bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid ionic current phenotyping (RICP) identifies mechanistic underpinnings of iPSC-CM AP heterogeneity
Authors: Clark Alexander P. , Wei Siyu , Fullerton Kristin , Krogh-Madsen Trine , Christini David J.
Published: August 2023

As a renewable, easily accessible, human-derivedin vitromodel, human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) are a promising tool for studying arrhythmia-related factors, including cardiotoxicity and congenital proarrhythmia risks. An oft-mentioned limitation of iPSC-CMs is the abundant cell-to-cell variability in recordings of their electrical activity. Here, we develop a new method, rapid ionic current phenotyping (RICP), that utilizes a short (10 s) voltage clamp protocol to quantify cell-to-cell heterogeneity in key ionic currents. We correlate these ionic current dynamics to action potential recordings from the same cells and produce mechanistic insights into cellular heterogeneity. We present evidence that the L-type calcium current is the main determinant of upstroke velocity, rapid delayed rectifier K+current is the main determinant of the maximal diastolic potential, and an outward current in the excitable range of slow delayed rectifier K+is the main determinant of action potential duration. We measure an unidentified outward current in several cells at 6 mV that is not recapitulated by iPSC-CM mathematical models but contributes to determining action potential duration. In this way, our study both quantifies cell-to-cell variability in membrane potential and ionic currents, and demonstrates how the ionic current variability gives rise to action potential heterogeneity. Based on these results, we argue that iPSC-CM heterogeneity should not be viewed simply as a problem to be solved but as a model system to understand the mechanistic underpinnings of cellular variability.

New & Noteworthy

We present rapid ionic current phenotyping (RICP), a current quantification approach based on an optimized voltage clamp protocol. The method captures a rich snapshot of ionic currents that provides quantitative information about multiple currents (e.g., ICaL, IKr) in the same cell. The protocol helped to identify key ionic determinants of cellular action potential heterogeneity in iPSC-CMs. This included unexpected results, such as the critical role of IKrin establishing the maximum diastolic potential.
A tryptophan metabolite modulates the host response to bacterial infection via kainate receptors
Authors: Parada-Kusz Margarita , Clatworthy Anne E. , Goering Emily R. , Blackwood Stephanie M. , Salm Elizabeth J. , Choi Catherine , Combs Senya , Lee Jenny S. W. , Rodriguez-Osorio Carlos , Tomita Susumu , Hung Deborah T.
Published: August 2023

Bacterial infection involves a complex interaction between the pathogen and host where the outcome of infection is not solely determined by pathogen eradication. To identify small molecules that promote host survival by altering the host-pathogen dynamic, we conducted anin vivochemical screen using zebrafish embryos and found that treatment with 3-hydroxy-kynurenine protects from lethal gram-negative bacterial infection. 3-hydroxy-kynurenine, a metabolite produced through host tryptophan metabolism, has no direct antibacterial activity but enhances host survival by restricting bacterial expansion in macrophages by targeting kainate-sensitive glutamate receptors. These findings reveal new mechanisms by which tryptophan metabolism and kainate-sensitive glutamate receptors function and interact to modulate immunity, with significant implications for the coordination between the immune and nervous systems in pathological conditions.
From sequences to therapeutics: Machine learning predicts chemically modified siRNA Activity
Authors: Martinelli Dominic D.
Published: August 2023

Abstract

Small interfering RNAs (siRNAs) exemplify the promise of genetic medicine in the discovery of novel therapeutic modalities. Their ability to selectively suppress gene expression makes them ideal candidates for development as oligonucleotide pharmaceuticals. Recent advancements in machine learning (ML) have facilitated unmodified siRNA design and efficacy prediction, but a model trained to predict the silencing activity of siRNAs with diverse chemical modification patterns has yet to be published, despite the importance of such chemical modifications in designing siRNAs with the potential to advance to the clinic. This study presents the first application of ML to classify efficient chemically modified siRNAs from sequence and chemical modification patterns alone. Three algorithms are evaluated at three classification thresholds and compared according to sensitivity, specificity, consistency of feature weights with empirical knowledge, and performance on an external validation dataset. Finally, possible directions for future research are proposed.
Dendritic cell-mediated responses to secretedCryptosporidiumeffectors are required for parasite-specific CD8+T cell responses
Authors: Haskins Breanne E. , Gullicksrud Jodi A. , Wallbank Bethan A. , Dumaine Jennifer E. , Guérin Amandine , Cohn Ian S. , O’Dea Keenan M. , Pardy Ryan D. , Merolle Maria I. , Shallberg Lindsey A. , Hunter Emma N. , Byerly Jessica H. , Smith Eleanor J. , Buenconsejo Gracyn Y. , McLeod Briana I. , Christian David A. , Striepen Boris , Hunter Christopher A.
Published: August 2023

