bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of non-neutral synonymous mutations when inferring selection on non-synonymous mutations
Authors: Martinez i Zurita Aina , Kyriazis Christopher C. , Lohmueller Kirk E.
Published: February 2024

The distribution of fitness effects (DFE) describes the proportions of new mutations that have different effects on reproductive fitness. Accurate measurements of the DFE are important because the DFE is a fundamental parameter in evolutionary genetics and has implications for our understanding of other phenomena like complex disease or inbreeding depression. Current computational methods to infer the DFE for nonsynonymous mutations from natural variation first estimate demographic parameters from synonymous variants to control for the effects of demography and background selection. Then, conditional on these parameters, the DFE is then inferred for nonsynonymous mutations. This approach relies on the assumption that synonymous variants are neutrally evolving. However, some evidence points toward synonymous mutations having measurable effects on fitness. To test whether selection on synonymous mutations affects inference of the DFE of nonsynonymous mutations, we simulated several possible models of selection on synonymous mutations using SLiM and attempted to recover the DFE of nonsynonymous mutations using Fit∂a∂i, a common method for DFE inference. Our results show that the presence of selection on synonymous variants leads to incorrect inferences of recent population growth. Furthermore, under certain parameter combinations, inferences of the DFE can have an inflated proportion of highly deleterious nonsynonymous mutations. However, this bias can be eliminated if the correct demographic parameters are used for DFE inference instead of the biased ones inferred from synonymous variants. Our work demonstrates how unmodeled selection on synonymous mutations may affect downstream inferences of the DFE.
Tension-induced adhesion mode switching: the interplay between focal adhesions and clathrin-containing adhesion complexes
Authors: Djakbarova Umida , Madraki Yasaman , Chan Emily T. , Wu Tianyao , Atreaga-Muniz Valeria , Akatay A. Ata , Kural Comert
Published: February 2024

Integrin-based adhesion complexes are crucial in various cellular processes, including proliferation, differentiation, and motility. While the dynamics of canonical focal adhesion complexes (FAs) have been extensively studied, the regulation and physiological implications of the recently identified clathrin-containing adhesion complexes (CCACs) are still not well understood. In this study, we investigated the spatiotemporal mechanoregulations of FAs and CCACs in a breast cancer model. Employing single-molecule force spectroscopy coupled with live-cell fluorescence microscopy, we discovered that FAs and CCACs are mutually exclusive and inversely regulated complexes. This regulation is orchestrated through the modulation of plasma membrane tension, in combination with distinct modes of actomyosin contractility that can either synergize with or counteract this modulation. Our findings indicate that increased membrane tension promotes the association of CCACs at integrin αVβ5 adhesion sites, leading to decreased cancer cell proliferation, spreading, and migration. Conversely, lower membrane tension promotes the formation of FAs, which correlates with the softer membranes observed in cancer cells, thus potentially facilitating cancer progression. Our research provides novel insights into the biomechanical regulation of CCACs and FAs, revealing their critical and contrasting roles in modulating cancer cell progression.
Mechanistic models of humoral kinetics following COVID-19 vaccination
Authors: Stocks Daniel , Thomas Amy , Finn Adam , Danon Leon , Brooks-Pollock Ellen
Published: February 2024

Introduction

Future COVID-19 vaccine programmes need to take into account the variable responses elicited by different vaccines and their waning protection over time. Existing descriptions of antibody response to COVID-19 vaccination convey limited information about the mechanisms of antibody production and maintenance.

Methods

We describe the antibody dynamics elicited by COVID-19 vaccination with two biologically-motivated mathematical models of antibody production by plasma cells and subsequent decay. We fit the models using Markov Chain Monte Carlo to seroprevalence data from 14,602 uninfected individuals collected via the primary care network in England between May 2020 and September 2022. We ensure our models are structurally and practically identifiable when using antibody data alone. We analyse the effect of age, vaccine type, number of doses, and the interval between doses on antibody production and longevity of response.

Results

We find evidence that individuals over 35 years of age who received a second dose of ChAdOx1-S generate a persistent antibody response suggestive of long-lived plasma cell induction, while individuals that receive two doses of BNT162b2, or one dose of either vaccine do not. We also find that plasamblast productive capacity, the likely driver of short-term antibody responses, is greater in younger people than older people (≤ 4.5 fold change in point estimates), people vaccinated with two doses than people vaccinated with one dose (≤ 12 fold change), and people vaccinated with BNT162b2 than people vaccinated with ChAdOx1-S (≤ 440 fold change). The effect of age on antibody dynamics is more pronounced in people vaccinated with BNT162b2 than people vaccinated with ChAdOx1-S. We find the half-life of an antibody to be between 23 – 106 days.

