bluuebunny/crossref_metadata_2025 huggingface dataset:
White matter integrity and its association with amyloid-PET and serum NfL in healthyAPOE4homozygotes, heterozygotes and non-carries
Authors: Tato-Fernández Claudia , Ekblad Laura L. , Pietilä Elina , Saunavaara Virva , Helin Semi , Parkkola Riitta , Zetterberg Henrik , Blennow Kaj , Rinne Juha O. , Snellman Anniina
Published: October 2023

Except for aging,APOE ε4allele (APOE4) is the most important risk factor for sporadic Alzheimer’s disease.APOE4carriers may have reduced capacity to recycle lipids, resulting in reduced white matter integrity. Here, we evaluated if white matter impairment measured by diffusion tensor imaging (DTI) differs between healthy individuals with different number ofAPOE4alleles and if white matter impairment associates with brain beta-amyloid (Aβ) load and serum levels of neurofilament light chain (NfL). We studied 96 participants (APOE4/4,N= 20;APOE4/3,N= 39;APOE3/3,N= 37; mean age 70.7 (SD 5.22) years, 63% females) with brain MRI including a DTI sequence (N = 96), Aβ-PET (N = 89) and a venous blood sample for serum NfL concentration measurement (N = 88). Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AxD) in sixa priori-selected white matter regions-of-interest (ROIs) were compared between the groups using ANCOVA, with sex and age as covariates. A voxel-weighted average of FA, MD, RD and AxD was calculated for each subject, and correlations with Aβ-PET and NfL levels were evaluated.APOE4/4carriers exhibited higher MD and higher RD in the body of corpus callosum thanAPOE4/3(p = 0.0053 and p = 0.0049, respectively) andAPOE3/3(p = 0.026 and p = 0.042).APOE4/4carriers had higher AxD thanAPOE4/3(p = 0.012) andAPOE3/3(p = 0.040) in the right cingulum adjacent to cingulate cortex. In the total sample, composite MD, RD and AxD positively correlated with cortical Aβ load (r = 0.26 to 0.33, p < 0.013 for all) and with serum NfL concentrations (r = 0.31 to 0.36, p < 0.0028 for all). In conclusion, reduced white matter integrity was detected in cognitively unimpairedAPOE4/4homozygotes compared toAPOE4/3andAPOE3/3carriers and reduced white matter integrity correlated with biomarkers of Alzheimer’s disease and neurodegeneration. White matter impairment seems to be an early phenomenon in the Alzheimer’s disease pathologic process inAPOE4/4homozygotes.

Highlights

Cognitively normal elderlyAPOE4homozygotes showed impaired white matter integrity

APOE4homozygotes showed higher diffusivity in corpus callosum and right cingulum

MD, RD and AxD correlate with amyloid load assessed by PET inAPOE4carriers

MD, RD and AxD correlate with serum neurofilament light chain inAPOE4carriers

White matter impairment may be an early phenomenon in the AD pathologic process
ANALYZING THE PATTERN OF USE OF ANTIBIOTICS IN A GHANAIAN DISTRICT HOSPITAL, ACROSS TWO DIFFERENT YEARS, USING THE WHO AWARE CLASSIFICATION
Authors: Opoku-Agyeman Kwame , Forson David , Acheampong Gerald Anim , Addo Daniel , Akwasi Thomas Afrifa , Asamoah Yaw Asiamah , Prince Ayim Britwum , Baffour Adade-Boateng Kyei , Frimpong Prince Boakye
Published: October 2023

Background

There has been an increment in the resistance of microorganisms to various antibiotics used in regional hospitals in the Ashanti region of Ghana and the country. This has led to difficulty in selecting agents to treat patients without the associated increment in side effects, the astronomical increase in the cost of medical care and a longer duration of hospitalization. In this study, we analyze the pattern of antibiotic use in a district hospital using the WHO AWaRe recommendation.

Objectives

To ascertain the general pattern of antibiotic use with reference to the Access, Watch and Reserve Classes using the selected parameters (year of visit and patient demographics) and to confirm if the standard set by the WHO with respect to Access Class antibiotics is met.

Method

Files of patients, in 2021 and 2022, were systematically sampled from the database of SDA Hospital - Kwadaso (the hospital involved), and data concerning the visits for which antibiotics were administered were extracted to carry out the analysis required. The data extracted included the year of visit, demographics of the patients involved (patient status, age and sex) and the antibiotics that were administered.

Results

This study seeks to ascertain the distribution of antibiotics used across the two years in the hospital of interest using the 2021 WHO AWaRe (Access, Watch and Reserve Antibiotics) Classification. Ultimately, the value, in percentage, of the distribution of the antibiotics used in the Access class will be compared to the target of at least 60% of the total antibiotic consumption being Access group antibiotics as recommended by WHO.
Early life factors associated with childhood trajectories of violence among the Birth to Twenty-Plus Cohort in Soweto, South Africa
Authors: Muchai Lilian , Naicker Sara , Kagura Juliana
Published: October 2023

