bluuebunny/crossref_metadata_2025 huggingface dataset:
The neurocomputational link between defensive cardiac states and approach-avoidance arbitration under threat
Authors: Klaassen Felix H. , de Voogd Lycia D. , Hulsman Anneloes M. , O’Reilly Jill X. , Klumpers Floris , Figner Bernd , Roelofs Karin
Published: November 2023

Fearful avoidance is a hallmark of anxiety disorders and often comes at a cost. It reduces the probability of threat and of obtaining rewards. Theoretical models predict that threat-induced psychophysiological states, such as freezing-related bradycardia, facilitate arbitration of approach-avoidance decisions. We indeed show that bradycardia states are linked to the neurocomputational underpinnings of approach-avoidance arbitration when facing varying reward and threat magnitudes. Bradycardia was not only linked toaversive value-related avoidance decisions but also tovalue comparison(a stronger tendency to approach vs. avoid when expected reward outweighs potential threat). An amygdala-striatal-prefrontal neural circuit supported approach-avoidance arbitration under threat, with specific involvement of the amygdala and dorsal anterior cingulate (dACC) in integrating subjective outcome values and bradycardia states. These findings highlight the role of human freezing states in value-based decision making, relevant for optimal threat coping. They point to a specific role for amygdala/dACC in state-value integration under threat.
Amplification of avian influenza viruses along poultry marketing chains in Bangladesh: a controlled field experiment
Authors: Kohnle Lisa , Das Tridip , Uddin Md. Helal , Nath Sanjib C. , Mohsin Md. Abu Shoieb , Mahmud Rashed , Biswas Paritosh K. , Hoque Md. Ahasanul , Pfeiffer Dirk U. , Fournié Guillaume
Published: November 2023

The prevalence of avian influenza viruses (AIVs) is commonly found to increase dramatically from farms to live bird markets (LBMs). Viral transmission dynamics along marketing chains is, however, poorly understood. To address this gap, we implemented a field experiment altering chicken supply to an LBM in Chattogram, Bangladesh. Chickens traded along altered (intervention) and conventional (control) marketing chains were tested for AIVs. Upon arrival at the LBM, the odds of detecting AIVs did not differ between control and intervention groups. However, 12 hours later, intervention group odds were lower, particularly for broiler chickens, indicating that viral shedding in LBM resulted partly from infections during transport and trade. Curtailing AIV prevalence in LBMs requires mitigating risk in marketing chain nodes preceding chickens’ delivery at LBMs.

Article Summary Line

The high prevalence of avian influenza viruses in marketed chickens cannot be solely attributed to viral transmission within live bird markets but is also influenced by infections occurring prior to the chickens’ supply to these markets.
Evolution of rarity and phylogeny determine above- and belowground biomass in plant-plant interactions
Authors: Nytko Alivia G. , Senior John K. , O’Reilly-Wapstra Julianne , Schweitzer Jennifer A. , Bailey Joseph K.
Published: November 2023

Rare species are often considered inferior competitors due to occupancy of small ranges, specific habitats, and small local populations. However, the phylogenetic relatedness and rarity level of interacting species in plant-plant interactions are not often considered when predicting the competitive response of rare plants. We used a common garden of 25 species of TasmanianEucalyptus, varying in rarity to allow us to differentiate the competitive abilities of rare versus common species when grown in mixtures varying in phylogenetic relatedness and rarity. We demonstrate increased biomass production of rare plant species when interacting with genetically intermediate neighbors through synergistic non-additive effects not seen in common species. Additionally, we also find that all plants, regardless of rarity status, maintain 47% greater aboveground and 69% greater belowground biomass when interacting with common species compared to the rarest species. However, species-specific interactions with one particular common species,E. globulus, yielded a 97% increase in biomass compared to average biomass yields in other interactions, suggesting the importance ofE. globulusintegration into rare species restoration plantings. These results are important because they suggest that the evolutionary processes driving species rarity and the phylogenetic divergence of traits interact to drive ecological dynamics of plant-plant interactions in non-additive ways. Through the ecological and evolutionary consideration of performance traits, rarity, and species-specific effects, we can more accurately predict plant-plant interaction dynamics varying in rarity and relatedness across the landscape.
Intestinal cDC1s provide IL-12 dependent and independent functions required for CD4+T cell-mediated resistance toCryptosporidium
Authors: Cohn Ian S. , Wallbank Bethan A. , Haskins Breanne E. , O’Dea Keenan M. , Pardy Ryan D. , Shaw Sebastian , Merolle Maria I. , Gullicksrud Jodi A. , Christian David A. , Striepen Boris , Hunter Christopher A.
Published: November 2023

Cryptosporidiumis an enteric pathogen that is a prominent cause of diarrheal disease. Control of this infection requires CD4+T cells, though the processes that lead to T cell-mediated resistance have been difficult to assess. Here,Cryptosporidiumparasites that express MHCII-restricted model antigens were generated to dissect the early events that influence CD4+T cell priming and effector function. These studies highlight that parasite-specific CD4+T cells are primed in the draining mesenteric lymph node (mesLN) and differentiate into Th1 cells in the gut, where they mediate IFN-γ-dependent control of the infection. Although type 1 conventional dendritic cells (cDC1s) were not required for initial priming of CD4+T cells, cDC1s were required for CD4+T cell expansion and gut homing. cDC1s were also a major source of IL-12 that was not required for priming but promoted full differentiation of CD4+T cells and local production of IFN-γ. Together, these studies reveal distinct roles for cDC1s in shaping CD4+T cell responses to enteric infection: first to drive early expansion in the mesLN and second to drive effector responses in the gut.