Conclusion

Routinely-collected seroprevalence data are a valuable source of information for characterising within-host mechanisms of antibody production and persistence. Extended sampling and linking seroprevalence data to outcomes would allow for powerful conclusions about how humoral kinetics protect against disease.
Multimodal Hox5 activity generates motor neuron diversity
Authors: KC Ritesh , López de Boer Raquel , Lin Minshan , Jeannotte Lucie , Philippidou Polyxeni
Published: February 2024

Motor neurons (MNs) are the final output of circuits driving fundamental behaviors, such as respiration and locomotion. Hox proteins are essential in generating the MN diversity required for accomplishing these functions, but the transcriptional mechanisms that enable Hox paralogs to assign distinct MN subtype identities despite their promiscuous DNA binding motif are not well understood. Here we show that Hoxa5 controls chromatin accessibility in all mouse spinal cervical MN subtypes and engages TALE co-factors to directly bind and regulate subtype-specific genes. We identify a paralog-specific interaction of Hoxa5 with the phrenic MN-specific transcription factor Scip and show that heterologous expression of Hoxa5 and Scip is sufficient to suppress limb-innervating MN identity. We also demonstrate that phrenic MN identity is stable after Hoxa5 downregulation and identify Klf proteins as potential regulators of phrenic MN maintenance. Our data identify multiple modes of Hoxa5 action that converge to induce and maintain MN identity.
Unveiling the regulatory network controlling natural transformation in lactococci
Authors: Toussaint Frédéric , Henry de Frahan Marie , Poncelet Félix , Ladrière Jean-Marc , Horvath Philippe , Fremaux Christophe , Hols Pascal
Published: February 2024

Lactococcus lactisis a lactic acid bacterium of major importance for food fermentation and biotechnological applications. The ability to manipulate its genome quickly and easily through competence for DNA transformation would accelerate its general use as a platform for a variety of applications. Natural transformation in this species requires the activation of the master regulator ComX. However, the growth conditions that lead to spontaneous transformation, as well as the regulators that control ComX production, are unknown. Here, we identified the carbon source, nitrogen supply, and pH as key factors controlling competence development in this species. Notably, we showed that these conditions are sensed by three global regulators (i.e., CcpA, CodY, and CovR), which represscomXtranscription directly. Furthermore, our systematic inactivation of known signaling systems suggests that classical pheromone-sensing regulators are not involved. Finally, we discovered that the ComX-degrading MecA-ClpCP machinery plays a predominant role based on the identification of a single amino-acid substitution in the adaptor protein MecA of a highly transformable strain. Contrasting with closely-related streptococci, the master competence regulator inL. lactisis regulated both proximally by general sensors and distantly by the Clp degradation machinery. This study not only highlights the diversity of regulatory networks for competence control in Gram-positive bacteria, but it also paves the way for the use of natural transformation as a tool to manipulate this biotechnologically important bacterium.

IMPORTANCE

Lactic acid bacteria (LAB) play important roles in our daily lives as members of our microbiota or as starters of dairy products. Understanding the natural horizontal gene transfer mechanisms that shape their genomes will allow us to better control and understand their evolution over time. The DNA transformation machinery is found in all beneficial LAB species. With the exception of streptococci, however, the conditions of its activation remain unknown. In this study, the physiological conditions that activate competence for DNA transformation inLactococcus lactis, the most important lactococcal species, were identified. We also unveiled the guardians of the master competence regulator ComX. In this species, it is directly repressed by global carbon and nitrogen regulators (CcpA and CodY) as well as the general stress system CovRS. Additionally, it was discovered that the Clp machinery degrading ComX plays a dominant role in the strict control of competence activation. In Gram-positive cocci, the hierarchical organization of these regulators for controlling competence development inL. lactisis unprecedented.
Transcription factors across theEscherichia colipangenome: a 3D perspective
Authors: Moreno-Hagelsieb Gabriel
Published: February 2024

Motivation

Identification of complete sets of transcription factors (TFs) is a foundational step in the inference of genetic regulatory networks. With the availability of high-quality predictions of protein three-dimensional structures (3D), it has become possible to use structural comparisons for the inference of homology beyond what is possible from sequence analyses alone. This work explores the potential to use predicted 3D structures for the identification of TFs in theEscherichia colipangenome.

Results

Comparisons between predicted structures and their experimentally confirmed counterparts confirmed the high-quality of predicted structures, with most 3D structural alignments showing TM-scores well above established structural similarity thresholds, though the quality seemed slightly lower for TFs than for other proteins. As expected, structural similarity decreased with sequence similarity, though most TM-scores still remained above the structural similarity threshold. This was true regardless of the aligned structures being experimental or predicted. Results at the lowest sequence identity levels revealed potential for 3D structural comparisons to extend homology inferences below the “twilight zone” of sequence-based methods. The body of predicted 3D structures covered 99.7% of available proteins from theE. colipangenome, missing only two of those matching TF domain sequence profiles. Structural analyses increased the inferred TFs in theE. colipangenome by 18% above the amount obtained with sequence profiles alone.
Experience and behavior modulate piriform cortex odor representation in freely moving mice
Authors: Chapman Ian F. , Raymond Martin A. , Fletcher Max L.
Published: February 2024