Cryptosporidiumcauses debilitating diarrheal disease in patients with primary and acquired defects in T cell function. However, it has been a challenge to understand how this infection generates T cell responses and how they mediate parasite control. Here,Cryptosporidiumwas engineered to express a parasite effector protein (MEDLE-2) that contains the MHC-I restricted SIINFEKL epitope which is recognized by TCR transgenic OT-I CD8+T cells. These modified parasites induced expansion of endogenous SIINFEKL-specific and OT-I CD8+T cells that were a source of IFN-γ that could restrict growth ofCryptosporidium. This T cell response was dependent on the translocation of the effector and similar results were observed with another secreted parasite effector (ROP1). Although infection and these translocated effector proteins are restricted to intestinal epithelial cells (IEC), type I dendritic cells (cDC1) were required to generate CD8+T cell responses to these model antigens. These data sets highlightCryptosporidiumeffectors as targets of the immune system and suggest that crosstalk between enterocytes and cDC1s is crucial for CD8+T cell responses toCryptosporidium.
A future food boom rescues the negative effects of cumulative early-life adversity on adult lifespan in a small mammal
Authors: Petrullo Lauren , Delaney David , Boutin Stan , Lane Jeffrey E. , McAdam Andrew G. , Dantzer Ben
Published: August 2023

Adverse early-life conditions, even when transient, can have long-lasting effects on individual phenotypes and reduce lifespan across species. If these effects can be mitigated. by a high quality later-life environment, then differences in future resource access may explain variation in vulnerability and resilience to early-life adversity. Using 32 years of data on 1,000+ wild North American red squirrels, we tested the hypothesis that the negative effects of early-life adversity on lifespan can be buffered by later-life food abundance. We found that although cumulative early-life adversity was negatively associated with adult lifespan, this relationship was modified by future food abundance. Squirrels that experienced a naturally-occurring future food boom in the second year of life did not suffer reduced longevity despite early-life adversity. Experimental supplementation with additional food did not replicate this effect, though it did increase adult lifespan overall. Our results suggest a non-deterministic role for early-life conditions on later-life phenotypes, and highlight the importance of contextualizing the influence of harsh early-life conditions over an animal’s entire life course.
In vitro investigation of antibacterial activity of Gum Arabic prepared by two different processing methods against Enterococcus faecalis
Authors: Elmubarak Nuha , Ibrahim Yahia , Gareeballah Abbas , Sanhouri Nada
Published: August 2023

Background

Entrococcus faecalis is a known cause of endodontic treatment failure. Synthetic drugs have been preferred for decades, but recently, many plants have been reported for their antibacterial activity.

Aim

To investigate the antibacterial effect of Gum Arabic (GA) processed with two different processing methods against Enterococcus faecalis.

Method

Antibacterial susceptibility tests against Enterococcus faecalis (ATCC 29212) were performed for 200mg/ml ethanolic extracts of spray-dried and mechanically ground GA using Agar disc diffusion. Sodium Hypochlorite (1%), Chlorhexidine (0.2%), and Antibiotic multi-disc were used as positive controls, and ethanol (20%) as a negative. The inhibition zones diameters were measured.

Serial dilutions of both types of Gum Arabic (100, 50, 25, 12.5 mg/ml) were tested for their antibacterial activity.

Results

In Concentration 200 mg/ml, spray-dried GA displayed a significantly greater inhibition zone against E. faecalis than mechanically ground(P=0.02).Both types of Gum Arabic exhibited lower antibacterial activity than chlorhexidine (0.2%). However, only mechanically ground GA showed significant result(P=0.005).Spray-dried GA showed significantly higher antibacterial activity against than Tetracycline 300mcg(P=0.005).

The antibacterial activity of spray-dried GA exceeded that of mechanically ground in all concentrations of serial dilutions, except for 12.5mg/ml, both are similar.

Conclusion

processing method of Gum Arabic affects its antibacterial potency against E. faecalis. In high concentrations, spray-dried GA is active antibacterial, while mechanically ground is non-active.

Decreasing the concentration of mechanically ground GA increases its inhibitory effect, but the opposite effect was observed with spray-dried GA.
Mapping Human Tissues with Highly Multiplexed RNA in situ Hybridization
Authors: Kalhor Kian , Chen Chien-Ju , Lee Ho Suk , Cai Matthew , Nafisi Mahsa , Que Richard , Palmer Carter , Yuan Yixu , Zhang Yida , Song Jinghui , Knoten Amanda , Lake Blue B. , Gaut Joseph P. , Keene Dirk , Lein Ed , Kharchenko Peter V. , Chun Jerold , Jain Sanjay , Fan Jian-Bing , Zhang Kun
Published: August 2023

In situ transcriptomic techniques promise a holistic view of tissue organization and cell-cell interactions. Recently there has been a surge of multiplexed RNA in situ techniques but their application to human tissues and clinical biopsies has been limited due to their large size, general lower tissue quality and high background autofluorescence. Here we report DART-FISH, a versatile padlock probe-based technology capable of profiling hundreds to thousands of genes in centimeter-sized human tissue sections at cellular resolution. We introduced an omni-cell type cytoplasmic stain, dubbed RiboSoma that substantially improves the segmentation of cell bodies. We developed a computational decoding-by-deconvolution workflow to extract gene spots even in the presence of optical crowding. Our enzyme-free isothermal decoding procedure allowed us to image 121 genes in a large section from the human neocortex in less than 10 hours, where we successfully recapitulated the cytoarchitecture of 20 neuronal and non-neuronal subclasses. Additionally, we demonstrated the detection of transcripts as short as 461 nucleotides, including neuropeptides and discovered new cortical layer markers. We further performed in situ mapping of 300 genes on a diseased human kidney, profiled >20 healthy and pathological cell states, and identified diseased niches enriched in transcriptionally altered epithelial cells and myofibroblasts.
Neural Networks Are Tuned Near Criticality During a Cognitive Task and Distanced from Criticality In a Psychopharmacological Model of Alzheimer’s Disease
Authors: Habibollahi Forough , Sun Dechuan , Burkitt Anthony N. , French Chris
Published: August 2023

