bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure of dimerized assimilatory NADPH-dependent sulfite reductase reveals the minimal interface for diflavin reductase binding
Authors: Esfahani Behrouz Ghazi , Walia Nidhi , Neselu Kasahun , Garg Yashika , Aragon Mahira , Askenasy Isabel , Wei Hui Alex , Mendez Joshua H. , Stroupe M. Elizabeth
Published: June 2024

Escherichia coliNADPH-dependent assimilatory sulfite reductase (SiR) reduces sulfite by six electrons to make sulfide for incorporation into sulfur-containing biomolecules. SiR has two subunits: an NADPH, FMN, and FAD-binding diflavin flavoprotein and a siroheme/Fe4S4cluster-containing hemoprotein. The molecular interactions that govern subunit binding have been unknown since the discovery of SiR over 50 years ago because SiR is flexible, thus has been intransigent for traditional high-resolution structural analysis. We used a combination of the chameleon® plunging system with a fluorinated lipid to overcome the challenges of preserving a flexible molecule to determine a 2.78 Å-resolution cryo-EM structure of a minimal heterodimer complex. chameleon®, combined with the fluorinated lipid, overcame persistent denaturation at the air-water interface. Using a previously characterized minimal heterodimer reduced the heterogeneity of a structurally heterogeneous complex to a level that could be analyzed using multi-conformer cryo-EM image analysis algorithms. Here, we report the first near-atomic resolution structure of the flavoprotein/hemoprotein complex, revealing how they interact in a minimal interface. Further, we determined the structural elements that discriminate between pairing a hemoprotein with a diflavin reductase, as in theE. colihomolog, or a ferredoxin partner, as in maize (Zea mays).

Significance Statement

Sulfur is one of the essential building blocks of life. Sulfur exists in numerous redox states but only one can be incorporated into biomass – S2-(sulfide). InEscherichia coli, a protein enzyme called sulfite reductase reduces sulfite by six electrons to make sulfide. Typical electron transfer reactions move one or two electrons at a time. The sequential transfer of two electrons three times to complete the conversion of sulfite to sulfide (or nitrite to ammonia) is unique to sulfite or nitrite reductases.E. coliSiR is a two-protein complex composed of a diflavin reductase flavoprotein and an iron metalloenzyme hemoprotein. Until now, the molecular interactions that govern subunit interactions remained a mystery because the extreme flexibility of the flavoprotein subunit, which has challenged X-ray or cryo-EM analysis for over 30 years. In overcoming these challenges, we used a combination of rapid plunging with a high critical-micelle-concentration lipid alongside a biochemically minimized complex to determine the 2.78 Å-resolution cryo-EM structure of a dimer between the flavoprotein and hemoprotein subunits.
δ-containing GABAAreceptors on parvalbumin interneurons modulate neuronal excitability and network dynamics in the mouse medial prefrontal cortex
Authors: Lu Xinguo , Shu Hong-Jin , Lambert Peter M. , Benz Ann , Zorumski Charles F. , Mennerick Steven
Published: June 2024

In medial prefrontal cortex (mPFC), fast-spiking parvalbumin (PV) interneurons regulate excitability and microcircuit oscillatory activity important for cognition. Although PV interneurons inhibit pyramidal neurons, they themselves express δ subunits of GABAA receptors important for slow inhibition. However, the specific contribution of δ-containing GABAA receptors to the function of PV interneurons in mPFC is unclear. We explored cellular, synaptic, and local-circuit activity in PV interneurons and pyramidal neurons in mouse mPFC after selectively deleting δ subunits in PV interneurons (cKO mice). In current-clamp recordings, cKO PV interneurons exhibited a higher frequency of action potentials and higher input resistance than wild type (WT) PV interneurons. Picrotoxin increased firing and GABA decreased firing in WT PV interneurons but not in cKO PV interneurons. The δ-preferring agonist THIP reduced spontaneous inhibitory postsynaptic currents in WT pyramidal neurons but not in cKO pyramidal neurons. In WT slices, depolarizing the network with 400 nM kainate increased firing of pyramidal neurons but had little effect on PV interneuron firing. By contrast, in cKO slices kainate recruited PV interneurons at the expense of pyramidal neurons. At the population level, kainate induced broadband increases in local field potentials in WT but not cKO slices. These results on cells and the network can be understood through increased excitability of cKO PV interneurons. In summary, our study demonstrates that δ-containing GABAA receptors in mPFC PV interneurons play a crucial role in regulating their excitability and the phasic inhibition of pyramidal neurons, elucidating intricate mechanisms governing cortical circuitry.

