bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interpreting SNP heritability in admixed populations
Authors: Huang Jinguo , Kleman Nicole , Basu Saonli , Shriver Mark D. , Zaidi Arslan A. 
Published: August 2023

AbstractSNP heritabilityis defined as the proportion of phenotypic variance explained by genotyped SNPs and is believed to be a lower bound of heritability (h2), being equal to it if all causal variants are known. Despite the simple intuition behind, its interpretation and equivalence toh2is unclear, particularly in the presence of population structure and assortative mating. It is well known that population structure can lead to inflation inestimates because of confounding due to linkage disequilibrium (LD) or shared environment. Here we use analytical theory and simulations to demonstrate thatestimates can be biased in admixed populations, even in the absence of confounding and even if all causal variants are known. This is because admixture generates LD, which contributes to the genetic variance, and therefore to heritability. Genome-wide restricted maximum likelihood (GREML) does not capture this contribution leading to under-or over-estimates ofrelative toh2, depending on the genetic architecture. In contrast, Haseman-Elston (HE) regression exaggerates the LD contribution leading to biases in the opposite direction. For the same reason, GREML and HE estimates of local ancestry heritabilityare also biased. We describe this bias inandas a function of admixture history and the genetic architecture of the trait and show that it can be recovered under some conditions. We clarify the interpretation ofin admixed populations and discuss its implication for genome-wide association studies and polygenic prediction.
Machine learning-based meta-analysis of colorectal cancer and inflammatory bowel disease
Authors: Sardari Aria , Usefi Hamid 
Published: August 2023

AbstractColorectal cancer (CRC) is a major global health concern, resulting in numerous cancer-related deaths. CRC detection, treatment, and prevention can be improved by identifying genes and biomarkers. Despite extensive research, the underlying mechanisms of CRC remain elusive, and previously identified biomarkers have not yielded satisfactory insights. This shortfall may be attributed to the predominance of univariate analysis methods, which overlook potential combinations of variants and genes contributing to disease development. Here, we address this knowledge gap by presenting a novel multivariate machine-learning strategy to pinpoint genes associated with CRC. Additionally, we applied our analysis pipeline to Inflammatory Bowel Disease (IBD), as IBD patients face substantial CRC risk. The importance of the identified genes was substantiated by rigorous validation across numerous independent datasets. Several of the discovered genes have been previously linked to CRC, while others represent novel findings warranting further investigation.
Balance of Activity during a Critical Period Tunes a Developing Network
Authors: Hunter Iain , Coulson Bramwell , Pettini Tom , Davies Jacob J. , Parkin Jill , Landgraf Matthias , Baines Richard A. 
Published: August 2023

AbstractDeveloping neural circuits are influenced by activity and are especially sensitive to changes in activity during critical periods (CPs) of development. Changes occurring during a CP often become ‘locked-in’ so that they affect the mature network. Indeed, several neurodevelopmental disorders have been linked to excessive activity during such periods. It is, therefore, important to identify those aspects of neural circuit development that are influenced by neural activity during a CP. In this study, we take advantage of the genetic tractability ofDrosophilato show that activity perturbation during an embryonic CP permanently alters properties of the locomotor circuit. Specific changes we identify include increased synchronicity of motoneuron activity, and greater strengthening of excitatory over inhibitory synaptic drive to motoneurons. These changes are sufficient to reduce network robustness, evidenced by increased sensitivity to induced seizure. We also show that we can rescue these changes when increased activity is mitigated by inhibition provided by mechanosensory neurons. Similarly, we demonstrate a dose-dependent relationship between inhibition experienced during the CP, and the extent to which it is possible to rescue the hyperexcitable phenotype characteristic of theparabssmutation. This suggests that developing circuits must be exposed to a properly balanced sum of excitation and inhibition during the CP to achieve normal mature network function. Our results, therefore, provide novel insight into how activity during a CP shapes specific elements of a circuit, and how activity during this period is integrated to tune neural circuits to the environment in which they will likely function.
ECM degradation in the stump region induced by Fgf during functional joint regeneration in frogs
Authors: Matsubara Haruka , Inoue Takeshi , Agata Kiyokazu 
Published: August 2023

