bluuebunny/crossref_metadata_2025 huggingface dataset:
Retinal vascular abnormality of non-perfusion and neovascularization in a toddler with neurofibromatosis type 1
Authors: Zeng Qiaozhu , Zhong Yusheng , Qian Tong , Cheng Yong
Published: October 2024

Purpose

This report describes the case of a 13-month-old boy diagnosed with neurofibromatosis type 1, who presented with retinal vascular abnormalities including extensive non-perfusion and neovascularization. We also discuss the observed changes following photocoagulation treatment.

Methods

A 13-month-old boy presented to the Department of Ophthalmology at Peking University People’s Hospital with a reduction in the width of the left palpebral fissure for the past 6 months.

Results

The boy exhibited more than six café-au-lait spots larger than 5 mm in diameter on his trunk and legs. Fundus examination of the left eye revealed significant neovascularization in the temporal periphery of the retina, with late leakage and non-perfusion also noted temporally in fluorescein angiography (FA). Magnetic resonance imaging of the brain and orbits showed an enlarged left sphenoid body, a widened left cavernous sinus, and a large plexiform neurofibroma. Laser treatment was performed on the left eye. Five months later, the neovascularization was controlled.

Conclusion

Careful fundus examinations and systemic reviews, especially FA, are essential. Timely laser treatment is crucial for controlling disease progression and preventing retinal detachment.
A Transdiagnostic Dimensional Approach to Behavioral Dysregulation: Examining Reward and Punishment Sensitivity Across Psychopathology
Authors: Oka Taiki , Sasaki Akihiro , Kobayashi Nao
Published: October 2024

Aim

Theoretically, deficits in reward/punishment sensitivity are considered an essential component associated with behavioral dysregulation, which is characteristic of compulsive-impulsive disorders. However, recent studies have indicated that several disorders are linked to problems with reward/punishment sensitivity, and their results have been inconsistent. This lack of clinical specificity and robustness might reflect more general problems with traditionally diagnostic categories of psychiatry. To address these concerns, we investigated whether a transdiagnostic dimensional approach could more effectively examine clinical associations related to reward/punishment sensitivity for behavioral dysregulation.

Methods

Using multiple psychiatric symptom scores and reward/punishment sensitivity in online general-population samples (N = 19505), we applied factor analyses to extract transdiagnostic symptom dimensions. Then, we conducted a mixed-effect generalized linear model to examine the relationships between psychopathology and reward/punishment sensitivity.

Results

We extracted three transdiagnostic dimensions, which were validated between two separate datasets: ‘Compulsive hypersensitivity (CH), ‘Social withdrawal (SW),’ and ‘Addictive behavior (AB).’ While SW was associated with reward sensitivity negatively and punishment sensitivity positively, AB showed opposite associations. On the other hand, CH was positively associated with both sensitivities.

Conclusion

Our results highlight the importance of reward/punishment sensitivity for our understanding of behavioral dysregulation, especially in the compulsive-impulsive dimension. Moreover, these findings underscore how transdiagnostic perspectives contribute to a more powerful examination of reward/punishment deficits than studies focusing on a categorical disorder.
Fine Social Discrimination of Siblings in Mice: Implications for Early Detection of Alzheimer’s Disease
Authors: Fauré Lola MP , Gauzin Sébastien , Lejards Camille , Rampon Claire , Verret Laure
Published: October 2024

The ability to distinguish between individuals is crucial for social species and supports behaviors such as reproduction, hierarchy formation, and cooperation. In rodents, social discrimination relies on memory and the recognition of individual-specific cues, known as "individual signatures". While olfactory signals are central, other sensory cues —such as auditory, visual, and tactile inputs — also play a role. However, little research has explored the fine discrimination of individuals with overlapping cues, such as siblings or cohabitating mice. This study investigates whether mice can discriminate between two closely related individuals: siblings from the same litter and cage. We tested the hypothesis that it would be more challenging for mice to distinguish between siblings than between unrelated mice due to shared cues. Moreover, social cognitive impairments are common in neurodegenerative diseases like Alzheimer’s disease (AD), where difficulties in recognizing faces and voices progressively disrupt social interactions in patients. Using a mouse model of AD (Tg2576), known for the progressive onset of cognitive deficits, we assessed whether the ability to discriminate between siblings is preserved in “pre-symptomatic” animals. Thus, we first demonstrated that male and female C57BL6/J mice can discriminate siblings, regardless of sex. Next, we revealed that “pre-symptomatic” 3-month-old Tg2576 mice exhibit impairments in fine social memory, while their general social memory remains unaffected. Thus, we demonstrate that the inability to perform fine social discrimination is an early cognitive impairment that arises before other well-documented memory abnormalities in this AD mouse model.