Significance statement

By selectively deleting δ-containing GABAA receptors in PV interneurons, we demonstrate the importance of these receptors on PV interneuron excitability, synaptic inhibition of pyramidal neurons, and circuit function.
On the demographic history of chimpanzees and some consequences of integrating population structure in chimpanzees and other great apes
Authors: Steux Camille , Couloigner Clément , Arredondo Armando , Rodríguez Willy , Mazet Olivier , Tournebize Rémi , Chikhi Lounès
Published: June 2024

Reconstructing the evolutionary history of great apes is of particular importance for our understanding of the demographic history of humans. The reason for this is that modern humans and their hominin ancestors evolved in Africa and thus shared the continent with the ancestors of chimpanzees and gorillas. Common chimpanzees (Pan troglodytes) are our closest relatives with bonobos (Pan paniscus) and most of what we know about their evolutionary history comes from genetic and genomic studies. Most evolutionary studies of common chimpanzees have assumed that the four currently recognised subspecies can be modelled using simple tree models where each subspecies is panmictic and represented by one branch of the evolutionary tree. However, several studies have identified the existence of significant population structure, both within and between subspecies, with evidence of isolation-by-distance (IBD) patterns. This suggests that demographic models integrating population structure may be necessary to improve our understanding of their evolutionary history. Here we propose to usen-island models within each subspecies to infer a demographic history integrating population structure and changes in connectivity (i.e.gene flow). For each subspecies, we use SNIF (structured non-stationary inference framework), a method developed to infer a piecewise stationaryn-island model using PSMC (pairwise sequentially Markovian coalescent) curves as summary statistics. We then propose a general model integrating the four subspecies metapopulations within a phylogenetic tree. We find that this model correctly predicts estimates of within subspecies genetic diversity and differentiation, but overestimates genetic differentiation between subspecies as a consequence of the tree structure. We argue that spatial models integrating gene flow between subspecies should improve the prediction of between subspecies differentiation and IBD patterns. We also use a simple spatially structured model for bonobos and chimpanzees (without admixture) and find that it explains signals of admixture between the two species that have been reported and could thus be spurious. This may have implications for our understanding of the evolutionary history of theHomogenus.
Marcks and Marcks-like 1 proteins promote spinal cord development and regeneration inXenopus
Authors: El Amri Mohamed , Pandit Abhay , Schlosser Gerhard
Published: June 2024

Marcks and Marcksl1 are abundant proteins that shuttle between the cytoplasm and membrane to modulate multiple cellular processes, including cytoskeletal dynamics, proliferation, and secretion. Here, we performed loss- and gain-of-function experiments inXenopus laevisto reveal the novel roles of these proteins in spinal cord development and regeneration. We show that Marcks and Marcksl1 have partly redundant functions and are required for normal neurite outgrowth and proliferation of neuro-glial progenitors during embryonic spinal cord development and for its regeneration during tadpole stages. Rescue experiments in Marcks and Marcksl1 knockout animals further suggested that some of the functions of Marcks and Marcksl1 in the spinal cord are mediated by phospholipase D (PLD) signaling. Taken together, these findings identify Marcks and Marcksl1 as critical new players in spinal cord development and regeneration and suggest new pathways to be targeted for therapeutic stimulation of spinal cord regeneration in human patients.
Ultrastructural sublaminar-specific diversity of excitatory synaptic boutons in layer 1 of the adult human temporal lobe neocortex
Authors: Rollenhagen Astrid , Sadeghi Akram , Walkenfort Bernd , Hilgetag Claus C. , Sätzler Kurt , Lübke Joachim HR
Published: June 2024

Layer (L)1, beside receiving massive cortico-cortical, commissural and associational projections, is the termination zone of tufted dendrites of pyramidal neurons and the area of Ca2+spike initiation. However, its synaptic organization in humans is not known. Quantitative 3D-models of synaptic boutons (SBs) in L1 of the human temporal lobe neocortex were generated from non-epileptic neocortical biopsy tissue using transmission electron microscopy, 3D-volume reconstructions and TEM tomography. Particularly, the size of active zones (AZs) and the readily releasable, recycling and resting pool of synaptic vesicles (SVs) were quantified.

The majority of SBs contained numerous mitochondria comprising ∼7% of the total volume of SBs, had a large macular, non-perforated AZs (∼0.20 µm2) and were predominantly located on dendritic spines. SBs had a total pool of ∼3500 SVs, a comparably large readily releasable (∼4 SVs), recycling (∼470 SVs) and resting (∼2900 SVs) pool. Astrocytic coverage of SBs suggests both synaptic cross talk or removal of spilled glutamate by astrocytic processes at synaptic complexes.

The structural composition of SBs in L1 may underlie the function of L1 networks that mediate, integrate and synchronize contextual and cross-modal information, enabling flexible and state-dependent processing of feedforward sensory inputs from other layers of the cortical column.
The effects of 17α-estradiol treatment on endocrine system revealed by single-nucleus transcriptomic sequencing of hypothalamus
Authors: Li Lei , Wu Guanghao , Xu Xiaolei , Yang Junling , Yi Lirong , Yang Ziqing , Mo Zheng , Xing Li , Shan Ying , Yu Zhuo , Li Yinchuan
Published: June 2024

