bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and associated factors of gender-based violence for female: Evidence from school students in Nepal- a cross sectional study
Authors: Gautam Laxmi , Sha Manisha , Khadka Mishra Durga , Dahal Padam Kanta , Gautam Sujan
Published: May 2024

Background

Gender-based violence (GBV) is a major global public health challenge in 21stcentury that remains a serious impact on women’s health and well-being. Therefore, this study aimed to access the prevalence and factors associated with GBV among secondary school female students in Sarlahi district of Nepal.

Methods

Using a cross-sectional study, we collected data from 225 secondary school female students in Sarlahi district of Nepal. Data was collected by using a semi-structured, self-administered questionnaire. Probability proportionate and simple random sampling techniques were used for sampling. The association were explored by using chi-square test and binary logistic regression where a p value <0.05 was considered statistically significant.

Results

The prevalence of GBV among the students during their lifetime was 45.33% followed by physical (16.89%), sexual (30.22%) and psychological (39.56%) violence respectively. The prevalence of physical violence from family members was 97.36%, followed by emotional violence (41.57%). Further, the prevalence of sexual violence from the non-family members was 91.17%. Type of family had a significant association with lifetime experience of GBV (p=0.003). Gender based discrimination in the family had a significant association with lifetime (p=0.001) as well as last 12 months (p=0.001) GBV experience. Experience of witnessing physical violence as a child was within last 12 months was associated with GBV (p=0.03).

Conclusion

GBV has been prevalent among the high school students, with limited level of awareness in that issue. This warrants the urgent need to establish preventive and responsive control measure within schools and communities to address the GBV effectively.
Movement of the endoplasmic reticulum is driven by multiple classes of vesicles marked by Rab-GTPases
Authors: Langley Allison , Abeling-Wang Sarah , Wagner Erinn , Salogiannis John
Published: May 2024

Peripheral endoplasmic reticulum (ER) tubules move along microtubules to interact with various organelles through membrane contact sites (MCS). Traditionally, ER moves by either sliding along stable microtubules via molecular motors or attaching to the plus ends of dynamic microtubules through tip attachment complexes (TAC). A recently discovered third process, hitchhiking, involves motile vesicles pulling ER tubules along microtubules. Previous research showed that ER hitchhikes on Rab5- and Rab7-marked endosomes, but it is uncertain if other Rab-vesicles can do the same. In U2OS cells, we screened Rabs for their ability to cotransport with ER tubules and found that ER hitchhikes on post-Golgi vesicles marked by Rab6 (isoforms a and b). Rab6-ER hitchhiking occurs independently of ER-endolysosome contacts and TAC-mediated ER movement. Disrupting either Rab6 or the motility of Rab6-vesicles reduces overall ER movement. Conversely, relocating these vesicles to the cell periphery causes peripheral ER accumulation, indicating that Rab6-vesicle motility is crucial for a subset of ER movements. Proximal post-Golgi vesicles marked by TGN46 are involved in Rab6-ER hitchhiking, while other post-Golgi vesicles (Rabs 8/10/11/13/14) are not essential for ER movement. Our further analysis finds that ER to Golgi vesicles marked by Rab1 are also capable of driving a subset of ER movements. Taken together, our findings suggest that ER hitchhiking on Rab-vesicles is a significant mode of ER movement.

SIGNIFICANCE STATEMENT

Peripheral endoplasmic reticulum tubules move on microtubules by either attaching to motors (cargo adaptor-mediated), dynamic microtubule-plus ends (tip attachment complexes) or motile vesicles (hitchhiking) but the prevalence of each mode is not clear

Post-Golgi vesicles marked by Rab6/TGN46 and ER to Golgi vesicles marked by Rab1 drive ER movements

ER hitchhiking on multiple classes of vesicles (endolysosomal, post-Golgi and ER to Golgi) marked by Rabs plays a prominent role in ER movement
FlaHMM: unistrandflamenco-like piRNA cluster prediction inDrosophilaspecies using hidden Markov models
Authors: Trapotsi Maria-Anna , van Lopik Jasper , Hannon Gregory J , Nicholson Benjamin Czech , Bornelöv Susanne
Published: May 2024

PIWI-interacting RNAs are a class of small non-coding RNAs that are essential for transposon control in animal gonads. InDrosophilaovarian somatic cells, piRNAs are transcribed from large genomic regions called piRNA clusters, which are enriched for transposon fragments and acts as a memory of past invasions. Despite being widely present acrossDrosophilaspecies, somatic piRNA clusters are notoriously difficult to identify and study due to their lack of sequence conservation and limited synteny. Current identification methods rely either on extensive manual curation or availability of high-throughput small RNA-seq data, limiting large-scale comparative studies. We now present FlaHMM, a hidden Markov model developed to automate genomic annotation offlamenco-like unistrand piRNA clusters inDrosophilaspecies without the need of experimental data beyond a genome assembly. FlaHMM uses transposable element content across 5 or 10 kb bins calculated from genome sequence alone and is thus able to detect candidate piRNA clusters without the need to obtain flies and experimentally perform small RNA sequencing. We show that FlaHMM performs on par with piRNA-guided or manual methods, and thus provides a scalable and efficient approach to piRNA cluster annotation in new genome assemblies. FlaHMM is freely available athttps://github.com/Hannon-lab/FlaHMMunder an MIT licence.
Longitudinal proteomic profiling of T cell differentiationin vivounveils dynamic proteome remodeling
Authors: Beusch Christian M. , Dawood Abdelhameed S. , Ozdilek Ahmet , Welbourn Sarah , Monaco Christopher M. , Flegle Alexandra S. , Malik Sakshi , Niavi Christina , Akhtar Akil , Roman Carly , Gavora Autumn A. , Gordon David E. , Abdel-Hakeem Mohamed S.
Published: May 2024