AbstractPrevious studies indicated the importance of the reciprocal interactions between residual tissues in the stump and the newly formed blastema for achieving functional joint regeneration after amputation at the joint level in newts. This reciprocal interaction during regeneration was named “reintegration”. When this reintegration mechanism was evoked inXenopus leavis, regeneration of a functional joint was induced in frogs. Interestingly, degradation of extracellular matrix (ECM) in the remaining joint cartilage was observed during regeneration in both newts and frogs. Histological and gene expression analyses suggested that the degradation of Type II collagen in the cartilage of the articular head might be performed by matrix metalloproteases (Mmps) which were transiently expressed after amputation. We found that fibroblast growth factor (Fgf) induced Mmps expression in the cartilage of the articular head. These results support the possibility that the Fgf signal induces ECM degradation in joint tissues via Mmps expression and that the ECM degradation and subsequent bone morphogenetic protein (Bmp) secretion promote cell proliferation, migration, and differentiation of the cells in the blastema to achieve functional joint regeneration.
Menin regulates androgen receptor- and MLL-driven condensation, upsetting regulation of cellular AR-driven transcription
Authors: Ahmed Junaid , Claridge Jolyon K , Meszaros Attila , Tompa Peter 
Published: August 2023

AbstractMenin is a protein that is regulated via protein-protein interactions by different binding partners, such as mixed lineage leukemia protein (MLL) and androgen receptor (AR). We observed that menin-AR and menin-MLL interactions are regulated by concentration-dependent dimerization of menin, and its interaction with cancer-related AR. As a result of its oligomerization-dependent interaction with both AR and MLL, menin is recruited into AR-RNA and MLL-RNA condensates formed by liquid-liquid phase separation (LLPS), with different outcomes under AR-overexpression or MLL-overexpression conditions representing different cancer types. At high concentrations promoting menin dimerization, it inhibits MLL-RNA LLPS, while making AR-RNA condensates less dynamic, i.e., more gel-like. Regions of AR show both negative/positive cooperativity in menin binding. AR contains a specific menin-binding region (MBR) in its intrinsically disordered N-terminal domain (NTD), menin binding of which is inhibited by the adjacent DNA-binding domain (DBD), but facilitated by a hinge region located between its DBD and ligand-binding domain (LBD) as well as by N terminus of AR. Interestingly, the hinge region reduces the propensity of full-length AR to undergo LLPS in the presence of RNA, which is facilitated by an alternative hinge region present in the tumor-specific AR isoform, AR-v7. As both menin and MLL are recruited into AR-driven, functional cellular condensates aggravated in the case of AR-v7, we posit that the menin-AR-MLL system represents a fine-tuned condensate module of transcription regulation that is balanced toward the tumor-suppressor activity of menin. Our results suggest that this balance can be upset by prevalent oncogenic events, such as menin upregulation and/or AR-v7 overexpression, in cancer.
The Influenza B Virus Victoria and Yamagata Lineages Display Distinct Cell Tropism and Infection Induced Host Gene Expression in Human Nasal Epithelial Cell Cultures
Authors: Wilson Jo L. , Akin Elgin , Zhou Ruifeng , Jedlicka Anne , Dziedzic Amanda , Liu Hsuan , Fenstermacher Katherine Z. , Rothman Richard , Pekosz Andrew 
Published: August 2023