In this study, we investigated the role of 17α-estradiol in lifespan extension and its potential side effects from long-term administration. Pooled hypothalami from aged male Norway brown rats treated with 17α-estradiol (O.T), aged male controls (O), and young male controls (Y) were subjected to single-nucleus transcriptomic sequencing (snRNA-seq). To evaluate the effects of 17α-estradiol on aging neurons, supervised clustering of neurons based on neuropeptides and their receptors were used to evaluate the responses of each neuron subtype during aging and after 17α-estradiol treatment. The elevated cellular metabolism, stress and decreased expression levels of pathways involved in synapse formation in neurons initiated by aging were significantly attenuated by 17α-estradiol. Assessment of changes in neuron populations showed that neurons related to food intake, reproduction, blood pressure, stress response, and electrolyte balance were sensitive to 17α-estradiol treatment. 17α-estradiol treatment not only increased serum Oxytocin (Oxt), but also heightened the activity of hypothalamic-pituitary-gonadal (HPG) axis, as evidenced by significantly elevated levels of plasma Gnrh, total testosterone, and decreased estradiol. Elevated Gnrh1 was confirmed to be one of the causal effects mediating the role of 17α-estradiol in energy homeostasis, neural synapse, and stress response. Notably,Crhneurons exhibited prominent stressed phenotype among all the checked neuron subtypes in O.T, which may indicate a potential side effect of 17α-estradiol treatment. Therefore, the HPG axis and energy metabolism may be key targets of 17α-estradiol in male hypothalamus. Additionally, supervised clustering of neurons was shown to be a useful method for assessing treatment responses among different neuron subtypes in the hypothalamus.
Cell- and state-specific plasticity of striatal glutamatergic synapses is critical to the expression of levodopa-induced dyskinesia
Authors: Shen Weixing , Zhai Shenyu , Francardo Veronica , Cui Qiaoling , Xie Zhong , Tkatch Tatiana , Cenci M. Angela , Surmeier D. James
Published: June 2024

Levodopa-induced dyskinesia (LID) is a debilitating complication of symptomatic therapy in Parkinson’s disease (PD). Although there is compelling evidence that striatal pathophysiology is a major driver of LID, the circuit-specific mechanisms contributing to dysfunction remain obscure. This lack of clarity is reflected in the limited options for diminishing established LID. To address this gap, molecular, cellular, and behavioral strategies were used to interrogate striatal indirect pathway spiny projection neurons (iSPNs) in a mouse model of LID. These studies revealed that LID induction led to an up-regulation of GluN2B-containing N-methyl-d-aspartate receptors (NMDARs) specifically at iSPN glutamatergic synapses. This up-regulation was correlated with increased numbers of ‘silent’ glutamatergic synapses in the hours after levodopa treatment. In this ‘off-state’, long-term potentiation (LTP) of iSPN glutamatergic synapses was readily induced and this induction was blocked by antagonists of adenosine type 2 receptors (A2aRs) or GluN2B-containing NMDARs. Systemic administration of the A2aR antagonist tozedenant at the beginning of the off-state significantly reduced the development of LID. More importantly, specifically knocking down the expression ofGRIN2BmRNA in iSPNs dramatically attenuated both development and expression of LID, without compromising the beneficial effects of levodopa on movement. Taken together, these studies demonstrate that dyskinesiogenic doses of levodopa trigger cell-specific synaptic adaptations during the off-state that make an important contribution to the network pathophysiology underlying LID and suggest that targeting GluN2B-containing NMDARs in iSPNs could be therapeutically useful.
Differential effects of diphenyl diselenide (PhSe)2on mitochondria-related pathways depending on the cellular energy status in Bovine Vascular Endothelial Cells
Authors: Galant Letícia Selinger , Doblado Laura , Radi Rafael , da Rocha João Batista Teixeira , de Bem Andreza Fabro , Monsalve Maria
Published: June 2024

Cellular energy metabolism varies depending on tissue and cell type, as well as the availability of energy substrates and energy demands. We recently investigated the variations in cellular metabolism and antioxidant responses in primary bovine vascular endothelial cells (BAECs) under different energetic substrate conditions in vitro, specifically glucose or galactose. In this context, pharmacological agents may exert different effects on cells depending on their energy metabolism status. In this study, we aimed to characterize the effects of (PhSe)2, a redox-active molecule known for its prominent cardiovascular effects, on redox-bioenergetic cellular pathways under glycolytic or oxidative conditions in BAECs. Under glucose conditions, (PhSe)2positively impacted mitochondrial oxidative capacity, as assessed by respirometry, and was associated with changes in mitochondrial cellular dynamics. However, these changes were not observed in cells cultured with galactose. Although (PhSe)2induced the nuclear translocation of NRF2 in both glucose and galactose media, NRF2 remained in the nuclei of cells cultured in galactose for a longer duration. Additionally, activation of FOXO3a was only detected in galactose media. Notably, (PhSe)2strongly induced the expression of genes controlling mitochondrial antioxidant capacity and glutathione synthesis and recycling in glucose media, whereas its effects in galactose media were primarily focused on glutathione homeostasis. In conclusion, our findings underscore the critical influence of cellular metabolic status on the antioxidant capacity of redox-active molecules such as (PhSe)2.
A higher order PUF complex is central to regulation of
C. elegans
germline stem cells
Authors: Qiu Chen , Crittenden Sarah L. , Carrick Brian H. , Dillard Lucas B. , Costa Dos Santos Stephany J. , Dandey Venkata P. , Dutcher Robert C. , Viverette Elizabeth G. , Wine Robert N. , Woodworth Jennifer , Campbell Zachary T. , Wickens Marvin , Borgnia Mario J. , Kimble Judith , Tanaka Hall Traci M.
Published: June 2024