T cell differentiation plays a pivotal role in orchestrating immune responses and is crucial for combating infection. Consequently, extensive studies on the cellular, transcriptional, and epigenetic levels have been conducted to deepen our understanding of T cell differentiation. Despite numerous studies revealing disparities between transcriptional and proteomic measurements of the same cells, there has been no direct ex-vivo proteomic profiling of antigen-specific T cell differentiation conducted thus far. In this study, we performed the first longitudinal proteomic profiling of T cell differentiationin vivo,utilizing the well-characterized lymphocytic choriomeningitis virus (LCMV) mouse model. We performedex-vivoprotein abundance profiling of effector to memory differentiation (TEFF/TMEM) and early to late exhausted T cell (TEX) differentiation following LCMV infection with the acute Armstrong and chronic Clone-13 strains, respectively. Our findings reveal dynamic alterations of the T cell proteome during differentiation that are either common or distinct for acute and chronic infection, recapitulating existing knowledge. Crucially, our proteomic analyses identify significant differences in the abundance of several proteins between cell states that were not previously highlighted through transcriptional profiling. Our study provides a comprehensive proteomics resource ofin vivoT cell differentiation within an antigen-specific context, complementing existing omics data and elucidating putative proteins with potential diagnostic and therapeutic relevance.
Tuning and functionalization of logic gates for time resolved programming of bacterial populations
Authors: Bäcker Leonard E. , Broux Kevin , Weckx Louise , Khanal Sadhana , Aertsen Abram
Published: May 2024

In order to increase our command over genetically engineered bacterial populations in bioprocessing and therapy, synthetic regulatory circuitry needs to enable the temporal programming of a number of consecutive functional tasks without external interventions. In this context, we have engineered a genetic circuit encoding an autonomous but chemically tunable timer inEscherichia coli, based on the concept of a transcription factor cascade mediated by the cytoplasmic dilution of repressors. As proof-of-concept, we used this circuit to impose a time-resolved two-staged synthetic pathway composed of a production-followed-by-lysis program, via a single input. Moreover, via a recombinase step, this synchronous timer was further engineered into an asynchronous timer in which the generational distance of differentiating daughter cells spawning off from a stem-cell like mother cell becomes a predictable driver and proxy for timer dynamics. Using this asynchronous timer circuit, a temporally defined population heterogeneity can be programmed in bacterial populations.

Graphical abstract
Spontaneous Fluctuations in Pupil Size Shape Retinal Responses to Visual Stimuli
Authors: Mathôt Sebastiaan , Weiden Daria , Dimigen Olaf
Published: May 2024

Visual perception is shaped at the earliest stage by the size of the eye’s pupil, which determines how much light enters the eye and how well this light is focused. But the exact role of pupil size in visual perception is still poorly understood. We recorded pupil size and electrical activity from the retina and brain while healthy human participants viewed full-screen flashes. We found that early retinal responses, which peaked ±25 ms after stimulus onset and predicted subsequent activity over visual cortex, were strongly affected by stimulus intensity. Importantly, pupil size, at least within the range of naturally occurring fluctuations, did not affect the amplitude of these early retinal responses, despite resulting in substantial changes in retinal light exposure. However, the direction of pupil-size change at the moment of stimulus presentation did modulate the amplitude of early retinal responses, which were enhanced during phases of dilation as compared to constriction. Based on these results, we suggest that fast-acting adaptation processes may normalize early retinal responses with respect to changes in retinal light exposure that result from spontaneous changes in pupil size: an initial form of brightness constancy. These results shed new light on, and raise important and previously unasked questions about, the role of pupil size in visual perception.
Unique RNA replication characteristics and nucleocapsid protein expression may explain differences in the replication capacity of SARS-COV-2 lineages
Authors: Corrêa Isadora Alonso , de Souza Marcos Romário Matos , da Silva Gustavo Peixoto Duarte , Pimentel Anna Beatriz Sampaio Vianna Macedo , Calil Pedro Telles , Cunha Marcela Sabino , Mariani Diana , de Moares Brindeiro Rodrigo , Costa Sara Mesquita , da Costa Simas Maria Clara , Ota Victor Akira , Pereira Elisa Cavalcante , Siqueira Marilda Mendonça , Resende Paola Cristina , Galliez Rafael Mello , Faffe Debora Souza , Silva Rosane , Castiñeiras Terezinha Marta Pereira Pinto , Tanuri Amilcar , da Costa Luciana Jesus
Published: May 2024

COVID-19 pandemic in Brazil was characterized by the sequential circulation of the SARS-CoV-2 lineages B.1.1.33, and variants Zeta (P.2), Gamma (P.1/P.1.*), Delta (B.1.617.2/AY.*), and Omicron (BA.*). Our research aimed to compare the biological traits of these lineages and variants by analyzing aspects of viral replication including binding, entry, RNA replication, and viral protein production. We demonstrated that the replication capacity of these variants varies depending on the cell type, with Omicron BA.1 exhibiting the lowest replication in the human pulmonary cells. Additionally, the nucleocapsid proteoforms generated during infection exhibit distinct patterns across variants. Our findings suggest that factors beyond the initial stages of virus entry influence the efficiency of viral replication among different SARS-CoV-2 variants. Thus, our study underscores the significance of RNA replication and the role of nucleocapsid proteins in shaping the replicative characteristics of SARS-CoV-2 variants.