Cryptosporidiumparasites that express model antigens were generated to dissect how parasite-specific CD4+T cells are primed and mediate effector functions required to control this enteric pathogen. cDC1s produced IL-12p40 and were required for early expansion and gut homing of CD4+T cells. However, IL-12p40 was only required for the development of Th1 CD4+T cell effector function in the gut.
Spatiotemporal overlap and contact rates among small Indian mongooses and free-roaming domestic dogs in Puerto Rico: Implications for rabies virus transmission
Authors: Sauvé Caroline C. , Berentsen Are R. , Gilbert Amy T. , Llanos Steven F. , Leighton Patrick A.
Published: November 2023

Small Indian mongooses (Urva auropunctata) are the primary terrestrial wildlife rabies reservoir on Puerto Rico, the Dominican Republic, Cuba and Grenada, where they represent a risk to public health through direct human exposure and through transmission of rabies virus to domestic animals that have close association with humans. Historically rabies virus was introduced via domestic dogs and then later shifted into mongoose populations on Puerto Rico and other islands, yet domestic dog-mongoose ecological interactions have been understudied throughout the Caribbean. In this study, we derived daily activity patterns from baited camera traps, and investigated the use of proximity and GPS tracking data acquired concomitantly from mongooses and free-ranging domestic dogs (FRDD) to characterise intra- and interspecific contacts and estimate contact rates. Our results highlight that although mongooses and FRDD are both relatively active in late afternoon, close interspecific contacts only occurred among 4% of collared mongoose-dog dyads, were infrequent (range: 0 – 0.19; median = 0 contacts per day), and were spatially restricted to road and forest edges. Mongooses were only documented to contact feral FRDD, whereas no mongoose contacts with stray FRDD were detected. The space use by stray FRDD and association to humans may play a role in limiting direct contacts with mongooses and the associated risks of rabies virus cross-species transmission. Intraspecific contacts were documented among 11% of collared mongoose-mongoose dyads, occurred at a rate ranging between 0 – 0.57 (median = 0) contacts per day, and took place within wildlands. Intraspecific contacts were documented among 30% of collared dog dyads, at rates ranging between 0 – 3.37 (median = 0) contacts per day, which was more frequent contact than observed for collared mongooses (χ2= 8.84;DF=2;P= 0.012). All dog-dog contacts occurred in proximity to human residential development and involved both stray-stray and stray-feral FRDD collared dyads. Feral FRDD may represent a rabies virus vector between mongooses and FRDD living close to humans. Home range overlap was a significant predictor of contact rates (P< 0.001) among intra- and interspecific dyads of both species and may represent a useful proxy for contact between species that also overlap in daily activity patterns. Transitional areas between wildlands and human residential development could represent hotspots for infectious disease transmission between mongooses and feral FRDDs. Characterization and quantification of contact rates in mongooses and FRDDs across the wildland-urban gradient across wet and dry seasons could help to inform animal rabies control strategies on Puerto Rico and other Caribbean islands with enzootic mongoose rabies.
A reference genome for the Andean cavefishTrichomycterus rosablanca(Siluriformes, Trichomycteridae): building genomic resources to study evolution in cave environments
Authors: Cadena Carlos Daniel , Pabón Laura , DoNascimiento Carlos , Abueg Linelle , Tiley Tatiana , O-Toole Brian , Absolon Dominic , Sims Ying , Formenti Giulio , Fedrigo Olivier , Jarvis Erich D. , Torres Mauricio
Published: November 2023

Animals living in caves are of broad relevance to evolutionary biologists interested in understanding the mechanisms underpinning convergent evolution. In the Eastern Andes of Colombia, populations from at least two distinct clades ofTrichomycteruscatfishes (Siluriformes) independently colonized cave environments and converged in phenotype by losing their eyes and pigmentation. We are pursuing several research questions using genomics to understand the evolutionary forces and molecular mechanisms responsible for repeated morphological changes in this system. As a foundation for such studies, here we describe a diploid, chromosome-scale, long-read reference genome forTrichomycterus rosablanca, a blind, depigmented species endemic to the karstic system of the department of Santander. The nuclear genome comprises 1Gb in 27 chromosomes, with a 40.0x HiFi long-read genome coverage having a N50 scaffold of 40.4 Mb and N50 contig of 13.1 Mb, with 96.9% (Eukaryota) and 95.4% (Actinopterygii) universal single-copy orthologs (BUSCO). This assembly provides the first reference genome for the speciose genusTrichomycterus, which will serve as a key resource for research on the genomics of phenotypic evolution.
In silico codon optimization of the variant antigen-encoding genes of diverse strains of Zika Virus
Authors: Hora Jahnvi , Panwar Vanshika , Mani Indra
Published: November 2023