PUF RNA-binding proteins are broadly conserved stem cell regulators. Nematode PUF proteins maintain germline stem cells (GSCs) and, with key partner proteins, repress differentiation mRNAs, including
gld-1
. Here we report that PUF protein FBF-2 and its partner LST-1 form a ternary complex that represses
gld-1
via a pair of adjacent FBF-2 binding elements (FBEs) in its 3’UTR. One LST-1 molecule links two FBF-2 molecules via motifs in the LST-1 intrinsically-disordered region; the
gld-1
FBE pair includes a well-established ‘canonical’ FBE and a newly-identified noncanonical FBE. Remarkably, this FBE pair drives both full RNA repression in GSCs and full RNA activation upon differentiation. Discovery of the LST-1–FBF-2 ternary complex, the
gld-1
adjacent FBEs, and their
in vivo
significance predicts an expanded regulatory repertoire of different assemblies of PUF-partner complexes in nematode germline stem cells. It also suggests analogous PUF controls may await discovery in other biological contexts and organisms.
Iterative deep learning-design of human enhancers exploits condensed sequence grammar to achieve cell type-specificity
Authors: Yin Christopher , Hair Sebastian Castillo , Byeon Gun Woo , Bromley Peter , Meuleman Wouter , Seelig Georg
Published: June 2024

An important and largely unsolved problem in synthetic biology is how to target gene expression to specific cell types. Here, we apply iterative deep learning to design synthetic enhancers with strong differential activity between two human cell lines. We initially train models on published datasets of enhancer activity and chromatin accessibility and use them to guide the design of synthetic enhancers that maximize predicted specificity. We experimentally validate these sequences, use the measurements to re-optimize the predictor, and design a second generation of enhancers with improved specificity. Our design methods embed relevant transcription factor binding site (TFBS) motifs with higher frequencies than comparable endogenous enhancers while using a more selective motif vocabulary, and we show that enhancer activity is correlated with transcription factor expression at the single cell level. Finally, we characterize causal features of top enhancers via perturbation experiments and show enhancers as short as 50bp can maintain specificity.
Improvement of the potency of a N1-methylpseudouridine-modified self-amplifying RNA through mutations in the RNA-dependent-RNA-polymerase
Authors: Quintana Verónica , Caillava Josefina , Byk Laura A. , Mondotte Juan A. , Battini Leandro , Tarte Prutha , Samsa Marcelo M. , Filomatori Claudia V. , Alvarez Diego E.
Published: June 2024

RNA vaccines are sensed as non-self molecules by the innate immune system, and balancing control of the immune activation and vaccine safety and efficacy has remained a challenge, especially for self-amplifying RNAs (saRNAs). Incorporation of modified nucleotides has been widely used to temper immune activation of RNA vaccines. However, it was previously reported that incorporation of modified nucleotides to saRNAs impeded antigen expression. Here, we used a reporter replicon of the attenuated TC-83 strain of Venezuelan equine encephalitis virus (VEEV) to investigate the impact of modified nucleotide incorporation on the replication capacity of the saRNA in transfected cells. ψ and ψ-modified molecules showed a profound defect in RNA synthesis compared to unmodified saRNA. Interestingly, the levels of RNA synthesis of m5C-modified RNAs were similar to unmodified molecules, positioning m5C as a promising candidate for saRNA modification. To overcome the impact of ψ or m1ψ-modified nucleotide incorporation in RNA synthesis, we explored two alternative approaches: engineering the UTR sequences and tuning polymerase fidelity. Our results uncover a previously unappreciated link between polymerase fidelity and saRNA amplification. Overall, we provide new insights for the design of saRNAs with high levels of heterologous protein expression and potential vaccine applications.
Addition of Soil Protists Enhances Performance of Agrochemical Seed Treatments
Authors: Hawxhurst Christopher J. , McClure Travis , Kirk Daniel , Shor Mikhael , Gage Daniel J. , Shor Leslie M.
Published: June 2024

Chemicals are an integral part of modern agriculture, and are applied through a variety of methods. Some agrochemicals applied for crop protection function by absorption through the root before translocation to the rest of the plant. To be absorbed by the root, the agrochemical must first be transported through the soil, often by water. Some agrochemicals suffer from poor water-based soil transmission due to their chemical properties, limiting their application as a traditional seed treatment. Two such agrochemicals are chlorantraniliprole and spinosad. Soil protists are an important component of the soil microbial community. Certain soil protists have been previously shown to facilitate transport and targeted delivery of suspended particles and cells through soil and microfluidic devices. We provide practical evidence that a soil protist,Colpoda sp., when co-inoculated with an agrochemical seed treatment, can substantially and robustly reduce subsequent pest feeding damage compared with the agrochemical alone. Using maize (Zea maysL.) and fall armyworm,Spodoptera frugiperda(J. E. Smith, 1797) (Lepidoptera: Noctuidae), in a plant damage assay, we directly compare pest feeding damage and mortality in plants that received no additional treatment, only protists, only agrochemical, and co-inoculation of agrochemical with protists. We discover for both agrochemicals tested, the co-inoculation of protists with the agrochemical increases protection in leaves when the efficacy of the agrochemical alone declines. Protist amendment is a simple, natural, inexpensive, chemical-free, soil-based transport enhancer that thus may be widely useful in a variety of contexts including more sustainable and cost-effective integrated pest management.

