bluuebunny/crossref_metadata_2025 huggingface dataset:
α-catenin phosphorylation is elevated during mitosis to resist apical rounding and epithelial barrier leak
Authors: Le Phuong M , Quinn Jeanne M , Steffeck Adam WT , Flozak Annette S , Huang Che-Fan , Gottardi Cara J
Published: September 2024

Epithelial cell cohesion and barrier function critically depend on α-catenin, an actin-binding protein and essential constituent of cadherin-catenin-based adherens junctions. α-catenin undergoes actomyosin force-dependent unfolding of both actin-binding and middle domains to strongly engage actin filaments and its various effectors, where this mechanosensitivity is critical for adherens junction function. We previously showed that α-catenin is highly phosphorylated in an unstructured region that links mechanosensitive middle- and actin-binding domains (known as the P-linker region), but the cellular processes that promote α-catenin phosphorylation have remained elusive. Here, we leverage a previously published phospho-proteomic data set to show that the α-catenin P-linker region is maximally phosphorylated during mitosis. By reconstituting α-catenin Crispr KO MDCK with wild-type, phospho-mutant and mimic forms of α-catenin, we show that full phosphorylation restrains mitotic cell rounding in the apical direction, strengthening interactions between dividing and non-dividing neighbors to limit epithelial barrier leak. Since major scaffold components of adherens junctions, tight junctions and desmosomes are also differentially phosphorylated during mitosis, we reason that epithelial cell division may be a tractable system to understand how junction complexes are coordinately regulated to sustain barrier function under tension-generating morphogenetic processes.
Antibiotic killing of drug-induced bacteriostatic cells
Authors: Gil-Gil Teresa , Berryhill Brandon A.
Published: September 2024

Synopsis

Background

There is a long-standing belief that bacteriostatic drugs are inherently antagonistic to the action of bactericidal antibiotics. This belief is primarily due to the fact that the action of most bactericidal antibiotics requires the target bacteria to be growing. Since bacteriostatic drugs stop the growth of treated bacteria, these drugs would necessarily work against one another. We have recently shown that bacteria treated with high concentrations of bacteriostatic drugs retain some metabolic activity, dividing on average once per day.

Objectives

We seek to determine if this low level of growth is sufficient to allow for bactericidal antibiotics of different classes to still kill after bacteria are treated with bacteriostatic drugs.

Methods

We first treatedEscherichia coliandStaphylococcus aureuswith two different bacteriostatic drugs, followed by one of three bactericidal drugs of three different classes. The density of these bacteria was tracked over six days to determine the amount of killing that occurred.

Results

Our results question this long-standing belief by demonstrating conditions where sequential treatment with a bacteriostatic then bactericidal antibiotic is as or more effective than treatment with a bactericidal drug alone.

Conclusions

These results raise the need to investigate the pharmacodynamics of the joint action of bacteriostatic and bactericidal antibioticsin vitroandin vivo.
Allosteric modulation of the Lon protease by effector binding and local charges
Authors: Ogdahl Justyne L , Chien Peter
Published: September 2024

The ATPase Associated with diverse cellular Activities (AAA+) family of proteases play crucial roles in cellular proteolysis and stress responses. Like other AAA+ proteases, the Lon protease is known to be allosterically regulated by nucleotide and substrate binding. Although it was originally classified as a DNA binding protein, the impact of DNA binding on Lon activity is unclear. In this study, we characterize the regulation of Lon by single-stranded DNA (ssDNA) binding and serendipitously identify general activation strategies for Lon. Upon binding to ssDNA, Lon’s ATP hydrolysis rate increases due to improved nucleotide binding, leading to enhanced degradation of protein substrates, including physiologically important targets. We demonstrate that mutations in basic residues that are crucial for Lon’s DNA binding not only reduces ssDNA binding but result in charge-specific consequences on Lon activity. Introducing negative charge at these sites induces activation akin to that induced by ssDNA binding, whereas neutralizing the charge reduces Lon’s activity. Based on single molecule measurements we find that this change in activity is correlated with changes in Lon oligomerization. Our study provides insights into the complex regulation of the Lon protease driven by electrostatic contributions from either DNA binding or mutations.

Highlights

ssDNA binding allosterically activates Lon ATP hydrolysis

Negative charge at DNA binding site is sufficient for Lon activation

Neutralization of charge at DNA binding site inhibits Lon ATP hydrolysis

Lon activity is linked to formation of stable Lon hexamers

Significance

The energy-dependent protease Lon is integral in both eukaryotic and prokaryotic physiology, contributing to protein quality control, stress management, developmental regulation, and pathogenicity. The ability to precisely regulate protein levels through targeted degradation underscores a need for tunability. We find that single-stranded DNA (ssDNA) acts as an allosteric regulator of Lon, leading to enhanced enzymatic activity. Mutations in basic residues crucial for DNA binding were found to affect Lon activity in a charge-specific manner highlighting the importance of electrostatic interactions regulating Lon’s function. Changes in Lon activity due to ssDNA binding or mutations were correlated with its oligomerization state. Our findings provide insights into the activation strategies of Lon, emphasizing the role of electrostatic contribution that modulate nucleotide affinity, oligomerization and proteolysis to advance our understanding of the complex regulatory mechanisms of the Lon protease.
In vivodetection of protein-protein interactions with single molecule resolution
Authors: Davi Marilyne , Ladant Daniel
Published: September 2024

