bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Rab GTPase Ypt1p governs the activation of Unfolded Protein Response (UPR) in Saccharomyces cerevisiae by promoting the preferential nuclear degradation of pre-HAC1 mRNA
Authors: Paira Sunirmal , Chakraborty Anish , Das Biswadip 
Published: August 2022

ABSTRACTInduction of unfolded protein response (UPR) involves activation of transcription factor Hac1p that facilitates the transactivation of genes encoding ER-chaperones. Hac1p is encoded by HAC1 pre-mRNA harboring an intron and a bipartite element (BE) at its 3′-UTR. This precursor RNA undergoes a reversible and differential intra-nuclear mRNA decay by the nuclear exosome/CTEXT at various phases of UPR. In this investigation, using a combination of genetic, and biochemical approach, the Rab-GTPase Ypt1p is demonstrated to control UPR signaling dynamics. Regulation of UPR by Ypt1p relies on its characteristic nuclear localization in absence of ER-stress resulting in its strong association with pre-HAC1 mRNA at its 3′-UTR that promotes sequential recruitments of Nrd1-Nab3p-Sen1p (NNS) complex → CTEXT → the nuclear exosome onto the pre-HAC1 mRNA that is accompanied by its rapid and selective nuclear decay. This accelerated 3′→5′ mRNA decay produces a pre-HAC1 mRNA pool lacking the functional BE thus causing its inefficient targeting to Ire1p foci leading to their diminished splicing and translation. ER stress triggers a rapid relocalization of Ypt1p to the cytoplasm with its consequent dissociation from pre-HAC1 mRNA thereby causing a decreased recruitment of NNS/exosome/CTEXT to precursor HAC1 RNA leading to its diminished 3′→5′ degradation by the exosome. This diminished decay produces an increased abundance of pre-HAC1 mRNA population with intact functional BE leading to its enhanced recruitment to Ire1p foci that is followed by its increased splicing and translation. This enhanced translation produces a huge burst of Hac1p that rapidly transactivates the genes encoding ER-chaperones.
Network analysis with either Illumina or MinION reveals that detecting vertebrate species requires metabarcoding of iDNA from a diverse fly community
Authors: Srivathsan Amrita , Ker Rebecca Loh , Ong Elliott James , Lee Leshon , Ang Yuchen , Kutty Sujatha Narayanan , Meier Rudolf 
Published: August 2022

ABSTRACTMetabarcoding of vertebrate DNA obtained from invertebrates (iDNA) has been used to survey vertebrate communities, but we here show that it can also be used to study species interactions between invertebrates and vertebrates in a spatial context. We sampled the dung and carrion fly community of a swamp forest remnant along a disturbance gradient (10 sites: 80-310m from a road). Approximately, 60% of the baited 407 flies yield 294 vertebrate identifications based on two COI fragments and 16S sequenced with Illumina and/or MinION. A bipartite network analysis finds no specialization in the interaction between flies and vertebrate species, but a spatial analysis revealed that surprisingly 18 of the 20 vertebrate species can be detected within 150m of the road. We show that the fly community sourced for iDNA was unexpectedly rich (24 species, 3 families) and carried DNA for mammals, birds, and reptiles. They included common and rare ground-dwelling (e.g., wild boar, Sunda pangolin), and arboreal species (e.g., long-tailed macaque, Raffles’ banded langur) as well as small bodied vertebrates (skinks, rats). All of our results were obtained with a new, greatly simplified iDNA protocol that eliminates DNA extraction by obtaining template directly through dissolving feces and regurgitates from individual flies with water. Lastly, we show that MinION- and Illumina-based metabarcoding yield similar results. Overall, flies from several families (calliphorids, muscids and sarcophagids) should be used in iDNA surveys because we show that uncommon fly species carry the signal for several vertebrate species that are otherwise difficult to detect with iDNA.
Pan-flavivirus analysis reveals sfRNA-independent, 3’UTR-biased siRNA production from an Insect-Specific Flavivirus
Authors: Besson Benoit , Overheul Gijs J. , Wolfinger Michael T. , Junglen Sandra , van Rij Ronald P. 
Published: August 2022