SIGNIFICANCE STATEMENT

Discriminating between individuals is vital for social species, supporting reproduction, hierarchy formation and cooperation. This study examined whether mice can perform fine social discrimination,i.e., distinguish between siblings from the same home cage. We found that both male and female C57BL6/J mice can discriminate siblings, regardless of their sex. Notably, this fine social discrimination ability is impaired in mouse model of Alzheimer’s disease (AD) at a very early stage of the pathology,i.e.,at an age when they can still recognize two unrelated mice from different home cages. This suggests that fine social discrimination deficits occur early in AD, and could serve as an early marker of the pathology.
A unified framework for drug–target interaction prediction by semantic-guided meta-path method
Authors: Li Haoyuan , Wang Jianxin , Zhao Haochen , Zheng Kai , Zhao Qichang
Published: October 2024

Drug-target interaction (DTI) prediction plays a crucial role in drug development, impacting areas such as virtual screening, drug repurposing, and the identification of potential drug side effects. Despite significant efforts dedicated to improving DTI prediction, existing methods still struggle with the challenges posed by the high sparsity of DTI datasets and the complexity of capturing heterogeneous information in biological networks. To address these challenges, we propose a unified framework for DTI prediction based on a semantics-guided meta-path walk. Specifically, we first pre-train drug and protein embeddings to capture their semantic information. This semantic information is then leveraged to guide a meta-path-based random walk on the biological heterogeneous network, generating sequences of interactions. These sequences are used to compute embedding features via a heterogeneous skip-gram model, which are subsequently fed into downstream tasks to predict DTIs. SGMDTI achieves substantial performance improvement over other state-of-the-art methods for drug–target interaction prediction. Moreover, it excels in the cold-start scenario, which is often a challenging case in DTI prediction. These results indicate the effectiveness of our approach in predicting drug-target interactions.Experimental datasets and experimental codes can be found inhttps://github.com/HYLPRC/SGMDTI
Better and faster collective decisions by larger fish shoals in the wild
Authors: Pacher Korbinian , Bierbach David , Sevinchan Yunus , Volmoeller Carla , Juarez-Lopez Alejandro , Jimenez-Jimenez Jesus Emmanuel , Krause Stefan , Wolf Max , Romanczuk Pawel , Arias-Rodriguez Lenin , Krause Jens
Published: October 2024

Studies on collective cognition have provided many examples of decision-making benefits in terms of animals sharing information about predators, prey or resources in their environment. It has been shown how the efficient spread of adaptive information within groups can pro-vide benefits which increase with group size. Little is known, however, to which extent groups also amplify maladaptive information such as false alarms and whether such costs reduce or even nullify the above benefits. Here, we investigated fish shoals in the wild that responded collectively with escape dives when attacked by birds. We analysed the response of shoals in reaction to hard-to-detect bird attacks and similar but harmless flybys as a func-tion of shoal size. With increasing shoal size fish increasingly detected predator attacks (true positives) while their false alarms remained constant. Therefore, larger shoals became better at correctly classifying potentially dangerous stimuli rather than becoming more sensitive to all stimuli potentially related to attacks. In addition, decision time decreased with increasing shoal size. Larger shoals were thus able to mitigate two major trade-offs inherent in solitary decision making: the trade-off between true and false positives and the trade-off between speed and accuracy. We report performance increases at shoal sizes of tens of thousands of fish and pose challenges for the modelling of the underlying mechanisms.
Calcium-modulatedcisandtransE-cadherin EC1-2 interactions play a key role in formation, dynamics and plasticity of cadherin junctions
Authors: Lai-Kee-Him J. , Fouillen A. , Chee M. , Lemercier N. , Feracci H. , Bron P.
Published: October 2024

Classical cadherins are ubiquitous calcium-dependent adhesive glycoproteins required in junction formation in metazoans. Calcium ions are essential for cadherin biological activity, but how they act in synergy is still a matter of controversy. We investigated by cryo-electron microscopy and cryo-electron tomography, a biomimetic system consisting of liposomes decorated with the two first E-cadherin extracellular modules, previously reported as functionally essential in junction formation. We showed that E-cadherin extracellular modules 1 and 2 are sufficient to form junctions in presence of calcium. Together with the first adhesive contacts, we observed the formation of cadherin patches and quasi-crystalline structures on the free surface of proteoliposomes suggesting that calcium complexation induces the self-interaction of the E-cadherin extracellular modules 1 and 2 throughcisinteractions. We propose that these calcium-dependent cadherin nanoplatforms, by facilitating the formation frequency oftransinteractions, most probably favor the formation of junctions. We also observed a cooperative effect betweentransandcisinteractions leading to the protein depletion of liposome surfaces. Additionally, Cryo-electron tomography experiments performed on extracellular E-cadherin modules 1 and 2-mediated junctions revealed the coexistence of different molecular arrangements previously described from crystallography studies. Thus, this study provides a new insight into biophysical mechanisms underlying how calcium binding modulates cadherin adhesive function, in showing that E-cadherin 1 and 2 modules play a key role through their intrinsic ability to form multiple calcium-dependentcisandtransinteractions, in the formation of cadherin junctions contributing to the dynamics and plasticity of cadherin-mediated cell junctions.
Optochemical profiling of NMDA receptor molecular diversity at synaptic and extrasynaptic sites
Authors: Sicard Antoine , Tian Meilin , Mostefai Zakaria , Shi Sophie , Cardoso Cécile , Zamith Joseph , McCort-Tranchepain Isabelle , Charrier Cécile , Paoletti Pierre , Mony Laetitia
Published: October 2024