Protein-protein interactions are central in all biological processes. Methods capable of detecting interactions within living, intact cells have been particularly useful to identify and characterize protein interaction networks. We describe here an exquisitely sensitive regulatory circuit that can detect in bacteria, protein-protein interaction with single molecule sensitivity. This approach involves the interaction-mediated reconstitution of a cyclic AMP signaling cascade inEscherichia colitaking advantage of the high catalytic activity of the adenylate cyclase (AC) fromBordetella pertussisupon activation by its natural activator, calmodulin (CaM). We show that a single complex of interacting hybrid proteins per cell is enough to confer a selectable trait to the host. Thisexquisitelysensitiveadenylatecyclasehybrid (ESACH) system allows for directin vivoselection of ligands exhibiting high affinity for given targets or for studying interactions involving toxic proteins. The extreme sensitivity of the AC/CaM/cAMP signaling cascade may thus be harnessed to interrogate biological processes with single molecule resolution in live bacteria and could be exploited to design novel synthetic regulatory networks operating at, or even below, the theoretical threshold limit of one molecule per cell.
Electrophysiological responses reveal a dedicated learning mechanism to process salient consonant sounds in human newborns
Authors: Barbieri Paolo , Sarasso Pietro , Rossi-Sebastiano Alice , Frascaroli Jacopo , Poles Karol , Peila Chiara , Coscia Alessandra , Garbarini Francesca , Ronga Irene
Published: September 2024

Isolating relevant sounds in the auditory stream is a crucial feature accomplished by human infants and a pivotal ability for language acquisition. Therefore, it is reasonable to postulate the existence of early mechanisms reorienting attention toward salient acoustic stimuli. Previous studies suggest that infants consider consonant sounds as more salient than dissonant ones, because the former resemble human vocalizations. However, systematic evidence investigating the neural processes underlying consonance tuning in newborns is still scarce. Here, we investigate newborns’ ability to recognize and learn salient auditory stimuli by collecting Mismatch Responses (MMRs) to consonant and dissonant sounds and by computing the trial-by-trial correlation of the neural signal with Bayesian Surprise (a theoretical measure of learning). We present 22 healthy newborns (40.4 ± 15.8 hours) with a pseudo-random sequence of deviant and standard auditory events, while we record their electroencephalogram. Our results show that newborns exhibit a neural encoding of auditory regularities for all sound types (consonant and dissonant), as demonstrated by the presence of MMRs and significant correlation of the neural signal with Bayesian Surprise. Furthermore, consonant and dissonant sounds elicited MMRs and correlations with Bayesian Surprise of opposite polarities, with consonant auditory stimulation evoking negative responses, reminiscent of an adult-like MMR. Overall, our findings suggest that newborns display a dedicated perceptual learning mechanism for salient consonant sounds. We speculate that this mechanism might represent an evolutionary-achieved neural tuning to detect and learn salient auditory stimuli with acoustic features resembling human vocalizations.

SIGNIFICANCE STATEMENT

Discriminating salient sounds in noisy sensory streams is a fundamental ability displayed by human infants, pivotal for acquiring crucial skills including language. Our study shed light on this ability by: (1) investigating perceptual learning mechanisms in newborns’ with a neurocomputational approach; (2) exploring the role of salient consonant sounds in modulating such mechanisms. Since human vocalizations are often consonant, the presence of a mechanism dedicated to enhance the processing of consonant sounds in newborns would confer evolutionary advantages. Our findings, indicating that newborns possess a dedicated and more refined perceptual learning mechanism to process consonance, corroborates this hypothesis. We speculate that this neural mechanism might facilitate the identification of salient acoustic input and support language acquisition in early infancy.
Single-cell transcriptome analysis reveals CD34 as a novel marker of human sinoatrial node pacemaker cardiomyocytes
Authors: Lim Amos A. , Pouyabahar Delaram , Ashraf Mishal , Huang Kate , Lohbihler Michelle , Chang Matthew L. , Murareanu Brandon M. , Tran Thinh , Mazine Amine , Bader Gary , Laksman Zachary , Protze Stephanie
Published: September 2024

The sinoatrial node (SAN) regulates the heart rate throughout life. Failure of this primary pacemaker results in life-threatening, slow heart rhythm. Despite its important function, the cellular and molecular composition of the human SAN is not completely resolved. Particularly, no cell surface marker to identify and isolate SAN pacemaker cells has been reported to date. Here we used single-nuclei/cell RNA sequencing of fetal and human pluripotent stem cell (hPSC)- derived SAN cells and show that the SAN consists of three subtypes of pacemaker cells, including Core SAN, SAN, and Transitional Cells. Our study identified a host of novel Core SAN markers including MYH11, BMP4, and the cell surface antigen CD34. We demonstrate that sorting for CD34+cells from cardiac hPSC differentiations enriches for SAN cells with a functional pacemaker phenotype. This novel SAN pacemaker cell surface marker is highly valuable for future hPSC- based disease modelling, drug discovery, cell replacement therapies, as well as the delivery of therapeutics to SAN cellsin vivousing antibody-drug conjugates.
A hippocampal astrocytic sequence emerges during learning and memory
Authors: Senne Ryan A. , Suthard Rebecca L. , Cao Rui , Monasterio Amy H. , Reusch Evan A. , Buzharsky Michelle D. , Howard Marc W. , Ramirez Steve
Published: September 2024

