bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular and molecular mechanisms involved in LTP induced by mild theta-burst stimulation in hippocampal slices from young male rats: from weaning to adulthood
Authors: Rodrigues NC , Silva-Cruz A , Caulino-Rocha A , Bento-Oliveira A , Ribeiro JA , Cunha-Reis D 
Published: April 2021

AbstractLong-term potentiation (LTP) is a highly studied cellular process yet determining the transduction and GABAergic pathways that are the essential vs. modulatory for LTP elicited by theta-burst stimulation (TBS) in the hippocampal CA1 area is still elusive, due to the use of different TBS intensities, patterns, or different rodent/cellular models. We now characterized the developmental maturation and the transduction and GABAergic pathways required for mild TBS-induced LTP in hippocampal CA1 area in male rats. LTP induced by TBS (5×4) (5 bursts of 4 pulses delivered at 100Hz) lasted for up to 3h and was increasingly larger from weaning to adulthood. Stronger TBS patterns - TBS (15×4) or three TBS (15×4) separated by 6 min induced nearly maximal LTP not being the best choice to study the value of LTP-enhancing drugs. LTP induced by TBS (5×4) in young adults was fully dependent on NMDA receptor and CaMKII activity but independent of PKA or PKC activity. Furthermore, it was partially dependent on GABABreceptor activation and was potentiated by GABAAreceptor blockade and less by GAT-1 transporter blockade. AMPA GluA1 phosphorylation on Ser831(CaMKII target) but not GluA1 Ser845(PKA target) was essential for LTP expression. The phosphorylation of the Kv4.2 channel was observed at Ser438(CaMKII target) but not at Thr602or Thr607(ERK/MAPK pathway target). This suggests that cellular kinases like PKA, PKC or kinases of the ERK/MAPK family although important modulators of TBS (5×4)-induced LTP may not be essential for its expression in the CA1 area of the hippocampus.Graphical abstractLTP induced by theta-burst stimulation (TBS) in young adult male rat hippocampal CA1 area is increasingly more robust with the number of bursts and number of spaced TBS trains. LTP induced by TBS shows developmental maturation increasing potentiation from weaning to adulthood. Expression of LTP induced bymild TBS (5×4)in young adults requires NMDA receptor and CaMKII activity and AMPA Ser831 phosphorylation, but not PKA or PKC activity, and is likely curtailed by Kv4.2 Ser438 phosphorylation.
Pooling in a predictive model of V1 explains functional and structural diversity across species
Authors: Franciosini Angelo , Boutin Victor , Chavane Frédéric , Perrinet Laurent U 
Published: April 2021

AbstractNeurons in the primary visual cortex are selective to orientation with various degrees of selectivity to the spatial phase, from high selectivity in simple cells to low selectivity in complex cells. Various computational models have suggested a possible link between the presence of phase invariant cells and the existence of cortical orientation maps in higher mammals’ V1. These models, however, do not explain the emergence of complex cells in animals that do not show orientation maps. In this study, we build a model of V1 based on a convolutional network called Sparse Deep Predictive Coding (SDPC) and show that a single computational mechanism, pooling, allows the SDPC model to account for the emergence of complex cells as well as cortical orientation maps in V1, as observed in distinct species of mammals. By using different pooling functions, our model developed complex cells in networks that exhibit orientation maps (e.g., like in carnivores and primates) or not (e.g., rodents and lagomorphs). The SDPC can therefore be viewed as a unifying framework that explains the diversity of structural and functional phenomena observed in V1. In particular, we show that orientation maps emerge naturally as the most cost-efficient structure to generate complex cells under the predictive coding principle.SignificanceCortical orientation maps are among the most fascinating structures observed in higher mammals brains: In such maps, similar orientations in the input image activate neighboring cells in the cortical surface. However, the computational advantage brought by these structures remains unclear, as some species (rodents and lagomorphs) completely lack orientation maps. In this study, we introduce a computational model that links the presence of orientation maps to a class of nonlinear neurons called complex cells. In particular, we propose that the presence or absence orientation maps correspond to different strategies employed by different species to generate invariance to complex stimuli.
AIE nanoparticles camouflaged with tumor cell-derived exosomes for NIR-II imaging-guided photothermal therapy
Authors: Li Yirun , Fan Xiaoxiao , Li Yuanyuan , Chen Runze , Ni Huwei , Zhang Yiyin , Xia Qiming , Feng Zhe , Tang Ben Zhong , Qian Jun , Lin Hui 
Published: April 2021