In rodents, activity in the piriform cortex (PC) has been shown to reliably encode the identity of olfactory information within single sessions of odor delivery. However, recent evidence from chronic PC recordings found significant unreliability in this ensemble code over longer periods. The causes of this phenomenon, termed representational drift, are still being investigated across multiple sensory systems, but prior work has suggested a role for animal behavior in this observed unreliability of coding. To explore this possibility in PC, we recorded from the same populations of neurons in freely-moving, awake mice using micro-endoscopic calcium imaging as they gained passive experience with a panel of odorants over 5 consecutive days. As in prior studies, PC odor responses within a single session could be used to accurately decode odor identity. However, responses became less consistent across days of experience as odor-evoked response properties of the neurons shifted with experience. During these recordings, within and across sessions, decreases in olfactory investigative behavior correlated with decreased odor-evoked response from PC neurons. Similarly, decreases in odor investigation correlated with a decrease in representational consistency, and trials with greater odor investigation could be used to decode odor identity from PC neurons more accurately over time. Overall, this data supports recent evidence of long-term shifts in the ensembles of PC neurons encoding odor-identity (drift) but supports a role for behavioral modulation of overall PC activity and ensemble response consistency.
Learning within a sensory-motor circuit links action to expected outcome
Authors: Zhou WenXi , Schneider David M.
Published: February 2024

The cortex integrates sound- and movement-related signals to predict the acoustic consequences of behavior and detect violations from expectations. Although expectation- and prediction-related activity has been observed in the auditory cortex of humans, monkeys, and mice during vocal and non-vocal acoustic behaviors, the specific cortical circuitry required for forming memories, recalling expectations, and making predictions remains unknown. By combining closed-loop behavior, electrophysiological recordings, longitudinal pharmacology, and targeted optogenetic circuit activation, we identify a cortical locus for the emergence of expectation and error signals. Movement-related expectation signals and sound-related error signals emerge in parallel in the auditory cortex and are concentrated in largely distinct neurons, consistent with a compartmentalization of different prediction-related computations. On a trial-by-trial basis, expectation and error signals are correlated in auditory cortex, consistent with a local circuit implementation of an internal model. Silencing the auditory cortex during motor-sensory learning prevents the emergence of expectation signals and error signals, revealing the auditory cortex as a necessary node for learning to make predictions. Prediction-like signals can be experimentally induced in the auditory cortex, even in the absence of behavioral experience, by pairing optogenetic motor cortical activation with sound playback, indicating that cortical circuits are sufficient for movement-like predictive processing. Finally, motor-sensory experience realigns the manifold dimensions in which auditory cortical populations encode movement and sound, consistent with predictive processing. These findings show that prediction-related signals reshape auditory cortex dynamics during behavior and reveal a cortical locus for the emergence of expectation and error.
Repetition in Social Contact Interactions: Implications in Modelling the Transmission of Respiratory Infectious Diseases in Pre-pandemic & Pandemic Settings
Authors: Loedy Neilshan , Wallinga Jacco , Hens Niel , Torneri Andrea
Published: February 2024

The spread of viral respiratory infections is intricately linked to human interactions, and this relationship can be characterised and modelled using social contact data. However, many analyses tend to overlook the recurrent nature of these contacts. To bridge this gap, we undertake the task of describing individuals’ contact patterns over time, by characterising the interactions made with distinct individuals during a week. Moreover, we gauge the implications of this temporal reconstruction on disease transmission by juxtaposing it with the assumption of random mixing over time. This involves the development of an age-structured individual-based model, utilising social contact data from a pre-pandemic scenario (the POLYMOD study) and a pandemic setting (the Belgian CoMix study), respectively. We found that accounting for the frequency of contacts impacts the number of new, distinct, contacts, revealing a lower total count than a naive approach, where contact repetition is neglected. As a consequence, failing to account for the repetition of contacts can result in an underestimation of the transmission probability given a contact, potentially leading to inaccurate conclusions when using mathematical models for disease control. We therefore underscore the necessity of acknowledging the longitudinal nature of contacts when formulating effective public health strategies.
Staff responses to management control systems changes in an Australian university
Authors: Billah Mamun , Ahmed Zahir Uddin , Ali Mohobbot
Published: February 2024

Purpose

This study aims to examine staff responses to management control systems (MCS) changes in an Australian university. Through the analysis of the category of staff responses, it aims to understand the perception gaps among the staff at different levels of the university.

Design/methodology/approach

Using a case study approach on an Australian university, data was collected from interviews with staff across three hierarchical levels to explore their behavioural responses.

Findings

This study finds that staff at all levels largely complied with MCS changes due to institutional enforcement. Top management emphasised aligning with government policies and funding, often using manipulation and compartmentalisation tactics in implementing the new MCS. Mid-level managers generally favour research strategies but feel excluded from decision-making and have limited influence over funding. They adopted a balancing tactic within a compromise strategy. Meanwhile, operating-level academics had mixed experiences, feeling largely powerless in influencing MCS while also showing instances of self-motivated compliance. Overall, the study reveals varying responses across different hierarchical levels, highlighting the complexities of MCS changes in staff behaviour and attitudes.

Research limitations/implications

The insights from this study can guide university administrators and policymakers in understanding the intricate variations in staff reactions to institutional changes. By recognising the factors that drive compliance and defiance, institutions can better navigate and implement changes in MCS.

