bluuebunny/crossref_metadata_2025_split huggingface dataset:
Food and temperature change photoperiodic responses in two vole species: different roles for hypothalamic genes
Authors: van Rosmalen Laura , Hut Roelof A. 
Published: January 2021

AbstractSeasonal timing of reproduction in voles is driven by photoperiod. Here we hypothesize that a negative energy balance can modify spring-programmed photoperiodic responses in the hypothalamus, controlling reproductive organ development. We manipulated energy balance by the ‘work-for-food’ protocol, in which voles were exposed to increasing levels of food scarcity at different ambient temperatures under long photoperiod. We reveal that common (Microtus arvalis) and tundra voles (Microtus oeconomus), reduce photoperiodic induced pars tuberalis thyroid-stimulating hormone β-subunit (Tshβ) expression to inhibit gonadal development when food is scarce. Reduction in gonadal size is more pronounced in tundra voles, in which the hypothalamic Kisspeptin (Kiss1) system seems involved in downregulating gonadal development, especially in males. Low temperature additionally leads to decreased hypothalamic RF-amide related peptide (Rfrp3) levels, which may facilitate further suppression of gonadal growth. Shutting off the photoperiodic-axis when food is scarce in spring may be an adaptive response to save energy, leading to delayed reproductive organ development until food resources are sufficient for reproduction, lactation and offspring survival. Defining the mechanisms through which metabolic cues modify photoperiodic responses will be important for a better understanding of how environmental cues impact reproduction.Summary statementThis study provides a better understanding of the molecular mechanism through which metabolic cues can modify photoperiodic responses, to adaptively adjust timing of reproductive organ development
Simulating lesion-dependent functional recovery mechanisms
Authors: Sajid Noor , Holmes Emma , Hope Thomas M. , Fountas Zafeirios , Price Cathy J. , Friston Karl J. 
Published: January 2021

AbstractFunctional recovery after brain damage varies widely and depends on many factors, including lesion site and extent. When a neuronal system is damaged, recovery may occur by engaging residual (e.g., perilesional) components. When damage is extensive, recovery depends on the availability of other intact neural structures that can reproduce the same functional output (i.e., degeneracy). A system’s response to damage may occur rapidly, require learning or both. Here, we simulate functional recovery from four different types of lesions, using a generative model of word repetition that comprised a default premorbid system and a less used alternative system. The synthetic lesions (i) completely disengaged the premorbid system, leaving the alternative system intact, (ii) partially damaged both premorbid and alternative systems, and (iii) limited the experience-dependent plasticity of both. The results, across 1000 trials, demonstrate that (i) a complete disconnection of the premorbid system naturally invoked the engagement of the other, (ii) incomplete damage to both systems had a much more devastating long-term effect on model performance and (iii) the effect of reducing learning capacity within each system. These findings contribute to formal frameworks for interpreting the effect of different types of lesions.
Codominance of two symbiont genera within the same coral host is associated with elevated symbiont productivity and lower host susceptibility to thermal stress
Authors: Abbott Evelyn , Dixon Groves , Matz Mikhail 
Published: January 2021

AbstractIn recent years, as sea surface temperature increases, many coral species that used to harbor symbionts of the genusCladocopiumhave become colonized with the thermally tolerant genus,Durusdinium.Here, we asked how the symbionts of one genus react to the presence of another symbiont genus within the same coral host, and what effect this interaction has on the host. We used previously published transcriptomic data fromAcropora hyacinthuscorals hostingCladocopiumand/orDurusdiniumsymbionts and looked at gene expression in all three symbiotic partners depending on the relative proportion of the two symbiont genera within the same host. We find that bothCladocopiumandDurusdiniumchange their expression the most when their proportions within the host are nearly equal (the state that we call “codominance”): both genera elevate expression of photosynthesis and ribosomal genes, suggesting increase in photosynthesis and growth (i.e. higher productivity). At the same time, the coral host also elevates production of ribosomes suggesting faster cellular growth, and, when heated, shows less pronounced stress response. These results can be explained in two alternative ways. One explanation is that increased competition between codominant symbionts switches them to the higher productivity mode, which benefits the host, making it more resilient to stress. Alternatively, the symbionts’ elevated productivity might be not the cause but the consequence of the host being particularly healthy. Under this explanation, rapid growth of the healthy host creates new space, lowering the symbioints’ competition and thus promoting their growth, which allows for codominance to happen where one genus would otherwise outcompete another. The latter explanation is supported by the fact that codominance is associated with lower symbiont densities, assessed as relative proportions of symbiont reads in the data. Irrespective of the causation direction, the presence of mixed symbiont communities could potentially be used as an instant indicator of coral well-being, which would be a useful tool for coral conservation and restoration.
PASV: Automatic protein partitioning and validation using conserved residues
Authors: Moore Ryan M. , Harrison Amelia O. , Nasko Daniel J. , Chopyk Jessica , Cebeci Metehan , Ferrell Barbra D. , Polson Shawn W. , Wommack K. Eric 
Published: January 2021