Author summary

The COVID-19 pandemic was characterized by the emergence of different viral variants that presents specific properties such as response to antibodies, pathogenicity and detection by diagnostic tests. The circulation of these variants presented a particular pattern depending on the global geographic regions. Despite the cessation of the pandemic, as officially declared by the World Health Organization in 2023, new viral variants continue to emerge while aspects of the virus-cell interaction that contribute to the replication of these variants have not yet been completely understood. In our study, we compared the biological characteristics of SARS-CoV-2 variants that circulated in Brazil during the pandemic, verifying aspects of entry, viral replication and production of viral RNA and proteins. Our results indicate that Omicron BA.1 variant has reduced replication and protein production in human lung cells. We also observed that the viral nucleocapsid protein presents proteoforms that vary according to the variant. These differences could help to explain the differences observed in viral replication in human pulmonary cells.
A novel feeding mechanism: Sunbirds drink nectar via intralingual suction
Authors: Cuban David , Wang-Claypool Cynthia , Yohanna Yohanna , Downs Colleen T. , Bowie Rauri C. K. , Brau Fabian , Johnson Steven D. , Rico-Guevara Alejandro
Published: May 2024

Nectarivory has independently evolved many times among birds, yet little is known about the diversity of feeding mechanisms that enable specialized taxa to efficiently collect this energyrich resource. Multiple avian groups have converged on evolving elongated bills and tube-like tongues adapted for nectar extraction. Old World sunbirds (family Nectariniidae) stand out as having the greatest degree of convergence in bill and tongue morphology with the well-studied and highly-specialized New World hummingbirds (family Trochilidae) which fill their tongues via elastic filling. However, using museum specimens, high-speed video, and fluid modeling, we show that sunbirds use a previously undescribed and unique drinking mechanism not found in any other animal: intralingual suction through the inside of hollow tubular tongues, a remarkable feat for animals without lips or cheeks.
Mouse exploratory behaviour in the open field with and without NAT-1 EEG device: Effects of MK801 and scopolamine
Authors: Lim Charmaine J.M. , Bray Jack , Janhunen Sanna K. , Platt Bettina , Riedel Gernot
Published: May 2024

Abstract

One aspect of reproducibility in preclinical research that is frequently overlooked is the physical condition in which physiological, pharmacological or behavioural recordings are conducted. In this study, the physical conditions of mice were altered through the attachments of wireless electrophysiological recording devices (Neural Activity Tracker-1, NAT-1). NAT-1 devices are miniaturised multichannel devices with on-board memory for direct high-resolution recording of brain activity for >48 hrs. Such devices may limit the mobility of animals and affect their behavioural performance due to the added weight (total weight of approximately 3.4 g). Mice were additionally treated with saline (control), N-methyl-D-aspartate (NMDA) receptor antagonist MK801 (0.85 mg/kg), or the muscarinic acetylcholine receptor blocker scopolamine (0.65 mg/kg) to allow exploration of the effect of NAT-1 attachments in pharmacologically treated mice. We found only minimal differences in behavioural outcomes with NAT-1 attachments in standard parameters of locomotor activity widely reported for the open field test between drug-treatments. Hypoactivity was globally observed as a consistent outcome in MK801-treated subjects and hyperactivity in scopolamine groups regardless of NAT-1 attachments. These data collectively confirm the reproducibility for combined behavioural, pharmacological and physiological endpoints even in the presence of lightweight wireless data loggers. The NAT-1 therefore constitutes a pertinent tool for investigating brain activity in e.g. drug discovery, models of neuropsychiatric and/or neurodegenerative diseases with minimal effects on pharmacological and behavioural outcomes.
Maize associated bacterial and fungal microbiomes show contrasting conformation patterns that are resilient to water availability
Authors: Díaz-González Sandra , González-Bodí Sara , González-Sanz Carlos , Marín Patricia , Brunner Frédéric , Sacristán Soledad
Published: May 2024

