bluuebunny/crossref_metadata_2025 huggingface dataset:
The integration of tactile and proprioceptive signals to achieve haptic object perception
Authors: Dogruoz R. Efe , Shelchkova Natalya S. , Sheets Drew E. , Greenspon Charles M. , Bensmaia Sliman J.
Published: November 2023

Abstract

Stereognosis, the sense of the 3-dimensional shape of objects held in hand, requires the integration of somatosensory signals about local features -such as edges and surface curvature- with proprioceptive signals about the conformation of the fingers on the object. However, the mechanism of this integration remains unknown. Here, we investigated the spatial model that is used to integrate information about the global shape of the object with information about its local features at each point of contact. To this end, human observers judged the dissimilarity of pairs of objects that differed in their global shape, their local features, or both. We then compared the dissimilarity ratings when both global shape and local features changed to ratings when only global shape or only local features changed. We tested this with object sets of different levels of complexity, including spheres of different sizes and surface features to more varied shapes and features. For all object sets, we found that ratings when both global shape and local features changed was approximately an additive combination of the ratings when only global shape or only local features changed. For the majority of subjects, a city-block spatial model best explained their responses. Our results suggest that information about global shape is encoded independently from that about local features during interactions with objects. This implies that the neural representations of object shape and local features, though integrated, are separable.
Multicellular magnetotactic bacterial consortia are metabolically differentiated and not clonal
Authors: Schaible George A. , Jay Zackary J. , Cliff John , Schulz Frederik , Gauvin Colin , Goudeau Danielle , Malmstrom Rex R. , Ruff S. Emil , Edgcomb Virginia , Hatzenpichler Roland
Published: November 2023

Consortia of multicellular magnetotactic bacteria (MMB) are currently the only known example of bacteria without a unicellular stage in their life cycle. Because of their recalcitrance to cultivation, most previous studies of MMB have been limited to microscopic observations. To study the biology of these unique organisms in more detail, we use multiple culture-independent approaches to analyze the genomics and physiology of MMB consortia at single cell resolution. We separately sequenced the metagenomes of 22 individual MMB consortia, representing eight new species, and quantified the genetic diversity within each MMB consortium. This revealed that, counter to conventional views, cells within MMB consortia are not clonal. Single consortia metagenomes were then used to reconstruct the species-specific metabolic potential and infer the physiological capabilities of MMB. To validate genomic predictions, we performed stable isotope probing (SIP) experiments and interrogated MMB consortia using fluorescencein situhybridization (FISH) combined with nano-scale secondary ion mass spectrometry (NanoSIMS). By coupling FISH with bioorthogonal non-canonical amino acid tagging (BONCAT) we explored theirin situactivity as well as variation of protein synthesis within cells. We demonstrate that MMB consortia are mixotrophic sulfate reducers and that they exhibit metabolic differentiation between individual cells, suggesting that MMB consortia are more complex than previously thought. These findings expand our understanding of MMB diversity, ecology, genomics, and physiology, as well as offer insights into the mechanisms underpinning the multicellular nature of their unique lifestyle.

Significance statement

The emergence of multicellular lifeforms represents a pivotal milestone in Earth’s history, ushering in a new era of biological complexity. Because of the relative scarcity of multicellularity in the domainsBacteriaandArchaea, research on the evolution of multicellularity has predominantly focused on eukaryotic model organisms. In this study, we explored the complexity of the only known bacteria without a unicellular stage in their life cycle, consortia of multicellular magnetotactic bacteria (MMB). Genomic and physiological analyses revealed that cells within individual MMB consortia are not clonal and exhibit metabolic differentiation. This implies a higher level of complexity than previously assumed for MMB consortia, prompting a reevaluation of the evolutionary factors that have led to the emergence of multicellularity. Because of their unique biology MMB consortia are ideally suited to become a model system to explore the underpinnings of bacterial multicellularity.
A Distinct Neural Code Supports Prospection of Future Probabilities During Instrumental Information-Seeking
Authors: Singletary Nicholas M. , Horga Guillermo , Gottlieb Jacqueline
Published: November 2023

To make adaptive decisions, we must actively demand information, but relatively little is known about the mechanisms of active information gathering. An open question is how the brain estimates expected information gains (EIG) when comparing the current decision uncertainty with the uncertainty that is expected after gathering information. We examined this question using fMRI in a task in which people placed bids to obtain information in conditions that varied independently by prior decision uncertainty, information diagnosticity, and the penalty for an erroneous choice. Consistent with value of information theory, bids were sensitive to EIG and its components of prior certainty and expected posterior certainty. Expected posterior certainty was decoded above chance from multivoxel activation patterns in the posterior parietal and extrastriate cortices. This representation was independent of instrumental rewards and overlapped with distinct representations of EIG and prior certainty. Thus, posterior parietal and extrastriate cortices are candidates for mediating the prospection of posterior probabilities as a key step to estimate EIG during active information gathering.
Proneural – Mesenchymal antagonism dominates the patterns of phenotypic heterogeneity in Glioblastoma
Authors: BV Harshavardhan , Jolly Mohit Kumar
Published: November 2023

