bluuebunny/crossref_metadata_2025_split huggingface dataset:
Building Transformers from Neurons and Astrocytes
Authors: Kozachkov Leo , Kastanenka Ksenia V. , Krotov Dmitry 
Published: October 2022

Glial cells account for roughly 90% of all human brain cells, and serve a variety of important developmental, structural, and metabolic functions. Recent experimental efforts suggest that astrocytes, a type of glial cell, are also directly involved in core cognitive processes such as learning and memory. While it is well-established that astrocytes and neurons are connected to one another in feedback loops across many time scales and spatial scales, there is a gap in understanding the computational role of neuron-astrocyte interactions. To help bridge this gap, we draw on recent advances in artificial intelligence (AI) and astrocyte imaging technology. In particular, we show that neuron-astrocyte networks can naturally perform the core computation of a Transformer, a particularly successful type of AI architecture. In doing so, we provide a concrete and experimentally testable account of neuron-astrocyte communication. Because Transformers are so successful across a wide variety of task domains, such as language, vision, and audition, our analysis may help explain the ubiquity, flexibility, and power of the brain’s neuron-astrocyte networks.Significance StatementTransformers have become the default choice of neural architecture for many machine learning applications. Their success across multiple domains such as language, vision, and speech raises the question: how can one build Transformers using biological computational units? At the same time, in the glial community there is a gradually accumulating evidence that astrocytes, formerly believed to be passive house-keeping cells in the brain, in fact play important role in brain’s information processing and computation. In this work we hypothesize that neuron-astrocyte networks can naturally implement the core computation performed by the Transformer block in AI. The omnipresence of astrocytes in almost any brain area may explain the success of Transformers across a diverse set of information domains and computational tasks.
Ventral subiculum inputs to nucleus accumbens medial shell preferentially innervate D2R medium spiny neurons and contain calcium permeable AMPARs
Authors: Boxer Emma E , Kim JungMin , Dunn Brett , Aoto Jason 
Published: October 2022

AbstractVentral subiculum (vSUB) is the major output region of ventral hippocampus (vHIPP) and sends major projections to nucleus accumbens medial shell (NAcMS). Hyperactivity of the vSUB-NAcMS circuit is associated with substance use disorders (SUDs) and the modulation of vSUB activity alters drug seeking and drug reinstatement behavior in rodents. However, to the best of our knowledge, the cell-type specific connectivity and synaptic transmission properties of the vSUB-NAcMS circuit have never been directly examined. Instead, previous functional studies have focused on total ventral hippocampal (vHIPP) output to NAcMS without distinguishing vSUB from other subregions of vHIPP, including ventral CA1 (vCA1). Usingex vivoelectrophysiology, we systematically characterized the vSUB-NAcMS circuit with cell-type and synapse specific resolution in male and female mice and found that vSUB output to dopamine receptor type-1 (D1R) and type-2 (D2R) expressing medium spiny neurons (MSNs) displays a functional connectivity bias for D2R MSNs. Furthermore, we found that vSUB-D1R and -D2R MSN synapses contain calcium-permeable AMPA receptors in drug-naïve mice. Finally, we find that, distinct from other glutamatergic inputs, cocaine exposure selectively induces plasticity at vSUB-D2R synapses. Importantly, we directly compared vSUB and vCA1 output to NAcMS and found that vSUB synapses are functionally distinct and that vCA1 output recapitulated the synaptic properties previously ascribed to vHIPP. Our work highlights the need to consider the contributions of individual subregions of vHIPP to SUDs and represents an important first step toward understanding how the vSUB-NAcMS circuit contributes to the etiologies that underlie SUDs.
Pf Bacteriophage Inhibits Neutrophil Migration in the Lung
Authors: Popescu Medeea C. , Pennetzdorfer Nina , Hargil Aviv , Kaber Gernot , Bollyky Paul L. 
Published: October 2022

ABSTRACTBacteriophages are abundant in the human body, including at sites of infection. We report that Pf4 phage, a filamentous bacteriophage produced byPseudomonas aeruginosa, dampens inflammatory responses in response to eitherP. aeruginosaairway infection in a mouse model of acute pneumonia or bacterial endotoxin treatment. Pf4 triggers TLR3-dependent type I interferon production and antagonize production of anti-bacterial cytokines and chemokines. In particular, Pf4 phages inhibit CXCL5, preventing efficient neutrophil chemotaxis in response to endotoxin. These results suggest that Pf4 phages alter innate immunity to bacteria potentially dampening inflammation and neutrophil migration at sites of bacterial colonization or infection.
Rapid transmission and tight bottlenecks constrain the evolution of highly transmissible SARS-CoV-2 variants
Authors: Bendall Emily E. , Callear Amy , Getz Amy , Goforth Kendra , Edwards Drew , Monto Arnold S. , Martin Emily T. , Lauring Adam S. 
Published: October 2022