Plant-associated microorganisms can help crops to alleviate water stress and increase the resilience of agricultural ecosystems to climate change. However, we still lack knowledge on the dynamics of bacterial and fungal microbial kingdoms within the soil and plant microbiomes and the response of these communities to different conditions such us, for example, water restrictions. This information is essential for the development of microbiome-based solutions to improve crop resilience to stressors associated to climate change. In this work, we explored: i) the conformation of the bacterial and fungal assemblages of different soil and plant compartments (bulk soil, rhizosphere, roots, leaves and grains) along the crop cycle of maize in an open field trial; and ii) the effect of water restriction on the maize microbiome comparing optimal irrigation with a 30% reduction of water supply. Our results show that microbial communities are highly structured along soil and plant compartments, with contrasting patterns for bacteria and fungi that were intensified towards the end of the plant cycle. Root showed the most differentiated bacterial assemblage while fungi conformed a very distinct community in the leaf, suggesting a relevant contribution of aerial fungal propagules to the microbiome of this plant organ. Despite the reductions in plant growth and yield, the microbiome of limited-watered plants did not show severe alterations. Still, significant impacts were observed within compartments, being fungi more responsive to limited watering than bacteria. Network analysis suggest that bacteria and fungi may play different roles in the shifts observed under water stress.
Uncovering the roles of the scaffolding protein CsoS2 in mediating the assembly and shape of the α-carboxysome shell
Authors: Li Tianpei , Chen Taiyu , Chang Ping , Ge Xingwu , Chriscoli Vincent , Dykes Gregory F. , Wang Qiang , Liu Lu-Ning
Published: May 2024

Carboxysomes are proteinaceous organelles featuring icosahedral protein shells that enclose the carbon-fixing enzymes, Rubisco, alone with carbonic anhydrase. The intrinsically disordered scaffolding protein CsoS2 plays a vital role in the construction of α-carboxysomes through bridging the shell and cargo enzymes. The N-terminal domain of CsoS2 binds Rubisco and facilitates Rubisco packaging within the α-carboxysome, whereas the C-terminal domain of CsoS2 (CsoS2-C) anchors to the shell and promotes shell assembly. However, the role of the middle region of CsoS2 (CsoS2-M) has remained elusive. Here, we conducted indepth examinations on the function of CsoS2-M in the assembly of the α-carboxysome shell by generating a series of recombinant shell variants in the absence of cargos. Our results reveal that CsoS2-M assists CsoS2-C in the assembly of the α-carboxysome shell and plays an important role in shaping the α-carboxysome shell through enhancing the association of shell proteins on both the facet-facet interfaces and flat shell facets. Moreover, CsoS2-M is responsible for recruiting the C-terminal truncated isoform of CsoS2, CsoS2A, into α-carboxysomes, which is crucial for Rubisco encapsulation and packaging. This study not only deepens our knowledge of how the carboxysome shell is constructed and regulated but also lays the groundwork for engineering and repurposing carboxysome-based nanostructures for diverse biotechnological purposes.
Engineered lysins to modulate human gut microbiome communities
Authors: Rodriguez Juan R. Diaz , Lu Wenbo , Papadopoulos James M. , Venturelli Ophelia S. , Romero Philip A.
Published: May 2024

The ability to precisely control the human gut microbiome’s composition, metabolic networks, and host interactions would revolutionize medicine and how we treat human disease. Microbiome remodeling approaches such as probiotics, prebiotics, antibiotics, and fecal microbiota transplantation are global perturbations with consequences that are difficult to predict. Lysins are enzymes produced by bacteriophages and bacteria that have exceptional specificity to lyse bacterial cells and could be applied for targeted microbiome remodeling. In this work we demonstrate the ability of lysins to target diverse human gut commensal bacteria, how domain recombination can give rise to chimeric lysins with altered species preferences, and how engineered lysins can directly remodel the structure and function of synthetic human gut microbiomes. Lysins represent a general platform that can be rapidly tailored through protein engineering to control complex microbial ecosystems.
Distinct functional classes of CA1 hippocampal interneurons are modulated by cerebellar stimulation in a coordinated manner
Authors: Froula Jessica M. , Rose Jarrett J , Krook-Magnuson Chris , Krook-Magnuson Esther
Published: May 2024

There is mounting evidence that the cerebellum impacts hippocampal functioning, but the impact of the cerebellum on hippocampal interneurons remains obscure. Using miniscopes in freely behaving animals, we find optogenetic stimulation of Purkinje cells alters the calcium activity of a large percentage of CA1 interneurons. This includes both increases and decreases in activity. Remarkably, this bidirectional impact occurs in a coordinated fashion, in line with interneurons’ functional properties. Specifically, CA1 interneurons activated by cerebellar stimulation are commonly locomotion-active, while those inhibited by cerebellar stimulation are commonly rest-active interneurons. We additionally find that subsets of CA1 interneurons show altered activity during object investigations, suggesting a role in the processing of objects in space. Importantly, these neurons also show coordinated modulation by cerebellar stimulation: CA1 interneurons that are activated by cerebellar stimulation are more likely to be activated, rather than inhibited, during object investigations, while interneurons that show decreased activity during cerebellar stimulation show the opposite profile. Therefore, CA1 interneurons play a role in object processingandin cerebellar impacts on the hippocampus, providing insight into previously noted altered CA1 processing of objects in space with cerebellar stimulation. We examined two different stimulation locations (IV/V Vermis; Simplex) and two different stimulation approaches (7Hz or a single 1s light pulse) – in all cases, the cerebellum induces similar coordinated CA1 interneuron changes congruent with an explorative state. Overall, our data show that the cerebellum impacts CA1 interneurons in a bidirectional and coordinated fashion, positioning them to play an important role in cerebello-hippocampal communication.