1

The aggressive nature of glioblastoma (GBM) – one of the deadliest forms of brain tumours – is majorly attributed to underlying phenotypic heterogeneity. Early attempts to classify this heterogeneity at a transcriptomic level in TCGA GBM cohort proposed the existence of four distinct molecular subtypes: Proneural, Neural, Classical and Mesenchymal. Further, a single-cell RNA-seq analysis of primary tumours also reported similar 4 subtypes mimicking neuro-developmental lineages. However, it remains unclear whether these 4 subtypes identified via bulk and single-cell transcriptomics are mutually exclusive or not. Here, we perform pairwise correlations among individual genes and gene signatures corresponding to these proposed subtypes, and show that the subtypes are not distinctly mutually antagonistic in either TCGA or single-cell RNA-sequencing data. We observed that the proneural (or neural progenitor-like) – mesenchymal axis is the most prominent antagonistic pair, with the other two subtypes lying on this spectrum. These results are reinforced through a meta-analysis of over 100 single-cell and bulk transcriptomic datasets as well as in terms of functional association with metabolic switching, cell cycle and immune evasion pathways. These results suggest rethinking GBM phenotypic characterization for more effective therapeutic targeting efforts.
The cryo-EM structure of trypanosome 3-methylcrotonyl-CoA carboxylase provides mechanistic and dynamic insights into enzymatic function
Authors: Plaza-Pegueroles Adrián , Aphasizheva Inna , Aphasizhev Ruslan , Fernández-Tornero Carlos , Ruiz Federico M.
Published: November 2023

3-methylcrotonyl-CoA carboxylase (MCC) catalyzes the two-step, biotin-dependent production of 3-methylglutaconyl-CoA, an essential intermediate in leucine catabolism. Given its critical metabolic role, deficiencies in this enzyme associate with organic aciduria, while its overexpression is linked to tumor development. MCC is a dodecameric enzyme composed of six copies of each α- and β-subunit. We present the cryo-EM structure of the endogenous MCC holoenzyme fromTrypanosoma bruceiin its soluble, non-filamentous state at 2.5 Å resolution. We unambiguously observe the position of biotin, covalently-bound to the BBCP domain of α-subunits and occupying a novel binding pocket next to the active site of a neighboring β-subunit dimer. Moreover, flexibility of key residues at the α/α- and α/β-subunit interfaces enables pivoting of α-subunit trimers to sequentially approach the otherwise distant active sites for the two steps in MCC catalysis. Our results provide a structural framework to understand the enzymatic mechanism of eukaryotic MCCs and assist drug discovery against trypanosome infections.
TRIBAL: Tree Inference of B cell Clonal Lineages
Authors: Weber Leah L. , Reiman Derek , Roddur Mrinmoy S. , Qi Yuanyuan , El-Kebir Mohammed , Khan Aly A.
Published: November 2023

B cells are a critical component of the adaptive immune system, responsible for producing antibodies that help protect the body from infections and foreign substances. Single cell RNA-sequencing (scRNA-seq) has allowed for both profiling of B cell receptor (BCR) sequences and gene expression. However, understanding the adaptive and evolutionary mechanisms of B cells in response to specific stimuli remains a significant challenge in the field of immunology. We introduce a new method, TRIBAL, which aims to infer the evolutionary history of clonally related B cells from scRNA-seq data. The key insight of TRIBAL is that inclusion of isotype data into the B cell lineage inference problem is valuable for reducing phylogenetic uncertainty that arises when only considering the receptor sequences. Consequently, the TRIBAL inferred B cell lineage trees jointly capture the somatic mutations introduced to the B cell receptor during affinity maturation and isotype transitions during class switch recombination. In addition, TRIBAL infers isotype transition probabilities that are valuable for gaining insight into the dynamics of class switching.

Viain silicoexperiments, we demonstrate that TRIBAL infers isotype transition probabilities with the ability to distinguish between direct versus sequential switching in a B cell population. This results in more accurate B cell lineage trees and corresponding ancestral sequence and class switch reconstruction compared to competing methods. Using real-world scRNA-seq datasets, we show that TRIBAL recapitulates expected biological trends in a model affinity maturation system. Furthermore, the B cell lineage trees inferred by TRIBAL were equally plausible for the BCR sequences as those inferred by competing methods but yielded lower entropic partitions for the isotypes of the sequenced B cell. Thus, our method holds the potential to further advance our understanding of vaccine responses, disease progression, and the identification of therapeutic antibodies.

Availability

TRIBAL is available athttps://github.com/elkebir-group/tribal
Oscillations in an Artificial Neural Network Convert Competing Inputs into a Temporal Code
Authors: Duecker Katharina , Idiart Marco , van Gerven Marcel AJ , Jensen Ole
Published: November 2023