AbstractNanoparticles (NPs) assisted photothermal therapy (PTT) is a promising cancer treatment modality and has attracted the attention of the scientific mainstream. However, developing NPs that exhibit efficient optical properties and specific tumor targeting capability simultaneously is difficult. Herein, we develop hybrid nanovesicles consisting of tumor cell-derived exosomes (EXO) and organic aggregation-induced emission (AIE) nanoparticles (TT3-oCB NP@EXOs) with enhanced second near-infrared (NIR-II, 900-1700 nm) fluorescence property and PTT functionality. Compared with TT3-oCB NPs, TT3-oCB NP@EXOs exhibit excellent biocompatibility, specific targeting abilityin vitro, homing to homologous tumorsin vivo, and prolonged circulation time. Furthermore, TT3-oCB NP@EXOs were utilized as biomimetic NPs for NIR-II fluorescence imaging-guided PTT of tumors, due to their high and stable photothermal conversion capacity under 808 nm irradiation. Therefore, the tumor cell-derived EXO/AIE NP hybrid nanovesicles may provide an alternative artificial targeting strategy for improving tumor diagnosis and PTT.
The power of universal contextualised protein embeddings in cross-species protein function prediction
Authors: van den Bent Irene , Makrodimitris Stavros , Reinders Marcel 
Published: April 2021

AbstractComputationally annotating proteins with a molecular function is a difficult problem that is made even harder due to the limited amount of available labelled protein training data. A recently published supervised molecular function predicting model partly circumvents this limitation by making its predictions based on the universal (i.e. task-agnostic) contextualised protein embeddings from the deep pre-trained unsupervised protein language model SeqVec. SeqVec embeddings incorporate contextual information of amino acids, thereby modelling the underlying principles of protein sequences insensitive to the context of species.We applied the existing SeqVec-based molecular function prediction model in a transfer learning task by training the model on annotated protein sequences of one training species and making predictions on the proteins of several test species with varying evolutionary distance. We show that this approach successfully generalises knowledge about protein function from one eukaryotic species to various other species, proving itself an effective method for molecular function prediction in inadequately annotated species from understudied taxonomic kingdoms. Furthermore, we submitted the performance of our SeqVec-based prediction models to detailed characterisation, first to advance the understanding of protein language models and second to determine areas of improvement.Author summaryProteins are diverse molecules that regulate all processes in biology. The field of synthetic biology aims to understand these protein functions to solve problems in medicine, manufacturing, and agriculture. Unfortunately, for many proteins only their amino acid sequence is known whereas their function remains unknown. Only a few species have been well-studied such as mouse, human and yeast. Hence, we need to increase knowledge on protein functions. Doing so is, however, complicated as determining protein functions experimentally is time-consuming, expensive, and technically limited. Computationally predicting protein functions offers a faster and more scalable approach but is hampered as it requires much data to design accurate function prediction algorithms. Here, we show that it is possible to computationally generalize knowledge on protein function from one well-studied training species to another test species. Additionally, we show that the quality of these protein function predictions depends on how structurally similar the proteins are between the species. Advantageously, the predictors require only the annotations of proteins from the training species and mere amino acid sequences of test species which may particularly benefit the function prediction of species from understudied taxonomic kingdoms such as the Plantae, Protozoa and Chromista.
Accurate assignment of disease liability to genetic variants using only population data
Authors: Collaco Joseph M. , Raraigh Karen S. , Betz Joshua , Aksit Melis Atalar , Blau Nenad , Brown Jordan , Dietz Harry C. , MacCarrick Gretchen , Nogee Lawrence M. , Sheridan Molly B. , Vernon Hilary J. , Beaty Terri H. , Louis Thomas A. , Cutting Garry R. 
Published: April 2021