Significance Statement

Acute manipulation of the cerebellum can affect the activity of cells in CA1, and perturbing normal cerebellar functioning can affect hippocampal-dependent spatial processing, including the processing of objects in space. Despite the importance of interneurons on the local hippocampal circuit, it was unknown how cerebellar activation impacts CA1 inhibitory neurons. We find that stimulating the cerebellum robustly affects multiple populations of CA1 interneurons in a bidirectional, coordinated manner, according to their functional profiles during behavior, including locomotion and object investigations. Our work also provides support for a role of CA1 interneurons in spatial processing of objects, with populations of interneurons showing altered activity during object investigations.
PDGF-BB overexpression in p53 null oligodendrocyte progenitors increases H3K27me3 and induces transcriptional changes which favor proliferation
Authors: Huang Dennis , Mela Angeliki , Bhanu Natarajan V. , Garcia Benjamin A. , Canoll Peter , Casaccia Patrizia
Published: May 2024

Proneural gliomas are brain tumors characterized by enrichment of oligodendrocyte progenitor cell (OPC) transcripts and genetic alterations. In this study we sought to identify transcriptional and epigenetic differences between OPCs withTrp53deletion and PDGF-BB overexpression (BB-p53n), which form tumors when transplanted in mouse brains, and those carrying only p53 deletion (p53n), which do not. We used unbiased histone proteomics and RNA-seq analysis on these two genetically modified OPC populations and detected higher levels of H3K27me3 in BB-p53n compared to p53n OPCs. The BB-p53n OPC were characterized by higher levels of transcripts related to proliferation and lower levels of those related to differentiation. Pharmacological inhibition of histone H3K27 trimethylation in BB-p53n OPC reduced cell cycle transcripts and increased the expression of differentiation markers. These data suggest that PDGF-BB overexpression in p53 null OPC results in histone post-translational modifications and consequent transcriptional changes favoring proliferation while halting differentiation, thereby promoting the early stages of transformation.
Synaptic pruning facilitates online Bayesian model selection
Authors: Tazawa Ukyo T. , Isomura Takuya
Published: May 2024

Identifying appropriate structures for generative or world models is essential for both biological organisms and machines. This work shows that synaptic pruning facilitates efficient statistical structure learning. We extend previously established canonical neural networks to derive a synaptic pruning scheme that is formally equivalent to an online Bayesian model selection. The proposed scheme, termed Bayesian synaptic model pruning (BSyMP), utilizes connectivity parameters to switch between the presence (ON) and absence (OFF) of synaptic connections. Mathematical analyses reveal that these parameters converge to zero for uninformative connections, thus providing reliable and efficient model reduction. This enables the identification of a plausible structure for the environmental model, particularly when the environment is characterized by sparse likelihood and transition matrices. Through causal inference and rule learning simulations, we demonstrate that BSyMP achieves model reduction more efficiently than the conventional Bayesian model reduction scheme. These findings indicate that synaptic pruning could be a neuronal substrate underlying structure learning and generalizability in the brain.
Counter-intuitive method improves yields of isotopically-labeled proteins expressed in flask-culturedEscherichia coli
Authors: Treviño Miguel Ángel
Published: May 2024

NMR is a powerful tool for the structural and dynamic study of proteins. One of the necessary conditions for the study of these proteins is their isotopic labeling with13C,15N and sometimes2H. One of the most widely used methods to obtain these labeled proteins is heterologous expression of the proteins inE. coliusing13C-D-glucose and15NH4Cl as the sole nutrient source. In recent years, the price of13C-D-glucose has almost tripled, making it essential to develop labelling methods that are as cost effective as possible. In this article, different parameters have been studied to achieve the most rational use of13C-D-glucose and an optimised method has been developed to obtain labeled proteins with high labelling, low13C-D-glucose consumption. Surprisingly, the optimised method is also simplier and does not require monitoring culture growth
Toxoplasma gondiiinfection accelerates the progression of hereditary spastic paraplegia
Authors: Alvin James R. , Ramírez-Flores Carlos J. , Mendina Caitlin A. , Audhya Anjon , Knoll Laura J. , Lettman Molly M.
Published: May 2024

The parasitic protozoaToxoplasma gondiichronically infects the central nervous system of an estimated one-third of the human population. Infection is generally subclinical, but immunocompromised individuals can experience a variety of neurological symptoms. Meta-analyses ofT. gondiiseropositivity have suggested a correlation betweenT. gondiiinfection and neurologic disease. While mechanistic studies on the relationship betweenT. gondiiinfection and neurologic disease have been attempted in mice, mice are particularly susceptible toT. gondii, making them an effective model for investigating mechanisms of infection, but not ideal for examining the relationship between long-term chronicT. gondiiinfection and neurologic disease. Rats more closely mimic human clearance ofT. gondiiafter acute infection, but a lack of rat models of neurologic disease has limited studies on the interplay betweenT. gondiiinfection and neurologic disease progression. We have employed a previously characterized rat model of a complex form of hereditary spastic paraplegia (HSP), a class of neurodegenerative disorders which cause axonal degeneration and lower limb spasticity, in order to assess the effect of chronicT. gondiiinfection on neurodegenerative disease. We find that infected rats with hereditary spastic paraplegia exhibit significantly exacerbated behavioral and neuromorphological HSP symptoms compared to uninfected HSP mutant rats, with little correlative effect in infected versus uninfected control animals. We further find that all infected rats regardless of genotype exhibit a robust immune response toT. gondiiinfection, effectively clearing the parasite below the limit of detection of multiple assays of parasitemia and exhibiting no detectable increase in neuroinflammation seven weeks post-infection. These results suggest that chronic undetectedT. gondiiinfection may exacerbate neurodegenerative disease even in immunocompetent individuals and may contribute to neurodegenerative disease heterogeneity.