The dorsal hippocampus is a heterogeneous structure with numerous cell types involved in generating and maintaining detailed representations of space and time. Prior work has established that pyramidal cells contribute to these crucial aspects of episodic memory. For example, hippocampal “time cells” encode temporal information through sequential activity. However, the role of non-neuronal cell types are less often explored. In this study, we investigated dorsal hippocampal CA1 astrocytes using one-photon calcium imaging in freely moving animals during a contextual fear conditioning paradigm. To our knowledge, this is the first time a study has successfully performed longitudinal registration of astrocytic cell population using 1p calcium imaging, thus permitting the tracking of a stable population of these cells in freely-moving mice. In response to foot shock, astrocytes generated robust calcium-event sequences with a time-compressed structure akin to canonical hippocampal time cells. Upon re-exposure to the conditioned context, these astrocytic sequences persisted in the absence of shock, maintaining their time-compressed structure. Moreover, astrocytes active on the previous day retained a preserved sequential structure, indicating memory-specific properties. This phenomenon was not observed in a context different from the initial fear conditioning chamber. Taken together, these results present a potentially paradigm-shifting notion that astrocytes play a significant role in the representation of temporal information processing across learning and memory.
Fast and slow synaptic plasticity enables concurrent control and learning
Authors: Bicknell Brendan A. , Latham Peter E.
Published: September 2024

During many tasks the brain receives real-time feedback about performance. What should it do with that information, at the synaptic level, so that tasks can be performed as well as possible? The conventional answer is that it should learn by incrementally adjusting synaptic strengths. We show, however, that learning on its own is severely suboptimal. To maximize performance, synaptic plasticity should also operate on a much faster timescale – essentially, the synaptic weights should act as a control signal. We propose a normative plasticity rule that embodies this principle. In this, fast synaptic weight changes greedily suppress downstream errors, while slow synaptic weight changes implement statistically optimal learning. This enables near-perfect task performance immediately, efficient task execution on longer timescales, and confers robustness to noise and other perturbations. Applied in a cerebellar microcircuit model, the theory explains longstanding experimental observations and makes novel testable predictions.
Full-length structure and heme binding in the transcriptional regulator HcpR
Authors: Belvin B. Ross , Musayev Faik N. , Escalante Carlos , Lewis Janina P.
Published: September 2024

HcpR is a CRP-family transcriptional regulator found in many Gram-negative anaerobic bacteria. In the perio-pathogenPorphyromonas gingivalis,HcpR is crucial for the response to reactive nitrogen species such as nitric oxide (NO). Binding of NO to the heme group of HcpR leads to transcription of the redox enzyme Hcp. However, the molecular mechanisms of heme binding to HcpR remain unknown. In this study we present the 2.3Å structure of theP. gingivalisHcpR. Interdomain interactions present in the structure help to form a hydrophobic pocket in the N-terminal sensing domain. A comparison analysis with other CRP-family members reveals that the molecular mechanisms of HcpR-mediated regulation may be distinct from other family members. Using docking studies, we identify a putative heme binding site in the sensing domain.In vitrocomplementation and mutagenesis studies verify Met68 as an important residue in activation of HcpR. Finally, heme binding studies with purified forms of recombinant HcpR support Met68 and His149 residues as important for proper heme coordination in HcpR.
Ultrastructure expansion microscopy of axonemal dynein in islet primary cilia
Authors: Dong Xinhang , Jo Jeong Hun , Hughes Jing
Published: September 2024

Primary cilia are vital sensory organelles whose structures are challenging to study due to their solitary nature and intricate cytoskeleton. Current imaging modalities are limited in their ability to visualize structural details that are important for understanding primary cilia function. Ultrastructure expansion microscopy (U-ExM) is a recent superresolution imaging technique that physically expands biological specimens using a swellable hydrogel, allowing structural interrogation of small cellular components such as cilia. In this study, we apply U-ExM to mouse and human pancreatic islets to visualize the axonemal cytoskeleton and associated proteins in primary cilia. Our study reveals the expression of axonemal dynein in islet primary cilia and centrioles, with DNAI1 being a principal subunit which we validate using targeted shRNA knockdown. We conclude that U-ExM is suitable for localizing protein expression in pancreatic islet cilia which contain axonemal dynein.
Appraising the HIV Prevention Cascade methodology to improve HIV prevention targets: Lessons learned from a general population pilot study in east Zimbabwe
Authors: Moorhouse Louisa R. , Imai-Eaton Jeffrey W , Maswera Rufuworkuda , Tsenesa Blessing , Magoge-Mandizvidza Phyllis , Moyo Brian , Mugurungi Owen , Nyamukapa Constance , Hallett Timothy B , Gregson Simon
Published: September 2024

Introduction

Multiple HIV Prevention Cascades (HPC) formulations have been proposed to assist advocacy, monitoring of progress of HIV prevention implementation and research to identify ways to increase use of HIV prevention methods. Schaefer and colleagues proposed a unifying formulation suitable for widespread use across different populations which could be used for routine monitoring or advocacy. Robust methods for defining and interpreting this HPC formulation using real world data is required.