Abstract

With the recent emergence of the coronavirus pandemic, the scare for other viral pandemics is on the rise. Already having caused an epidemic in 2015-16, Zika virus (ZIKV) poses a threat for potential havoc. Thus, there is an urgent need to produce drugs and vaccines for the same as no approved vaccinations exist for the virus as of now. With the optimization of codon usage, the process of vaccine development can be accelerated and efficacy can be ensured. ZIKV genome has 3 structural genes (envelope, capsid and membrane which is obtained from pre membrane) and 7 nonstructural genes (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5). We have used these 10 genes in 5 different strains of ZIKV for in silico DNA optimization inEscherichia coli.The mean CAI, GC% and AT% of wild-type DNA and optimized DNA of each were compared. It was observed that the CAI and GC% had increased in optimized DNA as compared to wild- type while the opposite was seen for AT%. The results show that codon optimization helps in efficient expression of proteins in the host. These could be used in the development of biotherapeutics. The ideal genes to be overexpressed in development of biotherapeutics are the membrane precursor (prM) and envelope (E) genes as the results have shown.
Multi-timescale reinforcement learning in the brain
Authors: Masset Paul , Tano Pablo , Kim HyungGoo R. , Malik Athar N. , Pouget Alexandre , Uchida Naoshige
Published: November 2023

To thrive in complex environments, animals and artificial agents must learn to act adaptively to maximize fitness and rewards. Such adaptive behavior can be learned through reinforcement learning1, a class of algorithms that has been successful at training artificial agents2–6and at characterizing the firing of dopamine neurons in the midbrain7–9. In classical reinforcement learning, agents discount future rewards exponentially according to a single time scale, controlled by the discount factor. Here, we explore the presence of multiple timescales in biological reinforcement learning. We first show that reinforcement agents learning at a multitude of timescales possess distinct computational benefits. Next, we report that dopamine neurons in mice performing two behavioral tasks encode reward prediction error with a diversity of discount time constants. Our model explains the heterogeneity of temporal discounting in both cue-evoked transient responses and slower timescale fluctuations known as dopamine ramps. Crucially, the measured discount factor of individual neurons is correlated across the two tasks suggesting that it is a cell-specific property. Together, our results provide a new paradigm to understand functional heterogeneity in dopamine neurons, a mechanistic basis for the empirical observation that humans and animals use non-exponential discounts in many situations10–14, and open new avenues for the design of more efficient reinforcement learning algorithms.
Characterizing Human KIF1Bß Motor Activity by Single-Molecule Motility Assays andCaenorhabtidis elegansGenetics
Authors: Iguchi Rei , Kita Tomoki , Watanabe Taisei , Chiba Kyoko , Niwa Shinsuke
Published: November 2023

The axonal transport of synaptic vesicle precursors relies on KIF1A and UNC-104 ortholog motors. In mammals, KIF1Bß is also responsible for the axonal transport of synaptic vesicle precursors. Mutations in KIF1A and KIF1Bß lead to a wide range of neuropathies. While previous studies have revealed the biochemical, biophysical and cell biological properties of KIF1A, and its defects in neurological disorders, the fundamental properties of KIF1Bß remain elusive. In this study, we determined the motile parameters of KIF1Bß through single-molecule motility assays. Additionally, we established simple methods for testing the axonal transport activity of human KIF1Bß usingCaenorhabditis elegansgenetics. Taking advantage of these methods, we demonstrated that these assays enable the detection of reduced KIF1Bß activities both in vitro and in vivo, that is caused by a disease-associated mutation.
The pathogenic p.N1662D SCN2A mutation reveals an essential molecular interaction for Nav1.2 channel inactivation
Authors: Berecki Géza , Tao Elaine , Howell Katherine B. , Coorg Rohini K. , Kahlig Kris , Wolff Markus , Corry Ben , Petrou Steven
Published: November 2023

Mutations in the SCN2A gene encoding the Nav1.2 sodium channel can lead to neurodevelopmental disorders. We studied the N1662D variant associated with severe early-onset developmental and epileptic encephalopathy (DEE). The N1662D mutation almost completely prevented fast inactivation without affecting activation. The comparison of wild-type and N1662D channel structures suggested that the ambifunctional hydrogen bond formation between residues N1662 and Q1494 is essential for fast inactivation. Fast inactivation could also be prevented with engineered Q1494A or Q1494L Nav1.2 channel variants, whereas Q1494E or Q1494K variants resulted in incomplete inactivation and persistent current. Molecular dynamics simulations revealed a reduced affinity of the hydrophobic IFM-motif to its receptor site with N1662D and Q1494L variants relative to wild-type. These results demonstrate that the interactions between N1662 and Q1494 underpin the stability and the orientation of the inactivation gate and are essential for the development of fast inactivation. Six DEE-associated Nav1.2 variants, with mutations mapped to channel segments known to be implicated in fast inactivation were also evaluated. Remarkably, the L1657P variant also prevented fast inactivation and produced biophysical characteristics similar to N1662D, whereas the M1501V, M1501T, F1651C, P1658S, and A1659V variants resulted in biophysical properties that were consistent with gain-of-function and enhanced action potential firing of hybrid neurons in dynamic action potential clamp experiments. Paradoxically, low densities of N1662D or L1657P currents potentiated action potential firing, whereas increased densities resulted in sustained depolarization. The contribution of non-inactivating Nav1.2 channels to neuronal excitability may constitute a novel cellular mechanism in the pathogenesis ofSCN2A-related DEE.