ABSTRACTRNA interference (RNAi) plays an essential role in mosquito antiviral immunity, but it is not known whether viral siRNA profiles differ between mosquito-borne and mosquito-specific viruses. A pan-Orthoflavivirus analysis inAedes albopictuscells revealed that viral siRNAs were evenly distributed across the viral genome of most representatives of theFlavivirusgenus. In contrast, siRNA production was biased towards the 3’ untranslated region (UTR) of the genomes of classical insect-specific flaviviruses (cISF), which was most pronounced for Kamiti River virus (KRV), a virus with a unique, 1.2 kb long 3’ UTR. KRV-derived siRNAs were produced in high quantities and almost exclusively mapped to the 3’ UTR. We mapped the 5’ end of KRV subgenomic flavivirus RNAs (sfRNAs), products of the 5’-3’ exoribonuclease XRN1/Pacman stalling on secondary RNA structures in the 3’ UTR of the viral genome. We found that KRV produces high copy numbers of a long, 1017 nt sfRNA1 and a short, 421 nt sfRNA2, corresponding to two predicted XRN1-resistant elements. Expression of both sfRNA1 and sfRNA2 was reduced inPacmandeficientAedes albopictuscells, however, this did not correlate with a shift in viral siRNA profiles. We suggest that cISFs and particularly KRV developed a unique mechanism to produce high amounts of siRNAs as a decoy for the antiviral RNAi response in an sfRNA-independent manner.IMPORTANCETheFlavivirusgenus contains diverse mosquito viruses ranging from insect-specific viruses circulating exclusively in mosquito populations to mosquito-borne viruses that cause disease in humans and animals. Studying the mechanisms of virus replication and antiviral immunity in mosquitoes is important to understand arbovirus transmission and may inform the development of disease control strategies. In insects, RNA interference (RNAi) provides broad antiviral activity and constitutes a major immune response against viruses. Comparing diverse members of theFlavivirusgenus, we found that all flaviviruses are targeted by RNAi. However, the insect-specific Kamiti River virus was unique in that small interfering RNAs are highly skewed towards its uniquely long 3’ untranslated region. These results suggest that mosquito-specific viruses have evolved unique mechanisms for genome replication and immune evasion.
Mental Health and Stress Level of Ukrainians Seeking Psychological Help Online
Authors: Asanov Noha Anastasiya-Mariya , Asanov Igor , Buenstorf Guido 
Published: August 2022

AbstractWe screen the mental well-being and psychological distress of 1165 refugees, migrants, internally displaced, and non-displaced people from Ukraine who seek psychological help online in Ukraine and across 24 countries of the European Union. We see that more than half of the respondents exhibit low levels of mental well-being and high psychological distress, with 81% being at risk of depression and 57% having severe psychological distress. Refugees and internally displaced people in our sample show a particularly high risk of depression and severe psychological distress. Nevertheless, the majority of Ukrainians seeking psychological help still work, study, or volunteer, and those who do have relatively alleviated mental levels of well-being.
Survival of mineral-bound peptides into the Miocene
Authors: Demarchi Beatrice , Mackie Meaghan , Li Ziheng , Deng Tao , Collins Matthew J. , Clarke Julia 
Published: August 2022

AbstractThe oldest authenticated peptide sequences to date were reported in 2016 from 3.8 Ma old ostrich eggshell (OES) from the site of Laetoli, Tanzania (Demarchi et al., 2016). Here we demonstrate survival of the same sequences in 6.5-9 Ma OES recovered from a palaeosteppe setting in northwestern China. The eggshell is thicker than those observed in extant species and consistent with the Liushu Struthio sp. ootaxon. These findings push the preservation of ancient proteins back to the Miocene and highlight their potential for paleontology, paleoecology and evolutionary biology.
Implications of taxonomic bias for microbial differential-abundance analysis
Authors: McLaren Michael R. , Nearing Jacob T. , Willis Amy D. , Lloyd Karen G. , Callahan Benjamin J. 
Published: August 2022