Deep convolutional neural networks (CNNs) resemble the hierarchically organised neural representations in the primate visual ventral stream. However, these models typically disregard the temporal dynamics experimentally observed in these areas. For instance, alpha oscillations dominate the dynamics of the human visual cortex, yet the computational relevance of oscillations is rarely considered in artificial neural networks (ANNs). We propose an ANN that embraces oscillatory dynamics with the computational purpose of converting simultaneous inputs, presented at two different locations, into a temporal code. The network was trained to classify three individually presented letters. Post-training, we added semi-realistic temporal dynamics to the hidden layer, introducing relaxation dynamics in the hidden units as well as pulsed inhibition mimicking neuronal alpha oscillations. Without these dynamics, the trained network correctly classified individual letters but produced a mixed output when presented with two letters simultaneously, elucidating a bottleneck problem. When introducing refraction and oscillatory inhibition, the output nodes corresponding to the two stimuli activated sequentially, ordered along the phase of the inhibitory oscillations. Our model provides a novel approach for implementing multiplexing in ANNs. It further produces experimentally testable predictions of how the primate visual system handles competing stimuli.
Biomolecular condensates in fungi are tuned to function at specific temperatures
Authors: Stormo Benjamin M. , McLaughlin Grace A. , Frederick Logan K. , Jalihal Ameya P. , Cole Sierra J , Seim Ian , Dietrich Fred S. , Gladfelter Amy S.
Published: November 2023

Temperature can impact every reaction and molecular interaction essential to a cell. For organisms that cannot regulate their own temperature, a major challenge is how to adapt to temperatures that fluctuate unpredictability and on variable timescales. Biomolecular condensation offers a possible mechanism for encoding temperature-responsiveness and robustness into cell biochemistry and organization. To explore this idea, we examined temperature adaptation in a filamentous-growing fungus calledAshbya gossypiithat engages biomolecular condensates containing the RNA-binding protein Whi3 to regulate mitosis and morphogenesis. We collected wild isolates ofAshbyathat originate in different climates and found that mitotic asynchrony and polarized growth, which are known to be controlled by the condensation of Whi3, are temperature sensitive. Sequence analysis in the wild strains revealed changes to specific domains within Whi3 known to be important in condensate formation. Using anin vitrocondensate reconstitution assay we found that temperature impacts the relative abundance of protein to RNA within condensates and that this directly impacts the material properties of the droplets. Finally, we found that exchanging Whi3 genes between warm and cold isolates was sufficient to rescue some, but not all, condensate-related phenotypes. Together these data demonstrate that material properties of Whi3 condensates are temperature sensitive, that these properties are important for function, and that sequence optimizes properties for a given climate.
Reversal of pulmonary veno-occlusive disease phenotypes by inhibition of the integrated stress response
Authors: Prabhakar Amit , Kumar Rahul , Wadhwa Meetu , Ghatpande Prajakta , Zhang Jingkun , Zhao Ziwen , Lizama Carlos O. , Kharbikar Bhushan N. , Gräf Stefan , Treacy Carmen M. , Morrell Nicholas W. , Graham Brian B. , Lagna Giorgio , Hata Akiko
Published: November 2023

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension arising from EIF2AK4 gene mutations or mitomycin C (MMC) administration. The lack of effective PVOD therapies is compounded by a limited understanding of the mechanisms driving the vascular remodeling in PVOD. We show that the administration of MMC in rats mediates the activation of protein kinase R (PKR) and the integrated stress response (ISR), which lead to the release of the endothelial adhesion molecule VE-Cadherin in the complex with Rad51 to the circulation, disruption of endothelial barrier, and vascular remodeling. Pharmacological inhibition of PKR or ISR attenuates the depletion of VE-Cadherin, elevation of vascular permeability, and vascular remodeling instigated by MMC, suggesting potential clinical intervention for PVOD. Finally, the severity of PVOD phenotypes was increased by a heterozygousBMPR2mutation that truncates the carboxyl tail of BMPR2, underscoring the role of deregulated BMP signal in the development of PVOD.
Characterizing breast cancer response to neoadjuvant therapy based on biophysical modeling and multiparametric magnetic resonance imaging data
Authors: Bowers Haley J. , Guthrie John A. , Krukoski Alaura , Thomas Alexandra , Weis Jared A.
Published: November 2023

Personalized medicine efforts are focused on identifying biomarkers to guide individualizing neoadjuvant therapy regimens. In this work, we aim to validate a previously developed image data-driven mathematical modeling approach for dynamic characterization of breast cancer response to neoadjuvant therapy using a large, multi-site cohort. We retrospectively analyzed patients enrolled in the BMMR2 ACRIN 6698 subset at 10 institutions. Patients enrolled received four MRI examinations during neoadjuvant therapy with acquisitions at baseline (T0), 3-weeks/early-treatment (T1), 12-weeks/mid-treatment (T2), and completion of therapy prior to surgery (T3). A biophysical mathematical model of tumor growth is used extract metrics to characterize the dynamics of treatment response. Using predicted response at therapy conclusion and histogram summary metrics to quantify estimated tumor proliferation maps, we found univariate model-based metrics able to predict pathological response, with area under the receiver operating characteristic curve (AUC) ranging from 0.58 and 0.69 analyzing between T0and T1, and AUCs ranging from 0.72-0.76 analyzing between T0and T2. For hormone receptor (HR)-negative, human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients our model-based metrics achieved an AUC of 0.9 analyzing between T0and T1and AUC of 1.0 analyzing between T0and T2. This data shows the significant promise in developing these imaging-based biophysical mathematical modeling methods of dynamic characterization into a clinical decision support tool for individualizing treatment regimens based on patient-specific response.
Male cuticular pheromones stimulate removal of the mating plug and promote re-mating through pC1 neurons inDrosophilafemales
Authors: Yun Minsik , Kim Do-Hyoung , Ha Tal Soo , Lee Kang-Min , Park Eungyu , Knaden Markus , Hansson Bill S. , Kim Young-Joon
Published: November 2023

