bluuebunny/crossref_metadata_2025 huggingface dataset:
Innate Immune Memory is Stimulus Specific
Authors: O’Farrell Aoife , Niu Zijian , Li Jingxin , Van Eyndhoven Laura C. , Sarma Kavitha , Raj Arjun
Published: January 2025

Innate immune memory (also termed trained immunity) is defined in part by its ability to cross-protect against heterologous pathogens, and can be generated by many different stimuli, suggesting a “universal” trained state. However, different stimuli could form distinct memories, leading to stimulus-specific trained responses. Here, we use primary human monocyte-derived macrophages to demonstrate phenotypic and epigenetic stimulus specificity of innate immune memory six days after initial exposure. Quantification of cytokine production with single-molecule RNA imaging demonstrates stimulus-specific patterns of response to restimulation at the single cell level. Differential licensing of inflammatory transcription factors is associated with encoding of specificities in chromatin. Trained cells show stronger responses to secondary stimuli that are more similar to the initial stimulus they experienced, suggesting a functional role for these stimulus-specific memories. Rather than activating a universal training state, our findings demonstrate that different stimuli impart specific memories that generate distinct training phenotypes in macrophages.
DMEM and EMEM are suitable surrogate media to mimic host environment and expand leptospiral pathogenesis studies usingin vitrotools
Authors: Garcia Leandro E. , Lin Zitong , Culos Sophie , Muenker M Catherine , Johnson Emily E. , Wang Zheng , Lopez-Giraldez Francesc , Giraud-Gatineau Alexandre , Jackson Angela , Picardeau Mathieu , Goodlett David R. , Townsend Jeffrey P. , Pětrošová Helena , Wunder Elsio A.
Published: January 2025

PathogenicLeptospiraspecies can survive and thrive in a wide range of environments. Distinct environments expose the bacteria to different temperatures, osmolarities, and amounts and sources of nutrition. However, leptospires are mostly cultured, in a laboratory setting underin vitroconditions that do not reflect natural environments. This constraint on laboratory cultures limits the applicability ofin vitrostudies to the understanding of even simple pathogenic processes. Here we report, investigate, and identify a medium and conditions that mimic the host environment during leptospirosis infection, expanding the availablein vitrotools to evaluate leptospiral pathogenesis. We quantified genome-wide gene expression of pathogenicLeptospira interroganscultured in differentin vitromedia compositions (EMJH, DMEM, EMEM, and HAN). Using EMJH as standard, we compared gene expression in these compositions to genome-wide gene expression gathered in a host environment: whole blood (WB) of hamsters after infection with pathogenic leptospires. Leptospires cultured in DMEM and EMEM media shared 40% and 47% of all differentially expressed genes (DEGs) of leptospires present within WB (FDR<0.01), while leptospires cultured in HAN media only shared 20% of DEGs with those from WB. Furthermore, gene and pathway expression of leptospires cultured on DMEM and EMEM media exhibited a better correlation with leptospires grown in WB, including promoting expression of a similar leptospiral lipid A profile to the one identified directly in host tissues. Taken together, these results indicate that commercial cell-culture media EMEM or DMEM are better surrogates forin vivopathogenic studies than EMJH or HAN media inLeptospira. These alternative culture conditions, using media that are a standard supply worldwide, provide a reproducible and cost-effective approach that can accelerate research investigation and reduce the number of animal infections necessary for basic research of leptospirosis.
Differential regulation of histone H1 subtypes by N6-methyladenosine RNA methylation
Authors: García-Gomis D , López-Gómez J , Andrés M , Serna-Pujol N , Ponte I , Jordan A , Roque A
Published: January 2025

Histone H1 is involved in the regulation of chromatin structure and gene expression. Up to seven H1 subtypes or variants are expressed in human somatic cells. The H1 complement, defined as the subtype composition and proportions in a given cell, is highly variable depending on the cell type, cell cycle, developmental stage, and several diseases such as cancer. It is the result of the combined action of the different regulatory processes. Epitranscriptome modifications have emerged as a new regulatory mechanism able to control all aspects of mRNA metabolism. In this work, we have examined the role of the most prevalent mRNA modification, N6-methyladenosine RNA methylation (m6A), in the regulation of H1 subtypes. MeRIP-seq showed that H1.0 and H1.4 are enriched in m6A, while H1.2 has medium levels of this mark. We found that m6A inhibition altered transcript and protein levels, de novo transcription, and ribosome occupancy at the translation start site of specific H1 subtypes. Pull-down experiments using biotinylated-specific probes followed by mass spectrometry or RNA-immunoprecipitation coupled with RT-qPCR, allowed the identification of IGF2BP1, hnRNPD, and YTHDF2 as m6A readers of H1 subtypes. Integration of the functional studies, with m6A inhibition and partial depletion of the m6A readers led us to propose the first model of the differential regulation of H1 subtypes by m6A. In this model, m6A promotes the degradation of H1.0 mRNA mediated by YTHDF2, the stabilization of H1.2 mRNA by IGF2BP1 binding, and the H1.4 mRNA translation mediated by hnRNPD. These findings suggest that m6A is involved in the subtype-specific regulation of H1 subtypes, adding another layer to their complex regulation and contributing to the variability of the H1 complement in cancer.
Fabricating microfluidic co-cultures of immortalised cell lines uncovers robust design principles for the simultaneous formation of patterned, vascularised, and stem cell-derived adipose tissue
Authors: Murphy Ashley R. , Franco Rose Ann , Allenby Mark C.
Published: January 2025