AbstractDifferential-abundance (DA) analyses enable microbiome researchers to assess how microbial species vary in relative or absolute abundance with specific host or environmental conditions, such as health status or pH. These analyses typically use sequencing-based community measurements that are taxonomically biased to measure some species more efficiently than others. Understanding the effects that taxonomic bias has on the results of a DA analysis is essential for achieving reliable and translatable findings; yet currently, these effects are unknown. Here, we characterized these effects for DA analyses of both relative and absolute abundances, using a combination of mathematical theory and data analysis of real and simulated case studies. We found that, for analyses based on species proportions, taxonomic bias can cause significant errors in DA results if the average measurement efficiency of the community is associated with the condition of interest. These errors can be avoided by using more robust DA methods (based on species ratios) or quantified and corrected using appropriate controls. Wide adoption of our recommendations can improve the reproducibility, interpretability, and translatability of microbiome DA studies.This manuscript was rendered from commit 7412a36 of https://github.com/mikemc/differential-abundance-theory. Supporting data analyses can be found in the accompanying computational research notebook. Please post comments or questions on GitHub. The manuscript is licensed under a CC BY 4.0 License. See the GitHub Releases or Zenodo record for earlier versions.
zDHHC5 expression is increased in cardiac hypertrophy and reduced in heart failure but this does not correlate with changes in substrate palmitoylation
Authors: Main Alice , Bogusalvskyii Andri , Howie Jacqueline , Kuo Chien-wen , Rankin Aileen , Burton Francis L. , Smith Godfrey L. , Hajjar Roger , Baillie George S. , Campbell Kenneth S. , Shattock Michael J. , Fuller William 
Published: August 2022

AbstractS-palmitoylation is an essential lipid modification catalysed by zDHHC-palmitoyl acyltransferases that regulates the localisation and activity of substrates in every class of protein and tissue investigated to date. In the heart, S-palmitoylation regulates sodiumcalcium exchanger (NCX1) inactivation, phospholemman (PLM) inhibition of the Na+/K+ ATPase, Nav1.5 influence on membrane excitability and membrane localisation of heterotrimeric G-proteins. The cell surface localised enzyme zDHHC5 palmitoylates NCX1 and PLM and is implicated in injury during anoxia/reperfusion. Information is lacking about how palmitoylation remodels in cardiac diseases. We investigated expression of zDHHC5 in animal models of left ventricular hypertrophy (LVH) and heart failure (HF), along with HF tissue from humans. zDHHC5 expression was rapidly elevated during onset of LVH, whilst HF was associated with decreased zDHHC5 expression. Paradoxically, palmitoylation of the zDHHC5 substrate NCX1 was significantly reduced in LVH but increased in human HF. Overexpression of zDHHC5 in rabbit ventricular cardiomyocytes was not sufficient to drive changes in palmitoylation of zDHHC5 substrates or overall cardiomyocyte contractility, suggesting changes in zDHHC5 expression in disease may not be a primary driver of pathology. zDHHC5 itself is regulated by post-translational modifications, including palmitoylation in its Cterminal tail, and we found the palmitoylation of zDHHC5 may be increased in heart failure in the same manner as NCX1, suggesting additional regulatory mechanisms such as acyl-CoA availability may be involved. Importantly, this study provides the first evidence that palmitoylation of cardiac substrates is altered in the setting of HF, and that expression of zDHHC5 is dysregulated in both hypertrophy and HF.
Genetically encoded sensors for measuring histamine release both in vitro and in vivo
Authors: Dong Hui , Li Mengyao , Yan Yuqi , Qian Tongrui , Lin Yunzhi , Ma Xiaoyuan , Vischer Henry F. , Liu Can , Li Guochuan , Wang Huan , Leurs Rob , Li Yulong 
Published: August 2022

AbstractHistamine (HA) is a key biogenic monoamine involved in a wide range of physiological and pathological processes in both the central nervous system and the periphery. Because the ability to directly measure extracellular HA in real-time will provide important insights into the functional role of HA in complex circuits under a variety of conditions, we developed a series of genetically encoded G protein-coupled receptor activation-based (GRAB) HA (GRABHA) sensors. These sensors produce a robust increase in fluorescence upon HA application, with good photostability, sub-second kinetics, nanomolar affinity, and high specificity. Using these GRABHA sensors, we measured electrical stimulation-evoked HA release in acute brain slices with high spatiotemporal resolution. Moreover, we recorded HA release in the preoptic area of the hypothalamus and in the medial prefrontal cortex during the sleep-wake cycle in freely moving mice, finding distinct patterns of HA release in these specific brain regions. Together, these in vitro and in vivo results show that our GRABHA sensors have high sensitivity and specificity for measuring extracellular HA, thus providing a robust new set of tools for examining the role of HA signaling in both health and disease.
A systems biology-based identification and in vivo functional screening of Alzheimer’s disease risk genes reveals modulators of memory function
Authors: Hudgins Adam D. , Zhou Shiyi , Arey Rachel N. , Murphy Coleen T. , Suh Yousin 
Published: August 2022