SIGNIFICANCE STATEMENT

SCN2Agene-related early-onset developmental and epileptic encephalopathy (EO-DEE) is a rare and severe disorder that manifests in early infancy and childhood.SCN2Amutations affecting the fast inactivation gating mechanism can cause altered voltage dependence and incomplete inactivation of the encoded Nav1.2 channel, leading to abnormal neuronal excitability. In this biophysical and clinical study of neuronal Nav1.2 variants, we identified amino acid residues that are critical for the stability and orientation of the inactivation gate during fast inactivation. Mutations of these residues prevent fast inactivation and may lead to EO-DEE via a novel pathophysiological mechanism. The results provide novel structural insights into the molecular mechanism of Nav1.2 channel fast inactivation and inform treatment strategies forSCN2A-related EO-DEE.
Assessing the Impact of Mask Mandates on SARS-CoV-2 Transmission: A Case Study of Utah
Authors: Horn Alicia C. , Shoemaker Holly E. , Keegan Lindsay T.
Published: November 2023

Background

Throughout the COVID-19 pandemic, the effectiveness of face masks mandates has been intensely debated. Many methods have been used to demonstrate mask effectiveness, including one that compares the change in reproduction number following implementing and removing face mask mandates1.

Methods

Using data from Utah, we calculated the effect of mask mandates (EFm) in each local health district from before and after three key mandates: the Salt Lake and Summit County (SLSC) mask mandates enacted; the Utah statewide mask mandate enacted; and the Utah statewide mandate was lifted.

Results

We found that most counties had a reduction in the growth rate of cases following the mandates. There were reductions in EFmin many counties after the introduction of the SLSC mask mandates and a more widespread reduction in EFmacross the state following the statewide mandate. Lifting the mandates, many counties across the states saw an increase in EFm.

Conclusion

Our data show mask mandates were an effective way to reduce transmission both within the jurisdiction they were enacted and in neighboring jurisdictions. We provide evidence to support mask mandates as a way to prevent transmission to be better equipped to respond to future pandemics.
Exposure toPseudomonas spp.increasesAnopheles gambiaeinsecticide resistance in a host-dependent manner
Authors: Silva Luís M. , Acerbi Gwendoline , Amann Marine , Koella Jacob C.
Published: November 2023

The microbiota of mosquitoes influences many aspects of their biology, including developmental processes, mating and sexual reproduction, immune functions, and refractoriness to pathogens. Here, we considered their role in resistance against insecticides. In particular, we assessed how larval infection of a permethrin-resistant and a sensitive colony ofAnopheles gambiaeby four strains belonging to three differentPseudomonasspecies affects several life history traits and the impact of the insecticide on adult mortality. Our data showed that all fourPseudomonasstrains persisted in adults until death. The bacteria increased the likelihood that mosquitoes survived 24 hours after exposure to permethrin by up to two-fold. The impact of the bacteria depended on the bacterial strains and the mosquito colony: in the resistant colony, all bacteria increased survival by about 2-fold, while in the sensitive colony, only two of the four strains increased survival. The benefit concerning insecticide resistance came with little to no impact on the other traits (i.e., larval mortality, developmental time and adult longevity). Altogether, our results highlight the importance of considering environmental microbial exposure and mosquito microbial communities in epidemiological and vector-control studies, while also suggesting a possible role forPseudomonas spp.as a symbiont inA. gambiae.
Comprehensive profiling of L1 retrotransposons in mouse
Authors: Zhang Xuanming , Celic Ivana , Mitchell Hannah , Stuckert Sam , Vedula Lalitha , Han Jeffrey S.
Published: November 2023

L1 elements are retrotransposons currently active in mammals. Although L1s are typically silenced in most normal tissues, elevated L1 expression is associated with a variety of conditions, including cancer, aging, infertility, and neurological disease. These associations have raised interest in the mapping of human endogenousde novoL1 insertions, and a variety of methods have been developed for this purpose. Adapting these methods to mouse genomes would allow us to monitor endogenousin vivoL1 activity in controlled, experimental conditions using mouse disease models. Here we use a modified version of transposon insertion profiling, called nanoTIPseq, to selectively enrich young mouse L1s. By linking this amplification step with nanopore sequencing, we identified >95% annotated L1s from C57BL/6 genomic DNA using only 200,000 sequencing reads. In the process, we discovered 82 unannotated L1 insertions from a single C57BL/6 genome. Most of these unannotated L1s were near repetitive sequence and were not found with short-read TIPseq. We used nanoTIPseq on individual mouse breast cancer cells and were able to identify the annotated and unannotated L1s, as well as new insertions specific to individual cells, providing proof of principle for using nanoTIPseq to interrogate retrotransposition activity at the single cell levelin vivo.
Extreme distributions in the preconfigured developing brain
Authors: Chini Mattia , Hnida Marilena , Kostka Johanna K. , Chen Yu-Nan , Hanganu-Opatz Ileana L.
Published: November 2023