Importance

Pest resistance, regulatory pressure, and environmental concerns are limiting many classes of pesticides which can be effectively used to protect valuable crops from pests. Other classes of pesticides, however, are limited by physical characteristics – water solubility or octane-water partition coefficient (KOW) fall outside the limit for an effective seed coating, or the per-unit cost is high enough to discourage broad application. Here, we provide data which supports the co-inoculation of a high value, low solubility, high KOWpesticides with a naturally-occurring soil protist as a seed treatment can enhance crop protection relative to the pesticide alone. This co-formulation reduced feeding damage by up to 30% compared with the pesticide alone. Co-inoculation of crop-protecting agrochemicals with natural soil protists may be employed as a more sustainable agriculture biotechnology, enabling the use of classes of agrochemicals which may not otherwise show sufficient performance for use as a seed treatment.
A BTB extension and ion-binding domain contribute to the pentameric structure and TFAP2A binding of KCTD1
Authors: Pinkas Daniel M. , Bufton Joshua C. , Hunt Alice E. , Manning Charlotte E. , Richardson William , Bullock Alex N.
Published: June 2024

KCTD family proteins typically assemble into Cullin-RING E3 ligases. KCTD1 is an atypical member that functions instead as a transcriptional repressor. Mutations in KCTD1 cause developmental abnormalities and kidney fibrosis in scalp-ear-nipple syndrome. Here, we present unexpected mechanistic insights from the structure of full-length KCTD1. Disease-causing mutation P20S maps to an unrecognized extension of the BTB domain that contributes both to its pentameric structure and TFAP2A binding. The C-terminal domain (CTD) shares its fold and pentameric assembly with the protein GFRP despite lacking discernible sequence similarity. Most surprisingly, the KCTD1 CTD establishes a central channel occupied by alternating sodium and iodide ions that restrict TFAP2A dissociation. The elucidation of the structure redefines the KCTD family BTB domain fold and identifies an unexpected ion pore for future study of KCTD1’s function in the ectoderm, neural crest and kidney.
Long-read RNA-seq demarcatescis- andtrans-directed alternative RNA splicing
Authors: Quinones-Valdez Giovanni , Amoah Kofi , Xiao Xinshu
Published: June 2024

Genetic regulation of alternative splicing constitutes an important link between genetic variation and disease. Nonetheless, RNA splicing is regulated by bothcis-acting elements andtrans-acting splicing factors. Determining splicing events that are directed primarily by thecis- ortrans-acting mechanisms will greatly inform our understanding of the genetic basis of disease. Here, we show that long-read RNA-seq, combined with our new method isoLASER, enables a clear segregation ofcis- andtrans-directed splicing events for individual samples. The genetic linkage of splicing is largely individual-specific, in stark contrast to the tissue-specific pattern of splicing profiles. Analysis of long-read RNA-seq data from human and mouse revealed thousands ofcis-directed splicing events susceptible to genetic regulation. We highlight such events in the HLA genes whose analysis was challenging with short-read data. We also highlight novelcis-directed splicing events in Alzheimer’s disease-relevant genes such asMAPTandBIN1. Together, the clear demarcation ofcis- andtrans-directed splicing paves ways for future studies of the genetic basis of disease.
Time-varying synergy/redundancy dominance in the human cerebral cortex
Authors: Pope Maria , Varley Thomas F. , Sporns Olaf
Published: June 2024

Recent work has emphasized the ubiquity of higher-order interactions in brain function. These interactions can be characterized as being either redundancy or synergy-dominated by the heuristic O-information [1]. Though the O-information can be decomposed into local values to measure the synergy-redundancy dominance at each point in a time series [2] no such analysis of fMRI dynamics has been carried out. Here we analyze the moment-to-moment synergy and redundancy dominance of the fMRI BOLD signal during rest for 95 unrelated subjects. We present results from several interaction sizes. The whole brain is rarely synergy-dominated, with some subjects never experiencing a whole-brain synergistic moment. Randomly sampled subsets of many sizes reveal that subsets that are the most redundancy dominated on average exhibit both the most synergistic and most redundant time points. Exhaustive calculation of the optimally synergistic and optimally redundant triads further emphasizes this finding, with recurrent nodes frequently belonging to a single coherent functional system. We find that when a triad is momentarily synergistic, it is often split between two instantaneously co-fluctuating communities, but is collectively co-fluctuating when it is momentarily redundant. After optimizing for synergy and redundancy in subsets of size five to seventy-five, we show that this effect is consistent across interaction sizes. Additionally, we find notable temporal structure in all optimized redundant and synergistic subsets: higher order redundant and synergistic interactions change smoothly in time and recur more than expected by chance.
A Path Integral Approach for Allele Frequency Dynamics Under Polygenic Selection
Authors: Anderson Nathan W. , Kirk Lloyd , Schraiber Joshua G. , Ragsdale Aaron P.
Published: June 2024

