bluuebunny/crossref_metadata_2025 huggingface dataset:
A mechanistic model of gossip, reputations, and cooperation
Authors: Kawakatsu Mari , Kessinger Taylor A. , Plotkin Joshua B.
Published: May 2024

Social reputations facilitate cooperation: those who help others gain a good reputation, making them more likely to receive help themselves. But when people hold private views of one another, this cycle of indirect reciprocity breaks down, as disagreements lead to the perception of unjustified behavior that ultimately undermines cooperation. Theoretical studies often assume population-wide agreement about reputations, invoking rapid gossip as an endogenous mechanism for reaching consensus. However, the theory of indirect reciprocity lacks a mechanistic description of how gossip actually generates consensus. Here, we develop a mechanistic model of gossip-based indirect reciprocity that incorporates two alternative forms of gossip: exchanging information with randomly selected peers or consulting a single gossip source. We show that these two forms of gossip are mathematically equivalent under an appropriate transformation of parameters. We derive an analytical expression for the minimum amount of gossip required to reach sufficient consensus and stabilize cooperation. We analyze how the amount of gossip necessary for cooperation depends on the benefits and costs of cooperation, the assessment rule (social norm), and errors in reputation assessment, strategy execution, and gossip transmission. Finally, we show that biased gossip can either facilitate or hinder cooperation, depending on the direction and magnitude of the bias. Our results contribute to the growing literature on cooperation facilitated by communication, and they highlight the need to study strategic interactions coupled with the spread of social information.
Dynamics of membrane tubulation coupled with fission by a two-component module
Authors: Bhattacharyya Soumya , Pucadyil Thomas J.
Published: May 2024

Membrane tubulation coupled with fission (MTCF) is a widespread phenomenon but mechanisms for their coordination remain unclear, partly because of the lack of assays to monitor dynamics of membrane tubulation and subsequent fission. Using polymer cushioned bilayer islands, we analyze the membrane tubulator Bridging Integrator 1 (BIN1) mixed with the fission catalyst dynamin2 (Dyn2). Our results reveal this mixture to constitute a minimal two-component module that demonstrates MTCF. MTCF is an emergent property and arises because BIN1 facilitates recruitment but inhibits membrane binding of Dyn2 in a dose-dependent manner. MTCF is therefore apparent only at high Dyn2 to BIN1 ratios. Because of their mutual involvement in T-tubules biogenesis, mutations in BIN1 and Dyn2 are associated with centronuclear myopathies and our analysis links the pathology with aberrant MTCF. Together, our results establish cushioned bilayer islands as a facile template for the analysis of membrane tubulation and inform of mechanisms that coordinate MTCF.
Mid-infrared Fine Structure Lines from the Galactic Warm Ionized Medium
Authors: Kulkarni S. R. , Beichman Charles , Ressler Michael E.
Published: May 2024

The Warm Ionized Medium (WIM) hosts most of the ionized gas in the Galaxy and occupies perhaps a quarter of the volume of the Galactic disk. Decoding the spectrum of the Galactic diffuse ionizing field is of fundamental interest. This can be done via direct measurements of ionization fractions of various elements. Based on current physical models for the WIM we predicted that mid-IR fine structure lines of Ne, Ar and S would be within the grasp of the Mid-Infrared Imager-Medium Resolution Spectrometer (MIRI-MRS), an Integral Field Unit (IFU) spectrograph, aboard the James Webb Space Telescope (JWST). Motivated thus we analyzed a pair of commissioning data sets and detected [Ne ii] 12.81 μm, [S iii] 18.71 μm and possibly [S iv] 10.51 μm. The inferred emission measure for these detections is about 10 cm−6 pc, typical of the WIM. These detections are broadly consistent with expectations of physical models for the WIM. The current detections are limited by uncorrected fringing (and to a lesser extent by baseline variations). In due course, we expect, as with other IFUs, the calibration pipeline to deliver photon-noise-limited spectra. The detections reported here bode well for the study of the WIM. Along most lines-of-sight hour-long MIRI-MRS observations should detect line emission from the WIM. When combined with optical observations by modern IFUs with high spectral resolution on large ground-based telescopes, the ionization fraction and temperature of neon and sulfur can be robustly inferred. Separately, the ionization of helium in the WIM can be probed by NIRspec. Finally, joint JWST and optical IFU studies will open up a new cottage industry of studying the WIM on arcsecond scales.
Introduction
Authors: Hebbar N. Nandini
Published: May 2024

The introductory chapter examines how the immense social value placed on technical education as a viable route to a good life, respectable middle-class identity, and high status have contributed to a specific kind of subject-making on engineering campuses across Tamil Nadu. While enforcing a performativity of the acceptable in the social realm, the institutional structure also propagates a pedagogy that is uncritical and mechanically derived; a pedagogy that emphasizes application over criticism, and structure over individual. Though students are not simply ‘interpellated’ by this pedagogy and disciplinary framework in an Althusserian manner, it does have a role to play in crafting a distinct subjectivity and sense of self-worth. Even as students negotiate these institutional constraints, it has become an integral part of college life and the ways in which ‘youth’ is experienced.
Identification of 2 Novel Subtypes of Hepatitis C Virus Genotype 8 and a Potential New Genotype Successfully Treated With Direct Acting Antivirals
Authors: Mbisa Jean L , Lapp Zena , Bibby David F , Phillips Laura T , Manso Carmen F , Packer Simon , Simmons Ruth , Harris Kathryn , Mohan Jaiganesh , Chinnappan Lalitha , Leitner Thomas , Bradshaw Daniel
Published: May 2024

Background

Hepatitis C virus (HCV) has high genetic diversity and is classified into 8 genotypes and >90 subtypes, with some endemic to specific world regions. This could compromise direct-acting antiviral efficacy and global HCV elimination.