Violence against children (VAC) has devastating and long-term negative consequences on individuals’ and society’s health, social and economic well-being. There is limited research on the life course experience of VAC, especially in Africa. This study aimed to identify sub-groups of physical & sexual violence victimization patterns separately in childhood, and evaluate early life factors predicting violence trajectories. This study used data from ages 5 to 18 years from the ongoing prospective Birth to Twenty Plus cohort (Bt20+). Children with data on physical and sexual violence in at least 2-time points between 5 and 18 years were included in the analyses. Group-based trajectory modelling was employed to identify groups of children with similar patterns of violence over time, while multivariable logistic regression was used to identify early life factors associated with violence trajectory group membership. Separately, two trajectory groups of physical violence (adolescent limited (65.1%) and chronic increasing (34.9%)) and sexual violence (adolescent limited (74.1%) and late increasing (25.9%)) victimization were identified. Early life factors associated with a higher risk of chronic increasing trajectory group membership, after adjusting for covariates, were being male (aOR 1.67, 95% CI 1.31; 2.10) and having a mother with at least secondary education compared to higher education (aOR 1.73, 95% CI 1.08; 2.76). In addition, residing in middle, compared to low, socioeconomic households (aOR 0.68, 95% CI 0.50; 0.92) was protective against membership in this group. Residing in high compared to low socioeconomic households, was the only early life factor with marginally significant (aOR 0.63, 95% CI 0.42; 0.95) association with membership in the late-increasing sexual violence victimization trajectory group. In conclusion, children follow different violence victimization trajectories over childhood. Identifying early life factors predicting violence trajectories provides key prevention intervention areas that can mitigate children’s violence experience.
Unlocking the Potential of Genetic Research in Pulmonary Arterial Hypertension: Insights from Clinicians, Researchers and Study Team
Authors: Swietlik Emilia M , Fay Michaela , Morrell Nicholas W
Published: October 2023

Background

While genetics has been incorporated into various subspecialties of medicine for some time, the significance of genetic research and testing in understanding the fundamental mechanisms of Pulmonary Arterial Hypertension (PAH) and formulating effective treatment approaches has only recently come to the forefront. We aimed to explore how attitudes toward genetic research among clinical and research teams impacted the engagement in genetic research and the integration of genetic insights into clinical practice.

Methods

Participants were selected from the National Institute for Health Research BioResource Rare Diseases study (NBR) and the Cohort study of idiopathic and heritable PAH (the PAH Cohort), representing a range of roles, ages, genders, and mutation statuses. We conducted a total of 53 semi-structured interviews and focus groups involving a total of 63 patients, clinicians, and researchers from nine UK PH centres. Following the principles of Grounded Theory, interview transcripts were thematically coded by two authors using MAXQDA (2022) software. In this paper, we focus on the researchers’, clinicians’ and study team’s perspectives.

Results

From the interview data, several key themes emerged, ranging from study design, recruitment and consent procedures to the return of individual genetic results. Additionally, participants reflected on both the successes of these studies and the future directions of genetic research. The analysis highlighted the critical importance of fostering collaborative networks firmly rooted in existing clinical and research infrastructure in rare disease study setups. Furthermore, the significance of trust-building, personalised communication, and transparency among stakeholders was underscored. The study offered valuable insights into the motivating and hindering factors to participant recruitment and consent procedures. Lastly, the findings gathered from processes surrounding the return of individual genetic results, genetic counselling, and the recruitment of relatives provided invaluable lessons regarding the integration of genetics into clinical practice.

Conclusions

This in-depth analysis yields a crucial understanding of attitudes to genetic research among various stakeholders and sheds light on the complexities of genetic research and the evidence-practice gap.
Outcomes and Management When Using High-sensitivity Versus Conventional Cardiac Troponin in Patients With Chest Pain: A Meta-analysis
Authors: Pilapil John Christopher A. , Cheng Paula Victoria Catherine Y. , Alad Paul Anthony O. , Aherrera Jaime Alfonso M.
Published: October 2023

Background

Cardiac troponin (cTn) measurement is pivotal in diagnosing and managing chest pain. High-sensitivity cTn (hs-cTn) assays are slowly supplanting conventional cardiac troponin (c-cTn) use, allowing earlier identification of high-risk patients and diagnosis of myocardial infarction (MI). This improved sensitivity is said to come at the cost of reduced specificity for MI. However, there is a paucity of data regarding the exact impact of this change in patient management and outcomes.

Objectives

To compare outcomes and management of patients with chest pain when using hs-cTn versus c-cTn.

Methods

We conducted a systematic search of studies in all languages across various databases. Inclusion criteria for studies were (1) observational or randomized trials, (2) included adult patients presenting with chest pain, (3) use of hs-cTn or c-cTn in diagnosis, (3) reported data on any of the pre-defined outcomes. The primary outcome was all-cause mortality and secondary outcomes were major adverse cardiovascular events (MACE), MI following index admission, coronary angiography, and revascularization. Study quality was appraised using the Cochrane Tool for Assessing Risk of Bias for randomized trials and the Newcastle-Ottawa Quality Assessment scale for observational studies. Outcomes were analyzed using Review Manager (RevMan) 5.3, employing Mantel-Haenszel analysis of random effects to compute for relative risk and odds ratio.

Results

Pooled analysis from 5 studies showed that among patients with chest pain, those for whom hs-cTn over c-cTn was used had no difference in all-cause mortality (RR 1.01, 95% CI 0.92-1.12, p=0.82, I2=0%), a significant decrease in MI (RR 0.74, 95% CI 0.63-0.87, p=0.0003) and a trend towards increase in MACE (RR 1.08, 95% CI 1.00-1.16, p=0.04, I2=0%). They were more likely to undergo coronary angiogram (OR 1.52, 95% CI 1.02-2.28, p=0.04) and revascularization (OR 1.34, 95% CI 1.03-1.75, p=0.03).