Methods

Data collected as part of the Manicaland Pilot HIV Prevention Cascades Study, east Zimbabwe, in 2018-19, was used to validate the HPC framework for PrEP, VMMC, male condom and combination prevention method use. Validation measures included feasibility of populating the HPC, contrasting simple vs complex measures of the HPC (using 2-sample proportion test), and testing ability of main bars to predict prevention use and testing whether sub-bars explained why people were lost from the HPC using logistic regression.

Results

It was possible to populate the HPC for both individual and combined prevention methods using pilot survey data. Most steps were associated with prevention method usage outcomes, except for VMMC. There were significant overlaps between individuals reporting positive responses for the main bar and those citing barriers to motivation. To refine the HPC’s access bar definition, it is suggested to also consider individuals who report access barriers. While the HPC framework identifies barriers to individual prevention methods, challenges arise in identifying those for combined prevention.

Discussion

Our study successfully utilised questionnaires from the Manicaland HPC pilot survey to measure the HPC for individual and combined prevention methods. This demonstrates the feasibility of populating this framework using general population survey data and designated questionnaire modules. We propose a final formulation of the HPC, questionnaire modules and methods to create it. With proper evaluation and promotion, the HPC can enhance prevention services, aiding in the crucial reduction of HIV incidence.
Digitalization capability and digital product and service innovation performance: empirical evidence from China
Authors: Yang Chen , Zhang Lu , Ling Xuehang , Qin Xin , Li Mingyue
Published: September 2024

Purpose

Digital product and service innovations (DPSI) has attracted widespread attention from both management scholars and practitioners. Previous studies have documented that information technology (IT) capability and digital orientation positively influence DPSI performance. However, the question of whether and how digitalization capability can facilitate DPSI performance remains unresolved. This paper fills these gaps by investigating the mediating role of improvisation capability and the moderating role of technological turbulence.

Design/methodology/approach

This study used two-wave data from 240 matched digital transformation department leaders and senior managers from Chinese firms and examined the hypotheses deploying hierarchical regression and bootstrapping.

Findings

Our analyses reveal positive, significant links between digitalization capability and improvisation capability and between improvisation capability and DPSI performance. The findings further show that the effect of digitalization capability on DPSI performance is partially mediated by improvisation capability and that technological turbulence strengthens the indirect relationship between digitalization capability and DPSI performance through improvisation capability.

Originality/value

Integrating resource-based view, this research provides evidence that the extent to which improvisation capability mediates the relationship between digitalization capability and DPSI performance depends on technological turbulence. It provides a new direction for digitalization capability and DPSI performance.
Optimal supply chain green innovation and subsidy strategy: producer subsidy versus consumer subsidy
Authors: Lai Zhixuan , Lou Gaoxiang , Guo Yuhan , Tu Xuechen , Zhao Yushan
Published: September 2024

Purpose

Considering two types of subsidies for producers (supplier and manufacturer) and one for consumers based on product greenness and sales quantity, this study aims to formulate optimal supply chain green innovation and subsidy strategies, and to achieve this goal with the support of information systems.

Design/methodology/approach

This study introduces a composite green-product supply chain where suppliers focus on green innovation for component greenness and manufacturers focus on green innovation for manufacturing process greenness. Game theory modeling is applied to investigate the differences of product greenness, supply chain members’ profit and social welfare under different government subsidy strategies.

Findings

Increasing the unit greenness subsidy coefficient can boost product greenness and supply chain members’ profits, but does not always raise social welfare. When the government exclusively offers subsidies to producers, subsidies should be allocated to suppliers when there is a significant disparity in supply chain green innovation costs. Conversely, it is more beneficial to subsidize manufacturers. Consumer subsidies have the potential to enhance both environmental and economic performance in the supply chain compared with producer-exclusive subsidies, but may not always maximize social welfare when supply chain members have low unit costs associated with green innovation.

