bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synaptic alterations associated with disrupted sensory encoding in a mouse model of tauopathy
Authors: Meftah Soraya , Cavallini Annalisa , Murray Tracey K. , Jankowski Lukasz , Bose Suchira , Ashby Michael C. , Brown Jonathan T. , Witton Jonathan 
Published: May 2023

AbstractSynapse loss is currently the best biological correlate of cognitive decline in Alzheimer’s disease and other tauopathies. Synapses seem to be highly vulnerable to tau-mediated disruption in neurodegenerative tauopathies. However, it is unclear how and when this leads to alterations in function in relation to the progression of tauopathy and neurodegeneration. We used the well-characterised rTg4510 mouse model of tauopathy, at 5-6 months and 7-8 months of age, to study the functional impact of cortical synapse loss. The earlier age was used as a model of prodromal tauopathy, with the later age corresponding to more advanced tau pathology and presumed progression of neurodegeneration. Analysis of synaptic protein expression in the somatosensory cortex showed significant reductions in synaptic proteins and NMDA and AMPA receptor subunit expression in rTg4510 mice. Surprisingly,in vitrowhole-cell patch clamp electrophysiology from putative pyramidal neurons in layer 2/3 of the somatosensory cortex suggested no functional alterations in layer 4 to layer 2/3 synaptic transmission at 5-6 months. From these same neurons, however, there were alterations in dendritic structure, with increased branching seen proximal to the soma in rTg4510 neurons. Therefore,in vivowhole-cell patch clamp recordings were utilised to investigate synaptic function and integration in putative pyramidal neurons in layer 2/3 of the somatosensory cortex. These recordings revealed a significant increase in the peak response to synaptically-driven sensory stimulation-evoked activity and a loss of temporal fidelity of the evoked signal to the input stimulus in rTg4510 neurons. Together, these data suggest that loss of synapses, changes in receptor expression, and dendritic restructuring may lead to alterations in synaptic integration at a network level. Understanding of these compensatory processes could identify targets to help delay symptomatic onset within dementia.Abbreviated summaryMeftah et al. report alterations to synaptic and dendrite properties in the rTg4510 mouse model of tauopathy associated with disrupted synaptic integrationin vivo. Therefore, disrupted synaptic and network integration may be early markers of synapse loss in neurodegenerative tauopathies.
Differential intra-host infection kinetics inAedes aegyptiunderlie superior transmissibility of African relative to Asian Zika virus
Authors: Phengchat Rinyaporn , Pakparnich Phonchanan , Pethrak Chatpong , Pengon Jutharat , Sartsanga Channarong , Chotiwan Nunya , Uppakara Kwanchanok , Suksirisawat Kittitat , Lambrechts Louis , Jupatanakul Natapong 
Published: May 2023

AbstractDespite numerous studies highlighting the higher transmissibility of the African Zika virus (ZIKV) lineage compared to the Asian lineage in mosquito vectors, little is known about how the viruses interact with different tissues during the early steps of mosquito infection. To address this gap, we aimed to characterize intra-host infection barriers by combining a tissue-level monitoring of infection using plaque assays and a novel quantitative analysis of single-cell level infection kinetics byin situimmunofluorescent staining. Our results revealed that, inAedes aegypti, an African ZIKV strain exhibited a higher replication rate across various tissues than an Asian ZIKV strain. This difference was potentially due to a higher virus production in individual cells, faster spread within tissues, or a combination of both factors. Furthermore, we observed that higher bloodmeal titers resulted in a faster viral spread to neighboring cells suggesting that intra-host infection dynamics depend on inoculum size. We also identified a significant bottleneck during midgut infection establishment for both ZIKV lineages, with only a small percentage of the virus population successfully initiating infection. Finally, thein situimmunofluorescent staining technique enabled the examination of virus infection characteristics in different cell types and revealed heterogeneity in viral replication. Together, these findings demonstrate that differences in intra-host infection kinetics underlie differential transmissibility between African and Asian ZIKV lineages. This information could serve as a starting point to further investigate the underlying mechanisms and ultimately inform the development of alternative control strategies.ImportanceThe recent Zika virus (ZIKV) epidemic in the Americas highlights its potential public health threat. While the Asian ZIKV lineage has been identified as the main cause of the epidemic, the African lineage, which has been primarily confined to Africa, has shown evidence of higher transmissibility inAedesmosquitoes. To gain a deeper understanding of this differential transmissibility, our study employed a combination of tissue-level infection kinetics and single-cell level infection kinetics usingin situimmunofluorescent staining. We discovered that the African ZIKV lineage propagates more rapidly and spreads more efficiently within mosquito cells and tissues than its Asian counterpart. This information lays the groundwork for future exploration of the viral and host determinants driving these variations in propagation efficiency.
An all-atom protein generative model
Authors: Chu Alexander E. , Cheng Lucy , El Nesr Gina , Xu Minkai , Huang Po-Ssu 
Published: May 2023