Dynamical systems exhibit transitions between ordered and disordered states and “criticality” occurs when the system lies at the borderline between these states at which the input is neither strongly damped nor excessively amplified. Impairments in brain function such as dementia or epilepsy could arise from failure of adaptive criticality, and deviation from criticality may be a potential biomarker for cognition-related neurological and psychiatric impairments. Miniscope wide-field calcium imaging of several hundred hippocampal CA1 neurons in freely-behaving mice was studied during rest, a cognitive task of novel object recognition (NOR), and novel object recognition following scopolamine administration that greatly impairs spatial memory encoding. We find that while hippocampal networks exhibit characteristics of a near-critical system at rest, the network activity shifts significantly closer to a critical state when the mice engaged in the NOR task. The dynamics shift away from criticality with impairment of novel object performance due to scopolamine-induced memory impairment. These results support the concept that hippocampal neural networks move closer to criticality when successfully processing increased cognitive load, taking advantage of maximal dynamical range, information content, and transmission that occur in critical regimes.
Distinct Microstructural Heterogeneities Underpin Specific Micromechanical Properties in Human ACL Femoral and Tibial Entheses
Authors: Fang Jinghua , Wang Xiaozhao , Lai Huinan , Li Wenyue , Pan Zongyou , Mao Renwei , Yan Yiyang , Xie Chang , Lin Junxin , Sun Wei , Li Rui , Wang Jiajie , Dai Jiacheng , Xu Kaiwang , Yu Xinning , Xu Tengjing , Duan Wangping , Qian Jin , Ouyang Hongwei , Dai Xuesong
Published: August 2023

The anterior cruciate ligament (ACL) is anchored to the femur and tibia by a specialized interface tissue called the enthesis, which transfers forces in multiple directions and magnitudes without accruing fatigue damage during loading cycles over a lifetime. However, the precise structural and mechanical characteristics of the ACL femoral enthesis (FE) and tibial enthesis (TE) and their intricate interplay are unknown. In this study, we identified two ultrathin-graded mineralization regions in the FE (∼21 μm) and TE (∼14 μm), both of which exhibited distinct biomolecular compositions and mineral assembly patterns. FE interface exhibited progressively maturing hydroxyapatites (HAps), whereas minerals at the TE interface region changed from an amorphous phase (ACP) to HAps with increasing crystallinity. The LC-MS/MS results revealed that MGP protein uniquely enriched at the TE interface may be favorable for stabilizing ACP, while CLEC11A enriched at the FE interface could facilitate osteogenesis of the interface. The finite element analysis results indicated that the FE model was more resistant to shearing, while the TE model facilitated tensile resistance. It suggested that the great discrepancy in biomolecular expression and the corresponding mineral assembling heterogeneities together contributed to the superior mechanical properties of both the FE and TE models. These findings provide new perspectives regarding the management of ACL injury and the development of high-performance interface materials.
Human intestinal organoid-derived PDGFRα+ mesenchymal stroma empowers LGR4+ epithelial stem cells
Authors: JunLong Chen , Horiuchi Shinichiro , Kuramochi So , Kawasaki Tomoyuki , Kawasumi Hayato , Akiyama Saeko , Arai Tomoki , Morinaga Kenichi , Kimura Tohru , Kiyono Tohru , Akutsu Hidenori , Ishida Seiichi , Umezawa Akihiro
Published: August 2023

The columnar epithelial cells comprising the intestinal tract, stomach, and uterus can be cultured in vitro as organoids or in adherent culture. However, the proliferation of these columnar epithelial cells in adherent culture is limited. Likewise, human pluripotent stem cell (hPSC)-derived intestinal epithelial cells do not show extensive or clonal propagation in vitro. In this study, we induced proliferation of hPSC-derived small intestinal epithelium for a longer time by utilizing mesenchymal stromal cells derived from self-organized intestinal organoids as feeders. The proliferating cells exhibited columnar form, microvilli and glycocalyx formation, and cell polarity, as well as expression of drug-metabolizing enzymes and transporters. It is noteworthy that small intestinal epithelial stem cells cannot be cultured in adherent culture alone, and the stromal cells cannot be replaced by other feeders. Organoid-derived mesenchymal stromal cells resemble the trophocytes essential for maintaining small intestinal epithelial stem cells, and play a crucial role in adherent culture. The high proliferative expansion, productivity, and functionality of hPSC-derived small intestinal epithelial stem cells could have potential applications in pharmacokinetic and toxicity studies and regenerative medicine.
Syntaxin clusters and cholesterol affect the mobility of Syntaxin1a
Authors: Weisgerber Alan W. , Otruba Zdeněk , Knowles Michelle K
Published: August 2023