Methods

We characterized HCV subtypes “rare” in the United Kingdom (non-1a/1b/2b/3a/4d) by means of whole-genome sequencing via a national surveillance program. Genetic analyses to determine the genotype of samples with unresolved genotypes were undertaken by comparison with International Committee on Taxonomy of Viruses HCV reference sequences.

Results

Two HCV variants were characterized as being closely related to the recently identified genotype (GT) 8, with >85% pairwise genetic distance similarity to GT8 sequences and within the typical intersubtype genetic distance range. The individuals infected by the variants were UK residents originally from Pakistan and India. In contrast, a third variant was only confidently identified to be more similar to GT6 compared with other genotypes across 6% of the genome and was isolated from a UK resident originally from Guyana. All 3 were cured with pangenotypic direct-acting antivirals (sofosbuvir-velpatasvir or glecaprevir-pibrentasvir) despite the presence of resistance polymorphisms in NS3 (80K/168E), NS5A (28V/30S/62L/92S/93S) and NS5B (159F).

Conclusions

This study expands our knowledge of HCV diversity by identifying 2 new GT8 subtypes and potentially a new genotype.
Prevalence of polymyxin-resistant bacterial strains in India: a systematic review and meta-analysis
Authors: Dwibedy Sambit K , Padhy Indira , Panda Aditya K , Mohapatra Saswat S
Published: May 2024

Introduction

Polymyxins, the cationic lipopeptide antibiotics, are the last line of therapeutics against the MDR Gram-negative bacterial (GNB) pathogens. Unfortunately, the rising cases of polymyxin-resistant strains from across the globe have adversely impacted their utility. While the molecular mechanisms responsible for developing polymyxin resistance (PolR) are largely understood, the prevalence of PolR strains in India has not been investigated systematically. The current study was undertaken to primarily determine the prevalence of PolR strains in India. Moreover, the extent of the spread of mobile colistin resistance (mcr) genes among the GNB strains in India was also determined.

Method

A systematic search for articles using the relevant inclusion and exclusion criteria was performed in the applicable databases for the period January 2015 to December 2023. The included 41 studies were subjected to a meta-analysis using the Comprehensive Meta-Analysis software (V4.0). Publication biases were assessed using funnel plots and Egger’s regression analysis.

Result

Considering a total of 41 studies including 24 589 bacterial isolates the present meta-analysis found the rate of PolR bacteria in India to be at 15.0% (95% CI: 11.2 to 19.8). Among the Indian States, Tamil Nadu topped with the highest prevalence of PolR at 28.3%. Investigating the contribution of the mcr genes, it was observed that among the PolR strains, 8.4% (95% CI: 4.8 to 14.3) were mcr positive.

Conclusion

The study determined the prevalence of PolR strains in India at 15.0%, which is higher than that of the global average at 10%. The study also determined that 8.4% of the PolR strains carried the mcr genes. The mcr-positive strains reported from India could be an underestimation of the actual numbers due to the non-inclusion of mcr screening in many previous studies. This study provides insight into the state of the PolR situation in India, which may be useful to develop a monitoring strategy to contain the spread of such strains and preserve the efficacy of the polymyxins.
The relationship between splenic dose and radiation-induced lymphopenia
Authors: Ma Yifu , Kong Yuehong , Zhang Shuying , Peng Yong , Xu Meiling , Zhang Junjun , Xu Hong , Hong Zhihui , Xing Pengfei , Qian Jianjun , Zhang Liyuan
Published: May 2024

Lymphocytes, which are highly sensitive to radiation, play a crucial role in the body’s defense against tumors. Radiation-induced lymphopenia has been associated with poorer outcomes in different cancer types. Despite being the largest secondary lymphoid organ, the spleen has not been officially designated as an organ at risk. This study hypothesizes a connection between spleen irradiation and lymphopenia and seeks to establish evidence-based dosage limits for the spleen. We retrospectively analyzed data from 96 patients with locally advanced gastric cancer who received postoperative chemoradiotherapy (CRT) between May 2010 and May 2017. Complete blood counts were collected before, during and after CRT. We established a model for predicting the minimum absolute lymphocyte count (Min ALC) and to investigate potential associations between spleen dosimetric variables and Min ALC. The median follow-up was 60 months. The 5-year overall survival (OS) and disease-free survival (DFS) were 65.2% and 56.8%, respectively. The median values of pre-treatment ALC, Min ALC and post-treatment ALC were 1.40 × 109, 0.23 × 109 and 0.28 × 109/L, respectively. Regression analysis confirmed that the primary tumor location, number of fractions and spleen V5 were significant predictors of Min ALC during radiation therapy. Changes in ALC (ΔALC) were identified as an independent predictor of both OS and DFS. Spleen V5 is an independent predictor for Min ALC, and the maximum dose of the spleen is associated with an increased risk of severe lymphopenia. Therefore, these doses should be restricted in clinical practice. Additionally, ΔALC can serve as a prognostic indicator for adjuvant radiotherapy in gastric cancer.
A case of spontaneous abdominal hemoperitoneum secondary to ruptured splenosis
Authors: Gunda Akshata , Martos Mary P , Dickey Erin M , Livingstone Alan S , Hester Caitlin
Published: May 2024