Originality/value

This study examines the optimal decisions for green supply chain innovation and government subsidy strategies. Supply chain members and the government can use the information system to collect and evaluate the cost of upstream and downstream green innovation, and then develop reasonable collaborative green innovation and subsidy strategies.
Trade dependence and cultural distance: An analysis of economic interactions and humanistic exchanges between China and ASEAN countries
Authors: Li Hanhui , Pamintuan Cavin , Nisar Asad , Rafique Rabia
Published: September 2024

This study examines the influence of trade dependence, encompassing both export and import dependence, and economic dependence on cultural distance within the context of China and ASEAN countries from 1995 to 2020. Employing random‐effects models and, we investigate the impact of these dependencies on cultural distance and explore the moderating effects of humanistic exchange. Our findings reveal that trade dependence, export dependence, import dependence, and economic dependence exert negative effects on cultural distance between China and ASEAN countries. These findings are supported by the robustness test. We further analyze the moderating effects of humanistic exchange on the relationship between trade dependence, economic dependence, and cultural distance, confirming significant moderating effects specifically for trade dependence. Additionally, we observe that regional trade agreements and cultural exchange programs have heterogeneous effects on the relationship between trade and economic dependence and cultural distance, particularly among China and ASEAN countries with established agreements and programs.
Understanding community hate crimes as an incorrigible proposition: Local political attitudes, path dependence, and the ceremonious reporting of hate crime statistics
Authors: Mills Jack M. , Lantz Brendan , Wenger Marin R.
Published: September 2024

The Hate Crime Statistics Act (HCSA) of 1990 requires the federal government to publicly release official hate crime statistics annually; the HCSA does not, however, mandate that local agencies submit hate crime reports to the government in the first place. Although research has evaluated the reporting of hate crime statistics in a dichotomous fashion (compliance vs. noncompliance), the current study suggests that the consistent and invariable reporting of zero hate crimes in a particular jurisdiction over time is unlikely and thus better conceptualized as a third response strategy: ceremonious compliance. We examine this strategy as a potentially unique institutional behavior, structured by local political and historical contexts, including discursive differences in the identification of hate crime as an important social problem, and localized histories of racial oppression. This research then uses multilevel multinomial logistic regression models to estimate variation in the likelihood of differential compliance strategies (i.e., true compliance, ceremonious compliance, noncompliance), according to several political and historical factors, including Republican vote share, location in the Confederate South, and historical lynchings. Findings reveal that political and historical contexts are important predictors of agency responses to hate crime, with a particular tendency toward ceremonious compliance in Republican‐leaning locales.
The accumulated impact of critical incident exposure on correctional officers’ mental health
Authors: Schwartz Joseph A. , Valgardson Bradon , Jodis Christopher A. , Mears Daniel P. , Steiner Benjamin
Published: September 2024

Despite compelling arguments that prison work influences officer mental health, little attention has been devoted to directly and rigorously assessing this relationship. Even less attention has been attributed to the potential impact of critical incident exposure on mental health outcomes among officers. Drawing from a longitudinal sample of correctional officers from three prisons in Minnesota, the current study develops and then tests a resiliency‐fatigue model by examining the impact of the accumulation of work‐related critical incident exposures on symptoms related to posttraumatic stress disorder, depression, and anxiety. As critical incident exposures accumulate, mental health symptoms are found to become more pronounced. The analyses also reveal evidence that mental health symptoms only increase to problematic levels once the accumulation of critical incidents reaches or surpasses an inflection point. The results underscore the importance of understanding the diverse groups affected by prisons and have downstream implications for incarcerated persons, as well as for prison systems more broadly.
The longevity factor spermidine is part of a highly heritable complex erythrocyte phenotype associated with longevity
Authors: Kaminsky Cameron J. , Mill Jericha , Patel Viharkumar , Pierce Dylan , Haj Amelia , Hess Aaron S. , Li Lingjun , Raife Thomas
Published: September 2024

Extreme longevity in humans is known to be a heritable trait. In a well‐established twin erythrocyte metabolomics and proteomics database, we identified the longevity factor spermidine and a cluster of correlated molecules with high heritability estimates. Erythrocyte spermidine is 82% heritable and significantly correlated with 59 metabolites and 22 proteins. Thirty‐eight metabolites and 19 proteins were >20% heritable, with a mean heritability of 61% for metabolites and 49% for proteins. Correlated metabolites are concentrated in energy metabolism, redox homeostasis, and autophagy pathways. Erythrocyte mean cell volume (MCV), an established heritable trait, was consistently negatively correlated with the top 25 biomolecules most strongly correlated with spermidine, indicating that smaller MCVs are associated with higher concentrations of spermidine and correlated molecules. Previous studies have linked larger MCVs with poorer memory, cognition, and all‐cause mortality. Analysis of 432,682 unique patient records showed a linear increase in MCV with age but a significant deviation toward smaller than expected MCVs above age 86, suggesting that smaller MCVs are associated with extreme longevity. Consistent with previous reports, a subset of 78,158 unique patient records showed a significant skewing toward larger MCV values in a deceased cohort compared to an age‐matched living cohort. Our study supports the existence of a complex, heritable phenotype in erythrocytes associated with health and longevity.
Social disharmony, inauthenticity and patriarchy: an Ubuntu perspective on the practice of female genital mutilation
Authors: Ally Tauseef Ahmad , Tandwa Lizeka Amanda
Published: September 2024