Syntaxin1a (Syx1a) is essential for stimulated exocytosis in neuroendocrine cells. The vesicle docking process involves the formation of nanoscale Syx1a domains on the plasma membrane and the Syx1a clusters disintegrate during the fusion process. Syx1a nanodomains are both static yet empty and refill; the process by which these clusters maintain this balance is unclear. In this work, the dynamics of the Syx1a molecules is elucidated relative to the cluster position through a labeling strategy that allows both the bulk position of the Syx clusters to be visualized concurrent with the trajectories of single Syx1a molecules on the surface of PC12 cells. Single Syx1a molecules were tracked in time relative to cluster positions to decipher how Syx1a moves within a cluster and when clusters are not present. Syx1a is mobile on the plasma membrane, more mobile at the center of clusters, and less mobile near the edges of clusters; this depends on the presence of the N-terminal Habc domain and cholesterol, which are essential for proper exocytosis. Simulations of the dynamics observed at clusters support a model where clusters are maintained by a large cage (r= 100 nm) within which Syx1a remains highly mobile within the cluster (r= 50 nm). The depletion of cholesterol dramatically reduces the mobility of Syx1a within clusters and less so over the rest of the plasma membrane. This suggests that fluidity of Syx1a supramolecular clusters is needed for function.

STATEMENT OF SIGNIFICANCE

Syntaxin1a (Syx1a) is essential for exocytosis where the vesicle docking process involves the formation of nanoscale Syx1a domains on the plasma membrane. Syx1a nanodomains are both static yet empty and refill; the process by which these clusters maintain this balance is unclear. In this work, the dynamics of the Syx1a molecules was elucidated relative to the cluster position on the surface of PC12 cells. Single molecules were tracked relative to clusters and Syx1a is mobile on the plasma membrane, more so within a cluster and less mobile near the edges of clusters. This depends on the presence of the N-terminal domain and cholesterol, which are essential for proper exocytosis. This suggests that fluidity of Syx1a clusters is needed for function.
Climate change should drive mammal defaunation in tropical dry forests
Authors: Moura Mario R. , Oliveira Gibran A. , Paglia Adriano P. , Pires Mathias M. , Santos Bráulio A.
Published: August 2023

Human-induced climate change has intensified negative impacts on socioeconomic factors, the environment, and biodiversity, including changes in rainfall patterns and an increase in global average temperatures. Drylands are particularly at risk, with projections suggesting they will become hotter, drier, and less suitable for a significant portion of their species, potentially leading to mammal defaunation. We use ecological niche modelling and community ecology biodiversity metrics to examine potential geographical range shifts of non-volant mammal species in the largest Neotropical dryland, the Caatinga, and evaluate impacts of climate change on mammal assemblages. According to projections, 85% of the mammal species will lose suitable habitats, with one quarter of species projected to completely lose suitable habitats by 2060. This will result in a decrease in species richness for more than 90% of assemblages and an increase in compositional similarity to nearby assemblages (i.e., reduction in spatial beta diversity) for 70% of the assemblages. Small-sized mammals will be the most impacted and lose most of their suitable habitats, especially in highlands. The scenario is even worse in the eastern half of Caatinga where habitat destruction already prevails, compounding the threats faced by species there. While species-specific responses can vary with respect to dispersal, behaviour, and energy requirements, our findings indicate that climate change can drive mammal assemblages to biotic homogenisation and species loss, with drastic changes in assemblage trophic structure. For successful long-term socioenvironmental policy and conservation planning, it is critical that findings from biodiversity forecasts are considered.
BMP7 promotes cardiomyocyte regeneration
Authors: Bongiovanni Chiara , Bueno-Levy Hanna , Pena Denise Posadas , Bono Irene Del , Redaelli Simone , Bergen Max , Pra Silvia Da , Sacchi Francesca , Miano Carmen , Boriati Stefano , Pontis Francesca , Romaniello Donatella , Mazzeschi Martina , Petraroia Ilaria , Tassinari Riccardo , Kellerer Laura , Lauriola Mattia , Ventura Carlo , Heermann Stephan , Weidinger Gilbert , Tzahor Eldad , D’Uva Gabriele
Published: August 2023

Zebrafish has a remarkable and lifelong ability for cardiac regeneration after severe damage, whereas mammals lose their innate capacity for heart regeneration during early postnatal development. This study aimed to investigate whether the decreased production of growth factors during postnatal mammalian development contributes to the exit of cardiomyocytes from the cell cycle and the reduction in cardiac regenerative ability.

We identified growth factors with declining expression levels during early postnatal life in the mouse model and assessed the pro-proliferative ability of these factors on neonatal murine primary cardiomyocytesin vitro. Our findings confirmed the previously reported pro-proliferative effects of NRG1, IL1b, RANKL, IGF2 and IL6, while also identifying novel potential pro-regenerative growth factors. Among them, BMP7 exhibited the most pronounced efficacy.