In vitroculture processes supporting the simultaneous formation of vessel networks alongside differentiation towards mature parenchymal tissue have numerous clinical and agricultural applications but remain unrealised due to contrasting culture requirements. Of specific interest is lab-grown vascularised adipose tissue to study metabolic syndrome, diabetes, obesity, cardiovascular diseases, and to advance cultivated meat technologies. We report a microfluidic 3D hydrogel culture device capable of supporting live-imaging of fluorescent reporter cell lines and generating counter-current gradients of vasculogenic and adipogenic growth factors. for the first time, we report experimental conditions capable of reproducibly forming diverse microvascular networks from telomerase immortalised endothelial and mesenchymal stem cells in both 2D and 3D hydrogel-embedded cultures. Using our novel microfluidic culture design, we demonstrate the generation of growth factor environments which support the 3D co-formation of integrated robust microvascular networks and lipid-producing adipocytes after 31 days gradient culture. We demonstrate microvascular networks substantially support parenchymal stromal cell differentiation to mature adipose tissue (67.4% lipid coverage), unachieved in avascular cultures (1.86% lipid coverage). We attempt to validate our co-culture model by applying inhibitors of vessel-mediated lipogenesis (spermidine and VO-OHpic), which are demonstrated to be ineffective in our novel human preclinical model.

Highlights

An optimised co-culture protocol for vasculogenesis of immortalised cell lines.

Immortalised co-cultures form reproducible microvessel networks up to 31 days.

Gradient co-culture enables simultaneous MSC adipogenesis and EC vasculogenesis.

MSC differentiation to dense, lipid-laden adipose tissue relies on EC co-culture.

Human vascularised adipose tissue formation is unaffected by a murine regulator.

Graphical Abstract
The microbiome of the human facial skin is unique compared to that of other hominids
Authors: Degregori Samuel , Manus Melissa B. , Qu Evan B. , Mendall Calen P. , Baker Jacob S. , Hopper Lydia M. , Amato Katherine R. , Lieberman Tami D.
Published: January 2025

The human facial skin microbiome is remarkably similar across all people sampled to date, dominated by facultative anaerobeCutibacterium. The origin of this genus is unknown, with no close relatives currently described from samples of primate skin. This apparent human-specific bacterial taxon could reflect the unique nature of human skin, which is significantly more oily than that of our closest primate relatives. However, previous studies have not sampled the facial skin microbiome of our closest primates. Here, we profiled the skin microbiome of zoo-housed chimpanzees (Pan troglodytes), and gorillas (Gorilla gorilla gorilla), alongside their human care staff, using both 16S and shotgun sequencing. We showed that facial skin microbiomes differ significantly across host species, with humans having the lowest diversity and most unique community among the three species. We were unable to find a close relative ofCutibacteriumon either chimpanzee or gorilla facial skin, consistent with human-specificity. Hominid skin microbiome functional profiles were more functionally similar compared to their taxonomic profiles. However, we still found notable functional differences including lower proportions of fatty acid biosynthesis on humans, consistent with microbes’ reliance on host-derived lipids. Our study highlights the uniqueness of the human facial skin microbiome and supports a horizontal acquisition of its dominant resident from a yet unknown source.

Importance

Understanding how and why human skin bacteria differ from our closest animal relatives provides crucial insights into human evolution and health. While we have known that human facial skin hosts distinct bacteria—particularlyCutibacterium acnes—we did not know if these bacteria and their associated genes were also present on the faces of our closest relatives, chimpanzees and gorillas. Our study shows that human facial skin hosts markedly different bacteria than other primates, withC. acnesbeing uniquely abundant on human faces. This finding suggests that this key bacterial species may have adapted specifically to human skin, which produces more oils than other primates.
South African brown locusts,Locustana pardalina, hosts fluconazole resistantCandidozyma(Candida)auris(Clade III)
Authors: Ogundeji Adepemi , Bello-Akinosho Maryam , Swart Vaughn , Featherston Jonathan , Bolsenbroek Armand , Beneke Carel , Musoke Jolly , Baker Tyla , Ismail Arshad , Sebolai Olihile , Albertyn Jacobus , Pohl Carolina
Published: January 2025

The environmental niche and mode of transmission from the environment to humans of the emerging pathogenic yeast,Candidozyma(Candida)aurisis a subject of speculation, with hypotheses including avian species and marine environments. Interestingly, yeasts related toC. aurishave been repeatedly observed associated with various insects. This lprompted us to investigate a thermophilic insect,Locustana pardalinaas possible host forC. auris. Here we report the isolation and identification of threeC aurisstrains from the gut ofL. pardalinaas well as the phenotypic characterisation of one of these isolates. Interestingly, the isolate was able to survive at 50oC and grew at 15% NaCl. In addition, it was susceptible to the tested disinfectants and antifungals, except fluconazole. Genome sequencing and SNP analyses placed the isolate in Clade III, which is common is South Africa. This highlights the role of insects in the evolution and dissemination of emerging pathogenic yeasts.
Ultrasound Applications in the Treatment of Major Depressive Disorder (MDD): A Systematic Review of Techniques and Efficacy
Authors: Tan Gansheng , Chen Hong , Leuthardt Eric C.
Published: January 2025