We present a case of spontaneous abdominal hemoperitoneum secondary to ruptured splenosis in a 35-year-old patient with a history of splenectomy secondary to trauma 23 years prior. Computed tomography imaging demonstrated a large amorphous mass-like structure in the mesentery of the left hemiabdomen with active extravasation and hemoperitoneum. The patient also had a separate focus of hyper-enhancing mass adjacent to the bladder representing a mass versus splenule. The patient’s radiographic and clinical presentation prompted management with exploratory laparotomy, hematoma evacuation, and resection of two splenules. With only a few cases of spontaneous abdominal hemoperitoneum from splenosis reported, this case describes successful management with surgical intervention.
Algebraic quantification of the contribution of active regions to the Sun’s dipole moment: applications to century-scale polar field estimates and solar cycle forecasting
Authors: Pal Shaonwita , Nandy Dibyendu
Published: May 2024

The solar cycle is generated by a magnetohydrodynamic dynamo mechanism which involves the induction and recycling of the toroidal and poloidal components of the Sun’s magnetic field. Recent observations indicate that the Babcock–Leighton (BL) mechanism – mediated via the emergence and evolution of tilted bipolar active regions – is the primary contributor to the Sun’s large-scale dipolar field. Surface flux transport models and dynamo models have been employed to simulate this mechanism, which also allows for physics-based solar cycle forecasts. Recently, an alternative analytic method has been proposed to quantify the contribution of individual active regions to the Sun’s dipole moment (DM). Utilizing solar cycle observations spanning a century, here, we test the efficacy of this algebraic approach. Our results demonstrate that the algebraic quantification approach is reasonably successful in estimating DMs at solar minima over the past century – providing a verification of the BL mechanism as the primary contributor to the Sun’s dipole field variations. We highlight that this algebraic methodology serves as an independent approach for estimating DMs at the minima of solar cycles, relying on characteristics of bipolar solar active regions. We also show how this method may be utilized for solar cycle predictions; our estimate of the Sun’s dipole field at the end of cycle 24 using this approach indicates that solar cycle 25 would be a moderately weak cycle, ranging between solar cycle 20 and cycle 24.
Paxillin regulates androgen receptor expression associated with granulosa cell focal adhesions
Authors: Weidner Adelaide E , Roy Anna , Vann Kenji , Walczyk Ariana C , Astapova Olga
Published: May 2024

Paxillin is a ubiquitously expressed adaptor protein integral to focal adhesions, cell motility, and apoptosis. Paxillin has also recently been implicated as a mediator of nongenomic androgen receptor (AR) signaling in prostate cancer and other cells. We sought to investigate the relationship between paxillin and AR in granulosa cells (GCs), where androgen actions, apoptosis, and focal adhesions are of known importance, but where the role of paxillin is understudied. We recently showed that paxillin knockout in mouse GCs increases fertility in older mice. Here, we demonstrate that paxillin knockdown in human granulosa-derived KGN cells, as well as knockout in mouse primary GCs, results in reduced AR protein but not reduced mRNA expression. Further, we find that both AR protein and mRNA half-lives are reduced by approximately one-third in the absence of paxillin, but that cells adapt to chronic loss of paxillin by upregulating AR gene expression. Using co-immunofluorescence and proximity ligation assays, we show that paxillin and AR co-localize at the plasma membrane in GCs in a focal adhesion kinase-dependent way, and that disruption of focal adhesions leads to reduced AR protein level. Our findings suggest that paxillin recruits AR to the GC membrane, where it may be sequestered from proteasomal degradation and poised for nongenomic signaling, as reported in other tissues. To investigate the physiological significance of this in disorders of androgen excess, we tested the effect of GC-specific paxillin knockout in a mouse model of polycystic ovary syndrome (PCOS) induced by chronic postnatal dihydrotestosterone (DHT) exposure. While none of the control mice had estrous cycles, 33% of paxillin knockout mice were cycling, indicating that paxillin deletion may offer partial protection from the negative effects of androgen excess by reducing AR expression. Paxillin-knockout GCs from mice with DHT-induced PCOS also produced more estradiol than GCs from littermate controls. Thus, paxillin may be a novel target in the management of androgen-related disorders in women, such as PCOS.
Sleep quality according to chronotype in nurses working 8-hour shifts
Authors: Yang H , Kim S , Yoo S-H , Mun Y , Choi M L , Lee J A , Song E
Published: May 2024

Background

To date, studies have been focused on sleep disturbances of nurses working during night shifts. There is a lack of understanding regarding the sleep quality of nurses working in the rapid rotation system for each type of shift work.