AbstractTransmission bottlenecks limit the spread of novel mutations and reduce the efficiency of natural selection along a transmission chain. Many viruses exhibit tight bottlenecks, and studies of early SARS-CoV-2 lineages identified a bottleneck of 1-3 infectious virions. While increased force of infection, host receptor binding, or immune evasion may influence bottleneck size, the relationship between transmissibility and the transmission bottleneck is unclear. Here, we compare the transmission bottleneck of non-variant-of-concern (non-VOC) SARS-CoV-2 lineages to those of the Alpha, Delta, and Omicron variants. We sequenced viruses from 168 individuals in 65 multiply infected households in duplicate to high depth of coverage. In 110 specimens collected close to the time of transmission, within-host diversity was extremely low. At a 2% frequency threshold, 51% had no intrahost single nucleotide variants (iSNV), and 42% had 1-2 iSNV. In 64 possible transmission pairs with detectable iSNV, we identified a bottleneck of 1 infectious virion (95% CI 1-1) for Alpha, Delta, and Omicron lineages and 2 (95% CI 2-2) in non-VOC lineages. The latter was driven by a single iSNV shared in one non-VOC household. The tight transmission bottleneck in SARS-CoV-2 is due to low genetic diversity at the time of transmission, a relationship that may be more pronounced in rapidly transmissible variants. The tight bottlenecks identified here will limit the development of highly mutated VOC in typical transmission chains, adding to the evidence that selection over prolonged infections in immunocompromised patients may drive their evolution.
Serology assays used in SARS-CoV-2 seroprevalence surveys worldwide: a systematic review and meta-analysis of assay features, testing algorithms, and performance
Authors: Ma Xiaomeng , Li Zihan , Whelan Mairead G. , Kim Dayoung , Cao Christian , Yanes-Lane Mercedes , Yan Tingting , Jaenisch Thomas , Chu May , Clifton David A. , Subissi Lorenzo , Bobrovitz Niklas , Arora Rahul K. 
Published: October 2022

AbstractBackgroundMany serological assays to detect SARS-CoV-2 antibodies were developed during the COVID-19 pandemic. Differences in the detection mechanism of SARS-CoV-2 serological assays limited the comparability of seroprevalence estimates for populations being tested.MethodsWe conducted a systematic review and meta-analysis of serological assays used in SARS-CoV-2 population seroprevalence surveys, searching for published articles, preprints, institutional sources, and grey literature between January 1, 2020, and November 19, 2021. We described features of all identified assays and mapped performance metrics by the manufacturers, third-party head-to-head, and independent group evaluations. We compared the reported assay performance by evaluation source with a mixed-effect beta regression model. A simulation was run to quantify how biased assay performance affects population seroprevalence estimates with test adjustment.ResultsAmong 1807 included serosurveys, 192 distinctive commercial assays and 380 self-developed assays were identified. According to manufacturers, 28.6% of all commercial assays met WHO criteria for emergency use (sensitivity [Sn.] >= 90.0%, specificity [Sp.] >= 97.0%). However, manufacturers overstated the absolute values of Sn. of commercial assays by 1.0% [0.1, 1.4%] and 3.3% [2.7, 3.4%], and Sp. by 0.9% [0.9, 0.9%] and 0.2% [-0.1, 0.4%] compared to third-party and independent evaluations, respectively. Reported performance data was not sufficient to support a similar analysis for self-developed assays. Simulations indicate that inaccurate Sn. and Sp. can bias seroprevalence estimates adjusted for assay performance; the error level changes with the background seroprevalence.ConclusionsThe Sn. and Sp. of the serological assay are not fixed properties, but varying features depending on the testing population. To achieve precise population estimates and to ensure the comparability of seroprevalence, serosurveys should select assays with high performance validated not only by their manufacturers and adjust seroprevalence estimates based on assured performance data. More investigation should be directed to consolidating the performance of self-developed assays.
Sexual dimorphic regulation of recombination by the synaptonemal complex
Authors: Cahoon Cori K. , Richter Colette M. , Dayton Amelia E. , Libuda Diana E. 
Published: October 2022