Objective

Major depressive disorder (MDD) is a debilitating mental health condition characterized by persistent feelings of sadness, loss of interest, and impaired daily functioning. It affects approximately 8% of the U.S. population, posing a significant personal and economic burden. Around 30% of patients with MDD do not respond to conventional antidepressant and psychotherapeutic treatments. Current treatment options for refractory MDD include transcranial magnetic stimulation (TMS) and invasive surgical procedures such as surgical ablation, vagus nerve stimulation, and deep brain stimulation. TMS has modest efficacy, and surgical procedures are associated with surgical risk and low patient acceptance. With the unique advantage of combining non-invasiveness with selective targeting, therapeutic ultrasound emerges as a promising alternative for treating refractory MDD. Over the past 10 years, there has been a growth in focused ultrasound research, leading to an exponential increase in academic and public interest in the technology. To support the continued development of ultrasound for treating MDD, we conducted a systematic review following Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines.

Methods

We included peer-reviewed prospective cohort studies, case-control studies, and randomized control trials that evaluate the efficacy of ultrasonic treatment for depression (PROSPERO registration number: CRD42024626093). We summarized ultrasonic techniques for treating depression and their efficacy. Furthermore, we identified key challenges and future directions for applying ultrasound in treating MDD.

Results

We identified 67 potentially relevant articles, of which 18 studies met all inclusion criteria. The techniques of applying ultrasound to treat depression include magnetic resonance-guided focused ultrasound (MRgFUS) for capsulotomy and low-intensity focused ultrasound (LIFUS) neuromodulation. In human trials, the response rate (≥50% improvement from baseline on depression score) is 53.85% for MRgFUS and 80.49% for LIFUS neuromodulation. In all preclinical studies using rodent models (8 studies), LIFUS neuromodulation had a medium to large effect (|Cohen’s d| > 0.6) on resolving depressive-like behavior in rodents without causing adverse effects such as tissue damage. MRgFUS faces inconsistent lesioning success and a limited response rate, while LIFUS neuromodulation lacks systematic exploration of parameter space and a clear understanding of its mechanistic effects. Future work should refine patient selection for MRgFUS and focus on individualized functional targeting.

Conclusion

LIFUS neuromodulation showed a medium to large effect in reducing depressive behaviors in both rodent models and human trials, representing a promising, noninvasive option for treating refractory MDD.
An updated vocal repertoire of wild adult bonobos (Pan paniscus)
Authors: Wegdell Franziska , Schamberg Isaac , Berthet Mélissa , Rothacher Yannik , Dellwo Volker , Surbeck Martin , Townsend Simon
Published: January 2025

While research over the last 20 years has shed important light on the vocal behaviour of our closest living relatives, bonobos and chimpanzees, a quantitative description of their full vocal repertoire is absent. Such data are critical for a holistic understanding of a species’ communication system and unpacking how these systems compare more broadly with other primate and non-primate species. Here we make key progress by providing the first quantitativePanvocal repertoire, specifically for wild bonobos. Using data comprising over 1500 calls from 53 adult individuals collected over 33 months, we employ machine-learning-based random forest analyses and describe 11 acoustically distinguishable call types. We discuss issues associated with resolving vocal repertoires from wild data in great apes and highlight potential future approaches to further capture the complexity of the bonobo vocal system.
Inverse hourglass pattern of conservation in rodent molar development
Authors: Ganofsky Jérémy , Estevez-Villar Mathilde , Mouginot Marion , Moretti Sébastien , Nyamari Marion , Robinson-Rechavi Marc , Pantalacci Sophie , Sémon Marie
Published: January 2025

Although it is well established that certain stages of development are more conserved than others, the reasons for this phenomenon remain largely unknown. We study molecular conservation in the development of an organ, the molar, by comparing the temporal profiles of expression in mice and hamsters. We find that molar development is characterized by a rarely observed pattern of conservation of expression level and coding sequences forming an inverse hourglass, with more conservation at the beginning and end of morphogenesis than at intermediate stages. As the development of the rodent molar is well described, we were able to link this pattern to the properties of the expressed genes and the activity of different developmental processes. Early and late stages mobilize different sets of pleiotropic genes, cell division for bud growth and secretion for tooth mineralization. The particularities of dental morphogenesis and homeostasis, with the degradation of certain tissues at the end of development and the hosting of immune cells, as well as heterochronies linked to adaptations, also probably contribute to the pattern. Our study of the different actors explains the inverted hourglass of molars by a combination of processes intrinsic to the teeth, and by negative and positive selection which is mostly extrinsic to the teeth. This is likely translatable to explain molecular conservation patterns in many other biological systems.
Malaria vector diversity, transmission, and insecticide resistance, in island communities along the Volta Lake in southern Ghana
Authors: Ebuako Abena Ahema , Owusu-Asenso Christopher Mfum , Mohammed Abdul Rahim , Sraku Isaac Kwame , Akuamoah-Boateng Yaw , Appiah-Kwarteng Cornelia , Forson Akua Obeng , Ayeh-Kumi Patrick Ferdinand , Afrane Yaw A.
Published: January 2025