Author Summary

The long-term consequences of previous acute infections are poorly understood, but are becoming increasingly appreciated, particularly in the era of long Covid. Altered progression of other diseases later in life may be among the long-term consequences of previous infections. Here we investigate the relationship between previous infection with the parasiteToxoplasma gondii, which infects ∼30% of the global population, and neurodegenerative disease using a rat model of hereditary spastic paraplegia (HSP). We find that previous infection withT. gondiiaccelerates motor dysfunction in HSP rats, despite robust clearance of the parasite by infected rats. Our results suggest that previously cleared infections may alter the progression of other diseases later in life and contribute to neurodegenerative disease heterogeneity.
MEK signaling represents a viable therapeutic vulnerability ofKRAS-driven somatic brain arteriovenous malformations
Authors: Suarez Carlos Perfecto Flores , Harb Omar Ashraf , Robledo Ariadna , Largoza Gabrielle , Ahn John J. , Alley Emily K. , Wu Ting , Veeraragavan Surabi , McClugage Samuel T. , Iacobas Ionela , Fish Jason E. , Kan Peter T. , Marrelli Sean P. , Wythe Joshua D.
Published: May 2024

Brain arteriovenous malformations (bAVMs) are direct connections between arteries and veins that remodel into a complex nidus susceptible to rupture and hemorrhage. Most sporadic bAVMs feature somatic activating mutations withinKRAS, and endothelial-specific expression of the constitutively active variant KRASG12Dmodels sporadic bAVM in mice. By leveraging 3D-based micro-CT imaging, we demonstrate that KRASG12D-driven bAVMs arise in stereotypical anatomical locations within the murine brain, which coincide with high endogenousKrasexpression. We extend these analyses to show that a distinct variant, KRASG12C, also generates bAVMs in predictable locations. Analysis of 15,000 human patients revealed that, similar to murine models, bAVMs preferentially occur in distinct regions of the adult brain. Furthermore, bAVM location correlates with hemorrhagic frequency. Quantification of 3D imaging revealed that G12D and G12C alter vessel density, tortuosity, and diameter within the mouse brain. Notably, aged G12D mice feature increased lethality, as well as impaired cognition and motor function. Critically, we show that pharmacological blockade of the downstream kinase, MEK, after lesion formation ameliorates KRASG12D-driven changes in the murine cerebrovasculature and may also impede bAVM progression in human pediatric patients. Collectively, these data show that distinct KRAS variants drive bAVMs in similar patterns and suggest MEK inhibition represents a non-surgical alternative therapy for sporadic bAVM.
Adventitial fibroblasts direct smooth muscle cell-state transition in pulmonary vascular disease
Authors: Crnkovic Slaven , Thekkekara Puthenparampil Helene , Mulch Shirin , Biasin Valentina , Radic Nemanja , Wilhelm Jochen , Bartkuhn Marek , Bonyadi Rad Ehsan , Wawrzen Alicja , Matzer Ingrid , Mitra Ankita , Leib Ryan D. , Nagy Bence Miklos , Sahu-Osen Anita , Valzano Francesco , Bordag Natalie , Evermann Matthias , Hoetzenecker Konrad , Olschewski Andrea , Ljubojevic-Holzer Senka , Wygrecka Malgorzata , Stenmark Kurt , Marsh Leigh M , de Jesus Perez Vinicio , Kwapiszewska Grazyna
Published: May 2024

Pulmonary vascular remodeling is a progressive pathological process characterized by functional alterations within pulmonary artery smooth muscle cells (PASMC) and adventitial fibroblasts (PAAF). Mechanisms driving the transition to a diseased phenotype remain elusive. Utilizing a combination of transcriptomic and proteomic profiling, along with phenotyping of source-matched cells from healthy controls and individuals with idiopathic pulmonary arterial hypertension (IPAH), our investigation uncovered that while PASMC and PAAF retained their original cellular identities, they acquired distinct disease-associated states. Though both cell types exhibited reduced mitochondrial content and hyperpolarization, IPAH-PASMC displayed heightened glycosaminoglycan production and downregulation of contractile machinery, contrasting a hyperproliferative phenotype of IPAH-PAAF. We investigated the involvement of cellular crosstalk in regulating cell state dynamics and identified pentraxin-3 and hepatocyte growth factor as potential modulators of PASMC phenotypic transition orchestrated by PAAF. Our findings contribute to a deeper understanding of pulmonary vascular mesenchyme dynamics in disease pathogenesis.
A harmonized public resource of deeply sequenced diverse human genomes
Authors: Koenig Zan , Yohannes Mary T. , Nkambule Lethukuthula L. , Zhao Xuefang , Goodrich Julia K. , Kim Heesu Ally , Wilson Michael W. , Tiao Grace , Hao Stephanie P. , Sahakian Nareh , Chao Katherine R. , Walker Mark A. , Lyu Yunfei ,   gnomAD Project Consortium, Rehm Heidi L. , Neale Benjamin M. , Talkowski Michael E. , Daly Mark J. , Brand Harrison , Karczewski Konrad J. , Atkinson Elizabeth G. , Martin Alicia R.
Published: May 2024