Originality/value

This research offers a unique perspective on the behavioural side of MCS changes in higher education. By focusing on varied hierarchical levels within a university, the study provides a granular understanding of individual responses, enriching the existing literature on MCS transitions in academia.
The social construction of anti-tourism protest in tourist cities: a case study of Barcelona
Authors: González-Reverté Francesc , Soliguer Guix Anna
Published: February 2024

Purpose

Focusing on critical discourse analysis, this paper aims to propose a framework for analysing the way activist anti-tourism groups construct their social action of protest. The authors argue that activist groups use different narrative strategies to construct and legitimise their discourse of protest to convey social meanings for social action practices. This study represents an attempt to explain how anti-tourism activist groups have the agency to build different paradigms of protest rooted in particular views of tourism.

Design/methodology/approach

As a result of the lack of research in this area, this study used a comparative case study methodology drawn on four case studies in the field of anti-tourism protest. Case study is deemed adequate to explore a complex social phenomenon, how activist groups differ from each other, in a specific socio-economic context. A critical discourse analysis method is used to study primary (interviews) and secondary sources (reports, websites and online campaigns documents) of information, which express the activist group motivations and objectives to protest against tourism.

Findings

This study’s findings provide evidence in how discourse differs among the protest groups. Three narrative paradigms of protest are identified, which guide their agency: scepticism, based on a global and ecological approach; non-interventionist transformation, rooted in local community issues; and direct transformation, based on a sectoral problem-solving approach. These differences are interpreted as the consequences of the emergence and the development of different paths of protest according to specific social contexts and power relations in which anti-tourism groups are embedded.

Originality/value

This paper provides a contemporary approach to anti-tourism activism within the context of social movements. This case study may be of interest to practitioners and international destination managers interested in gaining a better understanding of anti-tourism protest strategies, new anti-tourism narratives following COVID-19 and the opportunities and challenges for opening a dialogue with those involved in activism and social urban movements as part of sustainable tourism governance. Our results can also help activists to rethink how they integrate differences and particular strategic positions to avoid hindering collective action. This knowledge is especially useful for managers and authorities seeking to develop more accurate collaborative governance practices with local activists, and especially those interested in fostering participative action without marginalising the diverse range of local community perspectives.
Experimental study on adhesion recovery based on a circumferential test rig
Authors: Zhou Jiajun , Chen Chao , Tian Chun , Zhai Gengwei , Yu Hao
Published: February 2024

Purpose

To authenticate the existence and principles of the adhesion recovery phenomenon under water pollution conditions, an innovative circumferential rail–wheel adhesion test rig was used. The study conducted extensive tests on the adhesion characteristics under large sliding conditions.

Design/methodology/approach

Experiments were conducted to investigate the influence of speed, axle load and slip on adhesion recovery. Based on the experimental results, the adhesion recovery transition function was re-fitted.

Findings

The study reveals that the adhesion recovery phenomenon truly exists under water conditions. The adhesion coefficient shows an increasing trend with the growth of the slip ratio. Moreover, at the current speed and axle load levels, the adhesion recovery is directly proportional to the square of the slip ratio and inversely proportional to the axle load.

Originality/value

The phenomenon of adhesion recovery and the formulated equations in this study can serve as an experimental and theoretical foundation for the design of braking and anti-skid control algorithms for trains.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-11-2023-0379/
Performance appraisal process as a determinant of employee commitment: a serial mediation analysis
Authors: Ambilichu Charles Anyeng , Akaighe Godbless Onoriode , Pepple Dennis Gabriel
Published: February 2024

Purpose

This study draws on Organisation Justice Theory and Social Exchange Theory to examine the effects of the performance appraisal process (PAP) on employee commitment (ECO) via a serial mediation of performance appraisal outcome (PAO) and employee reward (ERE).

Design/methodology/approach

Survey data were collected from a sample of 363 academics across UK Higher Education Institutions (HEIs), including post-1992 and pre-1992 universities. We tested our hypotheses using partial least squares structural equation modeling (PLS-SEM) with a bias-corrected bootstrapping method.

Findings

The findings show that the PAP positively influences ECO and ERE. PAO and ERE mediate the relationship between the PAP and ECO. However, no significant relationship was found between PAO and ECO.

Practical implications

This study has significant implications for HEIs as it underscores the need for managers to ensure the clarity and accuracy of the PAP and to structure rewards to reflect employees’ efforts, considering they affect ECO.

Originality/value

This study contributes to the current debate on performance appraisal by highlighting the extent to which employees’ commitment to an organisation depends on the PAP, PAO and reward.
Accounting in the shadows of tradition: the role of national culture
Authors: Zahid R.M. Ammar , Khan Muhammad Kaleem , Demir Volkan
Published: February 2024

Purpose

Current research aims to investigate the relationships between Chinese national cultural values (uncertainty avoidance (UA), power distance, masculinity (MAS), individualism (IDV) and Confucian dynamism) and accounting practices (professionalism, uniformity, conservatism and secrecy).

Design/methodology/approach

A sample of 842 users/preparers of financial statements participated in this cross-sectional, questionnaire-based survey from China. Covariance-based structural equation modeling (CB-SEM) was used to test the proposed relationship.

Findings

Results show that cultural values strongly impact financial reporting practices in China. Chinese society is characterized by low UA, high power distance, collectivism, future orientation (Confucianism) and masculine traits. These values show an overall preference for uniformity, conservatism and secrecy in financial reporting with weak professionalism. The findings show that Chinese society emphasizes law abidance, strict codes of conduct, written rules and regulations and respect for consistent orthodox measures.