AbstractBackgroundIncreasingly, researchers use protein-coding genes from targeted PCR amplification or direct metagenomic sequencing in community and population ecology. Analysis of protein-coding genes presents different challenges from those encountered in traditional SSU rRNA studies. Most protein-coding sequences are annotated based on homology to other computationally-annotated sequences, which can lead to inaccurate annotations. Therefore, the results of sensitive homology searches must be validated to remove false-positives and assess functionality. Multiple lines of in silico evidence can be gathered by examining conserved domains and residues identified through biochemical investigations. However, manually validating sequences in this way can be time consuming and error prone, especially in large environmental studies.ResultsAn automated pipeline for protein active site validation (PASV) was developed to improve validation and partitioning accuracy for protein-coding sequences, combining multiple sequence alignment with expert domain knowledge. PASV was tested using commonly misannotated proteins: ribonucleotide reductase (RNR), alternative oxidase (AOX), and plastid terminal oxidase (PTOX). PASV partitioned 9,906 putative Class I alpha and Class II RNR sequences from bycatch in a global viral metagenomic investigation with >99% true positive and true negative rates. PASV predicted the class of 2,579 RNR sequences in >98% agreement with manual annotations. PASV correctly partitioned all 336 tested AOX and PTOX sequences.ConclusionsPASV provides an automated and accurate way to address post-homology search validation and partitioning of protein-coding marker genes. Source code is released under the MIT license and is found with documentation and usage examples on GitHub at https://github.com/mooreryan/pasv.
Direct simulation of a stochastically driven multi-step birth-death process
Authors: Gorin Gennady , Pachter Lior 
Published: January 2021

1AbstractThe description of transcription as a stochastic process provides a framework for the analysis of intrinsic and extrinsic noise in cells. To better understand the behaviors and possible extensions of existing models, we design an exact stochastic simulation algorithm for a multimolecular transcriptional system with an Ornstein-Uhlenbeck birth rate that is implemented via a special function-based time-stepping algorithm. We demonstrate that its joint copy-number distributions reduce to analytically well-studied cases in several limiting regimes, and suggest avenues for generalizations.
Regulation by Progestins, Corticosteroids and RU486 of Activation of Elephant Shark and Human Progesterone Receptors: An Evolutionary Perspective
Authors: Lin Xiaozhi , Takagi Wataru , Hyodo Susumu , Ijiri Shigeho , Katsu Yoshinao , Baker Michael E. 
Published: January 2021

AbstractWe investigated progestin and corticosteroid activation of the progesterone receptor (PR) from elephant shark, a cartilaginous fish belonging to the oldest group of jawed vertebrates. Comparison with human PR provides insights into the evolution of steroid activation of human PR. At 1 nM steroid, elephant shark PR is activated by progesterone, 17-hydroxy-progesterone, 20β-hydroxy-progesterone, 11-deoxycorticosterone (21-hydroxyprogesterone) and 11-deoxycortisol. Human PR, in comparison, is activated at 1 nM steroid, only by progesterone and 11-deoxycorticosterone, indicating increased progestin and corticosteroid specificity during the evolution of human PR. RU486, an important clinical antagonist of human PR, did not inhibit progesterone activation of elephant shark PR. Cys-528 in elephant shark PR corresponds to Gly-722 in human PR, which is essential for RU486 inhibition of human PR. Confirming the importance of Cys-528 in elephant shark PR, RU486 inhibited progesterone activation of the Cys528Gly mutant PR. Compared to wild-type human PR, there was an increase in activation of human Gly722Cys PR by11-deoxycortisol and a decrease in activation by corticosterone, which may have been important in selection for the mutation corresponding to human glycine-722 PR that first evolved in platypus PR, a basal mammal.
How to align arthropod legs
Authors: Bruce Heather S. 
Published: January 2021