In the adult brain, structural and functional parameters, such as synaptic sizes and neuronal firing rates, follow right-skewed and heavy-tailed distributions. While this organization is thought of having significant implications, its development is still largely unknown. Here, we address this knowledge gap by investigating a large-scale dataset recorded from the prefrontal cortex (PFC) and the olfactory bulb of mice aged 4-60 postnatal days. We show that firing rates and pairwise correlations have a largely stable distribution shape over age, and that neural activity displays a small-world architecture. Moreover, early brain activity displays an oligarchical organization, i.e., neurons with high firing rates are likely to have hub-like properties. Leveraging neural network modeling, we show that analogously extremely distributed synaptic parameters are necessary to recapitulate the experimental data. Thus, functional and structural parameters in the developing brain are already extremely distributed, suggesting that this organization is preconfigured and not experience-dependent.
SUMO protease and proteasome recruitment at the nuclear periphery differently affect replication dynamics at arrested forks
Authors: Schirmeisen Kamila , Naiman Karel , Fréon Karine , Besse Laetitia , Chakraborty Shrena , Carr Antony M. , Kramarz Karol , Lambert Sarah AE
Published: November 2023

Nuclear pores complexes (NPCs) are genome organizers, defining a particular nuclear compartment enriched for SUMO protease and proteasome activities, and acting as docking sites for DNA repair. In fission yeast, the anchorage of perturbed replication forks to NPCs is an integral part of the recombination-dependent replication restart mechanism (RDR) that resumes DNA synthesis at terminally dysfunctional forks. By mapping DNA polymerase usage, we report that SUMO protease Ulp1-associated NPCs ensure efficient initiation of restarted DNA synthesis, whereas proteasome-associated NPCs sustain the progression of restarted DNA polymerase. In contrast to Ulp1-dependent events, this last function occurs independently of SUMO chains formation. By analyzing the role of the nuclear basket, the nucleoplasmic extension of the NPC, we reveal that the activities of Ulp1 and the proteasome cannot compensate for each other and affect RDR dynamics in distinct ways. Our work probes the mechanisms by which the NPC environment ensures optimal RDR.

Highlights

● Ulp1-associated NPCs ensure efficient initiation of restarted DNA synthesis, in a SUMO chain-dependent manner

● Proteasome-associated NPCs foster the progression of restarted DNA synthesis, in a SUMO chain-independent manner

● The nucleoporin Nup60 promotes the spatial sequestration of Ulp1 at the nuclear periphery

● Ulp1 and proteasome activities are differently required for optimal recombination-mediated fork restart.
Oyster aquaculture enhances sediment microbial diversity– Insights from a multi-omics study
Authors: Stevens Joshua T.E. , Ray Nicholas E. , Al-Haj Alia N. , Fulweiler Robinson W. , Chowdhury Priyanka Roy
Published: November 2023

The global aquaculture industry has grown substantially, with consequences for coastal ecology and biogeochemistry. Oyster aquaculture can alter the availability of resources for microbes that live in sediments as oysters move large quantities of organic material to the sediments via filter feeding, possibly leading to changes in the structure and function of sediment microbial communities. Here, we use a chronosequence approach to investigate the impacts of oyster farming on sediment microbial communities over 7 years of aquaculture activity in a temperate coastal system. We detected shifts in bacterial composition (16S rRNA amplicon sequencing), changes in gene expression (meta-transcriptomics), and variations in sediment elemental concentrations (sediment geochemistry) across different durations of oyster farming. Our results indicate that both the structure and function of bacterial communities vary between control (no oysters) and farm sites, with an overall increase in diversity and a shift towards anoxic tolerance in farm sites. However, little to no variation was observed in either structure or function with respect to farming duration suggesting these sediment microbial communities are resilient to change. We also did not find any significant impact of farming on heavy metal accumulation in the sediments. The minimal influence of long-term oyster farming on sediment bacterial function and biogeochemical processes as observed here can bear important consequences for establishing best practices for sustainable farming in these areas.

Importance

Sediment microbial communities drive a range of important ecosystem processes such as nutrient recycling and filtration. Oysters are well-known ecological engineers, and their presence is increasing as aquaculture expands in coastal waters globally. Determining how oyster aquaculture impacts sediment microbial processes is key to understanding current and future estuarine biogeochemical processes. Here, we use a multi-omics approach to study the effect of different durations of oyster farming on the structure and function of bacteria and elemental accumulation in the farm sediments. Our results indicate an increase in the diversity of bacterial communities in the farm sites with no such increases observed for elemental concentrations. Further, these effects persist across multiple years of farming with an increase of anoxic tolerant bacteria at farm sites. The multi-omics approach used in this study can serve as a valuable tool to facilitate understanding of the environmental impacts of oyster aquaculture.
Sensory progenitors influence patterning of the mammalian auditory sensory epithelium
Authors: Young Caryl A. , Burt Emily , Munnamalai Vidhya
Published: November 2023

During embryonic development Wnt signaling has been shown to influence proliferation and sensory formation in the cochlea. How the dual nature of Wnt signaling is coordinated is unknown. In this study, we define a novel role for a Wnt regulated gene,Mybl2,which was already known to be important for proliferation, in influencing patterning and determining the size of the sensory epithelium in the murine cochlea. Using a quantitative spatial analysis approach and analyzingMybl2loss-of-function cochleas, we show thatMybl2simultaneously specifies the progenitor niche and the size of the sensory domain, and influences the positioning of the medial sensory domain boundary viaJag1regulation during the mid-gestational stages.Mybl2conditional knockout resulted in a decrease of proliferation within the progenitor niche. During the late embryonic stages, conditional knockout ofMybl2produced a wider sensory epithelium across the radial axis with an increase in ectopic inner hair cell formation. These data suggest thatMybl2-positive progenitors play a role in boundary formation and patterning the sensory epithelium.