Island communities along the Volta Lake in southern Ghana present unique challenges for malaria control, characterized by high transmission rates, limited vector control measures, and isolated ecosystems. This study assessed the malaria vector diversity, seasonal abundance, transmission, and insecticide resistance status of malaria vectors in these communities to inform effective control strategies. Mosquitoes were collected from three island communities (Tuanikope, Allorkpem, and Pediatorkope) using human landing catches, light traps, and prokopack aspirators during the dry and rainy seasons. Morphological and molecular techniques were used to identify mosquito species, determine blood meal sources, and detect insecticide resistance mutations. Sporozoite infections and entomological inoculation rates (EIRs) were also quantified. A total of 25,079 mosquitoes from four genera were collected; Culicine = 88.19%, Anopheline = 8.89%. Mansonia = 2.24%. The Anophelines predominantly comprisedAnopheles gambiaes.l. 1,911/2,230 (85.70%), followed byAn.pharoensis236/2,230 (10.58%) andAn. rufipes83/2,230 (3.72%). Indoor biting and resting densities were high across sites and seasons, with sporozoite-positive mosquitoes more frequently found indoors. Blood meal analysis revealed a strong anthropophilic feeding pattern (HBI = 80%). Annual EIRs ranged from 37.40 (ib/m/y) to 100.08 (ib/m/y). Low frequencies of insecticide resistance mutations (Vgsc-1014F, Vgsc-1014S, ACE-1, and Vgsc-1575Y) were observed. The study indicates high indoor biting and resting densities ofAnophelesmosquitoes. High sporozoite rate along with low resistance mutation frequencies observed, emphasize the urgent need for continuous resistance monitoring and the implementation of targeted vector control strategies in these hard-to-reach island communities.
Characterization of BvlzGluc, a Novel Antifungal β-Glucanase fromBacillus velezensis, with Potential Agricultural and Industrial Applications
Authors: Vela-Corcia D. , Colino-Palomino A.M. , de Vicente A. , Pérez García A. , Romero D.
Published: January 2025

β-glucanases play a critical role in degrading β-glucans, which are essential components of fungal cell walls that maintain fungal structure and physiology. This study characterizes BvlzGluc, a novel β-glucanase produced byBacillus velezensisCECT 8237, which has potent antifungal properties. BvlzGluc specifically targets the β-glucan layer ofBotrytis cinerea, causing significant structural malformations, impaired fungal development, and reduced virulence. These effects weaken the fungal cell wall, increasing its susceptibility to environmental stress and reducing its capacity to infect host plants. Notably, BvlzGluc is a noncanonical β-glucanase belonging to glycoside hydrolase family 16 (GH16) but presents unique structural features that distinguish it from typical members of this family, suggesting potential reclassification. Its physicochemical stability and simple structural design increase its suitability for scalable production, positioning it as a promising candidate for agricultural and industrial applications requiring efficient β-glucan degradation. This work builds on previous studies of microbial antifungal mechanisms, providing new insights into bacterial‒fungal interactions and reinforcing the potential of bacterial enzymes in sustainable pathogen management and advancing biotechnological innovations.
Cell-APP: A generalizable method for microscopic cell annotation, segmentation, and classification
Authors: Virdi Anish , Joglekar Ajit P.
Published: January 2025

High throughput fluorescence microscopy is an essential tool in systems biological studies of eukaryotic cells. Its power can be fully realized when all cells in a field of view and the entire time series can be accurately localized and quantified. These tasks can be mapped to the common paradigm in computer vision: instance segmentation. Recently, supervised deep learning-based methods have become state-of-the-art for cellular instance segmentation. However, these methods require large amounts of high-quality training data. This requirement challenges our ability to train increasingly performant object detectors due to the limited availability of annotated training data, which is typically assembled via laborious hand annotation. Here, we present a generalizable method for generating large instance segmentation training datasets for tissue-culture cells in transmitted light microscopy images. We use datasets created by this method to train vision transformer (ViT) based Mask-RCNNs (Region-based Convolutional Neural Networks) that produce instance segmentations wherein cells are classified as “m-phase” (dividing) or “interphase” (non-dividing). While training these models, we also address the dataset class imbalance between m-phase and interphase cell annotations, which arises for biological reasons, using probabilistically weighted loss functions and partisan training data collection methods. We demonstrate the validity of these approaches by producing highly accurate object detectors that can serve as general tools for the segmentation and classification of morphologically diverse cells. Since the methodology depends only on generic cellular features, we hypothesize that it can be further generalized to most adherent tissue culture cell lines.
Genetic Determinants of pOXA-48 Plasmid Maintenance and Propagation inEscherichia coli
Authors: Baffert Yannick , Fraikin Nathan , Makhloufi Yasmine , Baltenneck Julie , Val Marie-Eve , Dedieu-Berne Annick , Degosserie Jonathan , Iorga Bogdan I. , Bogaerts Pierre , Gueguen Erwan , Lesterlin Christian , Bigot Sarah
Published: January 2025