AbstractProteins mediate their functions through chemical interactions; modeling these interactions, which are typically through sidechains, is an important need in protein design. However, constructing an all-atom generative model requires an appropriate scheme for managing the jointly continuous and discrete nature of proteins encoded in the structure and sequence. We describe an all-atom diffusion model of protein structure, Protpardelle, which instantiates a “superposition” over the possible sidechain states, and collapses it to conduct reverse diffusion for sample generation. When combined with sequence design methods, our model is able to co-design all-atom protein structure and sequence. Generated proteins are of good quality under the typical quality, diversity, and novelty metrics, and sidechains reproduce the chemical features and behavior of natural proteins. Finally, we explore the potential of our model conduct all-atom protein design and scaffold functional motifs in a backbone- and rotamer-free way.
The T2T-CHM13 reference genome has more accurate sequences for immunoglobulin genes than GRCh38
Authors: Nie Junli , Tellier Julie , Tarasova Ilariya , Nutt Stephen L. , Smyth Gordon K. 
Published: May 2023

AbstractBackgroundThe production of antibody by members of the B-cell lineage is essential for protective immunity. The clonal selection theory posits that each mature B cell has a unique immunoglobulin receptor, generated through random gene recombination, and when stimulated to differentiate into an antibody-secreting cell has the capacity to produce only a single antibody specificity. Based on this classical, “one cell one antibody” dogma, analysis of single cell RNA sequencing data of antibody-secreting cells should reveal that each cell expresses only a single form of each of the immunoglobulin heavy and light chains. However, when using GRCh38 as the genome reference, many plasma cells appear to express multiple immunoglobulin isotypes.ResultsWe show that this false mapping is caused by the inaccurate immunoglobulin sequences provided by GRCh38. The newly published human genome reference T2T-CHM13, due to its more accurate sequences, avoids this false mapping caveat. In addition, further reads mapped to GRCh38 with ambiguity also settle down perfectly.ConclusionsThese studies reveal that the sequences of the immunoglobulin genes within T2T-CHM13 are more accurate than GRCh38. Thus T2T-CHM13 is the reference genome of choice for accurate mapping and identification of the human immunoglobulin genes.
Low-dimensional neural manifolds for the control of constrained and unconstrained movements
Authors: Altan Ege , Ma Xuan , Miller Lee E. , Perreault Eric J. , Solla Sara A. 
Published: May 2023

ABSTRACTAcross many brain areas, neural population activity appears to be constrained to a low-dimensional manifold within a neural state space of considerably higher dimension. Recent studies of the primary motor cortex (M1) suggest that the activity within the low-dimensional manifold, rather than the activity of individual neurons, underlies the computations required for planning and executing movements. To date, these studies have been limited to data obtained in constrained laboratory settings where monkeys executed repeated, stereotyped tasks. An open question is whether the observed low dimensionality of the neural manifolds is due to these constraints; the dimensionality of M1 activity during the execution of more natural and unconstrained movements, like walking and picking food, remains unknown. We have now found similarly low-dimensional manifolds associated with various unconstrained natural behaviors, with dimensionality only slightly higher than those associated with constrained laboratory behaviors. To quantify the extent to which these low-dimensional manifolds carry task-relevant information, we built task-specific linear decoders that predicted EMG activity from M1 manifold activity. In both settings, decoding performance based on activity within the estimated low-dimensional manifold was the same as decoding performance based on the activity of all recorded neurons. These results establish functional links between task-specific manifolds and motor behaviors, and highlight that both constrained and unconstrained behaviors are associated with low-dimensional M1 manifolds.
A comparative genomics approach reveals a local genetic signature ofLeishmania tropicain Morocco
Authors: Talimi Hasnaa , Daoui Othmane , Bussotti Giovanni , Mhaidi Idris , Boland Anne , Deleuze Jean-François , Fissoune Rachida , Späth Gerald F. , Lemrani Meryem 
Published: May 2023

