mechanical properties, and thus inform technique selection.

To investigate the value of histologic characterization, we conducted a systematic review and meta-analysis on the relationship between thrombus histology and recanalization, technique, etiology, procedural efficiency, and imaging findings.

In this meta-analysis, we identified studies published between March 2010 and March 2020 reporting findings related to the histologic composition of thrombi in large vessel occlusion stroke. Studies with at least 10 patients who underwent mechanical thrombectomy using stent retriever or aspiration were considered. Only studies in which retrieved thrombi were histologically processed were included. Patient-level data were requested when data could not be directly extracted. The primary outcome assessed was the relationship between thrombus histology and angiographic outcome.

A total of 22 studies encome.

Pericranial autograft is a popular option for duraplasty during Chiari decompression with several theoretical advantages, but comparisons to other materials have yielded mixed results.

To compare outcomes between pericranial autograft and AlloDerm (BioHorizons).

Consecutive suboccipital craniectomies for patients with type I Chiari malformation (CM-I) over an 8-yr period at a single institution were identified. Exclusion criteria included revision surgeries and suboccipital decompressions without duraplasty. Outcomes included incisional cerebrospinal fluid (CSF) leakage, length of stay (LOS), wound complication, aseptic meningitis, syrinx improvement, and symptomatic improvement.

A total of 101 patients (70 females and 31 males) with a median (interquartile range) age of 17 yr (11-32) met the inclusion criteria. There were 51 (50%) patients who underwent duraplasty with pericranial autograft, and the remainder underwent duraplasty with AlloDerm. There were 9 (9%) patients who experienced a postoperative CSF leak. After adjusting for confounding factors, obesity (odds ratio [OR] 4.69, 95% CI 1.03-25.6) and use of AlloDerm (OR 10.54, 95% CI 1.7-206.12) were associated with CSF leak. Wound complication occurred in 8 (8%) patients but was not associated with graft type (P=.8). Graft type was not associated with LOS, syrinx improvement, or symptom improvement. Reoperations occurred in 10 patients with 4 in the autograft group and 6 in the AlloDerm group (P=.71).

In patients with CM-I, expansile duraplasty with AlloDerm was associated with greater odds of CSF leakage than pericranial autograft. Obesity was also associated with increased odds of CSF leakage.

In patients with CM-I, expansile duraplasty with AlloDerm was associated with greater odds of CSF leakage than pericranial autograft. Obesity was also associated with increased odds of CSF leakage.Recently, researchers have documented variation between groups in collective behavior. However, how genetic variation within and between groups contributes to population-level variation for collective behavior remains unclear. Understanding how genetic variation of group members relates to group-level phenotypes is evolutionarily important because there is increasing evidence that group-level behavioral variation influences fitness and that the genetic architecture of group-level traits can affect the evolutionary dynamics of traits. Social insects are ideal for studying the complex relationship between individual and group-level variation because they exhibit behavioral variation at multiple scales of organization. To explore how the genetic composition of groups affects collective behavior, we constructed groups of pharaoh ants (Monomorium pharaonis) from 33 genetically distinct colonies of known pedigree. The groups consisted of either all workers from the same single colony or workers from two genetically different colonies, and we assayed the exploration and aggression of the groups. We found that collective exploration, but not aggression, depended on the specific genotypic combination of group members, i.e., we found evidence for genotype-by-genotype epistasis for exploration. Group collective behavior did not depend on the pedigree relatedness between genotypes within groups. Overall, this study highlights that specific combinations of genotypes influence group-level phenotypes, emphasizing the importance of considering nonadditive effects of genotypic interactions between group members.

To characterize a novel plasmid-mediated tigecycline resistance-related gene, tet(Y), in a clinical Acinetobacter baumannii isolate from China.

The tet(Y)-encoded tigecycline-resistant A. baumannii 2016GDAB1 was screened through antimicrobial susceptibility testing and WGS. The function of tet(Y) was verified by complementation of tet(Y). The plasmid transferability and stability were detected via plasmid conjugation and in vitro bacterial passaging. The 3D structure of Tet(Y) was predicted and docked using tFold and AutoDock Vina.

The tigecycline-resistant A. baumannii 2016GDAB1 was isolated from bronchoalveolar lavage fluid of a patient with hospital-acquired pneumonia. However, this strain did not harbour any common tigecycline resistance genes, determinants or mutations. 2016GDAB1 belongs to the non-epidemic clone ST355 (Oxford scheme), which has been mainly reported in animals. The tet(Y) gene was located on a 72 156 bp plasmid and genomic environment analysis revealed that Tn5393 may play a role in tet(Y) transmission, whereas phylogenetic analysis indicated the origin of tet(Y) as from Aeromonas.