Neurotransmitter receptors are the linchpin of neuronal communication. These receptors often form large multimeric complexes that differ in their subunit composition, distribution and signaling properties. Studying individual subtypes in native tissues with subunit stoichiometry resolution remains challenging. This is the case of NMDA receptors (NMDARs), a class of glutamate-gated ion channels playing essential roles in brain development and plasticity. These receptors co-exist as multiple subtypes, with GluN1/GluN2A (GluN2A diheteromers), GluN1/GluN2B (GluN2B diheteromers) and GluN1/GluN2A/GluN2B (GluN2A/GluN2B triheteromers) receptors prevailing in the adult forebrain. Despite numerous investigations, the relative abundance and subcellular distribution of these subtypes remain contentious. Here, we designed a photochemical tool (Opto2B) enabling specific and reversible modulation of GluN2B diheteromers, while leaving other receptor subtypes unaffected (in particular GluN2A/GluN2B tri-heteromers). Using Opto2B, we established the differential contribution of GluN2B diheteromers to synaptic and extrasynaptic NMDAR pools during development. In particular, we show that in adult hippocampal CA1 pyramidal cells, GluN2A-receptors predominate in both pools, with no preferential contribution of GluN2B diheteromers to extrasynaptic currents. Our study clarifies decades of controversial research on extrasynaptic NMDARs and paves the way for interrogating NMDAR signaling diversity with unprecedented molecular and spatio-temporal resolution.

Significance Statement

Pharmacological and genetic approaches, the gold standards for investigating receptor diversity, cannot easily distinguish between receptor populations containing one or more copies of the same subunit. For NMDARs, discriminating GluN2A/GluN2B triheteromers (containing one copy of GluN2A and one copy of GluN2B) from their diheteromeric counterparts (containing two copies of GluN2A or GluN2B) remains difficult. Here, we designed the first tool (Opto2B) allowing selective modulation of GluN2B diheteromers, leaving GluN2A/GluN2B triheteromers unaffected. Using Opto2B, we show that GluN2B diheteromers form a minor population in both synaptic and extrasynaptic compartments of the adult CA1 hippocampus, refuting the common belief of an enrichment of GluN2B diheteromers at extrasynaptic sites. This study should inform future drug discovery programs and studies on NMDAR molecular physiology.
Incorporating climatic extremes using the GEV distribution improves SDM range edge performance
Authors: Fonteyn Ward , Serra-Diaz Josep M. , Muys Bart , Van Meerbeek Koenraad
Published: October 2024

Aim

The changing frequency and intensity of climatic extremes due to climate change can have sudden and adverse impacts on the distribution of species. While species distribution modelling is a vital tool in ecological applications, current approaches fail to fully capture the distribution of climatic extremes, particularly of rare events with the most disruptive potential. Especially at the edges of species’ ranges, where conditions are already less favourable, predictions might be inaccurate when these extremes are not well represented.

Location

Europe

Taxon

Tree species

Methods

We present a novel approach to integrate extreme events into species distribution models based on the generalised extreme value (GEV) distribution. This distribution, following from the extreme value theory has been established as a valuable tool in analysing climatic extremes, both in an ecological context and beyond. The approach relying on the GEV distribution is broadly applicable, readily transferable across species and relies on widely available data. We demonstrate the efficacy of our approach for 28 European tree species, illustrating its superior ability to fully capture the distribution of climatic extremes compared to state-of-the-art methods.

Results

We found that incorporating parameters on climatic extremes derived from the GEV distribution increased model performance (AICmodel) and characterized range edges more accurately (AUCedge) compared to competing approaches. However, general AUC values were only marginally increased across the species and study period analysed. Overall, the GEV model predicted a narrower niche for the species included in this study.

Main conclusions

Incorporating climatic extremes can impact spatial predictions of species distribution models, especially at range margins. We found that using the GEV distribution to characterise extreme variables in SDMs yields the best performance at these distribution edges. Given the importance of range edges for species conservation, a detailed inclusion of extremes in SDMs employed for those applications will help ensure robust conclusions.
Prefoldin 5 is a microtubule-associated protein that suppresses Tau-aggregation and neurotoxicity
Authors: Bisht Anjali , Pippadpally Srikanth , Majumder Snehasis , Gopi Athulya T , Das Abhijit , Sahi Chandan , Ramaswami Mani , Kumar Vimlesh
Published: October 2024

Tauopathies represent a major class of neurodegenerative disorders associated with intracellular aggregates of the microtubule-associated protein Tau. To identify molecular modulators of Tau toxicity, we used a genetic screen to identify protein chaperones whose RNAi-mediated knockdown could modulate hTauV337M-induced eye-ommatidial degeneration inDrosophila. This screen identified the Prefoldins Pfdn5 and Pfdn6 as strong modifiers of hTauV337Mcytotoxicity. Consistent with the known function of Pfdn as a cotranslational chaperone for tubulin,Pfdn5mutants showed substantially reduced levels of tubulin monomer. However, additional microtubule-related functions were indicated by the robust unexpected association of Pfdn5 with axonal microtubulesin vivo,as well as binding with stabilized microtubules in biochemical assays. Loss of Pfdn5 resulted in neuromuscular junctions (NMJ) defects similar to those previously described in hTau-expressing flies: namely, increased supernumerary boutons and fewer microtubule loops within mature presynaptic boutons. Significantly, synaptic phenotypes caused by hTauV337Moverexpression were also strongly enhanced in aPfdn5mutant background. Consistent with a role in modulating Tau toxicity, not only did loss ofPfdn5result in increased accumulations of Tau-aggregates in hTauV337Mexpressing neurons, but also neuronal overexpression of Prefoldin strikingly ameliorated age-dependent neurodegeneration and memory deficits induced by pathological hTau. Together, these and other observations described herein: (a) provide new insight into Prefoldin-microtubule interactions; (b) point to essential posttranslational roles for Pfdn5 in controlling Tau-toxicityin vivo; and (c) demonstrate that Pfdn5 overexpression is sufficient to restrict Tau-induced neurodegeneration.
Integrative profiling of condensation-prone RNAs during early development
Authors: Klobučar Tajda , Novljan Jona , Iosub Ira A. , Kokot Boštjan , Urbančič Iztok , Jones D. Marc , Chakrabarti Anob M. , Luscombe Nicholas M. , Ule Jernej , Modic Miha
Published: October 2024