AbstractHow to align leg segments between the four groups of arthropods (insects, crustaceans, myriapods, and chelicerates) has tantalized generations of researchers, as this would answer over a century of speculation about the origins and homologies of the fascinating diversity of arthropod appendages and outgrowths. Here we compare the expression and loss-of-function phenotypes of leg patterning genes in crustaceans, insects, and arachnids using our own and previously published data. We find that all arthropod leg segments correspond to each other in a one-to-one fashion. This alignment suggests that chelicerates with seven leg segments incorporated a proximal leg segment into the body wall. In addition, this alignment suggests that insect and myriapod tracheae are convergent and homologous structures: each evolved via the independent internalization of an ancestral gill (respiratory exite) on the proximal-most leg segment of their shared ancestor. A framework for understanding the homologies of arthropod appendages opens up a powerful system for studying the origins of novel structures, the plasticity of morphogenetic fields across vast phylogenetic distances, and the convergent evolution of shared ancestral developmental fields.
High-throughput functional characterization of visceral afferents by optical recordings from thoracolumbar and lumbosacral dorsal root ganglions
Authors: Bian Zichao , Guo Tiantian , Jiang Shaowei , Chen Longtu , Liu Jia , Zheng Guoan , Feng Bin 
Published: January 2021

AbstractFunctional understanding of visceral afferents is important for developing new treatment to visceral hypersensitivity and pain. The sparse distribution of visceral afferents in dorsal root ganglions (DRGs) has challenged conventional electrophysiological recordings. Alternatively, Ca2+indicators like GCaMP6f allow functional characterization by optical recordings. Here we report a turnkey microscopy system that enables simultaneous Ca2+imaging at two parallel focal planes from intact DRG. By using consumer-grade optical components, the microscopy system is cost effective and can be made broadly available without loss of capacity. It records low-intensity fluorescent signals at a wide field of view (1.9 x 1.3 mm) to cover a whole mouse DRG, with a high pixel resolution of 0.7 micron/pixel, a fast frame rate of 50 frames/sec, and the capability of remote focusing without perturbing the sample. The wide scanning range (100 mm) of the motorized sample stage allows convenient recordings of multiple DRGs in thoracic, lumbar, and sacral vertebrae. As a demonstration, we characterized mechanical neural encoding of visceral afferents innervating distal colon and rectum (colorectum) in GCaMP6f mice driven by VGLUT2 promotor. A post-processing routine is developed for conducting unsupervised detection of visceral afferent responses from GCaMP6f recordings, which also compensates the motion artefacts caused by mechanical stimulation of the colorectum. The reported system offers a cost-effective solution for high-throughput recordings of visceral afferent activities from a large volume of DRG tissues. We anticipate a wide application of this microscopy system to expedite our functional understanding of visceral innervations in both health and diseases.
Abrupt increase in the UK coronavirus death-case ratio in December 2020
Authors: Wallace David J , Ackland Graeme J 
Published: January 2021