Practical implications

This study provides valuable input for policymakers in developing regulations and accounting standards in the Chinese market. Understanding the relationship between cultural dimensions and accounting values helps to address societal challenges and align policies with cultural values to acquire desired financial reporting values. Global firm managers must consider cultural dimensions in accounting when entering Chinese markets or negotiating with partners from different cultures. Findings also suggest local managers gain self-awareness of their cultural biases and accounting values, enabling them to navigate businesses and society's financial reporting needs.

Originality/value

This study enriches the existing literature on cultural and accounting practice studies by validating the role of stakeholder and social contract theories in Gray–Hofstede’s framework and highlighting the influence of dominant cultural values on accounting values. The study provides a unique empirical analysis of the Chinese market by using a questionnaire survey and structural equation modeling (SEM). Further, it also opens avenues for future research on the relationship between cultural dimensions, accounting practices and their global impact. These findings emphasize the importance of cultural sensitivity and adaptability, especially in multicultural environments.
Perceived psychological status among family caregivers of an autistic child: the role of coping strategies and self-esteem as predictors
Authors: Hasan Abd Alhadi , ALsulami Amal
Published: February 2024

Purpose

The purpose of this study is to assess psychological distress among parents of children with autism spectrum disorder (ASD), self-esteem as a predictor of such distress and the effect of coping strategies.

Design/methodology/approach

A descriptive correlational study design was conducted using a convenient sample of parents of ASD children (N = 93).

Findings

This study revealed that the parents of an ASD child experienced a high level of anxiety (M = 15.89), a moderate level of depression (M = 15.85) and a mild level of stress (M = 16.86). Parents of ASD children also reported a low self-esteem score (M= 13.27). Mothers of ASD children reported higher levels of psychological distress, lower levels of self-esteem and more frequent utilisation of maladaptive coping strategies than fathers of ASD children.

Practical implications

Parents of children with ASD experience a significant level of psychological distress; however, this may be improved by developing programmes and psychological interventions focused on improving parents’ self-esteem and using more active coping strategies.

Originality/value

To the best of the authors’ knowledge, this is the first study conducted in Saudi Arabia that predict the psychological status among family caregivers of an autistic child.
Policy Interventions to Enhance Medical Care for People With Obesity in the United States—Challenges, Opportunities, and Future Directions
Authors: JOLIN JAMES RENÉ , KWON MINSOO , BROCK ELIZABETH , CHEN JONATHAN , KOKAN AISHA , MURDOCK RYAN , STANFORD FATIMA CODY
Published: February 2024

Policy Points

Health policymakers have insufficiently addressed care for people with obesity (body mass index ≥ 30 kg/m2) in the United States. Current federal policies targeting obesity medications reflect this unfortunate reality.

We argue for a novel policy framework to increase access to effective obesity therapeutics and care, recognizing that, though prevention is critical, the epidemic proportions of obesity in the United States warrant immediate interventions to augment care.

Reducing barriers to and improving the quality of existing anti‐obesity medications, intensive behavioral therapy, weight management nutrition and dietary counseling, and bariatric surgery are critical. Moreover, to ensure continuity of care and patient–clinician trust, combating physician and broader weight stigma must represent a central component of any viable obesity care agenda.
Combining UHPLC‐HRMS targeted and suspect screening for a comprehensive analysis of nisin A and its variants in cow milk
Authors: Rocchetti Gabriele , Bellassi Paolo , Morelli Lorenzo , Lucini Luigi
Published: February 2024

A liquid chromatography method coupled with an Orbitrap analyser was used to detect nisin A and its variants in partially skimmed and raw cow milk. A suspect screening method enabled the identification of F, Q and Z variants. Adequate linearity was achieved (r2 = 0.9998–1 up to 250 μg/L) with a limit of quantitation for nisin A of 2.5 μg/L. Method accuracy (at 2.5, 25 and 250 μg/L) in milk ranged from 94 to 98% and precision in the range 0.4–1.9%. Nisin Z was abundant in partially skimmed samples. The method was suitable for determining these bacteriocins in cow milk.
Myofibrillar myopathies due to a novel mutation in exon 8 of the LDB3 gene
Authors: Du Hongjia , Chen Yan , Zeng Li , Wu Rui , Wu Tong , Zhu Jing
Published: February 2024

Myofibrillar myopathies (MFMs) are a group of genetically heterogeneous diseases affecting the skeletal and cardiac muscles. Myofibrillar myopathies are characterized by focal lysis of myogenic fibers and integration of degraded myogenic fiber products into inclusion bodies, which are typically rich in desmin and many other proteins. Herein, we report a case of a 54‐year‐old woman who experienced bilateral thigh weakness for over three years. She was diagnosed with MFMs based on muscle biopsy findings and the presence of a novel mutation in exon 8 of the LDB3 gene. Myofibrillar myopathies caused by a mutation in the LDB3 gene are extremely uncommon and often lack distinct clinical characteristics and typically exhibit a slow disease progression. When considering a diagnosis of MFMs, particularly in complex instances of autosomal dominant myopathies where muscle biopsies do not clearly indicate MFMs, it becomes crucial for clinicians to utilize genetic test as a diagnostic tool.
Morphine exposure modulates dimensional bias and set formation in anthropoids
Authors: Ghasemian Sadegh , Pascoe Alexander J. , Vardanjani Marzieh M. , Haque Zakia Z. , Ignatavicius Anna , Fehring Daniel J. , Sheibani Vahid , Mansouri Farshad A.
Published: February 2024