Complex RNA–protein networks play a pivotal role in the formation of many types of biomolecular condensates. How intrinsic RNA features contribute to condensate formation however remains unclear. Here, we integrate tailored transcriptomics assays to identify a distinct class of developmental condensation-prone RNAs termed ‘smOOPs’ (semi-extractable,orthogonalorganicphaseseparation-enriched RNAs). These transcripts are localised to larger intracellular foci, form denser RNA-RNA interaction subnetworks than expected and are heavily bound by RNA binding proteins (RBPs). Using an explainable deep learning framework, we reveal that smOOPs harbor characteristic sequence composition with lower sequence complexity, increased intramolecular folding and specific RBP binding patterns. Intriguingly, these RNAs encode proteins bearing extensive intrinsically disordered regions and are markedly predicted to be involved in biomolecular condensates, indicating an interplay between RNA- and protein-based features in phase separation. This work advances our understanding of condensation-prone RNAs and provides a versatile resource to further investigate RNA-driven condensation principles.
Cell shape noise strength regulates the rate of shape change during EMT-associated cell spreading
Authors: Pönisch Wolfram , Yanakieva Iskra , Salbreux Guillaume , Paluch Ewa K.
Published: October 2024

Cellular shape is intimately linked to cell function and state, and transitions between cell states are tightly coupled to shape changes. Yet, shape has been largely overlooked in state transitions studies. Here, we combine morphometric analysis with theoretical modeling and molecular perturbations to interrogate cell shape dynamics during epithelial-to-mesenchymal transition (EMT). Using stochastic inference, we extract the morphogenetic landscape underlying EMT. We show that within this landscape, EMT-associated cell spreading reflects a transition between shape attractors. Strikingly, we observe a peak in cell shape noise strength concomitant with spreading, and show that higher shape noise accelerates transitions between shape attractors. Our morphometric analysis framework will be widely applicable to quantitative cell shape investigations in physiology and disease. Together, our results identify a key role for cellular stochasticity as a regulator of shape change rate, and highlight that shape dynamics yield rich phenotypic information that enhances our understanding of cellular states.
Reasoning by exclusion in food-caching Eurasian jays (Garrulus glandarius)
Authors: Hawkins Isobelle , Huemer Michael , Carey Susan , Clayton Nicola S.
Published: October 2024

Two related methods have been widely used to test animals’ capacity to reason by exclusion: Call’s (2004) 2-cups task, where subjects choose between two cups in which one reward was hidden and the empty cup is revealed; and Premack & Premack’s task (1994) where one reward goes in each of the two cups and one reward is removed. In both cases, success is identifying the cup with the reward. It has been suggested that among corvids, the demands associated with caching may foster exclusion abilities by reinforcing the experience of relevant contraries (e.g., empty vs. full), or by supporting domain general capacities that support caching and exclusion inferences. However, Shaw et al. (2013) found that Eurasian jays, proficient cachers, failed a version of Call’s 2-cups task. To further test the caching hypothesis, we amended the procedure using invisible displacement to hide rewards, removing aspects of Shaw et al.’s procedure that may have masked competence of Eurasian jays. We tested seven Eurasian jays, who showed spontaneous success on both Call’s 1-reward/show-empty (80% correct) and Premack and Premack’s 2-reward/remove-1 (85% correct). These results align with the hypothesis that corvids’ exclusion reasoning is related to caching behaviour.
Greater distal activation of the biceps femoris long head reflects proximodistal differences in motor unit action potential properties
Authors: Albarello José Carlos dos Santos , Cabral Hélio V. , Negro Francesco , de Oliveira Liliam Fernandes
Published: October 2024

Purpose

Recent research has explored region-specific responses within the biceps femoris long head. However, evidence on regional muscle activation remains controversial, primarily because information derived solely from surface electromyograms (sEMG) amplitude does not necessarily provide an accurate estimate of neural drive to the muscle. To address this limitation, this study investigated whether there are proximodistal differences in motor unit properties of the biceps femoris long head during isometric hip extension and knee flexion tasks.