In birds and insects, the female uptakes sperm for a specific duration post-copulation known as the ejaculate holding period (EHP) before expelling unused sperm and the mating plug through sperm ejection. In this study, we found thatDrosophila melanogasterfemales shortens the EHP when incubated with males or mated females shortly after the first mating. This phenomenon, which we termedmale-inducedEHPshortening (MIES), requires Or47b+ olfactory and ppk23+ gustatory neurons, activated by 2-methyltetracosane and 7-tricosene, respectively. These odorants raise cAMP levels in pC1 neurons, responsible for processing male courtship cues and regulating female mating receptivity. Elevated cAMP levels in pC1 neurons reduce EHP and reinstate their responsiveness to male courtship cues, promoting re-mating with faster sperm ejection. This study established MIES as a genetically tractable model of sexual plasticity with a conserved neural mechanism.

Significance Statement

Sexual plasticity, the adaptation of reproductive behavior to social changes, was explored in the fruit fly, a genetically tractable model insect. Our findings revealed that inseminated females, encountering another courting male post-mating, shorten the ejaculate holding period (EHP). Specific olfactory and gustatory pathways regulating this phenomenon were identified, converging on the pC1 neurons in the brain-a conserved neural circuit that regulates female mating activity. Odors associated with EHP shortening increased the second messenger cAMP. The transient elevation of cAMP heightened the excitability of pC1 neurons, facilitating the prompt removal of the male ejaculate and subsequent re-mating . This study established a behavioral model of sexual plasticity and provided a framework for understanding the neural circuit processes involved.
Moodcafe: From Idea Conception to Raising Funds
Authors: Singla Chitra , Sethuram Shridhar , Jena Sanjay Kumar
Published: November 2023

The case on Moodcafe captures the journey of the start-up and its entrepreneurs from the beginning till the fund-raising stage. The case brings forth critical decisions that each entrepreneur or the team of co-founders have to address during their start-up journey. This short case gives opportunity to delve into two aspects mainly a) As a founder, which investor should one choose for seeking funds and what should be the terms and conditions of investment? and b) How can one review and assess the business model of a start-up?
Towards an understanding of how school climate strikes work as public pedagogy
Authors: Sutton Bronwyn A.
Published: November 2023

Purpose

School climate strikes are opening spaces of appearance, becoming differently active forms of public pedagogy where new and previously unthought collective climate action is possible. This inquiry contributes to understanding school climate strikes as important forms of climate justice activism by exploring how they work as public pedagogy.

Design/methodology/approach

The inquiry process involved poetic inquiry to produce an affective poetic witness statement to an event of school climate strikes, and then a performative enactment of diffractive reading using the poem created. The diffractive reading is used to conceptualise school climate strikes as public pedagogy and move towards an understanding of how school climate strikes work as public pedagogy. Diffused throughout is the question of where the more-than-human fits in public pedagogy and youth climate justice activism.

Findings

School climate strikes are dynamic and differently acting (diffracting) public pedagogies that work by open spaces of appearance that enable capacities for collective action in heterogeneous political spaces. Consideration of entanglements and intra-actions between learner, place, knowledge and climate change are productive in understanding how phenomena work as public pedagogy.

Originality/value

This inquiry extends on important considerations in both climate change education and public pedagogy scholarship. It diffuses consideration of the more-than-human throughout the inquiry and enacts a move beyond the humanist limits of existing public pedagogy scholarship by introducing climate intra-action, heterogeneous political spaces and non-conforming learning to an understanding of activist public pedagogies and the educative agent.
Propounding an integrated solution ecosystem to effectuate CSR in India: an alternate framework
Authors: G. Rajan Soumya
Published: November 2023

Purpose

Corporate social responsibility (CSR) was mandated and institutionalised in India through the Companies Act (2013), a decade ago. It is critical to understand the priorities of the models used by the companies to effectuate their CSR policy. This paper aims to understand the skewing of interest towards Education and Health interventions. The paper then proposes a framework to cross-level and effectuate CSR programme implementation.

Design/methodology/approach

The qualitative study conducted in-depth interviews of the stakeholders from the CSR environment. The findings are used to derive a model to effectuate CSR in India.

Findings

The findings may be divided into two sub-themes – (a) observations from the field study and (b) integrated solution ecosystem (ISE) framework. The qualitative study and the insights form the first component. The proposed framework which can enhance the efficiency of CSR practices may be found in the second sub-theme.

Research limitations/implications

Operationalisation of the proposed model, if adopted would require integrated efforts from multiple functional departments which could lead to an extended timeframe for implementation. This may eventually lead to a need to revise the model in the making. The research could also include perspectives from governmental stakeholders which is missing here.

Practical implications

The emerging model can present an opportunity for corporates and policymakers to revisit the CSR structure and frameworks. It can also be used to evaluate and audit the CSR practices of companies.