Many phenotypic traits have a polygenic genetic basis, making it challenging to learn their genetic architectures and predict individual phenotypes. One promising avenue to resolve the genetic basis of complex traits is through evolve-and-resequence experiments, in which laboratory populations are exposed to some selective pressure and trait-contributing loci are identified by extreme frequency changes over the course of the experiment. However, small laboratory populations will experience substantial random genetic drift, and it is difficult to determine whether selection played a roll in a given allele frequency change. Predicting how much allele frequencies change under drift and selection had remained an open problem well into the 21stcentury, even those contributing to simple, monogenic traits. Recently, there have been efforts to apply the path integral, a method borrowed from physics, to solve this problem. So far, this approach has been limited to genic selection, and is therefore inadequate to capture the complexity of quantitative, highly polygenic traits that are commonly studied. Here we extend one of these path integral methods, the perturbation approximation, to selection scenarios that are of interest to quantitative genetics. In particular, we derive analytic expressions for the transition probability (i.e., the probability that an allele will change in frequency fromx, toyin timet) of an allele contributing to a trait subject to stabilizing selection, as well as that of an allele contributing to a trait rapidly adapting to a new phenotypic optimum. We use these expressions to characterize the use of allele frequency change to test for selection, as well as explore optimal design choices for evolve-and-resequence experiments to uncover the genetic architecture of polygenic traits under selection.
Sparse Annotation is Sufficient for Bootstrapping Dense Segmentation
Authors: Thiyagarajan Vijay Venu , Sheridan Arlo , Harris Kristen M. , Manor Uri
Published: June 2024

Producing dense 3D reconstructions from biological imaging data is a challenging instance segmentation task that requires significant ground-truth training data for effective and accurate deep learning-based models. Generating training data requires intense human effort to annotate each instance of an object across serial section images. Our focus is on the especially complicated brain neuropil, comprising an extensive interdigitation of dendritic, axonal, and glial processes visualized through serial section electron microscopy. We developed a novel deep learning-based method to generate dense 3D segmentations rapidly from sparse 2D annotations of a few objects on single sections. Models trained on the rapidly generated segmentations achieved similar accuracy as those trained on expert dense ground-truth annotations. Human time to generate annotations was reduced by three orders of magnitude and could be produced by non-expert annotators. This capability will democratize generation of training data for large image volumes needed to achieve brain circuits and measures of circuit strengths.
Examining the impact of consumers’ showrooming behavior on sales staff job conditions: insights from the Indian apparel retail sector
Authors: Kumar Manoj , Gahlawat Neha , Singh Sumanjeet , Chamola Pankaj , Kala Devkant , Paliwal Minakshi
Published: June 2024

Purpose

This research aims to investigate the showrooming phenomenon in the context of the evolving omnichannel shopping landscape, which seamlessly integrates both physical and online retail channels. Showrooming, wherein customers browse products in physical stores but ultimately purchase from online competitors, poses a potential threat to the job security and job satisfaction of sales staff in brick-and-mortar (B&M) stores. To address this issue, this study explores the relationship between showrooming, self-efficacy, sales performance, job insecurity and job satisfaction of sales staff, using the job demands-resources (JDR-R) model as a theoretical framework.

Design/methodology/approach

This research employs quantitative research methods and gathers data from 219 sales staff working in Indian retail stores. Structural equation modeling is used to test the proposed hypotheses.

Findings

The results indicate that showrooming is associated with a decrease in the self-efficacy, sales performance and job satisfaction of sales staff. Furthermore, the result indicates that showrooming is positively associated with increased job insecurity among the sales staff.

Originality/value

This study offers valuable contributions to existing literature and offers insights for both retailers and salespeople regarding the potential repercussions of showrooming. It also suggests coping strategies to address the challenges posed by showrooming and the behavior of showroomers.
Using bibliometric analysis to determine the role of cutting-edge technologies in the development of future performance management system
Authors: Kumar Pankaj , Prakash Karuna , Dimri Anjali , Khulbe Manjula , Chandra Mishra Satish
Published: June 2024

Purpose

Performance management system (PMS) is a crucial element of strategic human resource practices in any organization. This research aims to provide a concise overview of how bibliometric analysis is employed to assess the influence and significance of cutting-edge technologies in shaping of PMS. This study seeks to identify key trends, emerging technologies and their impact on the evolution of performance management practices, contributing valuable insights for researchers, practitioners and policymakers in this field.

Design/methodology/approach

This investigation is carried out utilizing total of eight research questions, which are examined through VOS Viewer and Biblioshiny software. The research offers visual diagrams and tables depicting the data extracted from the Scopus Database.

Findings

The study’s results underscore a noticeable increase in research literature pertaining to PMS, indicating a shift from conventional methods to a strategic, technology-driven approach. These findings cover the way for further investigation across various disciplines, offering opportunities to enhance the efficacy and productivity of PMS.