Conclusion

Use of hs-cTn over conventional cTn led to higher rates of coronary angiography and revascularization. While there was significant reduction in myocardial infarction, there was no reduction in all-cause mortality and even a trends towards increased MACE.
Factors influencing the delayed presentation of patients with large vessel occlusion in acute ischemic stroke
Authors: Hong Gan-Ji , Zeng Shao-Hui , Yi Ting-Yu , Wu Yan-Min , Lin Ding-Lai , Pan Zhi-Nan , Zheng Xiu-Fen , Lin Xiao-Hui , Chen Rong-Cheng , Zeng Li-San , Ye Jin-hua , Chen Wen-Huo
Published: October 2023

Objective

The benefit of treatment for patients with large vessel occlusion (LVO) in acute ischemic stroke (AIS) is associated with timely access to reperfusion therapy. This study aimed to analyze the factors associated with delayed access to medical attention among patients with AIS-LVO.

Methods

Patients with acute ischemic stroke admitted to the cerebrovascular intervention department of Zhangzhou Hospital, Fujian Province, China, from September 1, 2020 to September 1, 2022, were enrolled in this study. Patients with AIS-LVO were divided into two groups based on whether they visited the hospital for more than 24 hours. Demographic data, NIHSS scores, clinical and radiological data, and in-hospital flow time were collected. Differences between the two groups were analyzed, and univariate and multivariate analyses were performed to identify factors associated with delayed presentation.

Results

A total of 1396 patients were included in the study, with 218 in the delayed group and 1178 in the non-delayed group. There were no significant differences between the two groups in terms of age, gender, or education level. However, the delayed group had a higher proportion of patients living alone (P<0.05). Regarding stroke risk factors, hypertension (83.5% vs 69.9%,P<0.001), diabetes mellitus (35.8% vs 26.1%,P=0.047), and smoking (39.5% vs 28.0%,P=0.020) were more prevalent in the delayed group compared with the non-delayed group. Conversely, the non-delayed group had a higher incidence of atrial fibrillation (37.5% vs 12.8%,P<0.001). After multivariate regression analysis, the independent predictors for the delay group were solitary OR=11.10 (95% CI 5.72-21.5), large artery atherosclerosis OR=2.63 (95% CI 1.40-4.94), presence of atrial fibrillation OR=0.41 (95% CI 0.19-0.87), and involvement of the middle cerebral artery OR=0.51 (95% CI 0.32-0.81).

Conclusions

Among patients with AIS-LVO who delay seeking medical attention for more than 24 hours, large artery atherosclerosis appears to be the predominant pathogenesis.
Landscaping of Urine Proteome: Unlocking Diagnostic Potential and Overcoming Unique Challenges
Authors: Budnik Bogdan , Amirkhani Hossein , Weinberger Klaus , Sargsyan Karine , Forouzanfar Mohammad H. , Afshin Ashkan
Published: October 2023

This study explores the application of deep proteomic profiling to extract disease-specific features from urine. Early detection of cancer and other chronic disorders is crucial for better outcomes, but traditional diagnostics as well as emerging genomic-based diagnostics are expensive and invasive. Our research reveals that a select group of urinary proteins can accurately detect early-stage diseases with high sensitivity, surpassing current tests. While urine-based protein panels could offer cost-effective and accurate alternatives to current screening methods, kidney factors and blood urine barrier pathologies could pose significant challenges. New diagnostic technologies may emerge because of these findings, ushering in an era of early detection for cancer and chronic diseases.

One-Sentence Summary

Urine-based protein panels show distinct patterns in early disease detection, promising opportunities for advancing diagnostic tests
The cytochrome P450 enzyme WsCYP71B35 fromWithania somniferahas a role in withanolides biosynthesis and defense against bacteria
Authors: Shilpashree H.B. , Narayanan Ananth Krishna , Kumar Sarma Rajeev , Barvkar Vitthal , Nagegowda Dinesh A.
Published: October 2023

The medicinal properties of Ashwagandha (Withania somniferaL. Dunal) are attributed to withanolides, which belong to the triterpenoid steroidal lactones class of compounds. Though it is proposed that intermediates of the universal phytosterol pathway are utilized by cytochrome P450 (CYP450) enzymes to form withanolides, studies on functional characterization of these enzymes has been sparse. This study reports the functional characterization of a CYP450 candidate fromW. somnifera(WsCYP71B35) that exhibited induced expression in response to methyl jasmonate treatment and showed higher expression in tissues that accumulate withanolides. Biochemical assay with yeast microsomal fraction expressing recombinant WsCYP71B35 indicated no activity when phytosterols and their intermediate 24-methylene cholesterol were used as substrates. However, WsCYP71B35 catalyzed product formation with withaferin A, withanolide A, withanolide B, and withanoside IV among the tested substrates. Moreover, virus-induced gene silencing (VIGS) and transient overexpression ofWsCYP71B35inW. somniferaleaves modulated the levels of withaferin A, withanolide A, and withanolide B, indicating the role ofWsCYP71B35in withanolides pathway. Furthermore, VIGS ofWsCYP71B35inW. somniferareduced its tolerance toPseudomonas syringae(DC3000) infection, whereas overexpression enhanced the tolerance to the bacterium inW. somniferaand transgenic tobacco. Overall, these results provide insights into the role ofW. somniferaWsCYP71B35 in withanolides biosynthesis and bacterial defense.
Biosensor capability of the endometrium is mediated in part, by altered miRNA cargo from conceptus-derived extracellular vesicles
Authors: De Bem Tiago H. C. , Bridi Alessandra , Tinning Haidee , Sampaio Rafael Vilar , Malo-Estepa Irene , Wang Dapeng , Vasconcelos Elton J. R. , Nociti Ricardo Perecin , de Ávila Ana C. F. C. M. , Sangalli Juliano Rodrigues , Motta Igor Garcia , Ataíde Gilmar Arantes , da Silva Júlio C. B. , Watanabe Yeda Fumie , Gonella-Diaza Angela , da Silveira Juliano C. , Pugliesi Guilherme , Meirelles Flávio Vieira , Forde Niamh
Published: October 2023