ABSTRACTIn sexually reproducing organisms, germ cells faithfully transmit the genome to the next generation by forming haploid gametes, such as eggs and sperm. Although most meiotic proteins are conserved between eggs and sperm, many aspects of meiosis are sexually dimorphic. The mechanisms regulating recombination display sex-specific differences in multiple organisms such that the same proteins in each sex are being utilized in different ways to produce sexually dimorphic outcomes. The synaptonemal complex (SC), a large ladder-like structure that forms between homologous chromosomes, is essential for regulating meiotic chromosome organization and promoting recombination. To assess whether sex-specific differences in the SC underpin sexually dimorphic aspects of meiosis, we examined twoCaenorhabditis elegansSC central region proteins, SYP-2 and SYP-3, in oogenesis and spermatogenesis and uncovered sex-specific roles for the SYPs in regulating meiotic recombination. We find that SC composition is regulated by sex-specific mechanisms throughout meiotic prophase I. During pachytene, both oocytes and spermatocytes differentially regulate the stability of SYP-2 and SYP-3 within an assembled SC, with increased SYP-2 dynamics in spermatocytes and increased SYP-3 dynamics in oocytes. Further, we uncover that the relative amount of SYP-2 and SYP-3 within the SC is independently regulated in both a sex-specific and a recombination-dependent manner. Specifically, we find that SYP-2 regulates the early steps of recombination in both sexes, while SYP-3 controls the timing and positioning of crossover recombination events across the genomic landscape in only oocytes. Taken together, we demonstrate dosage-dependent regulation of individual SC components with sex-specific functions in recombination. These sexual dimorphic features of the SC provide insights into how spermatogenesis and oogenesis adapted similar chromosome structures to differentially regulate and execute recombination.
SARS-CoV-2 immune complex triggers human monocyte necroptosis
Authors: Santos Leonardo Duarte , Antunes Krist Helen , Cassão Gisele , Gonçalves João Ismael , Abbadi Bruno Lopes , Bizarro Cristiano Valim , Basso Luiz Augusto , Machado Pablo , de Souza Ana Paula Duarte , Porto Bárbara Nery 
Published: October 2022

AbstractWe analyzed the ability of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) itself and SARS-CoV-2-IgG immune complexes to trigger human monocyte necroptosis. SARS-CoV-2 was able to induce monocyte necroptosis dependently of MLKL activation. Necroptosis-associated proteins (RIPK1, RIPK3 and MLKL) were involved in SARS-CoV-2 N1 gene expression in monocytes. SARS-CoV-2 immune complexes promoted monocyte necroptosis in a RIPK3- and MLKL-dependent manner, and Syk tyrosine kinase was necessary for SARS-CoV-2 immune complex-induced monocyte necroptosis, indicating the involvement of Fcγ receptors on necroptosis. Finally, we provide evidence that elevated LDH levels as a marker of lytic cell death are associated with COVID-19 pathogenesis.
Maternal omega-3 fatty acid deficiency affects fetal thermogenic development and postnatal musculoskeletal growth in mice
Authors: Srinivas Vilasagaram , Molangiri Archana , Varma Saikanth , Mallepogu Aswani , Kona Suryam Reddy , Ibrahim Ahamed , Duttaroy Asim K , Basak Sanjay 
Published: October 2022