ABSTRACTPurposeThe growing size of public variant repositories prompted us to test the accuracy of predicting pathogenicity of DNA variants using population data alone.MethodsUnder thea prioriassumption that the ratio of the prevalence of variants in healthy and affected populations form two distinct distributions (pathogenic and benign), we used a Bayesian method to assign probability of a variant belonging to either distribution.ResultsThe approach, termed BayPR, accurately parsed 300 of 313 expertly curatedcystic fibrosis transmembrane conductance regulator (CFTR)variants: 284 of 296 pathogenic/likely pathogenic (P/LP) variants in one distribution and 16 of 17 benign/likely benign (B/LB) variants in another. BayPR produced an area under the receiver operating curve (AUC) of 0.99 for 103 functionally-confirmed missenseCFTRvariants, equal to or exceeding ten commonly used algorithms (AUC range: 0.54 to 0.99). Application of BayPR to expertly curated variants in eight genes associated with seven Mendelian conditions assigned ≥80% disease-causing probability to 1,350 of 1,374 (98.3%) P/LP variants and ≤20% to 22 of 23 (95.7%) B/LB variants.ConclusionAgnostic to variant type or functional effect, BayPR provides probabilities of pathogenicity for DNA variants responsible for Mendelian disorders usingonlyvariant counts in affected and unaffected population samples.
Redundant neural circuits regulate olfactory masking
Authors: Yang Wenxing , Wu Taihong , Tu Shasha , Choi Myung-Kyu , Duan Fengyun , Zhang Yun 
Published: April 2021

ABSTRACTOlfactory masking is a complex olfactory response found in humans. However, the mechanisms whereby the presence of one odorant masks the sensory and behavioral responses elicited by another odorant are poorly understood. Here, we report thatCaenorhabditis elegansdisplays olfactory masking and that the presence of a repulsive odorant, 2-nonanone, that signals threat strongly masks the attraction of other odorants, such as isoamyl alcohol (IAA) or benzaldehyde that signals food. Using a forward genetic screen, we found that several genes,osm-5, osm-1, anddyf-7, known to regulate the structure and function of sensory neurons played a critical role in olfactory masking. Loss of these genes mildly reduces the response to 2-nonanone and disrupts the masking effect of 2-nonanone. Restoring the function of OSM-5 in either AWB or ASH, two sensory neurons known to mediate 2-nonanone-evoked avoidance, is sufficient to rescue olfactory masking. AWB is activated by the removal of 2-nonanone stimulation or the onset of IAA; however, the mixture of 2-nonanone and IAA stimulates AWB similarly as 2-nonanone alone, masking the cellular effect of IAA. The latency of the AWB response is critical for the masking effect. Thus, our results identify redundant neural circuits that regulate the robust masking effect of a repulsive odorant and uncover the neuronal and cellular basis for this complex olfactory task.AUTHOR SUMMARYIn their natural environment, animals, including humans, encounter complex olfactory stimuli. However, regardless how complex the stimuli are, the behavioral output can only be one. Thus, how the brain processes multiple sensory cues to generate a coherent behavioral output is critical for the survival of the animal. In the present study, we combined molecular cellular genetics, optical physiology and behavioral analysis to study olfactory masking, a common olfactory phenomenon in which the presence of one odorant masks the stimulation of another odorant. Our results show that olfactory masking is regulated by redundant neuronal circuits, a mechanism that likely ensures the robust behavioral response to the sensory cue representing information critical for the survival.
A fossil fish assemblage from the middle Miocene of the Cocinetas Basin, northern Colombia
Authors: Ballen Gustavo A. , Jaramillo Carlos , Dagosta Fernando C. P. , De Pinna Mario C. C. 
Published: April 2021