Underrepresented populations are often excluded from genomic studies owing in part to a lack of resources supporting their analyses. The 1000 Genomes Project (1kGP) and Human Genome Diversity Project (HGDP), which have recently been sequenced to high coverage, are valuable genomic resources because of the global diversity they capture and their open data sharing policies. Here, we harmonized a high-quality set of 4094 whole genomes from 80 populations in the HGDP and 1kGP with data from the Genome Aggregation Database (gnomAD) and identified over 153 million high-quality SNVs, indels, and SVs. We performed a detailed ancestry analysis of this cohort, characterizing population structure and patterns of admixture across populations, analyzing site frequency spectra, and measuring variant counts at global and subcontinental levels. We also show substantial added value from this data set compared with the prior versions of the component resources, typically combined via liftOver and variant intersection; for example, we catalog millions of new genetic variants, mostly rare, compared with previous releases. In addition to unrestricted individual-level public release, we provide detailed tutorials for conducting many of the most common quality-control steps and analyses with these data in a scalable cloud-computing environment and publicly release this new phased joint callset for use as a haplotype resource in phasing and imputation pipelines. This jointly called reference panel will serve as a key resource to support research of diverse ancestry populations.
Linking executive pay to ESG goals: the role of board gender diversity
Authors: Le Thanh Dat , Ngo Julie T.D.
Published: May 2024

Purpose

In recent years, US firms have increasingly integrated ESG performance goals into their executive remuneration packages. This study examines the relationship between board gender diversity and the tendency of firms to incorporate ESG metrics in performance-based compensation using data from US firms. The key questions this study addresses are: Are firms with more females on the board more likely to link executive compensation metrics? What components and types of ESG metrics are more likely to be adopted by firms with more females on the board?.

Design/methodology/approach

This study employs OLS regression, logistic regression, as well as instrumental variable, propensity score matching, and entropy balance methods to establish causality.

Findings

This study finds that firms with gender-diverse boards are more likely to shape their executive remuneration plans to be more ESG-oriented. The most significant positive relationship is observed with environmental and social sub-categories. The results also demonstrate that female directors are more likely to encourage firms to evaluate managers based on absolute and short-term ESG goals.

Originality/value

This study is one of the early studies that examine the adoption of ESG performance goals into executive compensation plans. It contributes to the existing literature by exploring the relationship between board gender diversity and the probability of firms incorporating ESG performance goals into executive compensation packages using a sample of US firms.
Impact of China's community of shared destiny policy (CCSDP) on development and its bearing on trade and ethnicity in Africa
Authors: Tasinda Odette Tougem , Ze Tian , Bekoe Bernard Boamah , Imanche Sunday Adiyoh , Taty Brandy Perkwang , Tasinda Raphael Fomukong , Mwizerwa Innocent Tayari
Published: May 2024

Purpose

This paper reports on the impact of China's Community of Shared Destiny Policy (CCSDP) on ethnicity, and the development and trade benefits in Africa, whilst proposing suggestions for improvements.

Design/methodology/approach

A mixed-research (desktop-based and online survey-based) approach was employed.

Findings

Trade and foreign direct investment alone can account for 11.8% of changes in the peaceful coexistence of China and some selected African countries, and cause changes to the mutual prosperity of China and African nations, to the tune of 6.3%. Therefore, the activation of mutual prosperity among these nations is not necessarily trade and foreign direct investment. The CCSDP is effective and has increased economic development for ethnic groups (50%), although with some negative concerns.

Research limitations/implications

Inadequate/small sample size for the study.

Originality/value

Chinese investment in Africa has had a transformative impact, driving economic growth, improving infrastructure, and fostering regional integration. The share of trade between China and Africa in the continent's overall external trade has increased dramatically. Overall, the CCSDP should be kept in place, but with some modifications to improve its effectiveness and mitigate its negative effects. Finally, as China's engagement with Africa evolves, it is vital that partnerships are founded on mutual understanding, respect, and benefit, and that policies reflect the different needs and ambitions of African communities.
Work pressure in higher education: a state of the art bibliometric analysis on academic work–life balance
Authors: Fauzi Muhammad Ashraf , Rahamaddulla Syed Radzi , Lee Chia Kuang , Ali Zuraina , Alias Umi Nabila
Published: May 2024

Purpose

The purpose of this study is to review the work–life balance (WLB) among academics. Academics are the pillars of higher education institutions’ (HEIs) mission to provide quality education to students and the community, supporting socioeconomic development. Most academics today are overworked and overburdened with duties, forcing them to work longer hours on weekends and at odd hours. This eventually affects their work–life balance and causes boundary conflicts between work and personal life.

Design/methodology/approach

This study proposes a bibliometric analysis to investigate the underlying knowledge structure of this phenomenon by uncovering the past and present themes and predicting future trends of WLB in academia. This review adopts two analyses (bibliographic coupling and co-word analysis), presenting the knowledge structure network. A total of 307 journal publications were retrieved from the Web of Science (WoS) database, revealing significant clusters and themes.