Practical implications

The implementation of new technologies such as Artificial intelligence (AI), machine learning and robotics etc. in PMS have also been analysed to give a sneak peak of the bigger future picture of AI and strategic human resource integration.

Originality/value

To the best of the authors' understanding, this analysis represents the inaugural application of bibliometric techniques to evaluate the advancement of research on Performance Management System (PMS) dating back to 1978, utilizing academic literature sourced from the Scopus database.
Investigating the role of relational factors on buyer-supplier relationship commitment to enhance firm performance through supply chain integration
Authors: Uddin Mohammed Belal
Published: June 2024

Purpose

This study assesses how relational factors and buyer-supplier relationship commitment (BSRC) influence supply chain integration (SCI) and firm performance in Bangladesh's apparel manufacturing sector. Firm performance includes operational performance and innovation performance.

Design/methodology/approach

Grounded in the social exchange theory, a survey data-based structural equation modeling (SEM) approach is applied. Based on two experts and four executives' opinions and an in-depth literature review, 28 measurement items were identified in the close-ended questionnaire design. Further, 144 valid questionnaires from the manufacturer-supplier dyads in Bangladesh were collected and used for SEM analysis.

Findings

Our study reveals that relational factors positively influence BSRC. BSRC directly impacts SCI, operational, and innovation performance, whereas SCI is significantly related to operational and innovation performance. Besides, SCI mediates the two relationships: BSRC and operational performance; and BSRC and innovation performance.

Originality/value

Our results contribute to the literature and offer a new way to understand relationships that connect relational factors of BSRC, BSRC, and outcomes not only by examining the focal firm but also by examining its dyadic supplier partner separately. Separate assessment in the dyad displays some similar and dissimilar results. Moreover, we suggest practical implications for managers to enhance firm performance by focusing on the significance of linking relational factors, BSRC, and SCI.
Maturity grading of jujube for industrial applications harnessing deep learning
Authors: Mahmood Atif , Tiwari Amod Kumar , Singh Sanjay Kumar
Published: June 2024

Purpose

To develop and examine an efficient and reliable jujube grading model with reduced computational time, which could be utilized in the food processing and packaging industries to perform quick grading and pricing of jujube as well as for the other similar types of fruits.

Design/methodology/approach

The whole process begins with manual analysis and collection of four jujube grades from the jujube tree, in addition to this jujube image acquisition was performed utilizing MVS which is further followed by image pre-processing and augmentation tasks. Eventually, classification models (i.e. proposed model, from scratch and pre-trained VGG16 and AlexNet) were trained and validated over the original and augmented datasets to discriminate the jujube into maturity grades.

Findings

The highest success rates reported over the original and augmented datasets were 97.53% (i.e. error of 2.47%) and 99.44% (i.e. error of 0.56%) respectively using Adam optimizer and a learning rate of 0.003.

Research limitations/implications

The investigation relies upon a single view of the jujube image and the outer appearance of the jujube. In the future, multi-view image capturing system could be employed for the model training/validation.

Practical implications

Due to the vast functional derivatives of jujube, the identification of maturity grades of jujube is paramount in the fruit industry, functional food production industries and pharmaceutical industry. Therefore, the proposed model which is practically feasible and easy to implement could be utilized in such industries.

Originality/value

This research examines the performance of proposed CNN models for selected optimizer and learning rates for the grading of jujube maturity into four classes and compares them with the classical models to depict the sublime model in terms of accuracy, the number of parameters, epochs and computational time. After a thorough investigation of the models, it was discovered that the proposed model transcends both classical models in all aspects for both the original and augmented datasets utilizing Adam optimizer with learning rate of 0.003.
Bifurcation analysis and control of an improved continuous traffic model considering weather effect
Authors: Ai Wenhuan , Lei Zheng Qing , Danyang Li , Zeng Jingming , Liu Dawei
Published: June 2024

Purpose

Highway traffic systems are complex and variable, and studying the bifurcation characteristics of traffic flow systems and designing control schemes for unstable bifurcation points can alleviate traffic congestion from a new perspective. Bifurcation analysis is used to explain the changes in system stability, identify the unstable bifurcation points of the system, and design feedback controllers to realize the control of the unstable bifurcation points of the traffic system. It helps to control the sudden changes in the stable behavior of the traffic system and helps to alleviate traffic congestion, which is of great practical significance.

Design/methodology/approach

In this paper, we improve the macroscopic traffic flow model by integrating severe weather factors such as rainfall, snowfall, and dust. We use traveling wave transform to convert it into a traffic flow stability model suitable for branching analysis, thus converting the traffic flow problem into a system stability analysis problem. First, this paper derives the existence conditions of the model Hopf bifurcation and saddle-node bifurcation for the improved macroscopic model, and finds the stability mutation point of the system. Secondly, the connection between the stability mutation points and bifurcation points of the traffic system is analyzed. Finally, for the unstable bifurcation point, a nonlinear system feedback controller is designed using Chebyshev polynomial approximation and stochastic feedback control method.