Summary Statement

Mybl2is a Wnt-regulated gene encoding a transcription factor that is expressed in the cochlear progenitor niche and influences the boundary formation between the niche and the sensory domain during mid-cochlear developmental stages, thereby impacting the size of the sensory epithelium.
Exploring viral particle, soil, and extraction buffer physicochemical characteristics and their impacts on extractable viral communities
Authors: Fudyma Jane D. , ter Horst Anneliek M. , Santos-Medellín Christian , Sorensen Jess , Gogul Grant , Hillary Luke , Geonczy Sara , Pett-Ridge Jennifer , Emerson Joanne B.
Published: November 2023

Soil viruses are expected to be pivotal members of soil ecosystems, and recent advances in viral size fraction metagenomic (viromic) approaches have substantially improved our ability to interrogate soil viral ecology. However, the first step of viromics relies on extraction buffers to effectively remove viral particles from the soil matrix for downstream analysis, and viral extraction efficiency at this stage could be affected by the interplay between viral particles, soils, and extraction buffer chemistry. Here, we investigated whether extraction buffer chemistry affected extractable viral community composition measured by viromics from different soil types, for both biological (samples collected 1 meter apart) and technical (subsamples from the same soil homogenate) replicates. We first investigated protein-supplemented phosphate-buffered saline pH (PPBS, pHs 4.5, 5.5, 6.5, and 7.5) on a forest, grassland and wetland soil that exhibited different soil edaphic properties, and then we tested different buffer chemistries (PPBS, Carbonated Buffer, Glycine, and Saline Magnesium) on just the wetland soil. Spatial distance, or where the sample was taken in the field (i.e., biological replicate), was the primary driver of extractable viral community composition across all buffers and soils tested. Differences in viral community composition according to extraction buffer properties were only observed in the grassland technical replicates at PPBS buffer pH 4.5, as well as in both the wetland technical and biological replicates treated with different buffer chemistries, but the effects of buffer chemistry were secondary to spatial distance in all cases where spatial distance was a factor. The lack of buffering capacity in the grassland soil technical replicates likely increased sorption of some viral particles at pH 4.5, but neither protein composition nor isoelectric point (both calculated bioinformatically) explained this phenomenon. Given that most soil viral ecological studies to date include sample collection schemes over distances much farther apart than the 1-meter distances considered here, results suggest that extraction buffer chemistry is likely of much lower importance than ecological considerations, such as spatial distance, in the design of future soil viral ecological investigations.

HIGHLIGHTS

Spatial distance was the main driver of extractable viral community composition.

Extraction buffer chemistry secondarily structured wetland viral communities.

At pH 4.5, PPBS buffer likely increased viral sorption in homogenized grassland soil.

Increased sorption was not explained by estimated viral protein isoelectric points.
Right ventricular pressure-strain relationship-derived myocardial work reflects contractility: validation with invasive pressure-volume analysis
Authors: Lakatos Bálint Károly , Rako Zvonimir , Szijártó Ádám , da Rocha Bruno R. Brito , Richter Manuel J. , Fábián Alexandra , Gall Henning , Ghofrani Hossein A. , Kremer Nils , Seeger Werner , Zedler Daniel , Yildiz Selin , Yogeswaran Athiththan , Merkely Béla , Tello Khodr , Kovács Attila
Published: November 2023

Background

Three-dimensional (3D) echocardiography-derived right ventricular (RV) ejection fraction (EF) and global longitudinal strain (GLS) are valuable RV functional markers; nevertheless, they are substantially load-dependent. Global myocardial work index (GMWI) adjusts myocardial deformation to instantaneous pressure; therefore, it may better reflect contractility. Accordingly, we aimed to calculate RV GMWI using 3D echocardiography and examine its relationship with RV contractility’s gold standard invasive measurement.

Methods

Sixty patients (65±14 years, 65% female) with suspected or established pulmonary hypertension were enrolled. Detailed 3D echocardiography was performed to quantify RV EF and GLS using the ReVISION software. Patients underwent RV pressure-conductance catheterization to obtain the RV pressure curve and to assess contractility (end-systolic elastance - Ees) and ventriculo-arterial coupling (Ees/arterial elastance - Ees/Ea). RV GMWI was calculated using the RV GLS and the RV pressure trace curve.

Results

While neither RV EF (r=-0.143, p=0.275) nor GLS (r=-0.067, p=0.611) correlated with Ees, GMWI showed a strong correlation with it (r=0.669, p<0.001). In contrast, RV EF and GLS showed a relationship with Ees/Ea (RVEF: r=0.552; GLS: r=0.460, both p<0.001). By dividing the population based on the Reveal Lite 2 risk classification, EF and GLS showed a significant decrease only in the high-risk group (low vs. intermediate vs. high risk; EF: 48.8±6.6 vs. 44.0±9.4 vs. 35.0±7.8%, ANOVA p<0.001; GLS: 18.6±3.6 vs. 17.0±4.5 vs. 13.3±3.9%, ANOVA p<0.001), whereas GMWI already showed an increase in the intermediate group (550±267 vs. 831±361 vs. 797±265 mmHg%, ANOVA p<0.01).