AbstractFreshwater fossil fish faunas have been long used to infer past drainage connections, as they are bounded by physical freshwater barriers. Here we study a middle Miocene (15.0-–15.5 Ma) freshwater fish fossil fauna (Makaraipao) from the Castilletes Formation in northern Colombia, nowadays west of the Andes. We record the presence of lungfishes (Lepidosiren), pacus (MylossomaandPiaractus), armored catfishes (Callichthyidae), and red-tail catfishes (Phractocephalus). Extant members of all those groups (except the Callichthyidae, due to lack of taxonomic resolution) are found in Amazonian faunas east of the Andes and are absent from faunas west of the Andes, indicating that the riverine systems of the Guajira Peninsula were connected to Amazonia during the middle Miocene. The similarity of La Venta (west of the Andes) and Rio Acre (east of the Andes) fish faunas during the late Miocene further indicates that the northern Andean uplift was not a complete barrier at least until∼11 Myr ago. However, there is a continental-wide structuring of the Miocene fish faunas that is also found in the extant faunas, suggesting that other factors such as ecological conditions, in addition to the uplift of the Andes, have shaped the biogeographic evolution of South American fish faunas.
The salmon-peloton: hydraulic habitat shifts of adult Atlantic salmon (Salmo salar) due to behaviour thermoregulation
Authors: O’Sullivan Antóin M. , Linnansaari Tommi , Leavitt Jaime , Samways Kurt M. , Kurylyk Barret L. , Curry R. Allen 
Published: April 2021

AbstractIn recent decades there has been an increase in conservation and restoration projects targeting Atlantic salmon (Salmo salar– AS), as populations in eastern Canada decline. Missing however, is an understanding of thermo-hydraulic habitat use by adult AS during summer, and thus the actual benefits of altering in-river physical structures. Here, we illustrated how optical and thermal infrared (TIR) imagery acquired from a UAV can be used in concert within-situdepth and velocity data to map adult AS and develop models of thermo-hydraulic habitats in the Miramichi River, New Brunswick. We found during optimal thermal conditions (< 19 °C) proximity to boulders and Froude numbers, a non-dimensional hydraulic metric, were key parameters that characterized adult AS habitat. However, during behavioural thermoregulation events (>19 °C), proximity to the cool thermal plume and Froude number, a non-dimensional hydraulic parameter, were critical controls on habitat use. We also observed AS formed a distinct geometric formation during behavioural thermoregulation events, and term this formation a ‘thermal-peloton’. The primary function of the peloton is undoubtedly to reduce thermally induced stressed; however, we conceptualize the geometry of the peloton attenuates hydraulic-drag, and reduces energetic expenditure of individuals practicing behavioural thermoregulation. These data provide an unrivaled viewpoint of thermo-hydraulic habitat selection by adult AS, and a blue print for restoration work. The use of UAV-based sensors has the potential to instigate a paradigm shift for river sciences. The age of applying hyper-resolution, remote sensing for river science and aquatic ecology is immensely exciting.
Microbial genomic trait evolution is dominated by frequent and rare pulsed evolution
Authors: Gao Yingnan , Wu Martin 
Published: April 2021

AbstractOn the macroevolutionary timescale, does trait evolution proceed gradually or by rapid bursts (pulses) separated by prolonged periods of stasis or slow evolution? Although studies have shown pulsed evolution is prevalent in animals, our knowledge about the tempo and mode of evolution across the tree of life is very limited. This long-standing debate calls for a test in bacteria and archaea, the most ancient and diverse forms of life with unique population genetic properties (asexual reproduction, large population sizes, short generation times, high dispersal rates and extensive lateral gene transfers). Using a likelihood-based framework, we analyzed evolutionary patterns of four microbial genomic traits (genome size, genome GC%, 16S rRNA GC% and the nitrogen use in proteins) on a broad macroevolutionary timescale. Our model fitting of phylogenetic comparative data shows that pulsed evolution is not only present, but also prevalent and predominant in microbial genomic trait evolution. Interestingly, for the first time, we detected two distinct types of pulsed evolution (small frequent and large rare jumps) that are predicted by the punctuated equilibrium and quantum evolution theories. Our findings suggest that major bacterial lineages could have originated in quick bursts and pulsed evolution is a common theme across the tree of life despite the drastically different population genetic properties of bacteria, archaea and eukaryotes.
In BRCA1 and BRCA2 breast cancers, chromosome breaks occur near herpes tumor virus sequences
Authors: Friedenson Bernard 
Published: April 2021