Conjugative plasmids are the main drivers of antibiotic resistance dissemination contributing to the emergence and extensive spread of multidrug resistance clinical bacterial pathogens. pOXA-48 plasmids, belonging to the IncL group, have emerged as the primary vehicle for carbapenem resistance inEnterobacteriaceae. Despite the problematic prevalence of pOXA-48, most research has focused on epidemiology and genomics, leaving gaps in our understanding of the mechanisms behind its propagation. In this study, we used a transposon sequencing approach to identify genetic elements critical for plasmid stability, replication, and conjugative transfer. Our results identified a novel type I toxin-antitoxin system, new essential maintenance factors, and components of the type IV secretion system and regulatory elements crucial for conjugation. This study advances our understanding of pOXA-48 biology, providing key insights into the genetic factors underlying its successful maintenance and spread in bacterial populations.
Homeostatic bidirectional plasticity in Upbound and Downbound micromodules of the olivocerebellar system
Authors: Fernández Santoro Elías M. , Landsmeer Lennart P.L. , Hamdioui Said , Strydis Christos , De Zeeuw Chris I. , Badura Aleksandra , Negrello Mario
Published: January 2025

Olivocerebellar learning is highly adaptable, unfolding over minutes to weeks depending on the task. However, the stabilizing mechanisms of the synaptic dynamics necessary for ongoing learning remain unclear. We constructed a model to examine plasticity dynamics under stochastic input and investigate the impact of inferior olive (IO) reverberations on Purkinje cell (PCs) activity and synaptic plasticity. We explored Upbound and Downbound cerebellar micromodules, which are organized loops of IO neurons, cerebellar nuclei neurons and microzones of PCs characterized by their unique molecular profiles and different levels of baseline firing. Our findings show synaptic weight convergence followed by stability of synaptic weights. In line with their relatively low and high intrinsic firing, we observed that Upbound and Downbound PCs have a propensity for potentiation and depression, respectively, with both PC types reaching stability at differential levels of overall strength of their parallel-fiber (PF) inputs. The oscillations and coupling of IO neurons participating in the Upbound and Downbound modules determine at which frequency band PFs can be stabilized optimally. Our results indicate that specific frequency components drive IO resonance and synchronicity, which, in turn, regulate temporal patterning across Upbound and Downbound zones, orchestrating their plasticity dynamics.

Author Summary

The olivocerebellar system is a part of the brain that facilitates learning and controlling movements. To coordinate movements it integrates sensorimotor information with motor command signals. The resulting behaviour needs to be continuously adjusted during motor learning. The leading hypothesis is that changes in strength of the synaptic connections between neurons underlie the learning process. The challenge is to elucidate the factors that determine the exact timing and precision of the learned movements. To answer this question we developed a computational model of the two main types of modules of the olivocerebellar system that can control different types of movements in a bidirectional fashion. We found that the rhythm and coupling of the olivary neurons play an important role in controlling and stabilizing plasticity in the cerebellar cortex of both types of modules, together shaping learning-dependent timing of motor behaviour.
Hypothalamic Vasopressin Neurons Enable Maternal Thermoregulatory Behaviors
Authors: Adahman Zahra , Ooyama Rumi , Gashi Dinore B. , Medik Zeyneb Z. , Hollosi Hannah K. , Sahoo Biswaranjan , Akowuah Nana D. , Riceberg Justin S. , Carcea Ioana
Published: January 2025

Newborns of many mammalian species are partial poikilotherms and require adult thermoregulatory care for survival. In mice, pup survival in cold and cool ambient temperature depends on the ability of adult caregivers to huddle pups and bring them into a high-quality nest. It is therefore essential that adult mice adjust parental care as a function of changes in ambient temperature. Here, we investigated how mouse maternal care adapts to a range of temperatures, from cold to warm. We show that changes in ambient temperature affect several individual and co-parenting maternal behaviors in both dams and virgin female mice, and modulate activity of vasopressin neurons. Furthermore, we establish that the effects of ambient temperature on both maternal care and the activity of vasopressin neurons depend in part on thermosensation, specifically on the TRPM8 sensor. Using trans-synaptic anterograde tracing and whole-brain activity mapping, we find that vasopressin neurons from the paraventricular hypothalamic nucleus connect synaptically with temperature-responsive brain structures implicated in maternal care. We then show that optogenetic activation of vasopressin projections to the central amygdala, a structure activated by cold ambient temperature, recapitulates the effects of cold on co-parenting behaviors. Our data provide a biological mechanism for maternal thermoregulatory behavior in mice with translational relevance to the reported association between ecosystem temperature fluctuations and variations in human child neglect cases.
Maturation of Hippocampus-Medial Prefrontal Cortex Projections Defines a Pathway-Specific Sensitive Period for Cognitive Flexibility
Authors: Cruz-Sanchez Arely , Abdusalom Anusha , Chasiotis Helen , Gugustea Radu , Mumtaz Unza , Hasantash Maryam , Anacker Christoph , Arruda-Carvalho Maithe
Published: January 2025