We tested the hypothesis that the biosensor capability of the endometrium is mediated in part, by the effect of different cargo contained in the extracellular vesicles secreted by the conceptus during the peri-implantation period of pregnancy. We transferredBos taurus taurusembryos of different origin:In vivo(high developmental potential (IV)),in vitro(intermediate developmental potential (IVF)), or cloned (low developmental potential (NT)), intoBos taurus indicusrecipients. Extracellular vesicles (EVs) recovered from Day 16 conceptus conditioned medium were characterized and their microRNA (miRNA) cargo sequenced alongside RNA sequencing of their respective endometria. There were substantial differences in the endometrial response toin vivoVsin vitroandin vivoVs cloned conceptuses (1153 and 334DEGs respectively) with limited differences betweenin vitroVs cloned conceptuses (36 DEGs). miRNA cargo was similar between all three groups (426 common cargo) differences betweenin vivoand cloned (8 miRNAs), andin vivoandin vitro(6 miRNAs) observed. Treatment of endometrial epithelial cells with mimic or inhibitors for miR-128 and miR-1298 changes to the proteomic content of target cells (96, and 85 respectively) of which mRNAs are altered in the endometriumin vivo(PLXDC2, COPG1, HSPA12A, MCM5, TBL1XR1, and TTF). In conclusion, we have determined that the biosensor capability of the endometrium is mediated in part, by its response to different EVs miRNA cargo produced by the conceptus during the peri-implantation period of pregnancy.

SIGNIFICANCE STATEMENT

During the peri-implantation period of pregnancy in mammals, the endometrium acts as a biosensor for the developmental competency of the embryo. However, the mechanism by which biosensor capability of the endometrium is established, remains elusive. In this study, we show that embryos of different developmental competencies have distinct microRNA cargo contained in their extracellular vesicles (EVs). Exposure of the endometrium to these conceptuses alters the transcriptional response of the endometrium during the process of pregnancy recognition. This differential response is mediated in part, by the delivery and action of the these differentially abundant microRNAs into EVs. Here we propose differences in EV-mediated miRNA cargo are responsible in part for this biosensor capability of the endometrium.
Transport and inhibition mechanism for VMAT2-mediated synaptic loading of monoamines
Authors: Wang Yuwei , Zhang Pei , Chao Yulin , Zhu Zhini , Yang Chuanhui , Zhou Zixuan , Li Yaohui , Long Yonghui , Liu Yuehua , Li Dianfan , Wang Sheng , Qu Qianhui
Published: October 2023

Monoamine neurotransmitters such as serotonin and dopamine are loaded by vesicular monoamine transporter 2 (VMAT2) into synaptic vesicles for storage and subsequent release in neurons. Impaired VMAT2 function underlies various neuropsychiatric diseases. VMAT2 inhibitors reserpine and tetrabenazine are used to treat hypertension, movement disorders associated with Huntington’s Disease and Tardive Dyskinesia. Despite its physiological and pharmacological significance, the structural basis underlying substrate recognition, and inhibition by varying mechanisms remains unknown. Here we present cryo-EM structures of human apo VMAT2 in addition to states bound to serotonin, tetrabenazine, and reserpine. These structures collectively capture three states, namely the lumen-facing, occluded, and cytosol-facing conformations. Notably, tetrabenazine induces a substantial rearrangement of TM2 and TM7, extending beyond the typical rocker-switch movement. These functionally dynamic snapshots, complemented by biochemical analysis, unveil the essential components responsible for ligand recognition, elucidate the proton-driven exchange cycle, and provide a framework to design improved pharmaceutics targeting VMAT2.
Machine learning of three-dimensional protein structures to predict the functional impacts of genome variation
Authors: Shukla Kriti , Idanwekhai Kelvin , Naradikian Martin , Ting Stephanie , Schoenberger Stephen P. , Brunk Elizabeth
Published: October 2023

Research in the human genome sciences generates a substantial amount of genetic data for hundreds of thousands of individuals, which concomitantly increases the number of variants with unknown significance (VUS). Bioinformatic analyses can successfully reveal rare variants and variants with clear associations to disease-related phenotypes. These studies have made a significant impact on how clinical genetic screens are interpreted and how patients are stratified for treatment. There are few, if any, comparable computational methods for variants to biological activity predictions. To address this gap, we developed a machine learning method that uses protein three-dimensional structures from AlphaFold to predict how a variant will influence changes to a gene’s downstream biological pathways. We trained state-of-the-art machine learning classifiers to predict which protein regions will most likely impact transcriptional activities of two proto-oncogenes, nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) and c-MYC. We have identified classifiers that attain accuracies higher than 80%, which have allowed us to identify a set of key protein regions that lead to significant perturbations in c-MYC or Nrf2 transcriptional pathway activities.