Aims

To determine the relationship between chronotype and sleep quality according to shift type (i.e. day, evening and night shifts) in nurses working 8-hour rotating shifts.

Methods

A cross-sectional, descriptive study was conducted from two tertiary hospitals in South Korea from December 2021 to September 2022, including nurses working 8-hour rotating shifts (N = 74). They completed questionnaires to measure general, occupational and sleep-related characteristics, chronotype, insomnia severity and daytime sleepiness. Additionally, sleep parameters were collected from actigraphy and sleep diaries for 7 days.

Results

A total of 64% of nurses had an evening chronotype and 37% of nurses had an intermediate chronotype. Nurses had significantly less total sleep time and worsened sleep latency and efficiency during the day shift compared to other shift types. Compared to nurses with an intermediate chronotype, those with an evening chronotype had poorer sleep quality during day shift work.

Conclusions

Strategies to enhance nurses’ sleep quality during day shifts should consider a two-level approach: individual approaches, such as improving sleep hygiene, and administrative approaches, such as establishing a chronotype-based shift system for scheduling.
Evidence-Based Therapist-Supported Digital Mental Health Intervention for Patients Experiencing Medical Multimorbidity: A Retrospective Cohort Intent-to-Treat Study
Authors: Nelson Benjamin W. , Peiper Nicholas C. , Aschbacher Kirstin , Forman-Hoffman Valerie L.
Published: May 2024

Objective

Multimorbidity or the co-occurrence of multiple health conditions is increasing globally and is associated with significant psychological complications. It is unclear whether digital mental health (DMH) interventions for patients experiencing multimorbidity are effective, particularly given that this patient population faces more treatment resistance. The goal of the current study was to examine the impact of smartphone-delivered DMH interventions for patients presenting with elevated internalizing symptoms that have reported multiple lifetime medical conditions.

Methods

This preregistered (see https://osf.io/vh2et/) retrospective cohort intent-to-treat study with 2819 patients enrolled in a therapist-supported DMH intervention examined the associations between medical multimorbidity (MMB) and mental health outcomes.

Results

Results indicated that more MMB was significantly associated with greater presenting mental health symptom severity. MMB did not have a deleterious influence on depressive symptom trajectories across treatment, although having one medical condition was associated with a steeper decrease in anxiety symptoms compared to patients with no medical conditions. Finally, MMB was not associated with time to dropout, but was associated with higher dropout and was differentially associated with fewer beneficial treatment outcomes, although this is likely attributable to higher presenting symptom severity, rather than lesser symptom reductions during treatment.

Conclusions

Overall, the Meru Health Program was associated with large effect size decreases in depressive and anxiety symptoms regardless of the number of MMB. Future DMH treatments and research might investigate tailored barrier reduction and extended treatment lengths for patients experiencing MMB to allow for greater treatment dose to reduce symptoms below clinical outcome thresholds.
New Directions in Geroscience: Integrating Social and Behavioral Drivers of Biological Aging
Authors: Nielsen Lisbeth , Marsland Anna L. , Hamlat Elissa J. , Epel Elissa S.
Published: May 2024

The “geroscience hypothesis” posits that slowing the physiological processes of aging would lead to delayed disease onset and longer healthspan and lifespan. This shift from a focus on solely treating existing disease to slowing the aging process is a shift toward prevention, including a focus on risk factors found in the social environment. Although geroscience traditionally has focused on the molecular and cellular drivers of biological aging, more fundamental causes of aging may be found in the social exposome—the complex array of human social environmental exposures that shape health and disease. The social exposome may interact with physiological processes to accelerate aging biology. In this commentary, we review the potential of these insights to shape the emerging field of translational geroscience. The articles in this special issue highlight how social stress and social determinants of health are associated with biomarkers of aging such as inflammation, epigenetic clocks, and telomeres, and spotlight promising interventions to mitigate stress-related inflammation. For geroscience to incorporate the social exposome into its translational agenda, studies are needed that elucidate and quantify the effects of social exposures on aging and that consider social exposures as intervention targets. The life course perspective allows us to measure both exposures and aging biology over time including sensitive periods of development and major social transitions. In addition, given rapid changes in the measurement of aging biology, which include machine learning techniques, multisystem phenotypes of aging are being developed to better reflect whole body aging, replacing reliance on single system biomarkers. In this expanded and more integrated field of translational geroscience, strategies targeting factors in the social exposome hold promise for achieving aging health equity and extending healthy longevity.
Flavobacterium acetivorans sp. nov. and Flavobacterium galactosidilyticum sp. nov., psychrotolerant flavobacteria isolated from cultivated fish
Authors: Saticioglu Izzet Burcin , Ay Hilal , Altun Soner , Ajmi Nihed , Gunduz Enes Said , Gocmen Huban , Duman Muhammed
Published: May 2024