Social implications

The ISE posits a bunch of actionable themes which can deliver an impactful transition from the existing approach to CSR to a more far reaching one. While the ground rules are revisited, the approach also allows a critical departure from a corporate-driven model of engagement with the community. The modifications or corrections in this model would also mean a more inclusive layering of developmental interventions. The diversity which could potentially be brought in to designing interventions can be another key impact.

Originality/value

This paper presents insights for some of the pivotal stakeholders of CSR in countries like India. It presents a possible model of effective and optimal utilisation of CSR spending.
Changes in forest structure over 23 years under disturbances in a warm temperate rain forest on Yakushima Island, Japan
Authors: Niiyama Kaoru , Iida Yoshiko , Oguro Michio , Saito Satoshi
Published: November 2023

Clarifying the influence of disturbances by biotic and abiotic agents on long‐term changes in forest structure and demographic rates is an important task of forest ecology. Here, we investigated changes in forest structure and demographic rates and the effects of biotic and abiotic factors (sika deer, ambrosia beetle, neighborhood trees, and indices of strong wind and wetness) in a 4‐ha long‐term ecological study plot in a lowland warm temperate rain forest on Yakushima Island, Japan, from 1996 to 2019 for three regeneration groups related to gap dynamics (gap demander: GD, light shade tolerant: LS, and strong shade tolerant: SS). GD had relatively lower recruitment and survival than LS and/or SS. Changes in demographic rates were not significantly correlated with those in the index of strong wind in any regeneration group. The effects of sika deer on demographic rates did not differ among groups. Stems of Fagaceae species belonging to LS attacked by ambrosia beetles recorded in 2013 did not significantly differ in RGR and survival rates. Our results indicate that despite the relatively long monitoring period of 23 years, we did not detect significant effects of strong winds on demographic rates among regeneration groups, and shade‐tolerant species (LS and SS) showed better demographic performance than light‐demanding species (GD) and an increase in total basal area over time. We need longer monitoring of forest dynamics to understand forest responses to disturbances considering several factors, including the time lag of demographic responses to disturbances and the long‐term effects of disturbances.
Antifungal edible coatings for fruits based on zein and chitosan nanowhiskers
Authors: Almeida Carolina L. , Figueiredo Lucas R. F. , Ribeiro Diego V. M. , Santos Adillys M. C. , Souza Evandro L. , Oliveira Kataryne A. R. , Oliveira Juliano E. , Medeiros Eliton S.
Published: November 2023

Fresh produce have a more limited shelf life than processed ones. Their sensory attributes such as appearance and surface texture are important features in consumer perception and liking. The decomposition of fresh produce, which is caused by enzymes, chemical reactions, and microbial infections, often caused by Colletotrichum species, is inevitable. However, it can be slowed down. Several materials have been developed for this purpose, with an emphasis on active coatings using nanomaterials. In this study, the protective effects of a zein coating containing chitosan nanowhiskers (CSW) for the maintenance of fruit quality were investigated using guava (Psidium guajava L.) as a model fruit. CSW were previously characterized, and their antifungal effects against distinct Colletotrichum species (Colletotrichum asianum, Colletotrichum tropicale, Colletotrichum gloeosporioides, and Colletotrichum brevisporum) were proven. Coatings were characterized by thermogravimetric analysis, optical profilometry, and mechanical properties. Total soluble solids, pH, mass loss, and visual inspection of uncoated and coated guava fruits were also verified during 9 days. Results show that CSW length and aspect ratio decreased for longer extraction times. A similar behavior was found for x‐ray diffraction in which peak intensity decreases under the same conditions. CSW degradation (ca. 250–400°C) also depends on extraction time in which more crystalline whiskers are the most thermally stable ones. The addition of CSW did not significantly (p < 0.05) modify the homogeneity and continuity of coating but prevented microbial growth assuring fruit quality during storage. In summary, coatings protected guava fruits from post‐harvest spoilage while preserving quality and extending shelf life.

Practical Application

Fresh foods such as fruits and vegetables have a more limited shelf life than processed ones.
Implanting mechanically reprogrammed fibroblasts for aged tissue regeneration and wound healing
Authors: Roy Bibhas , Pekec Tina , Yuan Luezhen , Shivashankar G. V.
Published: November 2023

Cell‐based therapies are essential for tissue regeneration and wound healing during aging. Autologous transplantation of aging cells is ineffective due to their increased senescence and reduced tissue remodeling capabilities. Alternatively, implanting reprogrammed aged cells provides unique opportunities. In this paper, we demonstrate the implantation of partially reprogrammed aged human dermal fibroblasts into in vitro aged skin models for tissue regeneration and wound healing. The partially reprogrammed cells were obtained using our previously reported, highly efficient mechanical approach. Implanted cells showed enhanced expression of extracellular matrix proteins in the large area of aged tissue. In addition, the implanted cells at wound sites showed increased extracellular matrix protein synthesis and matrix alignment. Transcriptome analysis, combined with chromatin biomarkers, revealed these implanted cells upregulated tissue regeneration and wound healing pathways. Collectively our results provide a novel, nongenetic, partial reprogramming of aged cells for cell‐based therapies in regenerative medicine.
Factors influencing nursing and allied health recent graduates' rural versus urban preferred principal place of practice: A cross‐sectional data linkage study
Authors: Fisher Karin , Depczynski Julie , Mitchell Eleanor , Smith Anthony
Published: November 2023

Introduction

Disparities between metropolitan and non‐metropolitan health workforce must be addressed to reduce inequities in health care access. Understanding factors affecting early career practitioners' choice of practice location can inform workforce planning.