1AbstractObjectiveto determine the statistical relationship between reported deaths and infections in the UK coronavirus outbreakDesignPublicly available UK government data is used to determine a relationship between reported cases and deaths, taking into account various UK regions, age profiles and prevalence of the variant of concern (VOC) B.1.1.7.Main Outcome MeasuresEstablishing a simple statistical relationship between detected cases and subsequent mortality.ResultsThroughout October and November 2020, deaths in England are well described as 1/55th of detected cases from 12 days previously. After that, the relationship no longer holds and deaths are significantly higher. This is especially true in regions affected by the VOC B.1.1.7ConclusionsIn early December, some new factor emerged to increase the case-fatality rate in the UK.Summary BoxWhat is already known on this topicThe infection-mortality ratio enables one to predict future deaths based on current infections. Incomplete monitoring of infection may be sufficient to predict future trends.What the study addsFor the specific case of the second wave of coronavirus infection in the UK, we show a clear mathematical relationship between detected infections (positive tests) and subsequent deaths. This relationship begins to fail in December, with unexpectedly high death rates. This may be correlated in time and region with the emergence of the Variant of Concern B 1.1.7.
Detection and removal of pacing artifacts prior to automated analysis of 12-lead ECG
Authors: Haq Kazi T. , Javadekar Neeraj , Tereshchenko Larisa G. 
Published: January 2021

AbstractBackgroundPacing artifacts must be excluded from the analysis of paced ECG waveform. This study aimed to develop and validate an algorithm to identify and remove the pacing artifacts on ECG.MethodsWe developed a semi-automatic algorithm that identifies the onset and offset of a pacing artifact based on the ECG signal’ slope steepness and designed a graphical user interface that permits quality control and fine-tuning the constraining threshold values. We used 1,054 ECGs from the retrospective, multicenter cohort study “Global Electrical Heterogeneity and Clinical Outcomes,” including 3,825 atrial and 10,031 ventricular pacing artifacts for the algorithm development and 22 ECGs including 108 atrial and 241 ventricular pacing artifacts for validation. Validation was performed per digital sample. We used the kappa-statistic of interrater agreement between manually labeled sample (ground-truth) and automated detection.ResultsThe constraining parameter values were for onset threshold 13.06±6.21 μV/ms, offset threshold 34.77±17.80 μV/ms, and maximum window size 27.23 ± 3.53 ms. The automated algorithm detected a digital sample belonging to pacing artifact with a sensitivity of 74.5% and specificity of 99.6% and classified correctly 98.8% of digital samples (ROC AUC 0.871; 95%CI 0.853-0.878). The kappa-statistic was 0.785, indicating substantial agreement. The agreement was on 98.81% digital samples, significantly (P<0.00001) larger than the random agreement on 94.43% of digital samples.ConclusionsThe semi-automated algorithm can detect and remove ECG pacing artifacts with high accuracy and provide a user-friendly interface for quality control.HighlightsWe developed and validated a semi-automated algorithm to detect and remove pacing spike artifacts from a digital ECG signal.The semi-automated algorithm can detect and remove pacing spike artifacts with high accuracy and provide a user-friendly interface for quality control.
The photosensitive phase acts as a sensitive window for seasonal multisensory neuroplasticity in male and female starlings
Authors: Orije Jasmien , Cardon Emilie , Hamaide Julie , Jonckers Elisabeth , Darras Veerle M. , Verhoye Marleen , Van der Linden Annemie 
Published: January 2021

AbstractTraditionally, research unraveling seasonal neuroplasticity in songbirds has focused on the male song control system and testosterone. We longitudinally monitored the song and neuroplasticity in male and female starlings during multiple photoperiods using Diffusion Tensor and Fixel-Based techniques. These exploratory data-driven whole-brain methods resulted in a population-based tractogram uncovering microstructural sexual dimorphisms in the song control system and beyond. Male brains showed microstructural hemispheric asymmetries, whereas females had higher interhemispheric connectivity, which could not be attributed to brain size differences. Only females with large brains sing but differ from males in their song behavior by showing involvement of the hippocampus. Both sexes experienced multisensory neuroplasticity in the song control, auditory and visual system, and the cerebellum, mainly during the photosensitive period. This period with low gonadal hormones might represent a ‘sensitive window’ during which different sensory and motor systems in telencephalon and cerebellum can be seasonally re-shaped in both sexes.
Tristetraprolin prevents gastric metaplasia in mice by suppressing pathogenic inflammation
Authors: Busada Jonathan T. , Kadka Stuti , Peterson Kylie N. , Stumpo Deborah J. , Zhou Lecong , Cidlowski John A. , Blackshear Perry J. 
Published: January 2021