Humans demonstrate significant behavioural advantages with particular perceptual dimensions (such as colour or shape) and when the relevant dimension is repeated in consecutive trials. These dimension‐related behavioural modulations are significantly altered in neuropsychological and addiction disorders; however, their underlying mechanisms remain unclear. Here, we studied whether these behavioural modulations exist in other trichromatic primate species and whether repeated exposure to opioids influences them. In a target detection task where the target‐defining dimension (colour or shape) changed trial by trial, humans exhibited shorter response time (RT) and smaller event‐related electrodermal activity with colour dimension; however, macaque monkeys had shorter RT with shape dimension. Although the dimensional biases were in the opposite directions, both species were faster when the relevant dimension was repeated, compared with conditions when it changed, across consecutive trials. These indicate that both species formed dimensional sets and that resulted in a significant ‘switch cost’. Scheduled and repeated exposures to morphine, which is analogous to its clinical and recreational use, significantly augmented the dimensional bias in monkeys and also changed the switch cost depending on the relevant dimension. These cognitive effects occurred when monkeys were in abstinence periods (not under acute morphine effects) but expressing significant morphine‐induced conditioned place preference. These findings indicate that significant dimensional biases and set formation are evolutionarily preserved in humans' and monkeys' cognition and that repeated exposure to morphine interacts with their manifestation. Shared neural mechanisms might be involved in the long‐lasting effects of morphine and expression of dimensional biases and set formation in anthropoids.
Termites are key drivers of short‐term deadwood decay in Neotropical Cerrado across vegetation types
Authors: D'Angioli André M. , Zanne Amy E. , Constantino Reginaldo , Verona Larissa S. , Oliveira Rafael S.
Published: February 2024

The impact of deadwood in ecosystems is dependent on its longevity, as determined by decay rates controlled by decay agents. Despite the importance of macroclimate, significant variation of decay rates within a given macroclimatic envelope has been reported. Such variation may be driven by local‐scale microenvironmental conditions as regulated by the plant community structure as well as the presence of specific biotic and abiotic decay agents, decoupling the relation between macroclimate conditions and deadwood decay rates. In this study, we evaluated the relation between local‐scale variation in plant community structure with the decay rates of deadwood and the relative importance of biotic and abiotic decay agents in deadwood decay in Neotropical Cerrado. For this, we performed a wood mass loss experiment using Pinus taeda wood which was installed at three sites in three vegetation types differing in canopy cover—grasslands, savannas and woodlands; wood was divided into treatments according to deadwood exposure to decay agents—microorganism, termite and solar radiation. Across sites, we found termites and microbes decomposed wood twice as fast as microbes alone, while solar radiation was not a strong driver of deadwood decay in our sites. Additionally, local‐scale variation in plant community structure affected deadwood decay, as decay rates and frequency of wood blocks discovered by termites were lower in woodlands than in grasslands and savannas. Our study highlights the interactive effects of local‐scale variation in plant community structure and termites on deadwood turnover, mainly due to differences in termite foraging behaviour among vegetation types and highlights the key role of termites in deadwood decay throughout Neotropical savannas.
A multi‐analytical approach applied to pottery from Oman as a key to understanding ancient Indian Ocean maritime trade
Authors: Zampierin Daniele , Moita Patrícia , Lischi Silvia , van Aerde Marike , Barrulas Pedro , Mirão José
Published: February 2024

The populations in Sumhuram (third/second century bce to fifth century ce) and Hamr al‐Sharqiya 1 (HAS1) (first millennium bce to first/second century ce) were involved in one of the most important examples of large‐scale trade systems in antiquity: the maritime network connecting the coasts of the Indian Ocean. This research focuses on a total of 35 southwestern Arabian and Indian pottery sherds from both the settlements of Sumhuram and Hamr al‐Sharqiya 1, analysed through a multi‐analytical complementary approach. This study intends to test the input potential of this type of approach applied to ceramics in the context of the Indian Ocean trade network. The techniques adopted are powder X‐ray diffraction, optical microscopy, inductively coupled plasma–mass spectrometry and scanning electron microscopy coupled with energy‐dispersive X‐ray spectroscopy. The results obtained allow the identification of eight distinct groups, each characterized by unique (textural, mineralogical, geochemical) signatures, providing specific clues for determining their provenance, specifically from the Indian subcontinent and southwestern Arabia. This paper shows the importance of this type of archaeometric study that must be integrated into a transdisciplinary approach.
Determinants of early change in serum creatinine after initiation of dolutegravir‐based antiretroviral therapy in South Africa
Authors: Mpofu Rephaim , Kawuma Aida N. , Wasmann Roeland E. , Akpomiemie Godspower , Chandiwana Nomathemba , Sokhela Simiso Mandisa , Moorhouse Michelle , Venter Willem Daniel Francois , Denti Paolo , Wiesner Lubbe , Post Frank A. , Haas David W. , Maartens Gary , Sinxadi Phumla
Published: February 2024

Aims

Dolutegravir increases serum creatinine by inhibiting its renal tubular secretion and elimination. We investigated determinants of early changes in serum creatinine in a southern African cohort starting first‐line dolutegravir‐based antiretroviral therapy (ART).