AbstractMaternal omega-3 (n-3) polyunsaturated fatty acids (PUFAs) deficiency can affect offspring’s adiposity and metabolism by modulating lipid and glucose metabolism. However, the impact of n-3 PUFA deficiency on the development of fetal thermogenesis and its consequences is not reported. Using an n-3 PUFA deficient mice, we assessed fetal interscapular brown adipose tissue (iBAT), body fat composition, insulin growth factor-1 (IGF-1), glucose transporters (GLUTs), and expression of lipid storage & metabolic proteins in the offspring. The n-3 PUFA deficiency did not change the pups’ calorie intake, organ weight, and body weight. However, the offspring’s skeletal growth was altered due to excess fat to lean mass, reduced tibia & femur elongation, dysregulated IGF-1 in the mother and pups (p<0.05). Localization of uncoupling protein 1 (UCP1) in iBAT exhibited a reduced expression in the deficient fetus. Further, UCP1, GLUT1,GPR120were downregulated while FABP3, ADRP, GLUT4 expressions were upregulated in the BAT of the deficient offspring (p<0.05). The deficiency decreased endogenous conversion of the n-3 LCPUFAs from their precursors and upregulatedSCD1, FASN, andMFSD2AmRNAs in the liver (p<0.05). An altered musculoskeletal growth in the offspring is associated with impaired browning of the fetal adipose, dysregulated thermogenesis, growth hormone, and expression of glucose and fatty acid metabolic mediators due to maternal n-3 PUFA deficiency. BAT had higher metabolic sensitivity compared to WAT in n-3 PUFA deficiency. Maternal n-3 PUFA intake may prevent excess adiposity by modulating fetal development of thermogenesis and skeletal growth dynamics in the mice offspring.HighlightMaternal n-3 PUFA deficiency dysregulated the development of fetal adipose browningN-3 PUFA regulates fetal thermogenic development by altering UCP1 expressionBAT had higher metabolic sensitivity compared to WAT in n-3 PUFA deficiencyIncreased fat mass and IGF-1 played a role in promoting adiposity in n-3 PUFA deficiency
Streptococcus pyogenesϕ1207.3 is a temperate bacteriophage carrying the macrolide efflux gene pairmef(A)-msr(D) and capable to lysogenise different Streptococci
Authors: Santoro Francesco , Pastore Gabiria , Fox Valeria , Petit Marie-Agnes , Iannelli Francesco , Pozzi Gianni 
Published: October 2022

AbstractStreptococcus pyogenesprophage ϕ1207.3 (formerly Tn1207.3) carries themef(A)-msr(D) efflux resistance genes, responsible for type M macrolide resistance. To investigate if ϕ1207.3 is a functional bacteriophage, we transferred the element from the originalS. pyogeneshost in a prophage-free and competence-deficientS. pneumoniaestrain. Pneumococcal cultures of the ϕ1207.3-carrying lysogen were treated with mitomycin C to assess if ϕ1207.3 enters the lytic cycle. Mitomycin C induced a limited phage burst and a growth impairment resulting in early entrance in the stationary phase. To determine if ϕ1207.3 is able to produce mature phage particles we prepared concentrated supernatants recovered from a mitomycin C induced pneumococcal culture by sequential centrifugation and ultracentrifugation steps. Negative staining Transmission Electron Microscopy (TEM) of supernatants revealed the presence of phage particles with an icosahedral, electron dense capsid and a long, non-contractile tail, typical of a siphovirus. Quantification of ϕ1207.3 was performed by qPCR and semi-quantitatively by TEM. PCR quantified 3.34 × 104and 6.06 × 104excised forms of phage genome per ml of supernatant obtained from the untreated and mitomycin C treated cultures, respectively. By TEM, we estimated 3.02 × 103and 7.68 × 103phage particles per ml of supernatant. The phage preparations of ϕ1207.3 infected and lysogenised pneumococcal recipient strains at a frequency of 7.5 × 10−6lysogens/recipient, but did not show sufficient lytic activity to form plaques. Phage lysogenisation efficiently occurred after 30 minutes of contact of the phages with the recipient cells and required a minimum of 103phage particles.ImportanceBacteriophages play an important role in bacterial physiology and genome evolution. The widespread use of genome sequencing revealed that bacterial genomes can contain several different integrated temperate bacteriophages, which can constitute up to 20% of the genome. Most of these bacteriophages are only predictedin silicoand never shown to be functional. In fact, it is often difficult to induce the lytic cycle of temperate bacteriophages. In this work, we show that ϕ1207.3, a peculiar bacteriophage originally fromStreptococcus pyogenes, which can lysogenise different Streptococci and carries the macrolide resistancemef(A)-msr(D) gene pair, is capable of producing mature virions, but only at a low level, while not being able to produce plaques. This temperate phage is probably a partially functional phage, which seems to have lost lytic characteristics to specialize into lysogenisation. While we are not used to conceive phages separately from lysis, this behavior could actually be more frequent than expected.
DNA transposons ofmaTfamily in the Cnidaria
Authors: Puzakov Mikhail V. , Puzakova Lyudmila V. , Cheresiz Sergey V. , Shi Shasha 
Published: October 2022