SummaryGenome-wide association studies (GWAS) have uncovered over 40 genomic loci associated with risk for late-onset Alzheimer’s Disease (LOAD), but identification of the underlying causal genes remains challenging. While the role of glial biology in the mediation of LOAD genetic risk has been increasingly recognized, recent studies of induced pluripotent stem cell (iPSC)-derived neurons from LOAD patients have demonstrated the existence of neuronal cell-intrinsic functional defects, absent interactions with other brain cell types or exposure to neurotoxic insults. Here, we searched for genetic contributions to neuronal dysfunction in LOAD pathobiology, using an integrative systems approach that incorporated multi-evidence-based gene-mapping and network analysis-based prioritization. We found widespread dysfunction in neuronal gene co-expression networks in the LOAD brain and identified synaptic and endolysosomal function as being specifically impacted by LOAD-associated genetic variation. A systematic perturbation screening of candidate risk genes in C. elegans revealed that neuronal knockdown of the LOAD risk gene orthologs vha-10 (ATP6V1G2), cmd-1 (CALM3), amph-1 (BIN1), ephx-1 (NGEF), and pho-5 (ACP2) significantly alters short/intermediate-term memory function, the cognitive domain affected earliest during LOAD progression. These results highlight the impact of LOAD risk genes on evolutionarily conserved memory function, as mediated through neuronal endosomal dysfunction, and identify new targets for further mechanistic interrogation.
Coordinated Head Direction Representations in Mouse Anterodorsal Thalamic Nucleus and Retrosplenial Cortex
Authors: van der Goes Marie-Sophie H. , Voigts Jakob , Newman Jonathan P. , Toloza Enrique H. S. , Brown Norma J. , Murugan Pranav , Harnett Mark T. 
Published: August 2022

AbstractThe sense of direction is critical for survival in changing environments and relies on flexibly integrating self-motion signals with external sensory cues. While the anatomical substrates involved in head direction (HD) coding are well known, the mechanisms by which visual information updates HD representations remain poorly understood. Retrosplenial cortex (RSC) plays a key role in forming coherent representations of space in mammals and it encodes a variety of navigational variables, including HD. Here, we use simultaneous two-area tetrode recording to show that RSC HD representation is nearly synchronous with that of the anterodorsal nucleus of thalamus (ADn), the obligatory thalamic relay of HD to cortex, during rotation of a prominent visual cue. Moreover, coordination of HD representations in the two regions is maintained during darkness. We further show that anatomical and functional connectivity are consistent with a strong feedforward drive of HD information from ADn to RSC, with surprisingly little reciprocal drive in the corticothalamic direction. Together, our results provide direct evidence for a concerted global HD reference update across cortex and thalamus, and establish the underlying functional connectivity that supports this coordination.
Laparoscopic Assisted Vaginal Hysterectomy Verses Abdominal Hysterectomy: A systematic review and metanalysis
Authors: Menshawey Esraa , Menshawey Rahma 
Published: August 2022

AbstractOBJECTIVETo examine studies that explored the differences between laparoscopic assisted vaginal hysterectomy (LAVH) and total abdominal hysterectomy (TAH) in endometrial cancer (EC) patients, and to determine which surgical intervention has better outcomes.DATA SOURCESElectronic search of the following databases was performed; Google Scholar, PubMed/Medline, Wiley, Web of Science, Cochrane Library, Embase, and EBSCO Host.METHODS of STUDY SELECTIONAll full English articles in the form of randomized controlled trials (RCT), prospective cohort (PC), and retrospective cohort (RC) comparing LAVH and TAH outcomes in endometrial cancer patients was included in this study. A complete search of the literature comparing the outcomes of LAVH and AH in EC patients. This study was registered in PROSPERO [ID: CRD42021225509] and follows PRISMA and MOOSE guidelines. Outcomes included length of hospital stay, surgical duration, complications, blood transfusion requirements, and blood loss.TABULATIONROBINS-1, ROB 2.0, and ROBVIS was used to assess the risk of bias. Statistical tests used included relative risk (RR) for dichotomous and standard mean difference (SMD) for continuous variable. A P value less than 0.05 was considered significant. A forest plot was used to visually demonstrate the analyses for all outcomes.INTEGRATION and RESULTSA total of 13 articles (total cohort n=14,803) were included in the systematic review and metanalysis. The total cohort for LAVH patients was n=1845 and n=12,958 for TAH. Patients who underwent a TAH had significantly higher risk of complications [RR = 0.547, p<0.001], greater risk for blood transfusion [RR = 0.349, p<0.033], more blood loss [SMD = −3.256, p<0.001], and longer hospital stay [SMD = −1.351, p<0.001]. LAVH patients had longer operating time [SMD= 1.103, p<0.001] compared TAH patients.CONCLUSIONLAVH presented with lower of hospital stay, complications, amount of blood loss, and blood transfusion requirements when compared to TAH. LAVH in the appropriate setting and skills may be a safer alternative than TAH.
Increasing the sensitivity, recovery, and integrality of spatially resolved proteomics by LCM-MTA
Authors: Gu Lei , Li Xumiao , Li Ziyi , Wang Qinqin , Zheng Kuo , Yu Guanyu , Dai Chaoqun , Li Jingquan , Zhao Benpeng , Zhang Huiping , He Qizhi , Zhang Wei , Li Chen , Wang Hui 
Published: August 2022