AbstractInherited mutations in BRCA1 and BRCA2 genes increase risks for breast, ovarian, and other cancers. Both genes encode proteins for accurately repairing chromosome breaks. If mutations inactivate this function, broken chromosome fragments get lost or reattach indiscriminately. These mistakes are characteristic of hereditary breast cancer. We tested the hypothesis that mistakes in reattaching broken chromosomes preferentially occur near viral sequences on human chromosomes. We tested millions of DNA bases around breast cancer breakpoints for similarities to all known viral DNA. DNA around breakpoints often closely matched the Epstein-Barr virus (EBV) tumor variants HKHD40 and HKNPC60. Almost all breakpoints were near EBV anchor sites, EBV tumor variant homologies, and EBV-associated regulatory marks. On chromosome 2, EBV binding sites accounted for 90% of breakpoints (p<0.0001). On chromosome 4, 51/52 inter-chromosomal breakpoints were close to EBV variant sequences. Five viral anchor sites at critical genes were near breast cancer breakpoints. Twenty-five breast cancer breakpoints were within 1.25% of breakpoints in model EBV cancers. EBV-like sequence patterns around breast cancer breakpoints resemble gene fusion breakpoints in model EBV cancers. All BRCA1 and BRCA2 breast cancers had mutated genes essential for immune responses. Because of this immune compromise, herpes viruses can attach and produce nucleases that break chromosomes. Alternatively, anchored viruses can retard break repairs, whatever the causes. The results imply proactive treatment and prevention of herpes viral infections may benefit BRCA mutation carriers.
Axes of inter-sample variability among transcriptional neighborhoods reveal disease-associated cell states in single-cell data
Authors: Reshef Yakir , Rumker Laurie , Kang Joyce B. , Nathan Aparna , Korsunsky Ilya , Asgari Samira , Murray Megan B. , Moody D. Branch , Raychaudhuri Soumya 
Published: April 2021

AbstractAs single-cell datasets grow in sample size, there is a critical need to characterize cell states that vary across samples and associate with sample attributes like clinical phenotypes. Current statistical approaches typically map cells to cell-type clusters and examine sample differences through that lens alone. Here we present covarying neighborhood analysis (CNA), an unbiased method to identify cell populations of interest with greater flexibility and granularity. CNA characterizes dominant axes of variation across samples by identifying groups of very small regions in transcriptional space—termed neighborhoods—that covary in abundance across samples, suggesting shared function or regulation. CNA can then rigorously test for associations between any sample-level attribute and the abundances of these covarying neighborhood groups. We show in simulation that CNA enables more powerful and accurate identification of disease-associated cell states than a cluster-based approach. When applied to published datasets, CNA captures a Notch activation signature in rheumatoid arthritis, redefines monocyte populations expanded in sepsis, and identifies a previously undiscovered T-cell population associated with progression to active tuberculosis.
Improving the phylogenetic resolution of Malaysian and Javan mahseer (Cyprinidae),Tor tambroidesandTor tambra: Whole mitogenomes sequencing, phylogeny and potential mitogenome markers
Authors: Kit Lim Leonard Whye , Chung Hung Hui , Lin Lau Melinda Mei , Aziz Fazimah , Gan Han Ming 
Published: April 2021

AbstractThe true mahseer (Torspp.) is one of the highest valued fish in the world due to its high nutritional value and great unique taste. Nevertheless, its morphological characterization and single mitochondrial gene phylogeny in the past had yet to resolve the ambiguity in its taxonomical classification. In this study, we sequenced and assembled 11 complete mahseer mitogenomes collected from Java of Indonesia, Pahang and Terengganu of Peninsular Malaysia as well as Sarawak of East Malaysia. The mitogenome evolutionary relationships among closely relatedTorspp. samples were investigated based on maximum likelihood phylogenetic tree construction. Compared to the commonly used COX1 gene fragment, the complete COX1, Cytb, ND2, ND4 and ND5 genes appear to be better phylogenetic markers for genetic differentiation at the population level. In addition, a total of six population-specific mitolineage haplotypes were identified among the mahseer samples analyzed, which this offers hints towards its taxonomical landscape.