Objective

To investigate influences on rural practice location preferences of recent graduates.

Design

Cross‐sectional analysis linked university enrolment, Graduate Outcomes Survey (GOS) and Australian Health Professional Regulation Agency (Ahpra) principal place of practice (PPP) for 2018 and 2019 nursing and allied health graduates from two Australian universities. Chi‐squared tests and logistic regression compared rural versus urban PPP and locational preference.

Findings

Of 2979 graduates, 1295 (43.5%) completed the GOS, with 63.7% (n = 825) working in their profession and 84.0% of those (n = 693) in their preferred location. Ahpra PPP data were extracted for 669 (81.1%) of those working in their profession. Most reported influences were ‘proximity to family/friends’ (48.5%), ‘lifestyle of the area’ (41.7%) and ‘opportunity for career advancement’ (40.7%). Factors most influential for rural PPP were ‘cost of accommodation/housing’ (OR = 2.26, 95% CI = 1.23–4.17) and ‘being approached by an employer’ (OR = 2.10, 95% CI = 1.12–3.92). Having an urban PPP was most influenced by ‘spouse/partners employment/career’ (OR = 0.53, 95% CI = 0.30–0.93) and ‘proximity to family/friends’ (OR = 0.41, 95% CI = 0.24–0.72).

Discussion

While the findings add strength to the understanding that graduates who originated from a rural area are most likely to take up rural practice in their preferred location, varied social and professional factors are influential on decision‐making.

Conclusions

It is imperative to recruit students from non‐metropolitan regions into health professional degrees, as well as addressing other influences on choice of practice location.
Safety and immunopharmacology of ASP0892 in adults or adolescents with peanut allergy: two randomized trials
Authors: Ferslew Brian C. , Smulders Ronald , Zhu Tong , Blauwet Mary B. , Kusawake Tomohiro , Spence Anna , Aldridge Kelly , DeBerg Hannah A. , Khosa Sugandhika , Wambre Erik , Chichili Gurunadh R.
Published: November 2023

Background

New treatment options with improved safety and novel mechanisms of actions are needed for patients with peanut allergy.

Objectives

To evaluate the safety, tolerability, and immunogenicity of ASP0892, a peanut DNA vaccine, after intradermal (id) or intramuscular (im) administration in adult or adolescent patients with peanut allergy in two phase 1 studies.

Methods

ASP0892 or placebo was administered every 2 weeks for a total of 4 doses. The doses were 1 mg or 4 mg id or 4 mg im for adults, and 1 mg or 4 mg id for adolescents. Immunologic parameters were assessed longitudinally.

Results

Thirty‐one adults (mean age 24.3 years, 17 males) received ASP0892 (9, 8, 8 patients for 1 mg id, 4 mg id or 4 mg im, respectively) or placebo (2 patients/group). Twenty adolescents (mean age 14.2 years, 11 males) received ASP0892 (8 patients/group) or placebo (2 patients/group). In both studies, the most common treatment‐emergent adverse event (TEAE) was injection site pruritus. No deaths or treatment withdrawal were related to TEAEs. No serious TEAEs related to treatment were observed in adult or adolescent patients. ASP0892 treatment led to modest increases in allergen‐specific IgG and/or IgG4 in adults (1 mg id, 4 mg im) and adolescents (1 mg id, 4 mg id). No improvements in clinical outcomes, including double‐blind placebo‐controlled food challenge, were found after ASP0892 treatment.

Conclusions

In two phase 1 studies, ASP0892 was well tolerated with modest but not clinically relevant changes in immune responses.

ClinicalTrials.gov Identifiers

NCT02851277, NCT03755713.
Increased serum creatinine associated with testicular microlithiasis in adult Japanese men: A retrospective cohort study
Authors: Hagiuda Jun , Takamatsu Kiyoshi , Nakagawa Ken
Published: November 2023

Background

Testicular microlithiasis (TM) is thought to be associated with testicular tumors and impaired spermatogenesis; however, its etiology remains unclear.

Objectives

To identify factors, other than testicular function, that are associated with testicular microlithiasis.

Materials and methods

We enrolled males who underwent ultrasound examination of the scrotum at Tokyo Dental College Ichikawa General Hospital. The patients were categorized into two groups: those with or those without testicular microlithiasis. Background and blood test data were compared between the groups.

Results

Testicular microlithiasis was observed in 72 of the 828 (8.7%) patients enrolled. Ages ranged from 15 to 87 years (mean age, 40.0 years). A history of germ cell tumor was significantly more prevalent in patients with testicular microlithiasis than in those without (1.3 vs. 16.7%; p < 0.001). Blood test data showed that, patients with testicular microlithiasis had significantly higher serum creatinine levels (0.91 vs. 1.04 mg/dL; p = 0.046) and lower calcium levels (9.4 vs. 9.3 mg/dL; p = 0.031) than those without. Serum creatinine levels (> 1.00 mg/dL) and germ cell tumors were significantly associated with testicular microlithiasis in both univariate and multivariate analyses. The prevalence of testicular microlithiasis increased in patients older than 50 years. Age (> 50 years) was associated with testicular microlithiasis in univariate analysis. The mean body weight tended to be heavier (70.7 vs. 72.2 kg; p = 0.051) and epididymitis was observed more frequently (3.2 vs. 8.3%; p = 0.056) in patients with testicular microlithiasis than in those without.