Bmp7 knockdown interfered with the proliferation of neonatal mouse cardiomyocytes in culture and adult bmp7 mutant zebrafish displayed reduced cardiomyocyte proliferation during heart regeneration, indicating that Bmp7 is crucial for cardiomyocyte proliferation in the regenerative stages of mouse and zebrafish hearts. Conversely,bmp7overexpression was sufficient to boost cardiomyocyte cycling in regenerating zebrafish hearts, while BMP7 administration stimulated mouse cardiomyocyte cycling at postnatal-day-7, when cardiomyocytes ceased to proliferate, and enhanced cardiomyocyte regenerationin vivoin adult mice following myocardial infarction.

Mechanistically, BMP7-induced proliferation was mediated by type I BMP receptors BMPR1A and ACVR1, and type II receptors ACVR2A and BMPR2. Downstream signalling involved SMAD5, ERK and AKT.

In conclusion, the administration of BMP7 holds promise as a strategy to stimulate heart regeneration following cardiac injury.
Multi-omics analysis reveals critical cis-regulatory roles of transposable elements in livestock genomes
Authors: Wang Chao , Lei Bowen , Bao Yongzhou , Wang Zhen , Chen Choulin , Zhang Yuanyuan , Qin Shenghua , Sun Tao , Tang Zhonglin , Liu Yuwen
Published: August 2023

As a major source of genetic and regulatory variation in their host genome, transposable elements (TEs) have gained a growing interest in research on humans and model organisms. In this species, integrative analysis of multi-omics data has shed light on the regulatory functions of TEs. However, there remains a notable gap in our understanding of TEs in domesticated animals. we annotated TEs in the genomes of pigs, cattle, and chickens, respectively, and systematically compared the genome distributions and amplification patterns of TEs across these three species. Furthermore, by integrating multi-tissue RNA-seq, ATAC-seq, and histone modification ChIP-seq data, we explored the expression atlas of TEs and their contribution to cis-regulatory elements (CREs) in different tissues of the three species. Most importantly, we developed a novel computational framework that revealed TE-mediated gene regulatory networks (TE-GRNs) underlying tissue-related biological processes. To demonstrate the power of this approach, we applied our framework to analyze liver tissues across the three different species. Overall, our research provides novel insights into the regulatory functions of TEs in livestock animals and highlights a computational framework to uncover TE-GRNs in various biological contexts.
Pneumonic plague protection induced by a monophosphoryl lipid A decoratedYersiniaouter-membrane-vesicle vaccine
Authors: Majumder Saugata , Das Shreya , Li Peng , Yang Nicole , Dellario Hazel , Sui Haixin , Guan Ziqiang , Sun Wei
Published: August 2023

A newly constructedYersinia pseudotuberculosismutant (YptbS46) carrying thelpxEinsertion andpmrF-Jdeletion exclusively synthesized an adjuvant form of lipid A, monophosphoryl lipid A (MPLA). Outer membrane vesicles (OMVs) isolated from YptbS46 harboring anlcrVexpression plasmid, pSMV13, were designated OMV46-LcrV, which contained MPLA and high amounts of LcrV and displayed low activation of Toll-like receptor 4 (TLR4).

Similar to the previous OMV44-LcrV, intramuscular prime-boost immunization with 30 µg of OMV46-LcrV exhibited substantially reduced reactogenicity and conferred complete protection to mice against a high-dose of respiratoryY. pestischallenge. OMV46-LcrV immunization induced robust adaptive responses in both lung mucosal and systemic compartments and orchestrated innate immunity in the lung, which were correlated with rapid bacterial clearance and unremarkable lung damage duringY. pestischallenge. Additionally, OMV46-LcrV immunization conferred long-term protection. Moreover, immunization with reduced doses of OMV46-LcrV exhibited further lower reactogenicity and still provided great protection against pneumonic plague. Our studies strongly demonstrate the feasibility of OMV46-LcrV as a new type of plague vaccine candidate.
Comparative analysis of the molecular starvation response of Southern Ocean copepods
Authors: Berger Cory A. , Steinberg Deborah K. , Copeman Louise A. , Tarrant Ann M.
Published: August 2023

Large lipid-storing copepods dominate mesozooplankton biomass in the polar oceans and form a critical link between primary production and higher trophic levels. The ecological success of these species depends on their ability to survive periods of food deprivation in a highly seasonal environment, but the molecular changes that mediate starvation tolerance in these taxa are unknown. We conducted starvation experiments for two dominant Southern Ocean copepods,Calanoides acutusandCalanus propinquus, allowing us to compare the molecular starvation response between species. These species differ in life history, diet, and metabolic traits, and expressed overlapping but distinct transcriptomic responses to starvation. Most starvation-response genes were species-specific, but we identified a conserved core set of starvation-response genes related to RNA and protein metabolism. We used phylotranscriptomics to place these results in the context of copepod evolution and found that starvation-response genes are under strong purifying selection at the sequence level and stabilizing selection at the expression level, consistent with their role in mediating essential biological functions. Selection on starvation-response genes was especially strong in our focal lipid-storing lineage relative to other copepod taxa, underscoring the significance of starvation tolerance for these species. We also found that certain key lipid enzymes (elongases and desaturases) have experienced diversification and positive selection in lipid-storing lineages, reflecting the unique lipid storage needs of these animals. Our results shed light on the molecular adaptations of high-latitude zooplankton to variable food conditions, and suggest that starvation-response genes are under particularly strong sequence and expression constraints.
Surface-active antibiotic production is a multifunctional adaptation for postfire microbes
Authors: Liu Mira D. , Du Yongle , Koupaei Sara K. , Kim Nicole R. , Zhang Wenjun , Traxler Matthew F.
Published: August 2023