The septotemporal axis of the hippocampus separates it into domains with unique molecular, cellular, downstream connectivity and behavioral profiles, and yet very little is known about the ontogenesis of these highly specialized subcircuits. Here, we used viral tracing, optogenetic-assisted patch clamping, chemogenetics and behavior in mice to examine changes in domain-defined hippocampus efferent projections from postnatal day (P)10 to P60. We found distinct anatomical and synaptic developmental signatures in ventral and intermediate CA1 downstream connectivity, with unique contributions to the prelimbic and infralimbic subregions of the medial prefrontal cortex (mPFC). Inhibition of the ventral CA1 (vCA1)-mPFC pathway during juvenility led to a deficit in adult cognitive flexibility exclusively in females, establishing a sex- and pathway-specific sensitive period preceding the stabilization of vCA1-mPFC synaptic transmission. Our data elucidate domain- and target-defined postnatal maturation of hippocampus efferents, identifying a sex-specific sensitive period with crucial implications for early life influences on adult cognition.
Complex Water Networks Visualized through 2.2-2.3 Å Cryogenic Electron Microscopy of RNA
Authors: Kretsch Rachael C. , Li Shanshan , Pintilie Grigore , Palo Michael Z. , Case David A. , Das Rhiju , Zhang Kaiming , Chiu Wah
Published: January 2025

The stability and function of biomolecules are directly influenced by their myriad interactions with water. In this study, we investigated water through cryogenic electron microscopy (cryo-EM) on a highly solvated molecule, theTetrahymenaribozyme, determined at 2.2 and 2.3 Å resolutions. By employing segmentation-guided water and ion modeling (SWIM), an approach combining resolvability and chemical parameters, we automatically modeled and cross-validated water molecules and Mg2+ions in the ribozyme core, revealing the extensive involvement of water in mediating RNA non-canonical interactions. Unexpectedly, in regions where SWIM does not model ordered water, we observed highly similar densities in both cryo-EM maps. In many of these regions, the cryo-EM densities superimpose with complex water networks predicted by molecular dynamics (MD), supporting their assignment as water and suggesting a biophysical explanation for their elusiveness to conventional atomic coordinate modeling. Our study demonstrates an approach to unveil both rigid and flexible waters that surround biomolecules through cryo-EM map densities, statistical and chemical metrics, and MD simulations.
Evaluation of distal facial nerve branches contribution to facial nerve paralysis in rodents
Authors: Marin Barbara G , Grant Jordan L , Mei Christine , Tejeda Giancarlo , Taylor Ruby Rose , Lee Grant M , Ortega Victoria L , Cozzone Isabella G , Robbio Rachael M , Robbio Trinity , Prasad Abhishek , Gadkaree Shekhar K , Dumont Courtney M
Published: January 2025

Introduction/Aims: Facial nerve paralysis is a complex and devastating condition. Translational research of facial paralysis recovery remains largely limited to animal studies, for which there are many potential models employed. When studying facial nerve regeneration in rodents, it is important to understand the converging contributions of the motor supply into the whisker pad. A consensus surgical approach and animal model has yet to be defined. Of particular interest for movement of the nose and whiskers are the buccal and marginal mandibular nerves. This study aims to evaluate how these distal nerve branches contribute to facial nerve paralysis and identify key morphological changes at the neuromuscular junctions (NMJs) in the whisker pad of rodents. Methods: Adult rats underwent isolated transection of the buccal branch of the facial nerve, both the buccal and marginal mandibular branches of the facial nerve, or control sham surgery. Results: Histological, electrophysiological, and behavior assessments confirmed that the transection of the buccal branch alone did not cease whisker movement in rats, but when combined with a transection of the marginal mandibular branch, it resulted in full paralysis of the whisker and nose movement. Discussion: These results are indicative of the distinct roles of these nerves branches in facial paralysis repair following a transection injury. Further, our results suggest additional targets for facial nerve repair treatments.
Microbial cross-feeding is stabilized when a dependent mutant is segregated from its independent ancestor
Authors: Schakel Olivia F. , Fritts Ryan K. , Zmuda Anthony J. , Setayeshgar Sima , McKinlay James B.
Published: January 2025

Microbial gene loss is hypothesized to be beneficial when gene function is costly, and the gene product can be replaced via cross-feeding from a neighbor. However, cross-fed metabolites are often only available at low concentrations, limiting the growth rates of gene-loss mutants that are dependent on those metabolites. Here we define conditions that support a loss of function mutant in a three-member bacterial community of: (i) N2-utilizingRhodopseudomonas palustrisas an NH4+-excreting producer, (ii) N2-utilizingVibrio natriegensas the ancestor, and (iii) aV. natriegensN2-utilizaton mutant that is dependent on the producer for NH4+. Using experimental and simulated cocultures, we found that the ancestor outcompeted the mutant due to low NH4+availability under uniform conditions where bothV. natriegensstrains have equal access to nutrients. However, spatial structuring that separated the mutant from the ancestor, while maintaining access to NH4+from the producer, allowed the mutant to avoid extinction. Counter to predictions, mutant enrichment under spatially structured conditions did not require a growth rate advantage from gene loss and the mutant coexisted with its ancestor. Thus, cross-feeding can originate from loss-of-function mutations that are otherwise detrimental, provided that the mutant can segregate from a competitive ancestor.