ABSTRACTIn Morocco, cutaneous leishmaniasis (CL) caused byLeishmania(L.)tropicais an important health problem. Despite its high incidence in the country, the genomic heterogeneity of these parasites is still incompletely understood. In this study, we sequenced the genomes of 14 Moroccan isolates ofL. tropicacollected from confirmed cases of CL to investigate their genomic heterogeneity. Comparative genomics analyses were conducted by applying the recently established Genome Instability Pipeline (GIP), which allowed us to conduct phylogenomic and PCA analyses, and to assess genomic variations at the levels of the karyotype, gene copy number, and single nucleotide polymorphisms (SNPs). The results identified a core group of 12 isolates that were genetically highly related but evolutionarily distant to the reference genome as judged by the presence of over 100,000 SNPs, 75% of which were shared inside this core group. In addition, we identified two highly divergent strains, M3015 and Ltr_16, that were phylogenetically distinct between each other as well as to the core group and the reference genome. Read-depth analysis revealed important karyotypic variations across all isolates and uncovered important differences in gene copy number between the isolates of the core group and theL. tropicareference genome, as well as between the core group and M3015. In conclusion, our NGS results suggest the presence of a local SNP signature that distinguishes MoroccanL. tropicafrom other endemic regions and from the reference genome. These results pave the way for future research with a larger number of strains that will allow to correlate diverse phenotypes (resistance to treatments, virulence) and origins (geography, host species, year of isolation) to defined genomic signals that may represent interesting biomarker candidates.
CRISPR/Cas9-based depletion of 16S ribosomal RNA improves library complexity of single-cell RNA-sequencing
Authors: Wang Kuang-Tse , Adler Carolyn E. 
Published: May 2023

AbstractBackgroundSingle-cell RNA-sequencing (scRNA-seq) relies on PCR amplification to retrieve information from vanishingly small amounts of starting material. To selectively enrich mRNA from abundant non-polyadenylated transcripts, poly(A) selection is a key step during library preparation. However, some transcripts, such as mitochondrial genes, can escape this elimination and overwhelm libraries. Often, these transcripts are removedin silico, but whether physical depletion improves detection of rare transcripts in single cells is unclear.ResultsWe find that a single 16S ribosomal RNA is widely enriched in planarian scRNA-seq datasets, independent of the library preparation method. To deplete this transcript from scRNA-seq libraries, we design 30 single-guide RNAs spanning its length. To evaluate the effects of depletion, we perform a side-by-side comparison of the effects of eliminating the 16S transcript and find a substantial increase in the number of genes detected per cell, coupled with virtually complete loss of the 16S RNA. Moreover, we systematically determine that library complexity increases with a limited number of PCR cycles following CRISPR treatment. When compared toin silicodepletion of 16S, physically removing it reduces dropout rates, retrieves more clusters, and reveals more differentially-expressed genes.ConclusionsOur results show that abundant transcripts reduce the retrieval of informative transcripts in scRNA-seq and distort the analysis. Physical removal of these contaminants enables the detection of rare transcripts at lower sequencing depth, and also outperformsin silicodepletion. Importantly, this method can be easily customized to deplete any abundant transcript from scRNA-seq libraries.
Exploring the impact of incentive policy on the development of prefabricated buildings: a scenario-based system dynamics model
Authors: Han Yanhu , Fang Xiao , Zhao Xinyu , Wang Lufan 
Published: May 2023

PurposeThe development of prefabricated buildings has become one of the primary solutions to transform the traditional construction industry around the world. Incentive policy is one of the important driving factors for the development of prefabricated building. The policy system in the field of prefabricated buildings needs to be improved urgently. However, there is still a dearth of research on how incentive policies exert impact on the development of prefabricated buildings. This paper aims to reveal the impact mechanisms of different types of policies on the development system of prefabricated buildings.Design/methodology/approachThis study categorizes prefabricated building policies, constructs a system dynamics model of prefabricated building policies and conducts scenario simulations to examine the impact and sensitivity of different types of policies on the development system of prefabricated buildings.FindingsThe results show that compulsory policies play a greater role in the early stage of prefabricated building development and need to be withdrawn at the right time. Preferential and encouraging policies play an incentive role in the middle and later stages of prefabricated building development. Encouraging policies predominate in the later stage of prefabricated building development. Based on the research results, policy recommendations for prefabricated building development are put forward respectively from the government, developers and consumers.Originality/valueThe research results are expected to make up for the lack of clear policies paths in existing research and provide theoretical references for the formulation and optimization of future policies.
A contingency approach for time-cost trade-off in construction projects based on machine learning techniques
Authors: Wang Peipei , Wang Kun , Huang Yunhan , Fenn Peter 
Published: May 2023