AbstractUnderstanding Influenza B virus infections is of critical importance in our efforts to control severe influenza and influenza-related disease. Until 2020, two genetic lineages of influenza B virus – Yamagata and Victoria – circulated in the population. These lineages are antigenically distinct but differences in virus replication or the induction of host cell responses after infection have not been carefully studied. Recent IBV clinical isolates of both lineages were obtained from influenza surveillance efforts of the Johns Hopkins Center of Excellence in Influenza Research and Response and characterizedin vitro. B/Victoria and B/Yamagata clinical isolates were recognized less efficiently by serum from influenza-vaccinated individuals in comparison to the vaccine strains. B/Victoria lineages formed smaller plaques on MDCK cells compared to B/Yamagata, but infectious virus production in primary human nasal epithelial cell (hNEC) cultures showed no differences. While ciliated epithelial cells were the dominant cell type infected by both lineages, B/Victoria lineages had a slight preference for MUC5AC-positive cells, while B/Yamagata lineages infected more basal cells. Finally, while both lineages induced a strong interferon response 48 hours after infection of hNEC cultures, the B/Victoria lineages showed a much stronger induction of interferon related signaling pathways compared to B/Yamagata. This demonstrates that the two influenza B virus lineages differ not only in their antigenic structure but in their ability to induce host innate immune responses.
Is Inappropriate Pulse Timing Responsible for Poor Binaural Hearing with Cochlear Implants?
Authors: Schnupp Jan W. H. , Buchholz Sarah , Buck Alexa N. , Budig Henrike , Khurana Lakshay , Rosskothen-Kuhl Nicole 
Published: August 2023

AbstractCochlear implants (CIs) have restored enough of a sense of hearing to around one million severely hearing impaired patients to enable speech understanding in quiet. However, several aspects of hearing with CIs remain very poor. This includes a severely limited ability of CI patients to make use of interaural time difference (ITD) cues for spatial hearing and noise reduction. A major cause for this poor ITD sensitivity could be that current clinical devices fail to deliver ITD information in a manner that is accessible to the auditory pathway. CI processors measure the envelopes of incoming sounds and then stimulate the auditory nerve with electrical pulse trains which are amplitude modulated to reflect incoming sound envelopes. The timing of the pulses generated by the devices is largely or entirely independent of the incoming sounds. Consequently, bilateral CIs (biCIs) provide veridical envelope (ENV) ITDs but largely or entirely replace the “fine structure” ITDs that naturally occur in sounds with completely arbitrary electrical pulse timing (PT) ITDs. To assess the extent to which this matters, we devised experiments that measured the sensitivity of deafened rats to precisely and independently controlled PT and ENV ITDs for a variety of different CI pulse rates and envelope shapes. We observed that PT ITDs completely dominate ITD perception, while the sensitivity to ENV ITDs was almost negligible in comparison. This strongly suggests that the confusing yet powerful PT ITDs that contemporary clinical devices deliver to biCI patients may be a major cause of poor binaural hearing outcomes with biCIs.Significance StatementCIs deliver spectro-temporal envelopes, including speech formants, to severely deaf patients, but they do little to cater to the brain’s ability to process temporal sound features with sub-millisecond precision. CIs “sample” sound envelope signals rapidly and accurately, and thus provide information which should make it possible in principle for CI listeners to detect envelope ITDs in a similar way to normal listeners. However, here we demonstrate through behavioral experiments on CI implanted rats trained to detect sub-millisecond ITDs that pulse timing ITDs completely dominate binaural hearing. This provides the strongest confirmation to date that the arbitrary pulse timing widely used in current clinical CIs is a critical obstacle to good binaural hearing through prosthetic devices.
Effects of sex and gestational exercise on pain perception, BDNF and irisin levels in an animal model of ADHD
Authors: Tosta Andréa , Fonseca Ariene S. , Messender Débora , Ferreira Sérgio T. , Lourenco Mychael V. , Pandolfo Pablo 
Published: August 2023

AbstractAbnormal cognitive and sensorial properties have been reported in patients with psychiatric and neurodevelopmental conditions, such as attention deficit hyperactivity disorder (ADHD). ADHD patients exhibit impaired dopaminergic signaling and plasticity in brain areas related to cognitive and sensory processing. The spontaneous hypertensive rat (SHR), in comparison to the Wistar Kyoto rat (WKY), is the most used genetic animal model to study ADHD. Brain neurotrophic factor (BDNF), critical for midbrain and hippocampal dopaminergic neuron survival and differentiation, is reduced in both ADHD subjects and SHR. Physical exercise (e.g. swimming) promotes neuroplasticity and improves cognition by increasing BDNF and irisin. Here we investigate the effects of gestational swimming on sensorial and behavioral phenotypes, striatal dopaminergic parameters, and hippocampal FNDC5/irisin and BDNF levels observed in WKY and SHR. Gestational swimming improved nociceptive reflex impairment in SHR rats and increased hippocampal BDNF levels in a sex-dependent manner in adolescent offspring. Sex differences were observed in hippocampal FNDC5/irisin levels, with females presenting lower levels than males. Our results contribute to the notion that swimming during pregnancy is a promising alternative to improve ADHD phenotypes in the offspring.Graphical abstract
Multi-color live-cell optical nanoscopy using phasor analysis
Authors: Zhang Zhimin , Huang Yuran , Tao Wenli , Wei Yunfei , Xu Liang , Gong Wenwen , Zhang Yuhui , Zhou Jiaqiang , Cao Liangcai , Liu Yong , Han Yubing , Kuang Cuifang , Liu Xu 
Published: August 2023