Graphical abstract
Combined ADAMTS10 and ADAMTS17 inactivation exacerbates bone shortening and compromises extracellular matrix formation
Authors: Taye Nandaraj , Karoulias Stylianos Z. , Balic Zerina , Wang Lauren W. , Willard Belinda B. , Martin Daniel , Richard Daniel , Okamoto Alexander S. , Capellini Terence D. , Apte Suneel S. , Hubmacher Dirk
Published: January 2025

Weill-Marchesani syndrome (WMS) is characterized by severe short stature, short hands and feet (brachydactyly), joint contractures, tight skin, and heart valve, eye, and skin anomalies. Whereas recessive WMS is caused by mutations inADAMTS10,ADAMTS17, orLTBP2, dominant WMS is caused by mutations inFBN1(encoding fibrillin-1). Since bone growth is driven by chondrocyte proliferation and hypertrophy in the growth plates, the genetics of WMS suggests that the affected ECM proteins act within the same pathway to regulate chondrocyte and growth plate function. Here, we investigated the role of the secreted ADAMTS proteases ADAMTS10 and ADAMTS17 in growth plate function and ECM formation. We generatedAdamts10;Adamts17double knockout (DKO) mice, which showed significant postnatal lethality compared to singleAdamts10orAdamts17KO mice. Importantly, we observed severe bone shortening DKO mice, which correlated with a narrower hypertrophic zone in their growth plates. ADAMTS17 substrates identified by N-terminomics and yeast two-hybrid screening identified the ECM proteins fibronectin and collagen VI (COL6). However, validation experiments did not reveal direct proteolysis of either fibronectin or COL6 by ADAMTS17. We then investigated ECM formation in primary ADAMTS10- and ADAMTS17-deficient skin fibroblasts and observed compromised fibronectin deposition concomitant with aberrant intracellular accumulation of fibrillin-1. These findings support a role for ADAMTS17 in ECM protein secretion and assembly. Collectively, our data suggest that ADAMTS10 and ADAMTS17 regulate bone growth by regulating chondrocyte hypertrophy or hypertrophic chondrocyte turnover. Mechanistically, ADAMTS17 appears to be a critical regulator of ECM protein secretion or pericellular matrix assembly, whereas ADAMTS10 likely modulates ECM formation at later stages, possibly regulating the spatio-temporal deposition of fibrillin isoforms.
Frontal midline theta power accounts for inter-individual differences in motor learning ability
Authors: Fukuda Yuya , Uehara Kazumasa
Published: January 2025

Recent neurophysiological studies have demonstrated that frontal midline theta (FMT) activity plays a significant role in motor learning. One of the key challenges in motor learning is to understand the interindividual variability in learning proficiency rates, yet the underlying neural mechanisms remain unclear. To address this open question, this study recorded electroencephalogram activity during a visuomotor tracking task to investigate whether modulation of FMT power and the consistency of theta phase during motor preparation could explain individual differences in learning proficiency. We found a significant positive correlation between increased FMT power during motor preparation and learning proficiency rates. Specifically, individuals with greater FMT power exhibited faster learning rates. In contrast to this, no significant correlation was observed between the consistency of theta phase during motor preparation and learning proficiency. Together, these findings highlight that the FMT power, rather than phase synchrony, is closely associated with motor learning efficiency. This study provides a novel perspective for understanding the causes of individual differences in motor learning and further corroborates the previous evidence showing FMT power contributes to motor learning processes.
Loss of Fanconi anemia proteins causes a reliance on lysosomal exocytosis
Authors: Fu Becky Xu Hua , Xu Albert , Li Hua , Johnson Daniel E. , Grandis Jennifer R. , Gilbert Luke A.
Published: January 2025

Mutations in the FA pathway lead to a rare genetic disease that increases risk of bone marrow failure, acute myeloid leukemia, and solid tumors. FA patients have a 500 to 800-fold increase in head and neck squamous cell carcinoma compared to the general population and the treatment for these malignancies are ineffective and limited due to the deficiency in DNA damage repair. Using unbiased CRISPR-interference screening, we found the loss of FA function renders cells dependent on key exocytosis genes such as SNAP23. Further investigation revealed that loss of FA pathway function induced deficiencies in lysosomal health, dysregulation of autophagy and increased lysosomal exocytosis. The compromised cellular state caused by the loss of FA genes is accompanied with decreased lysosome abundance and increased lysosomal membrane permeabilization in cells. We found these signaturesin vitroacross multiple cell types and cell lines and in clinically relevant FA patient cancers. Our findings are the first to connect the FA pathway to lysosomal exocytosis and thus expands our understanding of FA as a disease and of induced dependencies in FA mutant cancers.
Black hole effective theory for strongly interacting matter
Authors: Järvinen Matti , Weissman Dorin
Published: January 2025

We establish a new tool for studying strongly coupled matter: an effective theory of black holes in gravity, which maps to a hydrodynamic description of field theories via the gauge-gravity duality. Our approach is inspired by previously known effective theories found in the limit of a high number of dimensions. We argue that the new approach can accurately describe phase transitions in a wide class of theories, such as the Yang-Mills and other nearly critical field theories. As an application to a previously unsolved problem, we analyze the interface between confining and deconfining phases in holographic Yang-Mills theory.