Discussion and conclusion

A history of testicular tumors and elevated serum creatinine levels were associated with testicular microlithiasis. Testicular microlithiasis was observed across all age groups, with a tendency to increase in patients older than 50 years. Patients with testicular microlithiasis were slightly heavier and had a higher prevalence of epididymitis than those without. Our findings suggest that, in addition to testicular dysgenesis, other factors are involved in the development of testicular microlithiasis.
The institutionalisation of urban community gardens in Cape Town, South Africa
Authors: Kanosvamhira Tinashe P.
Published: November 2023

Urban community gardens, once seen as a counter to neoliberal subjectivity, are now perceived as inadvertently reinforcing neoliberal dominance, challenging the progressive goals of urban gardening. This study investigates how the state shapes urban community gardens in alignment with neoliberal principles, potentially diluting their intended advantages. By analysing policies and interviewing state actors supporting urban gardening initiatives and activists, I argue that the state actively cultivates neoliberal subjectivities in these contexts. Unfortunately, state policies and projects often fail to address the root causes of food and nutrition insecurity in urban areas. This neoliberalisation of urban community gardening diminishes their potential to act as tools for advancing food justice in historically disadvantaged communities in Cape Town. Nevertheless, there is hope in the agency of gardeners who are not passive participants in this process. I conclude that relying on the state to implement projects for a more equitable food system may not be a dependable strategy. Instead, urban gardeners must carefully select their allies to effectively pursue their goals.
Bromodomain‐containing protein 4 inhibition improves the efficacy of cisplatin and radiotherapy in oral squamous cell carcinoma by suppressing programmed cell death‐ligand 1 expression
Authors: Ren Jiajie
Published: November 2023

The bromodomain‐containing protein 4 (BRD4) is highly expressed in oral squamous cell carcinoma (OSCC) and plays a crucial role in tumour progression. However, the impact of BRD4 on the efficacy of chemotherapy and radiotherapy by regulating the expression of programmed cell death‐ligand 1 (PD‐L1) in OSCC remains unclear. In this study, we found that the BRD4 inhibitor JQ1 effectively enhanced the inhibitory effects of cisplatin and radiotherapy on cell proliferation and promoted the apoptosis of OSCC cells by cisplatin and radiotherapy. Furthermore, treatment with JQ1 reversed the increase of the expression of PD‐L1 by cisplatin and radiotherapy, whereas the overexpression of PD‐L1 partially countered the beneficial effects of JQ1 on the anticancer efficacy of cisplatin and radiotherapy. These results demonstrate that the inhibition of BRD4 improves the anticancer effect of chemotherapy and radiotherapy by suppressing the expression of PD‐L1 in OSCC, suggesting that targeting BRD4 could be a promising therapeutic approach for chemo/radioresistant OSCC.
Language‐Specific Constraints on Conversation: Evidence from Danish and Norwegian
Authors: Dideriksen Christina , Christiansen Morten H. , Dingemanse Mark , Højmark‐Bertelsen Malte , Johansson Christer , Tylén Kristian , Fusaroli Riccardo
Published: November 2023

Establishing and maintaining mutual understanding in everyday conversations is crucial. To do so, people employ a variety of conversational devices, such as backchannels, repair, and linguistic entrainment. Here, we explore whether the use of conversational devices might be influenced by cross‐linguistic differences in the speakers’ native language, comparing two matched languages—Danish and Norwegian—differing primarily in their sound structure, with Danish being more opaque, that is, less acoustically distinguished. Across systematically manipulated conversational contexts, we find that processes supporting mutual understanding in conversations vary with external constraints: across different contexts and, crucially, across languages. In accord with our predictions, linguistic entrainment was overall higher in Danish than in Norwegian, while backchannels and repairs presented a more nuanced pattern. These findings are compatible with the hypothesis that native speakers of Danish may compensate for its opaque sound structure by adopting a top‐down strategy of building more conversational redundancy through entrainment, which also might reduce the need for repairs. These results suggest that linguistic differences might be met by systematic changes in language processing and use. This paves the way for further cross‐linguistic investigations and critical assessment of the interplay between cultural and linguistic factors on the one hand and conversational dynamics on the other.
A fast and non‐invasive artificial intelligence olfactory‐like system that aids diagnosis of Parkinson's disease
Authors: Cao Yina , Jiang Lina , Zhang Jingxin , Fu Yanlu , Li Qiwei , Fu Wei , Zhu Junjiang , Xiang Xiaohui , Zhao Guohua , Kong Dongdong , Chen Xing , Fang Jiajia
Published: November 2023

Background and purpose

Several previous studies have shown that skin sebum analysis can be used to diagnose Parkinson's disease (PD). The aim of this study was to develop a portable artificial intelligence olfactory‐like (AIO) system based on gas chromatographic analysis of the volatile organic compounds (VOCs) in patient sebum and explore its application value in the diagnosis of PD.