AbstractTransposable elements exert a significant influence on the structure and size of eukaryotic genomes. Representatives ofTc1/marinersuperfamily of DNA transposons form a prevalent and highly variable group, which includes the relatively well studiedTLE/DD34-38E,MLE/DD34D,maT/DD37D,Visitor/DD41D,Guest/DD39D,mosquito/DD37E andL18/DD37E families. A detailed study of distribution and diversity ofTc1/marinertransposons will help us to better investigate the co-evolution of TEs and eukaryotic genomes. We performed a profound analysis ofmaT/DD37D family in the cnidarians. maT transposons were shown to exist in a limited number of cnidarian species belonging to Cubozoa, Hydrozoa and Scyphozoa classes.maTtransposons of the cnidarians are thought to be the descendants of several individual invasion events, which have occurred at different times in the past. Themosquito/DD37E transposons of the cnidarians have also been described. These TEs were shown to be present in Hydridae family (class Hydrozoa) only. An analysis of TE distribution, diversity, evolutionary history and phylogeny established that theTEs undergo their unique evolution not only in different species, but also within a particular species. These results improve our knowledge ofTc1/marinerdiversity and evolution, as well as their influence of eukaryotic genomes.
Standardising Breast Radiotherapy Structure Naming Conventions: A Machine Learning Approach
Authors: Haidar Ali , Field Matthew , Batumalai Vikneswary , Cloak Kirrily , Mouiee Daniel Al , Chlap Phillip , Huang Xiaoshui , Chin Vicky , Aly Farhannah , Carolan Martin , Sykes Jonathan , Vinod Shalini K. , Delaney Geoffrey P , Holloway Lois 
Published: October 2022

AbstractIn progressing the use of big data in health systems, standardised nomenclature is required to enable data pooling and analyses. In many radiotherapy planning systems and their data archives, target volumes (TV) and organ-at-risk (OAR) structure nomenclature has not been standardised. Machine learning (ML) have been utilized to standardise volumes nomenclature in retrospective datasets. However, only subsets of the structures have been targeted. Within this paper, we proposed a new approach for standardizing all the structures nomenclature by using multi-modal artificial neural networks. A cohort consisting of 1613 breast cancer patients treated with radiotherapy was identified from Liverpool & Macarthur Cancer Therapy Centres, NSW, Australia. Four types of volume characteristics were generated to represent each target and OAR volume: textual features, geometric features, dosimetry features, and imaging data. Five datasets were created from the original cohort, the first four represented different subsets of volumes and the last one represented the whole list of volumes. For each dataset, 15 sets of combinations of features were generated to investigate the effect of using different characteristics on the standardisation performance. The best model reported 99.416% classification accuracy over the hold-out sample when used to standardise all the nomenclatures in a breast cancer radiotherapy plan into 21 classes. Our results showed that ML based automation methods can be used for standardising naming conventions in a radiotherapy plan taking into consideration the inclusion of multiple modalities to better represent each volume.
Dog-related deaths registered in England and Wales from 2001 to 2021
Authors: Tulloch John SP , Oxley James A , Christley Robert M , Westgarth Carri 
Published: October 2022

AbstractIntroductionThis study aimed to describe the incidence and demographics of fatal dog bites or strikes, as defined in English and Welsh mortality data (2001-2021).MethodsData from the Office for National Statistics registered deaths dataset were used to identify individuals whose cause of death was defined as ‘bitten or struck by a dog’. The average annual number of dog-related deaths and trends in incidence were calculated. Age and sex demographics of victims were described.ResultsThere were 3.3 (95%CI 0.3-6.3) dog-related deaths per year, a mean annual incidence of 0.59 (95%CI 0.06-1.11) deaths per 10 million population. There was no obvious trend in incidence. Of victims, 59% were male, 10% were <5 years, and 30% were ≥75 years.DiscussionDog-related deaths are rare in England and Wales and have not increased between 2001 and 2021. Further contextual information about the incidents is needed to be able to develop public health strategies and interventions.What is already known on this subject?Dog attacks can cause severe physical injury and psychological trauma, and can be fatal.Hospital admissions due to ‘dog bites or strikes’ in England have doubled between 1998 and 2018, with males and young children the most likely to be bitten.What this study adds?Deaths attributed to dog bites or strikes in England and Wales over a 20-year period are rare events and do not appear to be increasing in incidence.Registered deaths were more common in the very young and old, and in males.Further contextual information concerning dog-related deaths is needed to develop public health strategies and interventions.