Methods

We conducted a secondary analysis of data from participants in a randomized controlled trial of dolutegravir, emtricitabine and tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide fumarate (TAF) (ADVANCE, NCT03122262). We assessed clinical, pharmacokinetic and genetic factors associated with change in serum creatinine from baseline to Week 4 using linear regression models adjusted for age, sex, baseline serum creatinine, HIV‐1 RNA concentration, CD4 T‐cell count, total body weight and co‐trimoxazole use.

Results

We included 689 participants, of whom 470 had pharmacokinetic data and 315 had genetic data. Mean change in serum creatinine was 11.3 (SD 9.9) μmol.L−1. Factors that were positively associated with change in serum creatinine at Week 4 were increased log dolutegravir area under the 24‐h concentration–time curve (change in creatinine coefficient [β] = 2.78 μmol.L−1 [95% confidence interval (CI) 0.54, 5.01]), TDF use (β = 2.30 [0.53, 4.06]), male sex (β = 5.20 [2.92, 7.48]), baseline serum creatinine (β = −0.22 [−0.31, −0.12]) and UGT1A1 rs929596 A→G polymorphism with a dominant model (β = −2.33 [−4.49, −0.17]). The latter did not withstand correction for multiple testing.

Conclusions

Multiple clinical and pharmacokinetic factors were associated with early change in serum creatinine in individuals initiating dolutegravir‐based ART. UGT1A1 polymorphisms may play a role, but further research on genetic determinants is needed.
What curves are parallel? The core feature of preschoolers’ intuitive parallel category
Authors: Gao Shaojing , Hu Qingfen
Published: February 2024

Existing evidence has revealed that humans can spontaneously categorize many geometric shapes without formal education. Children around 4 years could distinguish between intersecting lines and parallel lines. Three features can be used to identify parallel lines, namely “translational congruence,” “never meet,” and “constant distance.” This study separated them by using pairs of curves that possess only one of these features. Two experiments across 2021–2023, respectively, compared the relative priority of “translational congruence” with “constant distance,” and “never meet” with “constant distance” among 3‐ to 5‐year‐old Chinese preschoolers (Ntotal = 314, 48% female). The results showed that preschoolers consistently grouped “constant distance” curves with parallel lines. This suggests that the core feature of intuitive parallel category is “constant distance” at this age.
Emerging functions and therapeutic targets of IL‐38 in central nervous system diseases
Authors: Gao Yuan , Cai Luwei , Wu Yulu , Jiang Min , Zhang Yidan , Ren Wenjing , Song Yirui , Li Lili , Lei Ziguang , Wu Youzhuang , Zhu Luwen , Li Jing , Li Dongya , Li Guohong , Luo Chengliang , Tao Luyang
Published: February 2024

Interleukin (IL)‐38 is a newly discovered cytokine of the IL‐1 family, which binds various receptors (i.e., IL‐36R, IL‐1 receptor accessory protein‐like 1, and IL‐1R1) in the central nervous system (CNS). The hallmark physiological function of IL‐38 is competitive binding to IL‐36R, as does the IL‐36R antagonist. Emerging research has shown that IL‐38 is abnormally expressed in the serum and brain tissue of patients with ischemic stroke (IS) and autism spectrum disorder (ASD), suggesting that IL‐38 may play an important role in neurological diseases. Important advances include that IL‐38 alleviates neuromyelitis optica disorder (NMOD) by inhibiting Th17 expression, improves IS by protecting against atherosclerosis via regulating immune cells and inflammation, and reduces IL‐1β and CXCL8 release through inhibiting human microglial activity post‐ASD. In contrast, IL‐38 mRNA is markedly increased and is mainly expressed in phagocytes in spinal cord injury (SCI). IL‐38 ablation attenuated SCI by reducing immune cell infiltration. However, the effect and underlying mechanism of IL‐38 in CNS diseases remain inadequately characterized. In this review, we summarize the biological characteristics, pathophysiological role, and potential mechanisms of IL‐38 in CNS diseases (e.g., NMOD, Alzheimer's disease, ASD, IS, TBI, and SCI), aiming to explore the therapeutic potential of IL‐38 in the prevention and treatment of CNS diseases.
Dysregulation of iron homeostasis and ferroptosis in sevoflurane and isoflurane associated perioperative neurocognitive disorders
Authors: Miao Mengrong , Han Yaqian , Wang Yangyang , Wang Jie , Zhu Ruilou , Yang Yitian , Fu Ningning , Li Ningning , Sun Mingyang , Zhang Jiaqiang
Published: February 2024