PurposeTime-cost trade-off is normal conduct in construction projects when projects are expectedly late for delivery. Existing research on time-cost trade-off strategic management mostly focused on the technical calculation towards the optimal combination of activities to be accelerated, while the managerial aspects are mostly neglected. This paper aims to understand the managerial efforts necessary to prepare construction projects ready for an upcoming trade-off implementation.Design/methodology/approachA preliminary list of critical factors was first identified from the literature and verified by a Delphi survey. Quantitative data was then collected by a questionnaire survey to first shortlist the preliminary factors and quantify the predictive model with different machine learning algorithms, i.e. k-nearest neighbours (kNN), radial basis function (RBF), multiplayer perceptron (MLP), multinomial logistic regression (MLR), naïve Bayes classifier (NBC) and Bayesian belief networks (BBNs).FindingsThe model's independent variable importance ranking revealed that the top challenges faced were the realism of contractual obligation, contractor planning and control and client management and monitoring. Among the tested machine learning algorithms, multilayer perceptron was demonstrated to be the most suitable in this case. This model accuracy reached 96.5% with the training dataset and 95.6% with an independent test dataset and could be used as the contingency approach for time-cost trade-offs.Originality/valueThe identified factor list contributed to the theoretical explanation of the failed implementation in general and practical managerial improvement to better avoid such failure. In addition, the established predictive model provided an ad-hoc early warning and diagnostic tool to better ensure time-cost implementation success.
Asymmetric information, capacity constraint and segmentation in credit markets
Authors: Chakraborty Pallabi , Mahanta Amarjyoti 
Published: May 2023

Purpose
The purpose of this study is to propose a model of competition between a formal lender (bank) and an informal lender (moneylender) with informational asymmetry between these two lenders. Further, the authors introduce capacity constraint on the lending capacity of the moneylender and assume that borrowers differ in risk and wealth.

Design/methodology/approach
The solution concept of Nash equilibrium has been used to derive the optimal strategies of the lenders.

Findings
The equilibrium strategies in most of the results depend on the difference between the expected returns from risky and safe projects where the risky project has higher expected returns. The credit market is segmented in terms of risk and wealth levels. Rationing of poor safe borrowers from the credit market is inevitable when the moneylender's capacity is sufficiently small, suggesting a low-income trap for them. Further, when moneylender has capacity constraint of some form, a zero-profit outcome is never a Nash equilibrium outcome.

Research limitations/implications
There is a possibility of collusion between the lenders. However, the authors do not derive all possible outcomes under capacity constraint

Practical implications
When the informal lender has limited capacity, competition between formal and informal lenders may not alleviate credit rationing, instead aggravate the problem. Thus, the government should devise policies to ensure credit availability to resource poor households

Originality/value
While the literature models strategic interaction between lenders under the assumption of zero-profit (Bertrand Paradox) condition, this study shows that zero profit is not the only outcome under such a set-up. Also, in presence of capacity constraint of the moneylender, a zero-profit outcome is never a Nash equilibrium outcome for the lenders. There is an optimal contract at which the lenders differentiate in terms of repayment and collateral and earn positive profits under certain conditions.
The relationship between perception of well-being and depression among adolescents in Jordan: using PERMA model as a theoretical framework
Authors: Ghannam Bushra , Al Khatib Husam , Alzayyat Abeer , Hamdan Mansour Ayman 
Published: May 2023

Purpose
Adolescence is a developmental stage of transition that is marked by multiple biopsychosocial changes that affect their well- and ill-being. This study aims to examine the multidimensional of well- and ill-being among adolescents, and to understand the relationship between well-being and depression using the PERMA model among school-age adolescents.

Design/methodology/approach
A descriptive, cross-sectional design was used to recruit 625 school-age adolescents (343 males and 282 females), using convenience sampling technique from the central district of Jordan. Self-administered questionnaire was used to collect data in relation to depression and well-being.

Findings
The analysis revealed that 32% had a well-being score below the median and 19% had severe depressive symptoms. Depression and well-being were moderately correlated, with the connectedness dimension being the most correlated to depression, whereas the engagement dimension was the least correlated. Females had higher scores on all subscales of depression and a significantly higher score on depression than males, whereas males had higher scores on all well-being dimensions and significantly higher scores on overall well-being than females.

Research limitations/implications
Adolescents’ mental health is compromised and affected by their perception of well-being, and a comprehensive psychoeducation for adolescents on how to enhance well-being might combat development of depressive symptoms.

Originality/value
This study used all PERMA model components to provide an in-depth description of adolescents’ well-being, which is a crucial initial phase in better understanding how this age group experiences well-being and how it connects to their ill-being, as indicated by their depressive symptoms. The in-depth description of adolescents’ well-being will aid in planning early intervention and prevention programs for mental illness.