Findings

The Hopf bifurcation is delayed and completely eliminated without changing the equilibrium point of the system, thus controlling the abrupt behavior of the traffic system.

Originality/value

Currently there are fewer studies to explain the changes in the stability of the transportation system through bifurcation analysis, in this paper; we design a feedback controller for the unstable bifurcation point of the system to realize the control of the transportation system. It is a new research method that helps to control the sudden change of the stable behavior of the traffic system and helps to alleviate traffic congestion, which is of great practical significance.
A sufficient descent hybrid conjugate gradient method without line search consideration and application
Authors: Salihu Nasiru , Kumam Poom , Ibrahim Sulaiman Mohammed , Babando Huzaifa Aliyu
Published: June 2024

Purpose

Previous RMIL versions of the conjugate gradient method proposed in literature exhibit sufficient descent with Wolfe line search conditions, yet their global convergence depends on certain restrictions. To alleviate these assumptions, a hybrid conjugate gradient method is proposed based on the conjugacy condition.

Design/methodology/approach

The conjugate gradient (CG) method strategically alternates between RMIL and KMD CG methods by using a convex combination of the two schemes, mitigating their respective weaknesses. The theoretical analysis of the hybrid method, conducted without line search consideration, demonstrates its sufficient descent property. This theoretical understanding of sufficient descent enables the removal of restrictions previously imposed on versions of the RMIL CG method for global convergence result.

Findings

Numerical experiments conducted using a hybrid strategy that combines the RMIL and KMD CG methods demonstrate superior performance compared to each method used individually and even outperform some recent versions of the RMIL method. Furthermore, when applied to solve an image reconstruction model, the method exhibits reliable results.

Originality/value

The strategy used to demonstrate the sufficient descent property and convergence result of RMIL CG without line search consideration through hybrid techniques has not been previously explored in literature. Additionally, the two CG schemes involved in the combination exhibit similar sufficient descent structures based on the assumption regarding the norm of the search direction.
Supplier relationship management and business performance of small-scale grapes processing firms in Dodoma, Tanzania: the moderating role of logistics capabilities
Authors: Kisinga Debora Chelestino , Mchopa Alban Dismas , Mwagike Leonada Raphael
Published: June 2024

Purpose

This paper aims to investigate the effect of supplier relationship management (SRM) on the business performance of small-scale grapes processing firms in Dodoma, Tanzania. The paper also examines the moderating role of logistics capabilities in the relationship between SRM and business performance.

Design/methodology/approach

This research uses a cross-sectional survey design. A structured questionnaire was used to collect data from 202 small-scale grape processing firms. The data were analysed through descriptive and structural equation modelling.

Findings

The findings revealed that buyer-supplier relationships, supplier development and supplier selection were positively and significantly related to business performance. Furthermore, knowledge transfer had no relationship with business performance. On the other hand, the findings showed that logistics capabilities significantly moderated the relationship between SRM and business performance.

Research limitations/implications

The study was cross-sectional, conducted only in Tanzania, and focussed entirely on small-scale firms processing grapes as raw materials. Thus, generalising the study findings to other countries with different conditions should be done cautiously. Also, this study used subjective measures, and other studies could use objective measures.

Practical implications

The study helps firm managers understand the importance of supplier relationship management on business performance. The findings also can be used by policymakers to create targeted policies and initiatives that support the firm’s growth and sustainability.

Originality/value

To the best of the researchers’ knowledge, this is the first attempt to find empirical support for the moderating role of logistics capability in supplier relationship management and the business performance of small-scale grapes processing firms in the Tanzanian context.
Educational aspirations of school adolescents in Kazakhstan, Kyrgyzstan and Tajikistan: how are these aspirations shaped?
Authors: Smailova Ainura , Tynaliev Urmatbek M. , Borbugulov Malik , Sadyrova Gulzat
Published: June 2024

Purpose

This study examines the factors influencing educational aspirations among adolescents in secondary and high schools across Kazakhstan, Kyrgyzstan (officially Kyrgyz Republic), and Tajikistan, with a focus on their aspirations for higher and postgraduate education. Through an analysis of a sample comprising 1360 students from grades 7 to 11, the research explores the likelihood of these students pursuing tertiary education.

Design/methodology/approach

The ordered logit regression models were used to analyze the impact of variables related to family background, including parents’ education, family support and SES, and school grade. Additionally, the Exploratory Factor Analysis was utilized to distill a smaller set of underlying factors or constructs from the measured variables.

Findings

The findings indicate that the mother's education level is significantly more influential compared to the father's education in shaping adolescents' aspirations for higher and postgraduate education in the Central Asian context. Additionally, hypotheses concerning the influence of family socioeconomic status (SES), family support, and grade-level differences on adolescents' higher educational aspirations have only been partially confirmed.

Originality/value

To the best of the authors' knowledge, no prior research work has indicated a significant impact of a mother's education on the educational aspirations of her offspring in the Central Asian region. This trend is consistent with the concept of educational hypogamy, wherein mothers possess higher educational levels than fathers, a phenomenon that is gaining prominence in contemporary family dynamics.