Published by the American Physical Society
2025
Studying novel high-pressure phases in laser-shock-affected silicon using poly: an algorithm for spot-wise phase identification
Authors: Doostkam Rasool , Gelisio Luca , Yurtsever Aycan , Rapp Ludovic , Rode Andrei V. , Beyerlein Kenneth R.
Published: January 2025

Fast quenching dynamics in confined laser-induced microexplosions have been shown to lead to localized shockwaves that can create nanometre-scale domains in novel high-pressure crystalline phases. In the case of silicon, new silicon polymorphs such as bt8-Si and st12-Si have been recently observed, which are predicted to have bandgaps desirable for photovoltaic applications. Identification of these phases has been previously achieved by analysis of selected-area electron diffraction (SAED) patterns taken from laser-shock-affected areas. However, this analysis was complicated by pattern overlap from the many crystallites in the selected area, and many spots were found to agree with multiple potential phases. To overcome this ambiguity and enable the identification of the phase of Bragg spots observed in SAED patterns from polymorphic nanomaterials, we developed a new algorithm that we termed poly. This method is based on maximizing the magnitude and angular correlation between observed diffraction spots and those values derived from a known potential phase. We present the performance of this algorithm on simulated electron diffraction patterns as well as experimental SAED patterns measured from laser-shock-affected silicon samples. We find that the most abundant phases in the affected areas are t32-Si and t32*-Si and report on their relaxation into other high-pressure silicon phases over the course of 90 days after the laser-induced confined microexplosion.
Designing a hybrid organization structure based on competences: the importance of the organizational structure
Authors: Bagni Gustavo , Marçola Josadak Astorino , Escrivão Filho Edmundo , Nagano Marcelo Seido , Philippsen Luiz
Published: January 2025

Purpose

The purpose of this study is to propose a comprehensive model of a hybrid organizational structure through action research, aiming to fill a gap in the literature on organizational structure implementation. The focus is on designing a model that integrates structural elements (centralization and specialization) and a non-structural element (competence), emphasizing operational efficiency and innovation capacity. The study was conducted in the production scheduling and control department (PSC) of a manufacturing company, with quantitative results demonstrating the feasibility of the proposed model.

Design/methodology/approach

The study employs an action research approach to develop a hybrid organizational structure model in three phases comprising ten steps. It focuses on integrating structured elements like centralization and specialization, alongside a non-structural component, competence. The research was conducted within the PSC of a manufacturing firm. This methodological framework facilitates the systematic design and implementation of the organizational structure model, allowing for a comprehensive analysis of its impact on performance indicators.

Findings

The quantitative results of the action research revealed a 3% increase in Overall Equipment Efficiency (OEE) and a 4% improvement in On Time/In Full (OTIF) performance metrics. These findings demonstrate the effectiveness and feasibility of the hybrid organizational structure model implemented in the PSC. The structured elements (centralization and specialization) combined with the non-structural element (competence) contributed to enhancing operational efficiency and meeting production goals, underscoring the significance of aligning organizational structure with strategic objectives for improved performance in dynamic competitive environments.

Originality/value

This study contributes to the literature by addressing the gap in research on implementing organizational structures. It offers a novel approach through action research, proposing a comprehensive model of a hybrid organizational structure. By integrating structured elements (centralization and specialization) with a non-structural element (competence), the model enhances operational efficiency and innovation capacity. The quantitative findings demonstrate the model’s effectiveness in improving performance metrics, emphasizing its value in guiding organizational design processes. This research underscores the importance of aligning organizational structures with strategic objectives to foster competitiveness and adaptability in dynamic business environments.
Demand forecasting in clearance season for fast fashion retail: a residual learning approach
Authors: Gülcan Nur , Tüzün Aksu Dilek , Goularas Dionysis
Published: January 2025

Purpose

This study focuses on forecasting demand for markdown pricing in situations where historical data are limited and proposes using a hybrid knowledge-based residual (KRL) network to enhance the accuracy of demand predictions in fast fashion retailing.

Design/methodology/approach

We use a hybrid KRL network structure to increase forecasting accuracy in fast fashion data by combining artificial neural network (ANN) and theoretical demand models (TDMs) such as linear, exponential and multinomial logit. We used a linear demand model (LDM) as a theoretical demand model, which is one of the popular TDMs in the literature, and combined it with neural networks utilizing the residual network structure. We tested it on real fast fashion data to estimate the next week’s demand at the clearance seasons of 5 years.

Findings

The results underscore KRL’s capability to derive mutual benefits from both neural networks and LDM, especially in the specific context of limited fast fashion data. Furthermore, KRL outperforms LDM and ANN models when used individually in forecasting accuracy.

Originality/value

The research paper proposes a scientific, quantitative method for forecasting the sales for markdown settings, combining data driven and TDMs using residual learning thereby resolving the issue of insufficient sales data in the fashion industry.