Wildfires affect soils in multiple ways, leading to numerous challenges for colonizing microbes. While it is thought that fire-adapted microbes lie at the forefront of postfire ecosystem recovery, the specific strategies that these microbes use to thrive in burned soils remain largely unknown. Through bioactivity screening of bacterial isolates from burned soils, we discovered that severalParaburkholderia spp.isolates produced a set of unusual rhamnolipid surfactants with a natural methyl ester modification. These rhamnolipid methyl esters (RLMEs) exhibited enhanced antimicrobial activity against other postfire microbial isolates, including pyrophilousPyronemafungi andAmycolatopsisbacteria, compared to the typical rhamnolipids made by organisms such asPseudomonas spp. RLMEs also showed enhanced surfactant properties and facilitated bacterial motility on agar surfaces.In vitroassays further demonstrated that RLMEs improved aqueous solubilization of polycyclic aromatic hydrocarbons, which are potential carbon sources found in char. Identification of the rhamnolipid biosynthesis genes in the postfire isolate,Paraburkholderia caledonicastr. F3, led to the discovery ofrhlM, whose gene product is responsible for the unique methylation of rhamnolipid substrates. RhlM is the first characterized bacterial representative of a large class of integral membrane methyltransferases that are widespread in bacteria. These results indicate multiple roles for RLMEs in the postfire lifestyle ofParaburkholderiaisolates, including enhanced dispersal, solubilization of potential nutrients, and inhibition of competitors. Our findings shed new light on the chemical adaptations that bacteria employ in order to navigate, grow, and outcompete other soil community members in postfire environments.

Significance Statement

Wildfires are increasing in frequency and intensity at a global scale. Microbes are the first colonizers of soil after fire events, but the adaptations that help these organisms survive in postfire environments are poorly understood. In this work, we show that a bacterium isolated from burned soil produces an unusual rhamnolipid biosurfactant that exhibits antimicrobial activity, enhances motility, and solubilizes potential nutrients derived from pyrolyzed organic matter. Collectively, our findings demonstrate that bacteria leverage specialized metabolites with multiple functions to meet the demands of life in postfire environments. Furthermore, this work reveals the potential of probing perturbed environments for the discovery of unique compounds and enzymes.
Complementary roles of orbitofrontal and prelimbic cortices in adaptation of reward motivated actions to learned anxiety
Authors: Jacobs David S. , Bogachuk Alina P. , Moghaddam Bita
Published: August 2023

Background

Anxiety is a common symptom of several mental health disorders and adversely affects motivated behaviors. Anxiety can emerge from associating risk of future harm while engaged in goal-guided actions. Using a recently developed behavioral paradigm to model this aspect of anxiety, we investigated the role of two cortical subregions, the prelimbic medial frontal cortex (PL) and lateral orbitofrontal cortex (lOFC), which have been implicated in anxiety and outcome expectation, in flexible representation of actions associated with harm risk.

Methods

A seek-take reward-guided instrumental task design was used to train animals to associate the seek action with a variable risk of punishment. After learning, animals underwent extinction training for this association. Fiber photometry was used to measure and compare neuronal activity in PL and lOFC during learning and extinction.

Results

Animals increased action suppression in response to punishment contingencies. This increase dissipated after extinction training. These behavioral changes were associated with region specific changes in neuronal activity. PL neuronal activity preferentially adapted to threat of punishment whereas lOFC activity adapted to safe aspects of the task. Moreover, correlated activity between these regions was suppressed during actions associated with harm risk suggesting that these regions may guide behavior independently under anxiety.

Conclusions

These findings suggest the PL and lOFC serve distinct but complementary roles in the representation of learned anxiety. This dissociation may provide a mechanism for how overlapping cortical systems are implicated in reward-guided action execution during anxiety.
A neural network model for the evolution of learning in changing environments
Authors: Kozielska Magdalena , Weissing Franz J.
Published: August 2023

The ability to learn from past experience is an important adaptation, but how natural selection shapes learning is not well understood. Here, we present a novel way of modelling learning using small neural networks and a simple, biology-inspired learning algorithm. Learning affects only part of the network, and it is governed by the difference between expectations and reality. We used this model to study the evolution of learning under various environmental conditions and different scenarios for the trade-off between exploration (learning) and exploitation (foraging). Efficient learning regularly evolved in our individual-based simulations. However, in line with previous studies, the evolution of learning was less likely in relatively constant environments (where genetic adaptation alone can lead to efficient foraging) or in the case of short-lived organisms (that cannot afford to spend much of their lifetime on exploration). Once learning did evolve, the characteristics of the learning strategy (the duration of the learning period and the learning rate) and the average performance after learning were surprisingly little affected by the frequency and/or magnitude of environmental change. In contrast, an organism’s lifespan and the distribution of resources in the environment had a strong effect on the evolved learning strategy. Interestingly, a longer learning period did not always lead to better performance, indicating that the evolved neural networks differ in the effectiveness of learning. Overall, however, we showed that a biologically inspired, yet relatively simple, learning mechanism can evolve to lead to an efficient adaptation in a changing environment.