Significance

The vast majority of mutations are either unspecified and/or their downstream biological implications are poorly understood. We have created a method that utilizes protein structure to cluster mutations from population-scale repositories to predict downstream functional impacts. The broader impacts of this approach include advanced filtering of mutations that are likely to impact genome function.
Reconstitution of cytolinker-mediated crosstalk between actin and vimentin
Authors: Petitjean Irene Istúriz , Tran Quang D. , Goutou Angeliki , Kabir Zima , Wiche Gerhard , Leduc Cécile , Koenderink Gijsje H.
Published: October 2023

Cell shape and motility are determined by the cytoskeleton, an interpenetrating network of actin filaments, microtubules, and intermediate filaments. The biophysical properties of each filament type individually have been studied extensively by cell-free reconstitution. By contrast, the interactions between the three cytoskeletal networks are relatively unexplored. They are coupled via crosslinkers of the plakin family such as plectin. These are challenging proteins for reconstitution because of their giant size and multidomain structure. Here we engineer a recombinant actin-vimentin crosslinker protein called ‘ACTIF’ that provides a minimal model system for plectin, recapitulating its modular design with actin-binding and intermediate filament-binding domains separated by a coiled-coil linker for dimerisation. We show by fluorescence and electron microscopy that ACTIF has a high binding affinity for vimentin and actin and creates mixed actin-vimentin bundles. Rheology measurements show that ACTIF-mediated crosslinking strongly stiffens actin-vimentin composites. Finally, we demonstrate the modularity of this approach by creating an ACTIF variant with the intermediate filament binding domain of Adenomatous Polyposis Coli. Our protein engineering approach provides a new cell-free system for the biophysical characterization of intermediate filament-binding crosslinkers and for understanding the mechanical synergy between actin and vimentin in mesenchymal cells.

HIGHLIGHTS

Engineering of a recombinant actin-vimentin crosslinker called ACTIF with the plectin intermediate filament binding domain (IFBD), calponin homology domains that mediate actin binding, and a coiled-coil linker.

ACTIF crosslinks F-actin and vimentin and mediates their co-localizationin vitro.

ACTIF has a binding affinity for vimentin that is about 500 times higher than for F-actin.

ACTIF forms composite bundles of F-actin and vimentin filaments.

Composite F-actin/vimentin networks stiffen upon crosslinking with ACTIF.

The design of actin-vimentin crosslinker is modular, as other IFBDs like APCn2 can also be used.
The core microbiome of cultured Pacific oyster spat develops with age but not mortality
Authors: Cho Anna , Finke Jan F. , Zhong Kevin X. , Chan Amy M. , Saunders Rob , Schulze Angela , Warne Snehal , Miller Kristina M. , Suttle Curtis A.
Published: October 2023

The Pacific oyster (Magallana gigas, also known asCrassostrea gigas) is the most widely cultured shellfish worldwide, but production has been affected by mortality events. This includes mortality events in hatcheries that can threaten the seed supply for growers. There are several pathogens that cause disease in oysters, but in many cases mortality events cannot be attributed to a single agent, and appear to be multifactorial and involve a combination of environmental variables, microbial interactions and disbiosis. In many organisms, a mature microbiome provides resilience against pathogens and environmental stressors. In this study we investigated the microbiomes of cohorts of freshly settled oyster spat, some of which experienced notable mortality. Deep sequencing of 16S rRNA gene fragments did not show a significant difference among the microbiomes of cohorts experiencing different levels of mortality, but revealed a characteristic core microbiome with 74 taxa. Irrespective of mortality, the spat core microbiomes changed significantly in the relative abundance of taxa as the spat aged; yet, remained distinct from the microbial community in the surrounding water. The core microbiome was dominated by bacteria in the familiesRhodobacteraceae,Nitrosomonadaceae,Flavobacteriaceae, PirellulaeceaeandSaprospiraceae. Of these, 14 taxa were indicative for the change in the core microbiome, which we designated as the “Hard-Core Microbiome”. The variability in diversity and richess of members of the core taxa decreased with oyster-spat aging, implying niche occupation. The study further accounts for the exchange of microbes with surrounding water during the core microbiome development. The observed shifts in the core microbiome with ageing oyster spat implies a crucial developmental period for the core microbiome of rearing spat.