Two yellow-coloured strains, F-29T and F-340T, were isolated from fish farms in Antalya and Mugla in 2015 and 2017 during surveillance studies. The 16S rRNA gene sequence analysis showed that both strains belong to the genus Flavobacterium. A polyphasic approach involving a comprehensive genome analysis was employed to ascertain the taxonomic provenance of the strains. The overall genome-relatedness indices of digital DNA–DNA hybridization (dDDH) and average nucleotide identity (ANI) between the strains and the other members of the genus Flavobacterium were found to be well below the established thresholds of 70 and 95 %, respectively. The whole-genome-based phylogenetic analysis revealed that strain F-29T is closely related to Flavobacterium granuli (dDDH 39.3 % and ANI 89.4 %), while strain F-340T has a close relationship with the type strain of Flavobacterium pygoscelis (dDDH 25.6 % and ANI 81.5 %). Both strains were psychrotolerant with an optimum growth temperature of 25 °C. The chemotaxonomic characteristics of the strains were typical of the genus Flavobacterium. Both strains had phosphatidylethanolamine, aminolipids and unidentified lipids in their polar lipid profile and MK-6 as the isoprenoid quinone. The major fatty acids were iso-C15 : 0 and anteiso-C15 : 0. The genome size of the strains was 3.5 Mb, while G+C contents were 35.3 mol% for strain F-29T and 33.4 mol% for strain F-340T. Overall, the characterizations confirmed that both strains are representatives of two novel species within the genus Flavobacterium, for which the names Flavobacterium acetivorans sp. nov. and Flavobacterium galactosidilyticum sp. nov. are proposed, with F-29T (JCM 34193T=KCTC 82253T) and F-340T (JCM 34203T=KCTC 82263T) as the type strains, respectively.
IhBlock Reveals Separation of Timescales in Pyloric Rhythm Response to Temperature Changes inCancer borealis
Authors: Schapiro Kyra A , Rittenberg JD , Kenngott Max , Marder Eve
Published: May 2024

Motor systems operate over a range of frequencies and relative timing (phase). We studied the contribution of the hyperpolarization-activated inward current (Ih) to frequency and phase in the pyloric rhythm of the stomatogastric ganglion (STG) of the crab,Cancer borealisas temperature was altered from 11°C to 21°C. Under control conditions, the frequency of the rhythm increased monotonically with temperature, while the phases of the pyloric dilator (PD), lateral pyloric (LP), and pyloric (PY) neurons remained constant. When we blocked Ihwith cesium (Cs+) PD offset, LP onset, and LP offset were all phase advanced in Cs+at 11°C, and the latter two further advanced as temperature increased. In Cs+the steady state increase in pyloric frequency with temperature diminished and the Q10of the pyloric frequency dropped from ∼1.75 to ∼1.35. Unexpectedly in Cs+, the frequency displayed non-monotonic dynamics during temperature transitions; the frequency initially dropped as temperature increased, then rose once temperature stabilized, creating a characteristic “jag”. Interestingly, these jags were still present during temperature transitions in Cs+when the pacemaker was isolated by picrotoxin, although the temperature-induced change in frequency recovered to control levels. Overall, these data suggest that Ihplays an important role in the ability of this circuit to produce smooth transitory responses and persistent frequency increases by different mechanisms during temperature fluctuations.
Complex genetic architecture underlying the plasticity of tobacco leaf width provides insight into across-environment genomic prediction
Authors: Liu Li , Liu Wei , Sun Yiwen , Han Yu , Hao Ran , Zhang Wenjia , Guo Linjie , Zhao Jiarui , Zan Yanjun , Cheng Lirui , Si Huan
Published: May 2024

Phenotypic plasticity is the property of a given genotype to produce multiple phenotypes in response to changing environmental conditions. Understanding the genetic basis of phenotypic plasticity and establishing a predictive model is highly relevant for future agriculture under changing climate. Here, we investigated the genetic basis of leaf width plasticity in a tobacco MAGIC population across four different environments. Environmental changes not only resulted in differences in leaf width mean but also in leaf width plasticity. A total of 45 QTL were identified, including 14 QTL for leaf width mean and 43 for leaf width plasticity, with 12 overlap. Changes in the environment affected the magnitude of several QTL, thereby influencing phenotypic plasticity. We identified a QTL, qLW14, associated with leaf width plasticity and leaf width mean at Zhucheng, but had no significant impact at Guiyang, indicating that changes in the environment contributed to variations in leaf width plasticity. By integrating genetic diversity, environmental variation, and their interactions into a unified model, we were able to build a model for cross-environment predictions, and improved prediction accuracy by 7.2%. Overall, this study reveals complex genetic basis involving multiple alleles, and genotype interactions underlying variations of leaf width mean and plasticity. These findings contribute to assessing the role of plasticity in responding to climate or other environmental changes.
Quantification of nanocondensates formation at the single molecule level
Authors: Houx Justin , Copie Thomas , Gambin Yann , Sierecki Emma
Published: May 2024

Understanding the molecular mechanisms of biomolecular condensate formation through liquid-liquid phase separation is crucial for deciphering cellular cues in normal and pathological contexts. Recent studies have highlighted the existence of sub-micron assemblies, known as nanocondensates or mesoscopic clusters, in the organization of a significant portion of the proteome. However, as smaller condensates are invisible to classical microscopy, new tools must be developed to quantify their numbers and properties. Here, we establish a simple analysis framework using single molecule fluorescence spectroscopy to quantify the formation of nanocondensates diffusing in solution. We used the low-complexity domain of TAR DNA-binding protein 43 (TDP-43) as a model system to show that we can recapitulate the phase separation diagram of the protein in various conditions. Single molecule spectroscopy reveals rapid formation of TDP-43 nanoclusters at ten-fold lower concentrations than described previously by microscopy. We demonstrate how straightforward fingerprinting of individual nanocondensates provides an exquisite quantification of their formation, size, density, and their temporal evolution. Overall, this study highlights the potential of single molecule spectroscopy to investigate the formation of biomolecular condensates and liquid-liquid phase separation mechanisms in protein systems.
Unveiling the molecular choreography: In-depth single-cell transcriptomic exploration of the regenerative dynamics in stony coral
Authors: Han Tingyu , Chen J.-Y. , He Chunpeng , Lu Zuhong
Published: May 2024