Methods

The skin VOCs from 121 PD patients and 129 healthy controls were analyzed using the AIO system and three classic machine learning models were established, including the gradient boosting decision tree (GBDT), random forest and extreme gradient boosting, to assist the diagnosis of PD and predict its severity.

Results

A 20‐s time series of AIO system data were collected from each participant. The VOC peaks at a large number of time points roughly concentrated around 5–12 s were significantly higher in PD subjects. The gradient boosting decision tree model showed the best ability to differentiate PD from healthy controls, yielding a sensitivity of 83.33% and a specificity of 84.00%. However, the system failed to predict PD progression scored by Hoehn−Yahr stage.

Conclusions

This study provides a fast, low‐cost and non‐invasive method to distinguish PD patients from healthy controls. Furthermore, our study also indicates abnormal sebaceous gland secretion in PD patients, providing new evidence for exploring the pathogenesis of PD.
Listeria monocytogenes encephalitis in a donkey foal
Authors: Jula Catherine , Buechner‐Maxwell Virginia , Southard Teresa , LeCuyer Tessa
Published: November 2023

This is the first known case report of encephalitic listeriosis in a donkey (Equus asinus). A 5‐day‐old female donkey foal presented for fever, progressive weakness and loss of suckle reflex. Upon arrival, its vital parameters were normal, but the foal was collapsed. It had horizontal nystagmus, front limb paddling, minimal response to stimuli, prolapse of the left third eyelid and curling the neck to the left when in sternal recumbency. Samples collected for diagnostic evaluation included blood and cerebral spinal fluid. The cerebrospinal fluid (CSF) showed a pleocytosis consisting mainly of nondegenerative neutrophils and a normal protein concentration. Bacteria were not seen on Gram stain. After 24 h of treatment with intravenous fluids, anti‐inflammatories, antibiotics, nasogastric feedings of the dam's milk and supplemental nasal oxygen, little improvement was observed and the owners elected to euthanise the foal. Post‐mortem examination revealed multifocal, irregularly distributed hepatic necrosis and multifocal lymphohistiocytic encephalitis. Listeria monocytogenes was isolated from a section of brainstem.
The quest for new robust bacterial monoamine oxidases
Authors: Martins Lígia O.
Published: November 2023

Microbial enzymes are versatile, cost‐effective, and sustainable tools, making them a preferred choice for enzymatic processes. Santema et al. harnessed AlphaFold, a cutting‐edge structure prediction tool, to discover new thermophilic monoamine oxidases (MAO) that could be relevant for drug development and use in biotechnology fields. The new enzyme displays thermal robustness, offering a unique structure‐to‐function profile compared to known MAOs. This bacterial enzyme, paired with recent advancements in enzyme engineering, has the potential to meet the biotech sector's need for customized enzymes.
Does informal governance matter to institutional investors? Evidence from social capital
Authors: Huang Kershen , Shang Chenguang
Published: November 2023

We find a positive association between institutional ownership and social capital. The social norms in a region, while not imposed by businesses or laws, play a monitoring role that disciplines managers from self‐serving behaviors. The resulting trustworthiness, through its mitigation of agency problems, drives the investment preferences of institutions. Our subsample analyses based on information asymmetry and financial performance support this inference. Further, the positive association is evident for transient investors and quasi‐indexers but not for dedicated institutional investors. Overall, our study underscores the impact of informal governance on institutions' investment decisions.
Dust storms increase the tolerance of phytoplankton to thermal and pH changes
Authors: González‐Olalla Juan Manuel , Powell James A. , Brahney Janice
Published: November 2023

Aquatic communities are increasingly subjected to multiple stressors through global change, including warming, pH shifts, and elevated nutrient concentrations. These stressors often surpass species tolerance range, leading to unpredictable consequences for aquatic communities and ecosystem functioning. Phytoplankton, as the foundation of the aquatic food web, play a crucial role in controlling water quality and the transfer of nutrients and energy to higher trophic levels. Despite the significance in understanding the effect of multiple stressors, further research is required to explore the combined impact of multiple stressors on phytoplankton. In this study, we used a combination of crossed experiment and mechanistic model to analyze the ecological and biogeochemical effects of global change on aquatic ecosystems and to forecast phytoplankton dynamics. We examined the effect of dust (0–75 mg L−1), temperature (19–27°C), and pH (6.3–7.3) on the growth rate of the algal species Scenedesmus obliquus. Furthermore, we carried out a geospatial analysis to identify regions of the planet where aquatic systems could be most affected by atmospheric dust deposition. Our mechanistic model and our empirical data show that dust exerts a positive effect on phytoplankton growth rate, broadening its thermal and pH tolerance range. Finally, our geospatial analysis identifies several high‐risk areas including the highlands of the Tibetan Plateau, western United States, South America, central and southern Africa, central Australia as well as the Mediterranean region where dust‐induced changes are expected to have the greatest impacts. Overall, our study shows that increasing dust storms associated with a more arid climate and land degradation can reverse the negative effects of high temperatures and low pH on phytoplankton growth, affecting the biogeochemistry of aquatic ecosystems and their role in the cycles of the elements and tolerance to global change.