Conclusions

RV EF and GLS reflect ventriculo-arterial coupling, while GMWI strongly correlates with contractility. RV GMWI may emerge as a useful clinical tool for risk stratification and follow-up in patients with pulmonary hypertension.
The non-mitotic role of HMMR in regulating the localization of TPX2 and the dynamics of microtubules in neurons
Authors: Chen Yi-Ju , Tseng Shun-Cheng , Chen Peng-Tzu , Hwang Eric
Published: November 2023

A functional nervous system is built upon the proper morphogenesis of neurons to establish the intricate connection between them. The microtubule cytoskeleton is known to play various essential roles in this morphogenetic process. While many microtubule-associated proteins (MAPs) have been demonstrated to participate in neuronal morphogenesis, the function of many more remains to be determined. This study focuses on a MAP called HMMR, which was originally identified as a hyaluronan binding protein and later found to possess microtubule and centrosome binding capacity. HMMR exhibits high abundance on neuronal microtubules and altering the level of HMMR significantly affects the morphology of neurons. Instead of confining to the centrosome(s) like cells in mitosis, HMMR localizes to microtubules along axons and dendrites. Furthermore, transiently expressing HMMR enhances the stability of neuronal microtubules and increases the formation frequency of growing microtubules along the neurites. HMMR regulates the microtubule localization of a non-centrosomal microtubule nucleator TPX2 along the neurite, offering an explanation for how HMMR contributes to the promotion of growing microtubules. This study sheds light on how progenitor cells utilize proteins involved in mitosis for non-mitotic functions.
Investigation of the impact of bromodomain inhibition on cytoskeleton stability and contraction
Authors: Bigger-Allen Alexander , Gheinani Ali Hashemi , Adam Rosalyn M.
Published: November 2023

Injury to contractile organs such as the heart, vasculature, urinary bladder and gut can stimulate a pathological response that results in loss of normal contractility. PDGF and TGFβ are among the most well studied initiators of the injury response and have been shown to induce aberrant contraction in mechanically active cells of hollow organs including smooth muscle cells (SMC) and fibroblasts. However the mechanisms driving contractile alterations downstream of PDGF and TGFβ in SMC and fibroblasts are incompletely understood, limiting therapeutic interventions. To identify potential molecular targets, we have leveraged the analysis of publicly available data, comparing transcriptomic changes in mechanically active cells stimulated with PDGF and TGFβ and identified a shared molecular profile regulated by MYC and members of the AP-1 transcription factor complex. We also analyzed data sets from SMC and fibroblasts treated in the presence or absence of the MYC inhibitor JQ1. This analysis revealed a unique set of cytoskeleton-associated genes that were sensitive to MYC inhibition. JQ1 was also able to attenuate TGFβ and PDGF induced changes to the cytoskeleton and contraction of smooth muscle cells and fibroblastsin vitro. These findings identify MYC as a key driver of aberrant cytoskeletal and contractile changes in fibroblasts and SMC, and suggest that JQ1 could be used to restore normal contractile function in hollow organs.
Unravelling the components of diffuse scattering using deep learning
Authors: Fuller Chloe A. , Rudden Lucas S. P.
Published: November 2023

Many technologically important material properties are underpinned by disorder and short-range structural correlations; therefore, elucidating structure–property relationships in functional materials requires understanding both the average and the local structures. The latter information is contained within diffuse scattering but is challenging to exploit, particularly in single-crystal systems. Separation of the diffuse scattering into its constituent components can greatly simplify analysis and allows for quantitative parameters describing the disorder to be extracted directly. Here, a deep-learning method, DSFU-Net, is presented based on the Pix2Pix generative adversarial network, which takes a plane of diffuse scattering as input and factorizes it into the contributions from the molecular form factor and the chemical short-range order. DSFU-Net was trained on 198 421 samples of simulated diffuse scattering data and performed extremely well on the unseen simulated validation dataset in this work. On a real experimental example, DSFU-Net successfully reproduced the two components with a quality sufficient to distinguish between similar structural models based on the form factor and to refine short-range-order parameters, achieving values comparable to other established methods. This new approach could streamline the analysis of diffuse scattering as it requires minimal prior knowledge of the system, allows access to both components in seconds and is able to compensate for small regions with missing data. DSFU-Net is freely available for use and represents a first step towards an automated workflow for the analysis of single-crystal diffuse scattering.
trans-Bis[bis(diphenylphosphanyl)methane-κ2
P,P′]dichloridoruthenium(II): a triclinic polymorph
Authors: Kelani Monsuru T. , Muller Alfred , Lammertsma Koop
Published: November 2023

The title compound, [RuCl2(C25H22P2)2] or [RuCl2(dppm)2] (dppm = bis(diphenylphosphanyl)methane, C25H22P2) crystallizes as two half-molecules (completed by inversion symmetry) in space group P\overline{1} (Z = 2), with the RuII atoms occupying inversion centers at 0,0,0 and 1/2, 1/2, 1/2, respectively. The bidentate phosphane ligands occupy equatorial positions while the chlorido ligands complete the distorted octahedral coordination spheres at axial positions. The bite angles of the phosphane chelates are similar for the two molecules [(P—Ru—P)
avg.
= 71.1°], while there are significant differences in the twisting of the methylene backbone, with a distance of the methylene C atom from the RuP4 plane of 0.659 (2) and 0.299 (3) Å, respectively, and also for the phenyl substituents for both molecules due to variations in weak C—H...Cl interactions.
Digital transformation: a challenging opportunity for the food industry companies
Authors: Marczewska Magdalena
Published: November 2023

Purpose

Common availability of digital technologies encouraged companies in almost all industries to focus on exploring various ways of benefiting from their adoption and thus taking steps toward their digital transformation. This paper aims to describe the digital transformation of small and medium enterprises (SMEs) as a challenging opportunity and identify ways in which companies from the food industry address it.