Methods

Seventeen resistance-trained males performed isometric knee flexion and hip extension tasks at 20% and 40% of maximal voluntary contraction. High-density sEMG were recorded from proximal and distal regions of the biceps femoris long head and decomposed into individual motor units. Central motor unit properties (mean discharge rate, discharge rate variability, recruitment and de-recruitment thresholds) and action potential properties (amplitude and conduction velocity) were analyzed. Bipolar sEMG amplitude was also calculated for each region to simulate traditional sEMG measurements.

Results

Bipolar sEMG amplitude, motor unit action potential amplitude and conduction velocity were significantly greater in the distal region during both tasks. In contrast, no proximodistal differences were observed in central motor unit properties.

Conclusion

These findings suggest that increased bipolar sEMG amplitude in the distal region of the biceps femoris long head is driven by motor unit action potential properties rather than differences in central modulation, likely influenced by intra-muscular variations in muscle mechanics and geometry. This emphasizes limitations of relying solely on sEMG amplitude to infer neural control strategies in the biceps femoris long head.
ATP-gated P2x7 receptor is a major channel type at type II auditory nerves and required for hearing sensitivity efferent controlling and noise protection
Authors: Liang Chun , Zhai Tian-Ying , Fang Shu , Chen Jin , Liu Li-Man , Yu Ning , Zhao Hong-Bo
Published: October 2024

Hearing sensitivity and noise protection are mediated and determined by negative feedback of the cochlear efferent system. Type II auditory nerves (ANs) innervate outer hair cells (OHCs) in the cochlea and provide an input to this efferent control. However, little is known about underlying channel information. Here, we report that ATP-gated P2x7 receptor had a predominant expression at type II ANs and the synaptic areas under inner hair cells and OHCs with lateral and medial olivocochlear efferent nerves. Knockout (KO) of P2x7 increased hearing sensitivity with enhanced acoustic startle response (ASR), auditory brainstem response (ABR), and cochlear microphonics (CM) by increasing OHC electromotility, an active cochlear amplifier in mammals. P2x7 KO also increased susceptibility to noise. Middle level noise exposure could impair active cochlear mechanics resulting in permanent hearing loss in P2x7 KO mice. These data demonstrate that P2x7 receptors have a critical role in type II AN function and the cochlear efferent system to control hearing sensitivity; deficiency of P2x7 receptors can impair the cochlear efferent suppression leading to hearing oversensitivity and susceptibility to noise.
Soluble TIM-3, likely produced by myeloid cells, predicts resistance to immune checkpoint inhibitors in metastatic clear cell renal cell carcinoma
Authors: Pourmir Ivan , Benhamouda Nadine , Tran Thi , Roux Hugo , Pineau Joséphine , Gey Alain , Munoz Andyara , Mabrouk Nesrine , Epaillard Nicolas , Verkarre Virginie , Vano Yann-Alexandre , Tartour Eric , Oudard Stéphane
Published: October 2024

Background and objectives

Immunotherapies targeting PD-1 and CTLA-4 are key components of the treatment of metastatic clear cell renal cell carcinoma (mccRCC). However, they have distinct safety profiles and resistance to treatment can occur. We assess soluble TIM-3 (sTIM-3) in the plasma of mccRCC patients as a potential theranostic biomarker, as well as its source and biological significance.

Methods

We analyzed the association of sTIM-3 with overall survival (OS), tumor response, and common clinical and biological factors across two mccRCC cohorts treated with anti-PD-1 (n = 27), anti- PD-1 or anti-PD-1 + anti-CTLA-4 (n = 124). The origin and role of sTIM-3 are studied on tumor and blood samples, using multiplex immunohistochemistry and flow cytometry as well as a syngeneic tumor model with antitumor vaccination. We also reanalyzed publicly available single-cell transcriptomic (scRNAseq) data and mass cytometry data.

Key findings and limitations

sTIM-3 is elevated in the plasma of patients with mccRCC and shows distinct associations with survival on anti-PD-1 vs anti-PD-1 + anti-CTLA-4. sTIM-3 is independent from other clinical and biological factors. Myeloid immune cells appear as the prominent source of sTIM-3, which may indicate their dysfunctional role in the antitumor immune response. Future investigations are warranted in patients treated with anti-PD-1 + antiangiogenic therapies. Further functional studies are needed to confirm its theranostic value and clarify its role in the immune response.

Conclusions and clinical implications

sTIM-3 appears to be a promising biomarker for optimizing treatment strategies in ccRCC as well as a potential therapeutic target.
Diversification of Dentate Gyrus Granule Cell Subtypes is Regulated by Neuregulin1 Nuclear Back Signaling
Authors: Rajebhosale Prithviraj , Jiang Li , Ressa Haylee J. , Johnson Kory R. , Desai Niraj , Jone Alice , Role Lorna W. , Talmage David A.
Published: October 2024