AbstractAberrant immune activation is associated with numerous inflammatory and autoimmune diseases and contributes to cancer development and progression. Within the stomach, inflammation drives a well-established sequence from gastritis to metaplasia, eventually resulting in adenocarcinoma. Unfortunately, the processes that regulate gastric inflammation and prevent carcinogenesis remain unknown. Tristetraprolin (TTP) is an RNA-binding protein that promotes the turnover of numerous pro-inflammatory and oncogenic mRNAs. Here, we utilized a TTP-overexpressing model, the TTPΔARE mouse, to examine whether TTP can protect the stomach from adrenalectomy (ADX)-induced gastric inflammation and spasmolytic polypeptide-expressing metaplasia (SPEM). We found that TTPΔARE mice were completely protected from ADX-induced gastric inflammation and SPEM. RNA sequencing revealed that TTP overexpression suppressed the expression of genes associated with the innate immune response. Finally, we show that protection from gastric inflammation was only partially due to suppression ofTnf, a well-known TTP target. Our results demonstrate that TTP exerts broad anti-inflammatory effects in the stomach and suggest that therapies that increase TTP expression may be effective treatments of pro-neoplastic gastric inflammation.
A rational blueprint for the design of chemically-controlled protein switches
Authors: Shui Sailan , Gainza Pablo , Scheller Leo , Yang Che , Kurumida Yoichi , Rosset Stéphane , Georgeon Sandrine , Correia Bruno E. 
Published: January 2021

AbstractSmall-molecule responsive protein switches are crucial components to control synthetic cellular activities. However, the repertoire of small-molecule protein switches is insufficient for many applications, including those in the translational spaces, where properties such as safety, immunogenicity, drug half-life, and drug side-effects are critical. Here, we present a computational protein design strategy to repurpose drug-inhibited protein-protein interactions as OFF- and ON-switches. The designed binders and drug-receptors form chemically-disruptable heterodimers (CDH) which dissociate in the presence of small molecules. To design ON-switches, we converted the CDHs into a multi-domain architecture which we refer to asactivation by inhibitor releaseswitches (AIR) that incorporate a rationally designed drug-insensitive receptor protein. CDHs and AIRs showed excellent performance as drug responsive switches to control combinations of synthetic circuits in mammalian cells. This approach effectively expands the chemical space and logic responses in living cells and provides a blueprint to develop new ON- and OFF-switches for basic and translational applications.
Clustering FunFams using sequence embeddings improves EC purity
Authors: Littmann Maria , Bordin Nicola , Heinzinger Michael , Schütze Konstantin , Dallago Christian , Orengo Christine , Rost Burkhard 
Published: January 2021

AbstractMotivationClassifying proteins into functional families can improve our understanding of protein function and can allow transferring annotations within one family. For this, functional families need to be “pure”, i.e., contain only proteins with identical function. Functional Families (FunFams) cluster proteins within CATH superfamilies into such groups of proteins sharing function. 11% of all FunFams (22,830 of 203,639) contain EC annotations and of those, 7% (1,526 of 22,830) have inconsistent functional annotations.ResultsWe propose an approach to further cluster FunFams into functionally more consistent sub-families by encoding their sequences through embeddings. These embeddings originate from language models transferring knowledge gained from predicting missing amino acids in a sequence (ProtBERT) and have been further optimized to distinguish between proteins belonging to the same or a different CATH superfamily (PB-Tucker). Using distances between embeddings and DBSCAN to cluster FunFams and identify outliers, doubled the number of pure clusters per FunFam compared to random clustering. Our approach was not limited to FunFams but also succeeded on families created using sequence similarity alone. Complementing EC annotations, we observed similar results for binding annotations. Thus, we expect an increased purity also for other aspects of function. Our results can help generating FunFams; the resulting clusters with improved functional consistency allow more reliable inference of annotations. We expect this approach to succeed equally for any other grouping of proteins by their phenotypes.AvailabilityCode and embeddings are available via GitHub:https://github.com/Rostlab/FunFamsClustering