Importance

The Pacific oyster (Magallana gigas, also known asCrassostrea gigas) is the most widely cultivated shellfish and is important to the economy of many coastal communities. However, high mortality of spat during the first few days following metamorphosis can affect the seed supply to oyster growers. Here, we show that the microbiome composition of recently settled oyster spat experiencing low or high mortality were not significantly different. Instead, development of the core microbiome were associated with spat aging and was partially driven by dispersal through the water. These findings imply the importance of early stage rearing conditons for spat microbiome development in aquaculture facilities. Furthermore, shellfish growers could gain information about the developmental state of the oyster spat microbiome by assessing key taxa. Additionally, the study provides a baseline micriobiome for future hypothesis testing on developing spat.
Attention, Musicality, and Familiarity Shape Cortical Speech Tracking at the Musical Cocktail Party
Authors: Brown Jane A. , Bidelman Gavin M.
Published: October 2023

The “cocktail party problem” challenges our ability to understand speech in noisy environments, which often include background music. Here, we explored the role of background music in speech-in-noise listening. Participants listened to an audiobook in familiar and unfamiliar music while tracking keywords in either speech or song lyrics. We used EEG to measure neural tracking of the audiobook. When speech was masked by music, the modeled peak latency at 50 ms (P1TRF) was prolonged compared to unmasked. Additionally, P1TRFamplitude was larger in unfamiliar background music, suggesting improved speech tracking. We observed prolonged latencies at 100 ms (N1TRF) when speech was not the attended stimulus, though only in less musical listeners. Our results suggest early neural representations of speech are enhanced with both attention and concurrent unfamiliar music, indicating familiar music is more distracting. One’s ability to perceptually filter “musical noise” at the cocktail party depends on objective musical abilities.
Stringent Control Over Cytoplasmic and Membrane Densities Defines Cell Geometry inEscherichia coli
Authors: Chure Griffin , de Silva Roshali T. , Sharma Richa , Lanz Michael C. , Cremer Jonas
Published: October 2023

Understanding how cells regulate their growth rate, macromolecular composition, and size have been central topics in the study of microbial physiology for the better part of a century. However, we lack a mechanistic understanding of how cells so tightly coordinate biosynthesis and size control across diverse environments. In this work, we present a biophysical model of cell size control that quantitatively predicts how rod-shaped bacterial cells such asE. coliregulate their surface-to-volume ratio as a function of their composition. Central to this theory is a biochemical constraint that the protein density within the cell membranes and the macromolecular density within the cell cytoplasm are strictly controlled and kept at a constant ratiometric value. Through a reanalysis of more than 30 published data sets coupled with our own experiments, we demonstrate that this theory quantitatively predicts how the surface-to-volume ratio scales with the total RNA-to-protein ratio. We further test and confirm this theory by directly adjusting the RNA-to-protein ratio through genetic control of cellular ppGpp concentrations. This work demonstrates that cellular composition, rather than the growth rate, drives the regulation of cell geometry and provides a candidate biophysical mechanism for how cell size homeostasis is manifest.
Natural genetic variation inGLK1-mediated photosynthetic acclimation in response to light
Authors: Muino Jose M , Großmann Christopher , Kleine Tatjana , Kaufmann Kerstin
Published: October 2023

GOLDEN-like (GLK) transcription factors are central regulators of chloroplast biogenesis in Arabidopsis and other species. Findings from Arabidopsis show that these factors also contribute to photosynthetic acclimation, e.g. to variation in light intensity, and are controlled by retrograde signals emanating from the chloroplast. However, the natural variation of GLK1-centered gene-regulatory networks is largely unexplored. By evaluating the activities of GLK1 target genes and GLK1 itself in vegetative leaves of natural Arabidopsis accessions grown under standard conditions, we uncovered a remarkable variation in the activity of GLK1 centered regulatory networks. This is linked with ecogeographic origin of the accessions, and can be associated with a complex genetic variation across loci acting in different functional pathways, including photosynthesis, ROS and brassinosteroid pathways. Our results identify candidate upstream regulators that contribute to GLK1 activity in rosette leaves. Indeed, accessions with higher GLK1 activity, arising from habitats with a high monthly variation in solar radiation levels, may show lower levels of photoinhibition at higher light intensities. Our results provide evidence for natural variation in GLK1 regulatory activities in vegetative leaves. This variation is associated with ecogeographic origin and can contribute to acclimation to high light conditions.
Diversity of RNA viruses in declining Mediterranean forests
Authors: Diez-Hermano Sergio , Pérez-Alonso Pedro Luis , Morell Wilson Acosta , Niño-Sanchez Jonatan , de la Peña Marcos , Diez Julio Javier
Published: October 2023

Global change alters forestry habitats and facilitates the entry of new pathogens that don’t share a co-evolution history with the forest, leading them into a spiral of decline. As a result, relationships between forests’ organisms get disbalanced. Under this scenario, RNA viruses are of particular interest, as they participate in many of such relationships thanks to their ability to infect a wide range of hosts, even from different kingdoms of life. For this reason, the study of RNA viruses is essential to understand how viral flow across different hosts might occur, and to prevent possible outbreaks of diseases in the future. In this work the RNA virus diversity found in trees, arthropods and fungi from declining Mediterranean forests is described. To this extent, three habitats (Quercus ilex, Castanea sativaandPinus radiata) were sampled and RNAseq was performed on tree tissues, arthropods and fungi. 146 viral sequences were detected by searching for matches to conserved motifs of the RNA-dependent RNA polymerase (RdRP) using Palmscan. Up to 15 viral families were identified, with Botourmiaviridae (28.7%) and Partitiviridae (9.6%) being the most abundant. In terms of genome type, ssRNA(+) viruses were the most represented (83.5%), followed by dsRNA (15%) and two ssRNA(-) representatives. Viruses belonging to families with cross-kingdom capabilities such as Hypoviridae (1), Mitoviridae (6) and Narnaviridae (5) were also found. Distribution of viruses across ecosystems was:Q.ilex(57.5%),P.radiata(26.7%) andC.sativa(15.8%). Interestingly, two RdRP sequences had no matches in available viral databases. This work constitutes a starting point to gain insight into virus evolution and diversity occurring in forests affected by decline, as well as searching for novel viruses that might be participating in unknown infectious pathways.
Phenotypic complexities of rare heterozygous neurexin-1 deletions
Authors: Fernando Michael B. , Fan Yu , Zhang Yanchun , Tokolyi Alex , Murphy Aleta N. , Kammourh Sarah , Deans P.J. Michael , Ghorbani Sadaf , Onatzevitch Ryan , Pero Adriana , Padilla Christopher , Williams Sarah , Flaherty Erin K. , Prytkova Iya A. , Cao Lei , Knowles David A. , Fang Gang , Slesinger Paul A. , Brennand Kristen J.
Published: October 2023