AbstractStimulated emission depletion microscopy (STED) is a powerful tool for studying nanoscale cell structure and activity, but the difficulties it encounters in multicolor imaging limit its application in biological research. To overcome the disadvantages of limited number of channels and high cost of multicolor STED imaging based on spectral identity, we introduced lifetime into live-cell multicolor STED imaging by separating selected dyes of the same spectrum by phasor analysis. Experimental results show that our method enables live-cell STED imaging with at least 4 colors, enabling observation of cellular activity beyond the diffraction limit.
Multi-objective optimization of FSW aviation-grade AA8090 alloy: an RSM-based design approach
Authors: Panwar Raghuraj , Chandna Pankaj 
Published: August 2023

Purpose
This study aims to determine the effect of different friction stir welding (FSW) parameters on mechanical and metallurgical characteristics of aviation-grade AA8090 alloy joints.

Design/methodology/approach
Response surface methodology with central composite design is used to design experiments. The mechanical and microstructure characteristics of the weld joints have been studied through a standardized method, and the influence of threaded pins on the joint microstructure has also been assessed.

Findings
From a desirability strategy, the optimum parameters setting of the friction stir welding was the tool rotational speed (TRS) of 800, 1,100 and 1,400 rpm; tool traverse speed (TTS) of 20, 30 and 40 mm/min; and tilt angle 1°, 2° and 3° with different tool pin profiles, i.e. cylindrical threaded (CT), square threaded and triangular threaded (TT), for achieving the maximum tensile strength, yield strength (YTS) and % elongation as an output parameter. The TRS speed was the highest weld joint characteristics influencing parameter. Peak tensile strength (378 MPa), percentage elongation (10.1) and YTS (308 MPa) were observed for the optimized parametric value of TRS-1,400, TTS-40 mm/min and TA (3°) along with CT pin profile. Microstructure study of the welded surface was achieved by using scanning electron microscope of output parameters. When the tool rotation speed, tool transverse speed, tilt angle and tool profile are set to moderately optimal levels, a mixed mode of ductile and brittle fracture has been seen during the microstructure analysis of the welded joint. This has been aided by the material’s plastic deformation and the small cracks surrounding the weld zone.

Originality/value
From the reported literature, it has been observed that limited work has been reported on aviation-grade AA8090 alloys. Further thermal behavior of welded joints has also been observed in this experimental work.
Incremental population density improvement via missing middle housing under density-based and form-based zoning ordinances
Authors: Zhang Xingrui , Yang Eunhwa , Huang Liming , Wang Yunpeng 
Published: August 2023

Purpose
The purpose of the study is to observe the feasibility of missing middle housing’s (MMH) realization under density-based zoning, form-based zoning and a combination of both while simultaneously providing affordable housing, improving quality of life and making efficient use of land.

Design/methodology/approach
This study takes a theorist approach and designs three hypothetical cottage court projects that comply with all relevant official local zoning ordinances to showcase design feasibility, followed by an analytical component in the form of a financial model constructed using official local economic and demographic conditions.

Findings
MMH, and in particular cottage clusters, can be implemented under rigorous density-based, form-based and hybrid (density-based + form-based) zoning ordinances and provide affordable housing (Atlanta, GA), improve quality of life (Blackpool, UK) and make efficient use of land (Jinan, China). All hypothetical projects are financially feasible under reasonable conditions.