Author Summary

The ability to learn from experience is an important adaptation. However, it is still unclear how learning is shaped by natural selection. Here, we present a novel way of modelling the evolution of learning using small neural networks and a simple, biology-inspired learning mechanism. Computer simulations reveal that efficient learning readily evolves in this model. However, the evolution of learning is less likely in relatively constant environments (where evolved inborn preferences can guide animal behaviour) and in short-lived organisms (that cannot afford to spend much of their lifetime on learning). If learning does evolve, the evolved learning strategy is strongly affected by the lifespan and environmental richness but surprisingly little by the rate and degree of environmental change. In summary, we show that a simple and biologically plausible mechanism can help understand the evolution of learning and the structure of the evolved learning strategies.
A dissociation between the use of implicit and explicit priors in perceptual inference
Authors: Bévalot Caroline , Meyniel Florent
Published: August 2023

The brain constantly uses prior knowledge of the statistics of its environment to shape perception. These statistics are often implicit (not directly observable) and gradually learned from observation; but they can also be explicitly communicated to the observer, especially in humans. In value-based decision-making, these priors are treated differently depending on their implicit or explicit origin creating the “experience-description gap”. Here, we show that the same distinction also applies to perception. We created a pair of categorization tasks with implicit and explicit priors respectively, and manipulated the strength of priors and sensory likelihood within the same human subjects. Perceptual decisions were influenced by priors in both tasks, and subjects updated their priors in the implicit task as the true statistics changed. Using Bayesian models of learning and perception, we found that the weight of the sensory likelihood in perceptual decisions was highly correlated across subjects between tasks, and slightly stronger in the implicit task. By contrast, the weight of priors was much less correlated across tasks, and it increased markedly from the explicit task to the implicit task. The same conclusion holds when using the subjects’ reported priors. Model comparison also showed that different computations underpinned perceptual decisions depending on the origin of the priors. Taken together, those results support a dissociation in perceptual inference between the use of implicit and explicit priors. This conclusion could resolve conflicting results generated by the indiscriminate use of implicit and explicit priors when studying perception in healthy subjects and patients.

Significance Statement

The use of prior knowledge is ubiquitous in brain processes. However, this use is not always appropriate, and the weights assigned to priors in perceptual decisions are quite heterogeneous across studies. Here, we tested whether the origin of priors can partially explain this heterogeneity. Priors that are explicitly communicated (e.g., a road sign indicating the likely presence of wildlife) appear to be used differently from priors that remain implicit and are learned from experience (e.g., previous encounters with wildlife). We show that the use of implicit and explicit priors is unrelated across subjects. This dissociation may explain why previous findings on the use of explicit and implicit priors (e.g. abnormally strong or weak priors) are often inconsistent.
Remote laboratory training for high school students: grocery store based hands-on project in protein crystallography
Authors: Fox Ali Lillian , Teteris Alyssa R. , Mathews Irimpan I.
Published: August 2023

The COVID-19 pandemic measures forced students to stay home and confined them to remote learning. This had a large impact on laboratory experiments, which are often impossible to complete from home. This article is a resource for instructors/educators to introduce the topic of structural biology and crystallographic methods. The main focus is to describe a hands-on crystallization laboratory exercise that can be carried out remotely at home with safe household products. X-ray crystallography is a vital technique for determining protein structure and function. This information can be used to understand fundamental biological processes and to help in the design of life-saving medications. Here, a method was developed to teach crystallography using reagents and equipment that can be found in grocery stores. The steps involved in a crystallography experiment are detailed with links and references to additional resources.
CatMass: software for calculating optimal sample masses for X-ray absorption spectroscopy experiments involving complex sample compositions
Authors: Perez-Aguilar Jorge E. , Caine Ash , Bare Simon R. , Hoffman Adam S.
Published: August 2023

This paper presents software for calculating the optimal mass of samples with complex compositions (e.g.supported metal catalysts) for X-ray absorption spectroscopy (XAS) and scattering measurements. The ability to calculate the sample mass and other relevant parameters needed for an XAS measurement allows experimentalists to be better prepared in terms of detector selection, energy range of scan and overall time needed to complete the measurement, thus increasing efficiency.CatMassbuilds on existing sample mass calculators allowing users to determine the optimum sample preparation, collection geometry, usable energy range for a scan and approximate edge step of the absorption event. Visualization tools present the absorption calculation results in a format familiar to XAS experimentalists, with the added ability to save calculations and plots for future reference or recalculation.CatMassis a program broadly applicable in catalysis and is helpful for users with complex samples due to composition/stoichiometry or multiple competing elements.
Sociodemographic differences and experienced effects of young adults who use cannabis mainly for self-medication versus recreationally in Finland
Authors: Hupli Aleksi , Unlu Ali , Jylkkä Jussi , Oksanen Atte
Published: August 2023

Purpose

Cannabis use continues to increase worldwide, and a number of nation states are changing their cannabis policies. Policy changes require research into key populations, namely, people who use cannabis. This study aims to examine sociodemographic differences of young Finns who reported using cannabis mainly for self-medication versus mainly recreationally, as well as their reported effects of cannabis use.