In recent years, sevoflurane and isoflurane are the most popular anesthetics in general anesthesia for their safe, rapid onset, and well tolerant. Nevertheless, many studies reported their neurotoxicity among pediatric and aged populations. This effect is usually manifested as cognitive impairment such as perioperative neurocognitive disorders. The wide application of sevoflurane and isoflurane during general anesthesia makes their safety a major health concern. Evidence indicates that iron dyshomeostasis and ferroptosis may establish a role in neurotoxicity of sevoflurane and isoflurane. However, the mechanisms of sevoflurane‐ and isoflurane‐induced neuronal injury were not fully understood, which poses a barrier to the treatment of its neurotoxicity. We, therefore, reviewed the current knowledge on mechanisms of iron dyshomeostasis and ferroptosis and aimed to promote a better understanding of their roles in sevoflurane‐ and isoflurane‐induced neurotoxicity.
S‐9‐PAHSA's neuroprotective effect mediated by CAIII suppresses apoptosis and oxidative stress in a mouse model of type 2 diabetes
Authors: Wang Jian‐tao , Wang Xin‐ru , Ren Jiao‐qi , Lin Jin‐hong , Yu Zhong‐yu , Huang Shan‐shan , Hu Yue , Fu Jia‐yu , Wang Meng , Zhang Yan‐li , Wang Xue‐chun , Guo Jing‐chun , Xiao Ji‐chang , Zhou Hou‐guang
Published: February 2024

Background

With the rapidly increasing prevalence of metabolic diseases such as type 2 diabetes mellitus (T2DM), neuronal complications associated with these diseases have resulted in significant burdens on healthcare systems. Meanwhile, effective therapies have remained insufficient. A novel fatty acid called S‐9‐PAHSA has been reported to provide metabolic benefits in T2DM by regulating glucose metabolism. However, whether S‐9‐PAHSA has a neuroprotective effect in mouse models of T2DM remains unclear.

Methods

This in vivo study in mice fed a high‐fat diet (HFD) for 5 months used fasting blood glucose, glucose tolerance, and insulin tolerance tests to examine the effect of S‐9‐PAHSA on glucose metabolism. The Morris water maze test was also used to assess the impact of S‐9‐PAHSA on cognition in the mice, while the neuroprotective effect of S‐9‐PAHSA was evaluated by measuring the expression of proteins related to apoptosis and oxidative stress. In addition, an in vitro study in PC12 cells assessed apoptosis, oxidative stress, and mitochondrial membrane potential with or without CAIII knockdown to determine the role of CAIII in the neuroprotective effect of S‐9‐PAHSA.

Results

S‐9‐PAHSA reduced fasting blood glucose levels significantly, increased insulin sensitivity in the HFD mice and also suppressed apoptosis and oxidative stress in the cortex of the mice and PC12 cells in a diabetic setting. By suppressing oxidative stress and apoptosis, S‐9‐PAHSA protected both neuronal cells and microvascular endothelial cells in in vivo and in vitro diabetic environments. Interestingly, this protective effect of S‐9‐PAHSA was reduced significantly when CAIII was knocked down in the PC12 cells, suggesting that CAIII has a major role in the neuroprotective effect of S‐9‐PAHSA. However, overexpression of CAIII did not significantly enhance the protective effect of S‐9‐PAHSA.

Conclusion

S‐9‐PAHSA mediated by CAIII has the potential to exert a neuroprotective effect by suppressing apoptosis and oxidative stress in neuronal cells exposed to diabetic conditions. Furthermore, S‐9‐PAHSA has the capability to reduce fasting blood glucose and LDL levels and enhance insulin sensitivity in mice fed with HFD.
HTRA1 promotes EMT through the HDAC6/Ac‐α‐tubulin pathway in human GBM cells
Authors: Zhao Wenbo , Wu Yibo , Wang Shuai , Zhao Feihu , Liu Wenyu , Xue Zhiyi , Zhang Lin , Wang Jian , Han Mingzhi , Li Xingang , Huang Bin
Published: February 2024

Background

The infiltrative nature of human gliomas renders complete surgical removal of tumors futile. Thus, illuminating mechanisms of their infiltrative properties may improve therapies and outcomes of glioma patients.

Methods

Comprehensive bioinformatic analyses of PRSS family were undertaken. Transfection of HTRA1 siRNAs was used to suppress HTRA1 expression. CCK‐8, EdU, and colony formation assay were employed to assess cell viability, and cell migration/invasion was detected by transwell, wound healing, and 3D tumor spheroid invasion assays. Immunoprecipitation was applied to study the mechanism that HTRA1 affected cell migration. In addition, in situ xenograft tumor model was employed to explore the role of HTRA1 in glioma growth in vivo.

Results

HTRA1 knockdown could lead to suppression of cell viability, migration and invasion, as well as increased apoptosis. Immunoprecipitation results indicates HTRA1 might facilitate combination between HDAC6 and α‐tubulin to enhance cell migration by decreasing α‐tubulin acetylation. Besides, HTRA1 knockdown inhibited the growth of xenografts derived from orthotopic implantation of GBM cells and prolonged the survival time of tumor‐bearing mice.

Conclusion

Our results indicate that HTRA1 promotes the proliferation and migration of GBM cells in vitro and in vivo, and thus may be a potential target for treatment in gliomas.