Neuronal heterogeneity is a defining feature of the developing mammalian brain, but the mechanisms regulating the diversification of closely related cell types remain elusive. In this study, we investigated the heterogeneity of dentate gyrus (DG) granule cells (GCs) and the influence of a psychosis associated V321L mutation in Neuregulin1 (Nrg1) on GC subtype composition. Using morpho-electric characterization, single-nucleus gene expression, and chromatin accessibility profiling, we identified distinct morphological and molecular features of typical GCs and a rare subtype known as semilunar granule cells (SGCs). The V321L mutation disrupts Nrg1 nuclear back-signaling, resulting in an overabundance of SGC-like cells. We discovered pseudotime gene expression trajectories suggesting the potential for GC-to-SGC transitions, supported by the accessibility of SGC-specific genes in other GCs. Intriguingly, we found an increase in SGC-marker expression over the adolescence to adulthood transition window in wild-type mice, coinciding with a decline in Nrg1 nuclear back-signaling capacity. This suggests that intact Nrg1 signaling suppresses SGC-like fate acquisition, and that its natural downregulation may underlie the emergence of SGC-like cells during postnatal development. Similarly, a pathological block of nuclear back signaling by the V321L mutation in Nrg1, may result in acquisition of the SGC-like fate due to loss of the repressive mechanisms maintained by intact nuclear back signaling. Our findings reveal a novel role for Nrg1 in maintaining DG cell-type composition and suggest that disrupted subtype regulation may contribute to disease-associated changes in DG GC morphology and function. Understanding these mechanisms provides new insights into mechanisms of cell-type diversity and its potential role in psychiatric pathology.
Synchrony dynamics underlie irregular neocortical spiking
Authors: Pattadkal Jagruti J. , O’Shea Ronan T , Hansel David , Taillefumier Thibaud , Brager Darrin , Priebe Nicholas J.
Published: October 2024

Cortical neurons are characterized by their variable spiking patterns. We challenge prevalent theories for the origin of spiking variability. We examine the specific hypothesis that cortical synchrony drives spiking variabilityin vivo. Using dynamic clamp, we demonstrate that intrinsic neuronal properties do not contribute substantially to spiking variability, but rather spiking variability emerges from weakly synchronous network drive. With large-scale electrophysiology we quantify the degree of synchrony and its time scale in cortical networksin vivo. We demonstrate that physiological levels of synchrony are sufficient to generate irregular responses foundin vivo. Further, this synchrony shifts over timescales ranging from 25 to 200 ms, depending on the presence of external sensory input. Such shifts occur when the network moves from spontaneous to driven modes, leading naturally to a decline in response variability as observed across cortical areas. Finally, while individual neurons exhibit reliable responses to physiological drive, different neurons respond in a distinct fashion according to their intrinsic properties, contributing to stable synchrony across the neural network.
SERPINB5-TGF-β signalling modulates desmoplakin membrane localization and ameliorates pemphigus vulgaris skin blistering
Authors: Rathod Maitreyi , Zimmermann Aude , Franz Henriette , Cunha Tomás , Didona Dario , Hertl Michael , Schmidt Enno , Spindler Volker
Published: October 2024

Impairment of desmosomal cell-cell adhesion leads to several life-threatening diseases such as the autoimmune skin blistering disorder pemphigus vulgaris (PV). Disease management strategies that stabilize intercellular adhesion, in addition to the existing immunosuppression therapies, may result in improved clinical outcomes. Previous findings showed that the serine protease inhibitor SERPINB5 promotes intercellular adhesion by binding to and regulating the localization of the desmosomal adapter molecule desmoplakin (DSP) at the plasma membrane. We here show that SERPINB5 overexpression prevents PV-IgG-mediated loss of cell-cell adhesion and the loss of DSP from the cell membrane. We mechanistically demonstrate that SERPINB5 loss deregulates TGF-β signalling, a pathway known to destabilize DSP in keratinocytes. TGF-β signalling was also activated in skin biopsies of PV patients and keratinocytes treated with PV autoantibodies, suggesting a contribution to disease. Inhibition of TGF-β activation ameliorated PV-IgG-mediated loss of cell-cell adhesion, increased DSP membrane expression, and prevented PV-IgG-induced blister formation in a humanex-vivoskin model. Together, SERPINB5 modulates DSP and intercellular adhesion through the regulation of TGF-β signalling. Further, TGF-β signalling was identified as a potential target for pemphigus treatment.
Dynamic Multiday Seizure Cycles and Evolving Rhythms in a Tetanus Toxin Rat Model of Epilepsy
Authors: Zarei Eskikand Parvin , Cook Mark J. , Burkitt Anthony N. , Grayden David B.
Published: October 2024

Epilepsy is characterized by recurrent, unpredictable seizures that impose significant challenges in daily management and treatment. One emerging area of interest is the identification of seizure cycles, including multiday patterns, which may offer insights into seizure prediction and treatment optimization. This study investigated multiday seizure cycles in a Tetanus Toxin (TT) rat model of epilepsy. Six TT-injected rats were observed over a 40-day period, with continuous EEG monitoring to record seizure events. Wavelet transform analysis revealed significant multiday cycles in seizure occurrences, with periods ranging from 4 to 7 days across different rats. Synchronization Index (SI) analysis demonstrated variable phase locking, with some rats showing strong synchronization of seizures with specific phases of the cycle. Importantly, the study revealed that these seizure cycles are dynamic and evolve over time, with some rats exhibiting shifts in cycle periods during the recording period. This suggests that the underlying neural mechanisms driving these cycles may change as the epileptic state progresses. The identification of stable and evolving multiday rhythms in seizure activity, independent of external factors, highlights a potential intrinsic biological basis for seizure timing. These findings offer promising avenues for improving seizure forecasting and designing personalized, timing-based therapeutic interventions in epilepsy. Future research should explore the underlying neural mechanisms and clinical applications of multiday seizure cycles.
Muon-induced baryon number violation
Authors: Fox Patrick J. , Hostert Matheus , Menzo Tony , Pospelov Maxim , Zupan Jure
Published: October 2024