Design/methodology/approach

The data come from an anonymous online survey (N = 247, 70.0% males, 25.9% females, 4.1% other) that was analysed using multiple logistic regression. The authors focused on whether various demographic indicators differed between those who reportedly used cannabis mainly for recreational purposes and mainly for self-medicinal purposes. The authors also qualitatively examined the respondents’ experienced effects of cannabis, both desired and undesired.

Findings

Being older and female, living in a smaller city and earlier age of initiation of cannabis use were statistically significant in predicting the medicinal use of cannabis. The majority of recreational effects were related to themes such as relaxation and pleasure, but many participants also reported desired medical effects. Similarly, many participants reported several undesired effects.

Research limitations/implications

Understanding especially young people’s motivations to use cannabis, which include using it for various medical effects, can improve the design of harm reduction and treatment programmes as well as enhance the well-being of people who use cannabis.

Originality/value

This study gives a nuanced account of sociodemographic factors and motivations of young people who use cannabis in Finland as well as the reported effects it has on them, which complements data from national drug surveys.
Ransys Partners Ltd: digitalizing supply chain
Authors: Sinha Ranit , Padhi Sidhartha S. , Dhaigude Amol S.
Published: August 2023

Learning outcomes

The case depicts an opportunity for undergraduate and postgraduate students to be exposed to the basic digitization of supply chain management, technology adoption, change management and cost-benefit analysis concepts. The study aims to encourage them to use the data given in the case and exhibits to compare and contrast physical and digital supply chains (SC); design the digitized version of the traditional SC; examine the nitty-gritty of technology adoption in the SC context; develop the change management plans for the successful adoption and implementation of SC digitization; design the risk register and Explore the business process management; and conduct the return on investment analysis.

Case overview/synopsis

Amber Yen, Chief Operating Officer Apparel Sourcing at Ransys Partners Ltd (RSL), was presented with the task of reducing physical sample production cost and time without impeding order pipeline. RSL was experiencing significant capacity constrain during the COVID-19 crisis, failing to deliver physical samples to international brands. To win large export orders, RSL had to adopt a new innovative way to reduce the sample approval process while meeting customer requirements. Ms Yen wanted to convert the entire sample approval process into a digital mode. She was facing multiple challenges related to the design, implementation and adoption of the digital sample approval process to coordinate the entire SC. She had limited time and was grappling with other impending constraints such as increasing cost, intense competition, demanding customers, shortage of labor due to COVID-19, reducing the bottom line. It was her time to test the idiom “necessity is the mother of innovation”.

Complexity academic level

The target audience for this case is management or business school students. This case can be used to teach digitization of SC, operations management, organization behavior, digitization of enterprises, IT for business, new service development, supplier management technology adoption, and change management in management or business schools.

Supplementary material

Teaching notes are available for educators only.

Subject code

CSS 9: Operations and Logistics.
The impact of corporate governance mechanisms on corporate failure: an empirical evidence from Palestine Exchange
Authors: Nour Abdulnaser Ibrahim , Najjar Mohammad , Al Koni Saed , Abudiak Abullateef , Noor Mahmoud Ibrahim , Shahwan Rani
Published: August 2023

Purpose

The purpose of this research is to examine the impact of governance mechanisms on corporate failure.

Design/methodology/approach

This study used a hypothesis-testing research design to collect data from the annual reports of 35 companies listed on Palestine Exchange from 2010 to 2019. Descriptive and inferential statistics were employed, along with correlation analysis to evaluate linear relationships between variables. The variance inflation factor was used to test multicollinearity, and binary logistic regression was utilized to develop the research model.

Findings

There is a significant positive relationship between board of directors' independency, institutional ownership and the quality of external audit, and corporate failure reduction. No significant relationship has been found among corporate governance variables such as board size, board meetings' frequency, board members' remuneration and audit committee existence, and corporate failure reduction.

Research limitations/implications

Several empirical research studies have developed models to predict corporate failure using accounting and financial data. However, limited research has empirically investigated the impact of the different mechanisms of governance on corporate failure prediction.

Practical implications

The research highlighted the significance of companies' commitment to governance principles and their impact on predicting failure. The study suggests that decision-makers and managers can adopt different governance mechanisms to support corporate success and avoid those that may lead to negative consequences and failure.

Originality/value

This research is the first in Palestine to use a comprehensive list of corporate governance mechanisms to predict the failure of companies listed on the Palestine Stock Exchange between 2010 and 2019.