Originality/value
To the best of the author’s knowledge, this paper is the first in the body of knowledge to discuss how the MMH can be integrated into urban density-based zoning rather than converting density-based zoning into form-based so that the MMH can fit. The paper also takes a cross-national perspective and discusses the feasibility of MMH in the resolution of housing issues in the USA, China and the UK. The study also concludes that the issue of housing unaffordability in the UK was caused by high construction cost relative to median income.
Reflectance confocal microscopy features of vulvar lichen sclerosus in Chinese juvenile girls
Authors: Chen Lixin , Wang Ying , Qin Bei , Fang Hongwei , Li Qinfeng 
Published: August 2023

AbstractVulvar lichen sclerosus (VLS) is a chronic inflammatory dermatosis of unknown pathogenesis, characterized by porcelain‐white atrophic plaques around the vulvar and anal areas in girls. With this communication, we performed the study on 16 female girls with clinically and histologically confirmed VLS, described the main identifying characteristics of the lesions in reflectance confocal microscopy (RCM) and elucidated the corresponding relationship between RCM findings and histology. We recommend RCM, a noninvasive technique, as a complementary diagnostic tool for VLS.
Ecological significance of standing dead phytomass: Marcescence as a puzzle piece to the nutrient cycle in temperate ecosystems
Authors: Mudrák Ondřej , Angst Šárka , Angst Gerrit , Veselá Hana , Schnablová Renáta , Herben Tomáš , Frouz Jan 
Published: August 2023

Abstract

The plant economics spectrum (PES) drives nutrient cycling through effects on soil decomposers. However, dead phytomass may remain standing or unshed (marcescent), hardly accessible to decomposers and be photodegraded. In arid zones, the significant part of marcescent phytomass can be decomposed without touching the ground. In temperate zones, photodegradation of marcescent phytomass is low but prompts important chemical changes, which affect its subsequent decomposability in the soil and alters the surrounding environment. It is unknown, however, how common marcescence is among different taxa and in which habitats, and how it is coordinated by PES traits.

We sampled standing (marcescent) and lying (shed) dead phytomass from a broad spectrum of 127 herbaceous temperate species in a common garden experiment and related these parameters to PES traits, species ecological preferences and phylogeny.

Nearly all species (97%) kept their phytomass marcescent. Tall species with a small leaf area and high leaf carbon had a high level of marcescence. Marcescent species also preferred sites affected by severe (but not necessarily frequent) disturbance. The degree of marcescence was considerably conserved in phylogeny.

Synthesis. Marcescence extends PES trait effects on ecosystems, particularly in immature habitats, being a common but overlooked phenomenon of the temperate flora.
Effect of osmotic stress and salinity on germination and mucilage expansion of seeds of Plantago albicans L. (Plantaginaceae): Inter‐population variation
Authors: Mira Sara , Veiga‐Barbosa Luciana , Martínez‐Laborde Juan Bautista , Pérez‐García Félix , González‐Benito M. Elena 
Published: August 2023

AbstractPlantago albicans L. (Plantaginaceae) grows in wastelands, slopes, and stony pastures, with dry and sun‐exposed soils. Its seeds produce a mucilaginous coat. The main aim of this study was to evaluate intraspecific variation of osmotic and salinity stress response and mucilage production in P. albicans seeds. The relationships between osmotic and salinity stress, germination characteristics, and mucilage expansion were studied in eight populations of P. albicans. Seeds were germinated in distilled water, 20% (w/v) polyethylene glycol 6000 (PEG), or 100 mM NaCl solutions. In most populations, PEG and NaCl reduced final germination. Also, germination was slowed more significantly under osmotic stress than under salinity, while mucilage expansion was more affected by salinity. Therefore, there was an inverse correlation between mucilage expansion and germination under salinity and osmotic stress. Seed populations with similar climatic parameters showed different germination response; however, a correlation was found between mucilage expansion and some climatic parameters. Seeds from drier habitats germinated faster under water stress and produced more mucilage under control and water stress than populations from more humid areas.