The coral reef ecosystem faces increasing threats under global climate challenges. One of the core issues is the inability of fragments to quickly grow into a size that can resist environmental pressures in coral transplantation. The observation of accelerated growth during the early stages of coral regeneration provides new insights for addressing this challenge. To investigate related molecular mechanisms, our study focused on the fast-growing stony coralAcropora muricata(with chromosome-scale reference genome). Employing diverse techniques, including single-cell RNA sequencing (scRNA-seq), we unveiled related intricate cellular dynamics. Single-cell analysis revealed notable shifts in calicoblasts and epidermal cells around 2-4 weeks post-injury. Gene expression analysis revealed enrichment in immune response and biomineralization pathways. Pseudotime analysis explained the differentiation of epidermal cells into calicoblasts, while time-course analysis identified key genes associated with dynamic biomineralization changes. This study enhances our understanding of coral regeneration, offering insights for protective strategies to foster coral growth.
Developmental oligodendrocytes regulate brain function through the mediation of synchronized spontaneous activity
Authors: Masumura Ryo , Goda Kyosuke , Sekiguchi Mariko , Uesaka Naofumi
Published: May 2024

Synchronized spontaneous neural activity is a fundamental feature of developing central nervous systems, hypothesized to be critical for brain development. However, the mechanisms regulating this synchronization and its long-term functional implications remain poorly understood. Here, we unveil a novel role for oligodendrocytes in orchestrating synchronized spontaneous activity during a critical developmental window, with profound consequences for adult brain function. Using cell-specific genetic manipulation in the mouse cerebellum, we demonstrate that oligodendrocyte deficiency during early postnatal development, but not after weaning, disrupts the synchronization of Purkinje cell activity in both developmental and adult stages. These early disruption of oligodendrocytes and neural synchrony resulted in persistent alterations in adult cerebellar-dependent behaviors, including anxiety, sociality, and motor function. Our findings establish a causal link between developmental oligodendrocyte-regulated neural synchrony and the emergence of complex brain functions. This study ensures the proper developmental trajectory necessary for driving brain function and opens new avenues for understanding neurodevelopmental disorders.
A Rapid Method for Producing Adeno-Associated Viral Vectors Suitable for Transducing Rodent Neuronsin vitroandin vivo
Authors: Howard Doug B. , Svarcbahs Reinis , Gore Lana N. , Harvey Brandon K. , Richie Christopher T.
Published: May 2024

The use of adeno-associated viral vectors for delivery of genetic information into the mammalian CNS remains popular but producing highly purified vectors for in vivo applications requires a significant investment of resources and time that can impede the development and testing of AAV vectors for experimentation. To address this issue, we have developed a simplified AAV packaging protocol that does not require large capital equipment (ultracentrifugation or chromatography machines) yet still produces virus in quantities that are sufficient for testing AAV prototypes in the rodent CNS. This protocol is serotype agnostic, and has been successful with AAV1, AAV9, AAV-DJ, and rAAV2-retro. Intracranial injection of AAV-EF1a-GFP-KASH into rats demonstrated that our “small scale” AAV preps produce patterns of transgene expression and inflammation that are similar to those produced by the same AAV vector purified by affinity column chromatography. Our protocol allows for multiple vectors to be packaged and processed in parallel, making it ideal for testing multiple variants, constructs, and prototypes simultaneously.
Sodium azide mutagenesis induces a unique pattern of mutations
Authors: Liu Chaochih , Frascarelli Giulia , Stec Adrian O. , Heinen Shane , Lei Li , Wyant Skylar R. , Legg Erik , Spiller Monika , Muehlbauer Gary J. , Smith Kevin P. , Fay Justin C. , Morrell Peter L.
Published: May 2024

The nature and effect of mutations are of fundamental importance to the evolutionary process. The generation of mutations with mutagens has also played important roles in genetics. Applications of mutagens include dissecting the genetic basis of trait variation, inducing desirable traits in crops, and understanding the nature of genetic load. Previous studies of sodium azide-induced mutations have reported single nucleotide variants (SNVs) found in individual genes. To characterize the nature of mutations induced by sodium azide, we analyze whole-genome sequencing (WGS) of 11 barley lines derived from sodium azide mutagenesis, where all lines were selected for diminution of plant fitness owing to induced mutations. We contrast observed mutagen-induced variants with those found in standing variation in WGS of 13 barley landraces. Here, we report indels that are two orders of magnitude more abundant than expected based on nominal mutation rates. We found induced SNVs are very specific, with C→T changes occurring in a context followed by another C on the same strand (or the reverse complement). The codons most affected by the mutagen include the sodium azide-specific CC motif (or the reverse complement), resulting in a handful of amino acid changes and relatively few stop codons. The specific nature of induced mutations suggests that mutagens could be chosen based on experimental goals. Sodium azide would not be ideal for gene knockouts but will create many missense mutations with more subtle effects on protein function.
An ultra-short-acting benzodiazepine in thalamic nucleus reuniens undermines fear extinction via intermediation of hippocamposeptal circuits
Authors: Cheung Hoiyin , Yu Tong-Zhou , Yi Xin , Wu Yan-Jiao , Wang Qi , Gu Xue , Xu Miao , Cai Meihua , Wen Wen , Li Xin-Ni , Liu Ying-Xiao , Sun Ying , Zheng Jijian , Xu Tian-Le , Luo Yan , Zhang Mazhong , Li Wei-Guang
Published: May 2024

Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an ultra-short-acting benzodiazepine, we reveal its impact on the thalamic nucleus reuniens (RE) and interconnected hippocamposeptal circuits during fear extinction. Systemic or RE-specific administration of remimazolam impedes fear extinction by reducing RE activation through A type GABA receptors. Remimazolam enhances long-range GABAergic inhibition from lateral septum (LS) to RE, underlying the compromised fear extinction. RE projects to ventral hippocampus (vHPC), which in turn sends projections characterized by feed-forward inhibition to the GABAergic neurons of the LS. This is coupled with long-range GABAergic projections from the LS to RE, collectively constituting an overall positive feedback circuit construct that promotes fear extinction. RE-specific remimazolam negates the facilitation of fear extinction by disrupting this circuit. Thus, remimazolam in RE disrupts fear extinction caused by hippocamposeptal intermediation, offering mechanistic insights for the dilemma of combining anxiolytics with extinction-based exposure therapy.
Assessing sprint technique with shoe-mounted inertial sensors
Authors: Pla Gerard Aristizábal , Martini Douglas N. , Potter Michael V. , Hoogkamer Wouter , Cain Stephen M.
Published: May 2024

Negative foot speed (i.e., the speed of the backward and downward motion of the foot relative to the body at ground contact) is a strong predictor of sprinting performance. Inertial measurement units (IMUs) are becoming a popular approach for assessing sports performance. The primary aim of this study was to use IMUs to investigate the relationship between negative foot speed and top running speed attained during a sprint on an outdoor track. Seventeen participants performed 80-meter track sprints while wearing a shoe-mounted IMU. Anteroposterior and vertical components of negative foot speed were extracted from the IMU. For the mean peak stride speed of 7.98±0.78m/s, the adjusted R2values were 0.27 and 0.42 versus the anteroposterior and vertical components of negative foot speed, respectively. In conclusion, our findings support the common coaching tip of increasing negative foot speed to improve sprint speed. In addition, the results of this study support the use of IMUs for quantifying sprinting technique with actionable metrics.
The crystal structure of Nictaba reveals its carbohydrate-binding properties and a new lectin dimerization mode
Authors: Bloch Yehudi , Osterne Vinicius J.S. , Savvides Savvas N. , Van Damme Els J.M.
Published: May 2024

Nictaba is a (GlcNAc)n-binding, stress-inducible lectin from Nicotiana tabacum that serves as a representative for the family of Nictaba-related lectins, a group of proteins that play pivotal roles in plant defense mechanisms and stress response pathways. Despite extensive research into the biological activities and physiological role(s) of the lectin, the three-dimensional structure of Nictaba remained largely unknown. Here, we report crystal structures for Nictaba in the apo form and bound to chitotriose. The structures reveal a jelly-roll fold for the Nictaba protomer similar to the cucumber Cus17 lectin, but show an unprecedented dimerization mode among all structurally characterized lectins to date. The chitotriose binding mode, similar to Cus17, centers around the central GlcNAc residue, providing insights into the determinants of specificity of Nictaba towards carbohydrate structures. By integrating these structural insights with inputs from glycan arrays, molecular docking, and molecular dynamics simulations, we propose that Nictaba employs a single carbohydrate-recognition domain within each of the two subunits in the dimer to display pronounced specificity towards GlcNAc-containing carbohydrates. Furthermore, we identified amino acid residues involved in the extended binding site capable of accommodating structurally diverse high-mannose and complex N-glycans. Glycan array and in silico analyses revealed interactions centered around the conserved Man3GlcNAc2 core, explaining the broad recognition of N-glycan structures. Collectively, the structural and biochemical insights presented here fill a hitherto substantial void into the atlas of lectin structure-function relationships and pave the way for future developments in plant stress biology and lectin-based applications.
Maroon rice genomic diversity reflects 350 years of colonial history
Authors: van de Loosdrecht Marieke S. , Pinas Nicholaas M. , Tjoe Awie Jerry R. , Becker Frank F.M. , Maat Harro , van Velzen Robin , van Andel Tinde , Schranz M. Eric
Published: May 2024