The search for charged-lepton flavor violation in muon capture on nuclei is a powerful probe of heavy new physics. A smoking gun signal for μ→e conversion is a monochromatic electron with energy almost equal to the muon mass. We show that light new physics can mimic this signature and that it can also lead to electrons above the μ→e signal peak. A concrete example of such light new physics is μ−-nucleon annihilation into a light dark sector, which can produce an energetic e− as well as e+e− by-products. Due to the size of the muon mass, the exotic muon capture process can be kinematically allowed, while the otherwise stringent constraints, e.g., from proton decay, are kinematically forbidden. We also discuss other relevant constraints, including those from the stability of nuclei and muon capture in the interior of neutron stars.

Published by the American Physical Society
2024
Relational assets, environmental uncertainty and internationalization speed of Chinese multinational enterprises
Authors: Gao Rui , Du Xiaojun
Published: October 2024

Purpose

How to support the rapid internationalization of multinational enterprises (MNEs) is a hot topic in academia and industry. The main purpose of this work is to study the role of relational assets (R-assets) in promoting the speed of internationalization of MNEs, and to explore the moderating effect of environmental uncertainty (institutional environment and industry environment) on the relationship between R-assets and internationalization speed of MNEs.

Design/methodology/approach

This study uses the outward foreign investment data of China’s A-share listed enterprises from 2009 to 2021, and employs the Cox proportional hazards model to empirically test the research hypothesis.

Findings

The empirical results revealed that R-assets can promote enterprise internationalization speed. In addition, the study also finds that the institutional uncertainty of host countries weakens the promotion effect of R-assets on internationalization speed of MNEs, while the industry uncertainty strengthens the promotion effect of those. Heterogeneity analysis illustrates that, compared with state-owned enterprises, non-state-owned enterprises have a more significant effect on the above conclusions.

Originality/value

This study enriches the literature on internationalization speed of MNEs by focusing on the determinants of internationalization speed through R-assets. From the perspective of knowledge, the work also provides a theoretical reference whereby MNEs can use host country R-assets to accelerate knowledge acquisition and then internationalization practice. In conclusion, this study provides valuable insights for managers aiming to develop effective strategies through R-assets to achieve rapid internationalization, contributing to an emerging literature stream on catch-up for emerging-market MNEs.
Managing COVID-19 outbreaks in prisons – a brief review of literature and key lessons learnt
Authors: Guo Lin , Badrinath Padmanabhan , Mookherjee Jessica , Ghosh Anjan , McCallum Edyta , Dissanayake Nirosha , George Abraham
Published: October 2024

Purpose

During the COVID-19 pandemic, prisons faced a unique challenge of preventing and managing outbreaks with minimal adverse impact. This study aims to describe the epidemiology of COVID-19 in prisons, identify lessons learnt and make recommendations.

Design/methodology/approach

The authors used the PubMed advanced search function using MeSH terms; (coronavirus, sars) AND (prisons) AND (disease outbreaks). The authors included original research reporting COVID-19 outbreaks in prisons. All other types and non-English publications were excluded. The authors used a structured data abstraction template to extract data systematically, and a second author independently abstracted data from 10% of the papers for quality assurance.

Findings

The search yielded 96 hits. The authors included 15 studies meeting the inclusion criteria. These studies were from four countries. Seven studies reported individual outbreaks. The mean and median number of inmates and staff were 1,765, 1,126 and 575, 510. The mean and median number of cases among inmates and staff were 584, 464, and 72, 77. The number of reported deaths varied from 0 to 11. The authors present the prison-specific hazards grouped under human factors, healthcare factors and environmental factors. The authors also summarise interventions deployed as either primary prevention interventions, such as vaccinations, or secondary prevention interventions, including screening and contact tracing.

Originality/value

This narrative review summarises the prison-specific hazards, which include movement of people in and out of the person, moving in new prisoners from other prisons, mixing of prisoners when transporting to courts, limited medical and isolation resources, crowded dormitories, shared lavatories, small communal facilities, poor ventilation and overcrowding. The interventions included limiting non-medical transfers into and out of the persons, assigning staff members to specific areas, encouraging face coverings among prisoners and staff and social isolation measures within the constraints of the prison setting. The interventions were adopted by prison authorities to contain and manage the outbreaks. Public Health and prison authorities need to be aware of the risk of further outbreaks of COVID-19 and other infectious diseases in these settings and implement key measures identified in this review to minimise adverse outcomes.
Pandemic scars: long-term impact of COVID-19 on work stress among healthcare workers in China
Authors: Qian Hong , Lin Sihan , Zhang Lidan , Song Shanglin , Liu Ning
Published: October 2024

Purpose

This study mainly focused on the long-term effect of different risk exposure levels and prior anti-epidemic experience of healthcare workers in mitigating COVID-19 on their work stress in the post-COVID era.

Design/methodology/approach

The study sample included 359 physicians, 619 nurses, 229 technicians and 212 administrators, for a total of 1,419 healthcare workers working in the Lanzhou area during the investigation. Data were analyzed by multivariate regression models.