Design/methodology/approach

The paper presents empirical evidence based on a case study of the Polish freeze-drying market and companies operating on it. This study adopted a single case study research method to describe the digital transformation journey of SMEs. The sample constitutes a single sectoral case study with more than one unit of analysis – sixteen companies. The undertaken approach follows an embedded case study design and allows for an extensive and multidimensional analysis of rich empirical data.

Findings

The results of this analysis allowed to identify four significant trends describing human resources involvement in the digital transformation of freeze-drying companies in Poland (i.e. visionary top-down, cooperative task-oriented, persuasive bottom-up, chaotic), a detailed catalog of outcomes of digital transformation from the perspective of food industry companies grouped in seven categories and a list of main barriers to digital transformation.

Originality/value

This paper contributes to expanding knowledge on the practices of food industry companies in addressing challenges posed by the development of information technology and the dynamically changing environment after the COVID-19 pandemic. It contributes further to the discussion related to context-, industry- and country-specific barriers to digital transformation, identifying time-related constraints as an essential barrier to digital transformation.
E-waste supply chain risk management: a framework considering omnichannel and circular economy
Authors: Senna Pedro , Marujo Lino Guimarães , Santos Ana Carla de Souza Gomes dos , Ferreira Amanda Chousa , da Silva Luís Alfredo Aragão
Published: November 2023

Purpose

In the last few years, environmental issues have become a matter of survival. In this sense, e-waste management is among the major problems since it may be a way of mitigating mineral depletion. In this context, the literature lacks e-waste supply chain studies that systematically map supply chain challenges and risks concerning material recovery.

Design/methodology/approach

Given this context, the authors' paper conducted a systematic literature review (SLR) to build a framework to identify the constructs of e-waste supply chain risk management.

Findings

The paper revealed the theoretical relationship between important variables to achieve e-waste supply chain risk management via a circular economy (CE) framework. These variables include reverse logistics (RL), closed-loop supply chains (CLSC), supply chain risk management, supply chain resilience and smart cities.

Originality/value

The literature contributions of this paper are as follows: (1) a complete list of the risks of the e-waste supply chains, (2) the techniques being used to identify, assess and mitigate e-waste supply chain risks and (3) the constructs that form the theoretical framework of e-waste supply chain risk management. In addition, the authors' results address important literature gaps identified by researchers and serve as a guide to implementation.
‘Water in the Desert?’: Oil India's CSR Impact in Assam
Authors: Chaudhri Vidhi , Kaul Asha
Published: November 2023

Incorporated on February 18, 1959, Oil India Ltd. (OIL) was a leading public sector oil and gas company involved in the exploration, development, production and transportation of crude oil and natural gas in India. Since its inception, OIL had committed itself to being a socially responsible organisation in and around operational areas, particularly the north-eastern state of Assam where 90% of company operations were concentrated. Despite many successes, the “People's Company” continued to be a target for disgruntled local and student communities who frequently created operational hazards for the firm—from sit-ins and blockades to pilfering and disrupting production facilities. No less than 400 organisations, of which 50-60 had been consistently active, were currently in the forefront of demanding something from OIL. Many of these demands were beyond the purview of OIL's CSR policy and focus areas. Additionally, being a Public Sector Undertaking (PSU), OIL also faced multiple demands from the government. On February 16, 2019, news arrived that there was yet another blockade in Duliajan, Assam. What should OIL do to address and possibly mitigate operational interruptions?
Swachh Bharat Mission or the Mission to Make India Clean: Addressing Open Defecation at Massive Scale (A)
Authors: Iyer Parameswaran , Pandey Ajay , Vashisht Mahima , Smith Daniel W.
Published: November 2023

This case is the first of a three-part series that follows the managerial, strategic, and communications decisions of the Swachh Bharat Mission (SBM) or Clean India Mission, the flagship programme of the Government of India to eliminate the practice of open defecation (i.e., not using a toilet) from 2014 to 2019. As of 2014, 550 million people in India practiced open defecation. This problem posed a massive public health hazard and economic drag for the country as well as a threat to global health. Written from an insider's perspective, the cases centre on the decisions made by a new Secretary of the India's Ministry of Drinking Water and Sanitation, who was hired to manage SBM, and the team he assembled. Case A sets the stage for addressing open defecation in rural India and discusses the human resources and strategic challenges to implementing SBM from the vantage point of the new Secretary. It ends with strategic dilemmas related to what the new SBM team should do once they had sized up the challenges to eliminating open defecation by 2019. The case provides an opportunity to deliberate the managerial and strategic decisions of a globally relevant public behaviour change and rural infrastructure development program as well as different forms of public sector implementation in the Indian context.