Findings

Findings identified central themes, including the issue of women in academia, predictors and the impact of WLB in academia.

Research limitations/implications

Implications towards research and practice relevant to scholars and practitioners are discussed, particularly in balancing academics, professional work and personal life.

Originality/value

This study presents a state-of-the-art bibliometric analysis by uncovering the knowledge structure of academics’ work–life balance in HEIs.
Doubling down on dosage: exploring the interplay between dosage effects, antisocial traits, treatment attitudes, and recidivism-related therapy outcomes
Authors: Lester Michael , Scanlon Faith , Batastini Ashley
Published: May 2024

Purpose

Studies evaluating the external validity of theoretically informed (risk-need-responsivity [RNR]) cognitive behavioral therapy (CBT) programs have not systematically assessed antisocial personality traits as a source of variability in outcomes. The purpose of this brief report is to examine antisocial traits as a potential source of variability in outcomes.

Design/methodology/approach

Using longitudinal, program-evaluation data (a sample of incarcerated men who were exposed to RNR-informed CBT), the authors examined how antisocial personality traits, attitudes toward treatment and dosage impacted treatment outcomes. A linear regression assessed the relationship between antisocial personality traits and attitudes toward treatment. A latent profile analysis identified participants with elevated antisocial traits and negative attitudes toward treatment. Treatment dosage groups (0, 5, 10 and 15 weeks) were used to assess treatment response per pro-criminal attitudes, skills and rates of recidivism.

Findings

Antisocial traits predicted negative attitudes toward treatment. Elevated antisocial traits and negative treatment attitudes predicted less change in criminal attitudes among those who completed 15 weeks of treatment; higher dosage did not significantly improve rates of recidivism. Variable-centered post hoc analyses largely corroborated these findings. These results suggest RNR-informed CBT may need to be modified for justice-involved persons with elevated antisocial traits.

Originality/value

Few studies have empirically examined the sources of variability in treatment effects for justice-involved persons with antisocial personality traits. This brief report provides a structured examination of factors that may impact treatment outcomes in this population, and therefore aims to inform future research on the effectiveness of empirically supported interventions for people in the legal system.
Examining the impact of geopolitical risk on foreign remittances: evidence from top remittances receiving countries
Authors: Bajaj Namarta Kumari , Abbas Ghulam , Rajput Oad Suresh Kumar , Siyal Tariq Aziz
Published: May 2024

Purpose

This study investigates the impact of geopolitical risk (GPR) on foreign remittances (FRs) for the top remittance-receiving countries.

Design/methodology/approach

The sample includes Mexico, France, Egypt, China, the Philippines, India, Vietnam, Ukraine, Germany and Belgium for the annual period of 1998–2022 using the nonlinear panel autoregressive distributed lag (ARDL) model to determine the asymmetry in the relationship.

Findings

The results suggest that, in the short term, positive GPR shocks have a positive and significant impact on FRs received. On the other hand, the long-run results suggest that adverse GPR shocks negatively affect FRs received in the sampled countries. Additionally, the study confirms the asymmetric impact of GPR on top remittances received in countries.

Research limitations/implications

The policymakers, migrants and recipients should consider the asymmetric nature of GPR while making decisions regarding policies and the transfer of remittances. This information can be used to create more effective policies for controlling and reducing the effects of GPR on overseas remittances, such as assisting migrant workers and developing methods to lessen the volatility of these flows.

Originality/value

Acknowledging the potential fluctuations and uncertainties associated with GPR is crucial to make informed choices regarding remittance-related matters.
High-performance work practices and entrepreneurial firm performance: the moderating role of firm size and industry type
Authors: Duke Joseph Eyo , Tapang Arzizeh Tiesieh , Usang Obal , Kankpang Kechi Alphonsus , Etim Samuel Edet
Published: May 2024

Purpose

This paper examines the moderating role of firm size (FS) and industry type in the relationship between high-performance work practices (HPWPs) and entrepreneurial firm performance.

Design/methodology/approach

A descriptive research design involving a five-year dataset from firms in the retail and services industries of Nigeria was used in the analyses.

Findings

The use of HPWPs is widespread among entrepreneurial firms, with ability- and motivation-enhancing practices being dominant. Country context influences the types of HPWPs implemented by entrepreneurial firms. FS and industry type do not have significant moderating effects on the relationship between HPWPs and the performance of entrepreneurial firms. The positive effect of HPWPs on performance is consistent with findings made in prior studies.

Research limitations/implications

FS plays a neutral role in the relationship between HPWPs and entrepreneurial firm performance. Within the broader retail and services industries, this relationship is weaker in capital-intensive firms compared to less capital-intensive ones. The restricted focus on only retail and service industries may limit the universal applicability of the findings.

Practical implications

Findings indicate that the efficacy of HPWPs is neither influenced by FS nor industry type. Entrepreneurial firms with higher capital intensity benefit relatively more from the use of HPWPs.

Originality/value

Unlike other research efforts focusing on a single moderating influence, this study combines two important contextual factors, FS and industry type, to provide a better understanding of HPWPs. The study spotlights the effects of country context in the implementation of HPWPs in a way that prior studies have not done.