Maroons in Suriname and French Guiana descend from enslaved Africans who escaped the plantations during colonial times. Maroon farmers still cultivate a large rice diversity, their oldest staple crop. Maroon oral history and written records by colonial authorities provide contrasting perspectives on the origins of Maroon rice. Here, we integrated genomic ancestry analyses of 136 newly sequenced Maroon rice varieties with ethnobotanical and archival research to reconstruct the historical contexts associated with the introduction of rice varieties to the Guianas. We found that a large subset traces to West Africa, linked to the transatlantic slave trade (c.1530-1825). Maroons obtained other varieties from indentured laborers from Java (1890 onwards), USA rice breeders (1932 onwards), and Hmong refugees from the Vietnam War (1991). Furthermore, we found rice types never documented before, indicating Maroon farmers selected from crosses. Overall, our results demonstrate that the Maroon farming system prioritizes maintenance of a high stock diversity, which we posit reflects the expertise they inherited from their (African) ancestors. Ignored by agricultural modernization initiatives, Maroon farmers today are important custodians of a unique cultural heritage. Moreover, the genomic findings underline many Maroon stories about their past. This study hence demonstrates the power of cross-disciplinary crop research to reconstruct aspects of the human past for which historical records may be biased or incomplete. We anticipate that a similar study approach can be applied to other heirloom crops of (Indigenous) communities that may have preserved their history on their farms to reconstruct, acknowledge and honor the past.
Productivity of the eelgrass biotope and the resilience of fisher-hunter-gatherers in prehistoric Denmark
Authors: Meadows John , Fischer Anders
Published: May 2024

In the shallow coastal waters of the Danish archipelago, eelgrass (Zostera marina) forms extensive and extremely productive stands, which support food webs that are isotopically distinct from those based on the primary productivity of marine phytoplankton. The isotopic signatures of eelgrass and phytoplankton food webs explain much of the variation in δ13C, δ15N and δ34S values in marine vertebrate remains recovered from prehistoric coastal sites in Denmark. Isotope data from human and dog remains reflect the overwhelming importance of the eelgrass biotope to the fisher-hunter-gatherer (FHG) subsistence during the Late Mesolithic Ertebølle epoch (∼7400-5800 cal BP). By recognising eelgrass and pelagic resources as isotopically distinct, we obtain more accurate diet reconstructions and dietary14C reservoir effect corrections for Ertebølle individuals. Longstanding research issues, including technology, palaeodemography, and the resilience and sustainability of the FHG economy need to be reassessed in view of the isotopic signature and productivity of the eelgrass biotope in Danish waters. Eelgrass productivity is also pertinent to comparisons between Ertebølle and Neolithic economies in Denmark, and between FHG adaptations in Denmark and neighbouring regions, and may be key to understanding the much-discussed delay in the transition to farming.
Genome-wide screen ofMycobacterium tuberculosis-infected macrophages identified the GID/CTLH complex as a determinant of intracellular bacterial growth
Authors: Simwela Nelson V. , Johnston Luana , Pavinski Bitar Paulina , Jaecklein Eleni , Altier Craig , Sassetti Christopher M. , Russell David G.
Published: May 2024

Summary

The eukaryotic GID/CTLH complex is a highly conserved E3 ubiquitin ligase involved in a broad range of biological processes. However, a role of this complex in host antimicrobial defenses has not been described. We exploitedMycobacterium tuberculosis(Mtb) induced cytotoxicity in macrophages in a FACS based CRISPR genetic screen to identify host determinants of intracellularMtbgrowth restriction. Our screen identified 5 (GID8,YPEL5,WDR26,UBE2H,MAEA) of the 10 predicted members of the GID/CTLH complex as determinants of intracellular growth of bothMtbandSalmonellaserovar Typhimurium. We show that the antimicrobial properties of the GID/CTLH complex knockdown macrophages are mediated by enhanced GABAergic signaling, activated AMPK, increased autophagic flux and resistance to cell death. Meanwhile,Mtbisolated from GID/CTLH knockdown macrophages are nutritionally starved and oxidatively stressed. Our study identifies the GID/CTLH complex activity as broadly suppressive of host antimicrobial responses against intracellular bacterial infections.

Graphical abstract
Genome Assembly of Docynia delavayi Provides New Insights into α-Farnesene Biosynthesis
Authors: Tian Jinhong , Chen Zhuo , Jiang Can , Li Siguang , Yun Xinhua , He Chengzhong , Wang Dawei
Published: May 2024

Docynia delavayi is an economically significant fruit species with a high market potential due to the special aroma of its fruit. Here, a 653.34 Mb high-quality genome of D. delavayi was first reported, of which 93.8% of the sequences were assembled to 17 chromosomes. A total of 48325 protein-coding genes were annotated in D. delavayi genome. Ks analysis proved that two whole genome duplication (WGD) events occurred in D. delavayi, resulting in the expansion of genes associated with terpene biosynthesis, which promoted its fruit-specific aroma production. Combined multi-omics analysis, α-farnesene was detected as the most abundant aroma substance emitted by D. delavayi fruit during storage, meanwhile a α-farnesene synthase gene and 15 transcription factors (TFs) potentially involved in α-farnesene biosynthesis were identified. Further studies for the regulation network of α-farnesene biosynthesis revealed that DdebHLH, DdeERF1 and DdeMYB could activate the transcription of DdeAFS. To our knowledge, it is the first report that MYB TF plays a regulatory role in α-farnesene biosynthesis, which will greatly facilitate future breeding programs for D. delavayi.