Female Genital Mutilation (FGM) is a universal issue which affects girls in Africa, the Middle East, Asia and South America, and immigrant communities in Western Europe, North America, Australia and New Zealand. FGM is a cultural practice in approximately 29 countries in Africa, affecting over 140 million girls. FGM is practiced as a rite of passage, where girls are initiated into womanhood. This practice is promoted as a means for incorporation, thus ascribing personhood, and belonging for girls to their communities. African scholars hold conflicting positions about FGM, with some arguing that it is essential for relational fullness and harmony. While others believe FGM is unjustified because of the health and social risks associated with the practice. We argue, applying sustainable social harmony and Gyekye's views on cultural revitalization, that FGM is morally unjustified and should be prohibited. We believe the claims that FGM fosters harmony, a value of Ubuntu, are fallacious, and this perceived harmony is pretentious and unsustainable. We claim that FGM is inauthentic, unjust and steeped in patriarchal underpinnings that are unsustainable, thus it is a disharmonious practice. Cultural practices that are disharmonious should be refined and pruned and must be dynamic and responsive to current realities.
Water restriction alters seed bank traits and ecology in Atlantic Forest seasonal forests under climate change
Authors: Dias Patrícia Borges , Horn Kunz Sustanis , Pezzopane José Eduardo Macedo , Xavier Talita Miranda Teixeira , Zorzanelli João Paulo Fernandes , Toledo João Vitor , Gomes Lhoraynne Pereira , Gorsani Rodrigo Gomes
Published: September 2024

The soil seed bank (SSB) is one of the key mechanisms that ensure the perpetuity of forests, but how will it behave in the scenarios projected for the future climate? Faced with this main question, still little explored in seasonal tropical forests, this study evaluated the germination, ecological attributes, and functional traits of the SSB in a seasonal forest in the Atlantic Forest. Forty‐eight composite samples of the SSB were collected from 12 plots, distributed across four treatments, each with 12 replicates. The samples were placed in two climate‐controlled greenhouses, establishing two environments of controlled climatic conditions, both with two levels of water, as follows: Cur: current scenario without water restriction; Cur_WR: current scenario with water restriction; RCP8.5: future scenario without water restriction; RCP8.5_WR: future scenario with water restriction. The germinants were identified, and their ecological attributes and functional traits were obtained. Leaf area and biomass production, differences in abundance, richness, and diversity were evaluated, along with analysis of variance to assess the interaction between water levels and scenarios. All ecological attributes and functional traits evaluated drastically decreased in the future projection with water restriction, with this restriction being the main component influencing this response. The increased temperature in the future scenario significantly raised water consumption compared to the current scenario. However, persistent water restrictions in the future could undermine the resilience of seasonal forests, hindering seed germination in the soil. Richness and abundance were also adversely affected by water scarcity in the future scenario, revealing a low tolerance to the projected prolonged drought. These changes found in the results could alter the overall structure of seasonal forests in the future, as well as result in the loss of the regeneration potential of the SSB due to decreased seed viability and increased seedling mortality.
Cortical spreading depression-associated cerebral blood flow changes induced by mechanical stimulation are modulated by AMPA and GABA receptors
Authors: Holland PR , Akerman S , Goadsby PJ
Published: September 2024

Migraine is one of the most prevalent neurological disorders with some 30% of patients additionally suffering from focal neurological disturbances: the aura. The underlying mechanism behind the aura is generally considered to be a form of cortical spreading depression (CSD). We used mechanical stimulation to induce hyperaemia associated with CSD in cats and rats, and studied the effect of a glutamate, α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor, antagonist, and γ-aminobutyric acid (GABA)A and GABAB receptor agonists, to understand better the pharmacology of CSD. All three were able to inhibit CSD-associated cerebral blood flow changes in the rat and in a proportion of cats studied; non-responders showed altered speed of propagation and time to induction. The data suggest AMPA and GABA receptors may be targets of migraine therapy in inhibiting CSD and thus may alter the frequency of migraine aura.
Do politically connected subsidy recipients disclose less subsidy information?
Authors: Li Ningzhong , Tan Youchao , Zeng Cheng
Published: September 2024

This paper examines the association between firms’ political connections and their voluntary disclosure of information related to government subsidies, using a sample of Chinese non‐state‐owned enterprises. We find that politically connected subsidy recipients disclose less information about their subsidies (source and policy basis) in their annual reports than do unconnected firms. This association is mainly driven by connected firms whose subsidies are difficult to justify and are stronger for firms registered in more corrupt provinces and firms with higher media attention. In addition, connected firms disclosing more subsidy information receive fewer future subsidies than do other connected firms. These findings suggest that politically connected subsidy recipients tend to withhold subsidy information to reduce the costs that accompany public scrutiny of subsidies granted through relationships.
Psychometric properties of two ADHD rating scales used in children with ADHD and intellectual disability
Authors: Palmer M. , Fang Z. , Carter Leno V. , Simonoff E.
Published: September 2024

Background

Attention deficit hyperactivity disorder (ADHD) is often present in people with intellectual disability (ID) and autism. However, few ADHD measures have been developed specifically for individuals with these conditions. There is little literature exploring how well ADHD measures are performing at picking up specific symptoms at the item level.