Given the large number of genes significantly associated with risk for neuropsychiatric disorders, a critical unanswered question is the extent to which diverse mutations --sometimes impacting the same gene--will require tailored therapeutic strategies. Here we consider this in the context of rare neuropsychiatric disorder-associated copy number variants (2p16.3) resulting in heterozygous deletions inNRXN1, a pre-synaptic cell adhesion protein that serves as a critical synaptic organizer in the brain. Complex patterns ofNRXN1alternative splicing are fundamental to establishing diverse neurocircuitry, vary between the cell types of the brain, and are differentially impacted by unique (non-recurrent) deletions. We contrast the cell-type-specific impact of patient-specific mutations inNRXN1using human induced pluripotent stem cells, finding that perturbations inNRXN1splicing result in divergent cell-type-specific synaptic outcomes. Via distinct loss-of-function (LOF) and gain-of-function (GOF) mechanisms,NRXN1+/-deletions cause decreased synaptic activity in glutamatergic neurons, yet increased synaptic activity in GABAergic neurons. Reciprocal isogenic manipulations causally demonstrate that aberrant splicing drives these changes in synaptic activity. ForNRXN1deletions, and perhaps more broadly, precision medicine will require stratifying patients based on whether their gene mutations act through LOF or GOF mechanisms, in order to achieve individualized restoration ofNRXN1isoform repertoires by increasing wildtype, or ablating mutant isoforms. Given the increasing number of mutations predicted to engender both LOF and GOF mechanisms in brain disorders, our findings add nuance to future considerations of precision medicine.
Delineation of the pathogenic presynaptic mechanisms of synaptotagmin-1 variants
Authors: Melland Holly , Venter Kyla , Leech Stephanie L. , Ferreira Amy , Arvell Elyas H. , Baker Kate , Gordon Sarah L.
Published: October 2023

Missense variants in the presynaptic calcium sensor synaptotagmin-1 (SYT1) are associated with an autosomal dominant neurodevelopmental disorder (NDD). These cause dominant-negative impairment of evoked neurotransmitter release in a mutation-specific manner; however, whether NDD-associated variants also perturb the auxiliary functions of SYT1 remains unknown. We investigated whether the expression of SYT1 variants in cultured hippocampal neurons altered either action potential-independent spontaneous synaptic vesicle exocytosis or synaptic vesicle endocytosis. SYT1 variants did not induce dominant-negative impairment of either process, confirming that defective evoked exocytosis is the major pathogenic mechanism of SYT1-associated NDD. To examine the differential impacts of human variants on evoked exocytosis, both NDD-associated and strategic mutations were used to explore the functional importance of two distinct Ca2+-binding residues in the C2B domain. We show that both the nature of the amino acid change and the specific residues targeted determine the severity of exocytic disturbance. Together, this work informs understanding of SYT1 function and further clarifies potential mechanistic targets for treating SYT1-associated NDD.
Factors determining migration intentions in Bangladesh: from land to factory
Authors: Sohad Muhammad Kazim Nur , Celi Giuseppe , Sica Edgardo
Published: October 2023

Purpose

This article explores the migration intentions (MIs) embedded in population movements from rural to urban areas in Bangladesh. In this country, urban-centric development policies have made cities epicentres of commerce and industrialisation, offering significant employment and livelihood opportunities. This rapid transformation has generated several socio-psychological factors that are influencing the willingness of rural populations to migrate to cities for better jobs, lifestyles and services.

Design/methodology/approach

The present study adopted the theory of planned behaviour (TPB) as a conceptual model to assess the behavioural and psychological factors underlying MIs.

Findings

The results of the structural equation modelling (SEM) indicate that MIs are mainly influenced by subjective norms (SN) and, to a lesser extent, attitudes towards migration (ATM) and perceived behavioural control (PBC).

Originality/value

The analysis drew on an original dataset built through interviews with migrants from rural areas employed in the ready-made garment (RMG) industry in four selective areas of the Metropolitan City of Chittagong.
Shame on you! How incivility and absence of supporting evidence in likeminded Facebook comments influence evaluations of ingroup members and online political participation
Authors: Kim Yonghwan
Published: October 2023

Purpose

This study examined how likeminded Facebook comments with incivility and without supporting evidence influence readers' evaluations of the commenter and online political participation intention. This study also investigated whether the indirect effect of exposure to uncivil comments and comments without evidence on online political participation through evaluations of the commenters is contingent on the strength of partisanship.