AbstractConventional proteomic approaches neglect tissue heterogeneity and spatial localization information. Laser capture microdissection (LCM) can isolate specific cell populations or histological areas from heterogeneous tissue specimens while preserving spatial localization information. Formalin-fixed paraffin-embedded (FFPE) is currently a standardized method for long-term stable preservation of clinical tissue specimens. However, spatially resolved proteomics (SRP) studies of FFPE tissues by combined LCM and mass spectrometry (MS)-based proteomics face challenges, such as formalin-induced protein crosslinking limits protein extraction and digestion, protein loss during sample preparation, and the detectability of MS for trace tissues. Therefore, it is necessary to specifically develop SRP sample preparation methods and MS methods suitable for trace FFPE tissues. Here, we provide an SRP method suitable for trace FFPE tissues produced by LCM, termed LCM-Magnetic Trace Analysis (LCM-MTA), which can significantly increase the sensitivity, recovery, and integrality of SRP. The starting material has been reduced to about 15 cells, which resolution is comparable to existing spatially resolved transcriptome (SRT). We also apply our LCM-MTA into SRP studies on clinical colorectal cancer (CRC) tissues and accurately distinguish the functional differences of different cell types. In conclusion, LCM-MTA is a convenient, universal, and scalable method for SRP of trace FFPE tissues, which can be widely used in clinical and non-clinical research fields.
Genome-wide quantification of RNA flow across subcellular compartments reveals determinants of the mammalian transcript life cycle
Authors: Smalec Brendan M. , Ietswaart Robert , Choquet Karine , McShane Erik , West Emma R. , Churchman L. Stirling 
Published: August 2022

AbstractDissecting the myriad regulatory mechanisms controlling eukaryotic transcripts from production to degradation requires quantitative measurements of mRNA flow across the cell. We developed subcellular TimeLapse-seq to measure the rates at which RNAs are released from chromatin, exported from the nucleus, loaded onto polysomes, and degraded within the nucleus and cytoplasm. These rates varied substantially, yet transcripts from genes with related functions or targeted by the same transcription factors and RNA binding proteins flowed across subcellular compartments with similar kinetics. Verifying these associations uncovered roles for DDX3X and PABPC4 in nuclear export. For hundreds of genes, most transcripts were degraded within the nucleus, while the remaining molecules were exported and persisted with stable lifespans. Transcripts residing on chromatin for longer had extended poly(A) tails, whereas the reverse was observed for cytoplasmic mRNAs. Finally, a machine learning model identified additional molecular features that underlie the diverse life cycles of mammalian mRNAs.
Combinatorial expression motifs in signaling pathways
Authors: Granados Alejandro A. , Kanrar Nivedita , Elowitz Michael B. 
Published: August 2022

AbstractCell-cell signaling pathways comprise sets of variant receptors that are expressed in different combinations in different cell types. This architecture allows one pathway to be used in a variety of configurations, which could provide distinct functional capabilities, such as responding to different ligand variants. While individual pathways have been well-studied, we have lacked a comprehensive understanding of what receptor combinations are expressed and how they are distributed across cell types. Here, combining data from multiple single-cell gene expression atlases, we analyzed the expression profiles of core signaling pathways, including TGF-β, Notch, Wnt, and Eph-ephrin, as well as non-signaling pathways. In many pathways, a limited set of receptor expression profiles are used recurrently in many distinct cell types. While some recurrent profiles are restricted to groups of closely related cells, others, which we term pathway expression motifs, reappear in distantly related cell types spanning diverse tissues and organs. Motif usage was generally uncorrelated between pathways, remained stable in a given cell type during aging, but could change in sudden punctuated transitions during development. These results suggest a mosaic view of pathway usage, in which the same core pathways can be active in many or most cell types, but operate in one of a handful of distinct modes.