Methods

Analyses were conducted on data from 122 children aged 7–15 years old with diagnoses of both ADHD and ID enrolled in the Hyperactivity and Special Educational Needs trial. Parents and teachers completed ratings of ADHD symptoms on the Aberrant Behavior Checklist (ABC) hyperactivity subscale and the revised Conners' Rating Scales hyperactivity scale and ADHD index. Cronbach's alpha was used to examine the reliability of these measures. Item response theory explores the performance of individual items. Multiple indicators, multiple causes models were used to test for measurement invariance by ID severity, co‐occurring autism traits and child age.

Results

The reliability of parent and teacher reports of ADHD symptoms on the Conners' and ABC was acceptable across the range of ID. Item performance was generally good, and information was provided across the continuum of ADHD traits. Few items on either measure were non‐invariant (i.e., item endorsement generally did not differ based on other child characteristics). When non‐invariance was found, the effect was small.

Conclusions

Both the parent‐reported and teacher‐reported versions of the Conners' hyperactivity scale and ADHD index and the ABC hyperactivity subscale appear to function well in the current sample of children with co‐occurring ADHD and ID.
Outcomes after childhood stroke in an inpatient paediatric rehabilitation unit: A retrospective study
Authors: McGowan Timothy , Danielson Janet , Gehrmann Frances , Hilton Nicola , Lunn Erin , McLennan Kim , Ryan Elizabeth , Ireland Penelope J
Published: September 2024

Aim

Childhood stroke has an estimated incidence of 2–13 per 100 000 children. Limited consensus exists regarding best practice recommendations for childhood stroke rehabilitation. A retrospective study completed at a tertiary institution identified potential associations between factors including type of stroke, functional presentation, muscle strength and length of stay (LOS).

Methods

A retrospective study of children post‐stroke admitted 2014–2019 evaluated factors influencing outcome within inpatient rehabilitation. Exploratory analyses were completed to investigate relationships between variables including LOS, functional change, premorbid comorbidities and muscle strength.

Results

Data on 42 episodes of care (42 children: 18 males) following stroke were sourced from 2014 to 2019. Descriptive statistics were calculated for patient demographics, stroke characteristics, surgical treatment, premorbid comorbidities and muscle strength. Differences in WeeFIM scores between admission and discharge from the inpatient rehabilitation unit were tested using paired t tests. A higher number of children sustained ischaemic stroke (AIS, n = 24) when compared with haemorrhagic stroke (HS, n = 16). The average proportion of rehabilitation LOS to total hospital stay across all stroke types was 54.5%. Assessment of function demonstrated significant improvement between admission and discharge scores across all WeeFIM domains. Presence of comorbidities across stroke survivors was correlated with lower functional levels at discharge despite similar rehabilitation LOS.

Conclusion

Limited consensus exists guiding paediatric rehabilitation post‐childhood stroke. This paper provides preliminary data on a cohort post‐childhood stroke at a tertiary‐level inpatient service. Paediatric stroke survivors showed significant functional improvements after inpatient rehabilitation, with the self‐care domain showing greater improvements than mobility and cognition domains, respectively.
Perceptions, practices and preferences of veterinarians and veterinary nurses in the UK on consent for cardiopulmonary resuscitation in pets
Authors: Gane K. , Sparks T. , Thomas E.
Published: September 2024

Objectives

Cardiopulmonary resuscitation can be a difficult topic to discuss. The barriers surrounding its discussion are well documented in human medicine but have not previously been examined in veterinary medicine. The objectives of this study is to describe the perceptions, practices and preferences of veterinarians and registered veterinary nurses towards discussing cardiopulmonary resuscitation with pet owners.

Materials and Methods

An online survey was circulated to veterinarians and registered veterinary nurses in the UK. Open and closed questions were used, with multiple choice and free text answer formats, all of which related to the timing and content, participants' preferences and perceived barriers to cardiopulmonary resuscitation discussions.

Results

In total, 290 responses met the inclusion criteria. Almost half of participants [140/290 (48%)] worked in first opinion practice. In total, 100 of 290 (34%) participants were “very likely” to discuss cardiopulmonary resuscitation preferences on admission. However, 244 of 272 (90%) said they would rather discuss cardiopulmonary resuscitation prospectively than at the time of a critical event. Most respondents [174/290 (60%)] stated that their practice does not include resuscitation preferences on admission consent forms despite 163 of 290 (56%) “strongly agreeing” that cardiopulmonary resuscitation preferences should be routinely discussed on admission. Over half [168/290 (58%)] never discussed costs associated with cardiopulmonary resuscitation and 67 of 290 (23%) never discussed likelihood of survival to discharge with the most common reason being “unaware of survival statistics.” Barriers to discussion included fear of causing upset, concerns for owner reactions and unrealistic owner expectations.