Design/methodology/approach

The study used a 2 (uncivil comments vs civil comments) × 2 (comments without supporting evidence vs comments with supporting evidence) factorial design with a scenario about reading similar viewpoints about the gun control issue in Facebook comments.

Findings

The results showed that compared to exposure to civil agreeing comments, exposure to uncivil likeminded comments resulted in higher levels of negative evaluations of the commenters, which in turn decreased willingness to participate in political activities online. Exposure to comments without evidence led to more negative evaluations of the commenters, but it did not significantly influence online political participation. In addition, the strength of partisanship did not significantly moderate the indirect effect of exposure to uncivil comments and comments without evidence on online political participation through evaluations of the commenters.

Originality/value

Although previous studies have demonstrated the significant effects of incivility and reasoned argument, little is known about whether and how people evaluate ingroup members' comments that are uncivil and lacking reasoned arguments. Most of these studies have examined incivility in political contexts, but few have extended the context to the effect of likeminded comments, especially when the comments are uncivil and lack supporting evidence. The current study aims to fill this gap in the literature.
Palliative radiotherapy is effective for both well‐ and poorly differentiated neuroendocrine neoplasms
Authors: O'Reilly Eileen , Lao Louis , Woodhouse Braden , Sharples Katrina , Print Cris , Lawrence Ben
Published: October 2023

Introduction

The outcomes of palliative radiation therapy (RT) for neuroendocrine neoplasms (NEN) are seldom reported. We investigated outcomes following palliative radiotherapy in a cohort of patients with NENs. We hypothesised that well‐differentiated NEN will be less likely to have a clinical response than poorly differentiated NEN.

Methods

Patients who received at least one course of palliative RT were identified using the New Zealand NETwork! Registry. Patients with Merkel cell carcinoma, pulmonary small cell carcinoma or asymptomatic patients were excluded. Clinical response to RT within 90 days and overall survival were analysed alongside clinical variables (fractionation, RT site, tumour differentiation and tumour primary site).

Results

The cohort comprised 79 patients, with 147 courses of palliative RT delivered. Clinical response was measurable for 100 courses, with clinical response rate of 76%. A course delivered to a well‐differentiated NEN was associated with 2.02‐fold (95% CI 0.67, 6.12; P = 0.21) increase in odds of a clinical response compared to a poorly differentiated NEN. Median overall survival from the first fraction of RT was 94 days (95% CI 80, 138 days). Overall survival was higher in well‐differentiated NEN than in poorly differentiated NEN (HR 0.2, 95% CI 0.10–0.40, P‐value < 0.001); 30‐day mortality was 7%. There were significantly reduced odds of clinical response for non‐bone sites, and for courses >10 fractions compared to a single fraction.

Conclusion

Palliative RT is an appropriate option for management of symptoms in patients with both well‐ and poorly differentiated metastatic NEN.
Under what conditions do gender differences exist in power and achievement values? The moderating role of gender ideology
Authors: Prati Gabriele , Stefani Serena
Published: October 2023

Previous studies revealed differences between men and women in value priorities. It has been asserted that men do inherently attribute more importance than women to power and achievement values. Our study brings a sociocultural lens into account employing gender ideology as a moderator of the gender differences in these values. Specifically, we hypothesized that internalization and endorsement of gender role ideology shape gender differences in power and achievement values. We focused on two components of gender ideology as moderators of the gender differences in values: primacy of the breadwinner role, and acceptance of male privilege. We used data from the World Values Survey wave six (89,565 participants from 60 countries). Results indicated that gender ideology moderated the relationship between gender and the endorsement of achievement and power values. Specifically, the relationship between gender and achievement was significantly moderated by acceptance of male privilege, but not of primacy of the breadwinner role. In addition, the association between gender and power was significantly moderated by primacy of the breadwinner role, but not by acceptance of male privilege. In other words, when participants endorse egalitarian gender ideologies, gender differences in power and achievement disappear or even reverse. We contrast previous perspectives assuming inherent gender differences in human values and argue that such differences are related to beliefs in gendered separate spheres.
Governing European educational research through ideas? Incremental ideational change in the European Union's Framework Programme (1994–2020)
Authors: Marques Marcelo
Published: October 2023

The European Union Framework Programme (EUFP) is the most institutionalised form of supranational thematic programming in the world and the centrepiece of European Union research policy. Since 1994, the EUFP has also funded collaborative research projects in the social sciences. Surprisingly, little attention has been paid to its genesis, development, and effects in shaping the development of European science, especially examined by discipline or multidisciplinary fields. The EUFP is thus analysed here through an instruments‐as‐institutions approach that conceptualises the EUFP as an institution. Content analysis of the official documents of each funding cycle (n = 5) and a sample of European‐funded educational research projects (n = 122) was analysed in conducting this research. The results show incremental ideational change of the EUFP's guiding ideas: from knowledge as an instrument to knowledge as a resource; within‐the‐EU to outside‐the‐EU internationalisation; and cooperation to an integration rationale of Europeanisation from the EUFP4 and EUFP5 (1994–2002) to the EUFP6 onwards (2002–2020). European‐funded educational research contents are shaped by such representations of what is expected of European research. If the policy instrument steers European‐funded educational research, ideas more than regulatory features significantly—though incrementally—change the direction of European social science.