Findings

Our findings indicated that the interaction between pandemic effect mitigation experience and high-risk exposure significantly affected healthcare workers in the post-COVID era by increasing their work stress (p < 0.001) and reducing their rest time (p < 0.001). Healthcare workers may have experienced worse outcomes in the long term if they had higher levels of risk exposure and more experience in fighting epidemics. Furthermore, poor mental health (p < 0.001) and prior experience with SARS (p < 0.001) further amplified these adverse effects. However, surprisingly, we did not observe any effect of prior anti-epidemic experience or high-risk exposure on the mental health of healthcare workers in the post-COVID era (p > 0.1).

Research limitations/implications

The adverse impact of COVID-19 may have left long-lasting effects on Health professionals (HPs), particularly those with high Risk exposure (RE) and more mitigation experience. Poor Mental health (MH) and previous experience in mitigating previous similar outbreaks (such as SARS) are risk factors that should be considered. Support programs must be designed and promoted to help HPs respond and improve their performance.

Originality/value

Our study presents compelling evidence that the COVID-19 pandemic will have long-term detrimental effects on the work stress of healthcare workers.
Understanding technology transfer effectiveness in emerging economies: policy lessons for India
Authors: Roy Ipsita
Published: October 2024

Purpose

Despite technology transfer being emphasised in most public policy documents globally, it is not always clear how its effectiveness plays out in developing and emerging economies. This paper aims to bridge this gap by providing a systematic understanding of the processes of technology transfer, the antecedents and determinants, and finally how to measure its effectiveness, particularly in technologically dependent and emerging economies.

Design/methodology/approach

The paper puts forward a modified contingent effectiveness model of technology transfer based on Bozeman (2000) and Bozeman et al. (2015) and adapts it to incorporate the characteristics of emerging economies. Four major elements of technology transfer are discussed, namely, transfer object, actor characteristics, transfer environment, local environment and how they interact to determine effectiveness. Thereafter, the study shifts its focus to India’s evolving science technology and innovation (STI) ecosystem and discuss the current status, structure and major stakeholders associated with technology transfer. The study also reflects upon the challenges that inhibit effective technology transfer in India. In the last part, the study offers policy recommendations for improving the effectiveness of technology transfer, keeping in view India’s sustainable developmental goals.

Findings

A significant distinction of the conceptual model from its predecessors lies in its examination of the four dimensions of technology transfer effectiveness through the lens of developing and emerging economies, keeping in mind the inherent strengths, weaknesses and STI practices of the attendant local economy. As a novel contribution, the paper also discusses India’s evolving STI ecosystem backed by recent policy initiatives on technology transfer and the major stakeholders involved.

Originality/value

The paper constructs a modified contingent effectiveness model of technology transfer with particular emphasis on emerging economies. It also provides a comprehensive overview of India’s complex STI and technology transfer ecosystem, the challenges involved and offers recommendations for policy intervention.
Self-regulated learning, self-efficacy and life-long learning: the mediating role of future orientation
Authors: Stănescu Dan Florin , Frunzaru Valeriu , Stefanita Oana
Published: October 2024

Purpose

This study aims to investigate the intricate relations between self-regulated learning, life-long learning and academic self-efficacy, while also evaluating the mediating influence of future time orientation.

Design/methodology/approach

Utilizing a cross-sectional research design, data were amassed from 2,943 Romanian secondary school students in 11th and 12th grades via structured questionnaires: the self-regulated learning questionnaire, the academic self-efficacy scale, the future orientation scale derived from the Zimbardo time perspective inventory (ZTPI) and the lifelong learning scale.

Findings

The findings corroborate that self-regulated learning and academic self-efficacy when mediated by future time orientation, bolster life-long learning.

Practical implications

These results indicate that enhancing comprehension of future time orientation within the educational framework could potentially boost life-long learning.

Originality/value

This work is an original contribution, synthesizing existing literature, empirical findings and theoretical frameworks to advance our understanding of the multifaceted relationships shaping individuals' learning journey throughout their lives. Our focus on the mediating influence of future orientation adds a novel dimension to understanding the mechanisms through which individuals actively engage in learning throughout their lives.
Leveraging HR analytics for employee development: good for employees, organizations, and society
Authors: Yin Jiarui
Published: October 2024

Purpose

This paper aims to provide a new perspective on HR analytics that moves beyond the current narrative of its strategic value for organizations yet oftentimes at the cost of employee well-being. The paper argues that analytics-enabled employee development can unleash the positive impact of HR analytics on employees, organizations, and society.

Design/methodology/approach

This is a conceptual paper drawing on relevant literature and HR analytics applications.

Findings

Analytics-enabled employee development can help organizations gain employee buy-in by demonstrating the direct positive impact of HR analytics on employees. It contributes to social sustainability by focusing on developing employees' current and future skills, which benefits individuals, communities, and society. Moreover, it enhances organizations' human capital by aligning employees' skills and knowledge with business goals, creating a competitive edge.

Originality/value

This paper affords a new perspective on HR analytics implementation by focusing on the positive impact of analytics-enabled employee development. It provides three rationales for why organizations should invest in analytics-enabled employee development: gaining employee buy-in, contributing to social sustainability, and enhancing human capital.