Clinical Significance

Veterinary professionals in the UK face multiple challenges when discussing cardiopulmonary resuscitation with pet owners. Whilst communication skills are an increasing area of focus in veterinary education, specific teaching on the topic of cardiopulmonary resuscitation discussion may be beneficial. Pet owner education may also mitigate some of the challenges to conversation.
Cardiovascular disease and testosterone therapy in male hypogonadism
Authors: de Silva Nipun Lakshitha , Grant Bonnie , Minhas Suks , Jayasena Channa N.
Published: September 2024

This review assesses the evidence of the physiological effects of testosterone on cardiovascular health, the association between male hypogonadism and cardiovascular health, and the effects of testosterone therapy on cardiovascular health in male hypogonadism. Preclinical studies suggest complex effects of testosterone on cardiovascular risk by acting on skeletal muscle, cardiomyocytes, vasculature, adipocytes, insulin action, and erythropoiesis. Furthermore, low testosterone has a bi‐directional association with cardiometabolic risk. Observational studies have reported worse metabolic profiles in men with organic hypogonadism. However, a consistent association between major cardiovascular events and male hypogonadism has not been established. Hematocrit increases with testosterone therapy; however, most studies do not report an increase in venous thromboembolism risk. Although some observational studies and a small randomized controlled study reported an increased risk of cardiovascular disease, recent data confirm the medium‐term cardiovascular safety of testosterone therapy in middle‐aged and older men with low testosterone.
The Principle of Limb Reconstruction—“One Walking, Two Lines, and Three Balances”: A Retrospective Analysis of Post‐Traumatic Lower Limb Deformity Correction
Authors: Zang Jiancheng , Wei Fangyuan , Shi Lei , Qin Sihe
Published: September 2024

Objective

The principles of limb reconstruction are crucial for treatment success, but there is no unified standard for complex limb deformities. The aim of this study was to analyze the characteristics of the cases of post‐traumatic lower limb deformity and explore the new principle of limb reconstruction.

Method

A retrospective analysis was conducted of 148 patients with post‐traumatic lower limb deformity who underwent surgery from May 1978 to December 2023; 85 were males (57.4%) and 63 were females (42.6%); 65 cases of left side (43.9%), 79 cases of right side(53.4%), and 4 cases were on both sides (2.7%), the average age was 24.64 years (5–69). There were 4 cases suffering hip deformities, 40 cases of femoral deformities, 18 cases from knee, 40 cases from tibiofibular, 93 cases of foot and ankle deformities, and some patients also had two or more types. All patients underwent surgical intervention in an average of 40.5 months (12–96) after injury. According to the evaluation of limb deformities, deformity correction and functional reconstruction with external fixation were implemented, following the principle of “one walking, two lines, and three balances.” The clinical evaluation adopts the criteria of Qinsihe lower limb deformity correction and functional reconstruction.

Result

148 patients with post‐traumatic lower limb deformities were followed up for 40.9 (12–356) months. The main surgical procedures implemented were tendon lengthening and soft tissue release (84 cases), osteotomy (93 cases), joint fusion (30 cases), and tendon transposition (16 cases); there were multiple surgical procedures in some patients. Among them, 124 cases used external fixators for stress control and 27 cases used internal fixation, while 3 cases used plaster or brace. There were 5 wire reactions postoperatively, which improved after dressing change and oral antibiotics. There were 2 pin infections, which improved by pin removing. No surgical related deep infections occurred, and no surgical related neurovascular damage occurred. At the last follow‐up, all limb deformities were corrected, limb function improved, and the results of treatment was very satisfactory. According to Qinsihe evaluation criteria for lower limb deformities, 74 cases were excellent, 56 cases good, and 18 cases fair, with an excellent and good rate of 87.84%.

Conclusion

Stress control with external fixation is effective, safe, and controllable in correcting and reconstructing post‐traumatic lower limb deformities. The principle of “one walking, two lines, and three balances” plays an important role in the entire process of stress control limb reconstruction.
Thyroid Function Trends in Dialysis: Unveiling Peritoneal and Hemodialysis Disparities
Authors: Ita Jelić Pranjić , Lidija Orlić , Lori Srdoč Nemarnik , Tea Vrdoljak Margeta , Jelena Šimić , Ivan Bubić
Published: September 2024

Background

The interplay between peritoneal dialysis (PD), residual kidney function (RKF), and thyroid function remains poorly understood, with limited prospective studies comparing thyroid function in PD versus hemodialysis (HD) patients.

Methods

This prospective single‐center study assessed thyroid function in 18 PD patients over a 24‐month follow‐up period at the Department of Nephrology, Dialysis, and Kidney Transplantation, UHC Rijeka, Croatia. Data were compared to 24 concurrently treated HD patients.

Results

Initially, some PD patients exhibited elevated TSH levels, which normalized during follow‐up despite longer dialysis duration. Compared to HD patients, PD patients demonstrated significantly higher T4 concentrations at baseline and higher FT4 concentrations at 12 and 24 months. Furthermore, FT3 levels were significantly higher in PD patients at baseline and at both 12 and 24 months, with T3 levels also within the reference interval after the beginning of the study. Additionally, a positive association was observed between T4 levels and 24‐h diuresis after 12 months in PD patients.

Conclusion

Recognizing additional risk factors and potential impacts on RKF and cardiovascular comorbidities in dialysis patients can enhance patient care, influence dialysis modality selection, and guide ongoing patient monitoring. Thorough evaluation of thyroid function in PD and HD patients is essential for optimizing clinical outcomes and overall well‐being. This study contributes to understanding the complex interplay between thyroid function, RKF, and dialysis modality, emphasizing the need for further research to inform comprehensive patient care strategies.