bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of hemoglobin levels with clinical outcomes in acute coronary syndromes in Koreans
Authors: Kang Se Hun , Moon Jae Youn , Kim Sang Hoon , Sung Jung Hoon , Kim In Jai , Lim Sang Wook , Cha Dong Hun , Kim Won-Jang
Published: December 2022

Anemia is a well-known risk factor for cardiovascular disease. However, there are limited data on whether anemia on admission is a long-term prognostic factor in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention. We sought to evaluate the prevalence and prognostic consequences of anemia in patients with ACS treated with percutaneous coronary intervention in Korea. We retrospectively enrolled 1930 consecutive patients. Among the anemic population (hemoglobin [Hb] < 13 g/dL in men, and < 12 g/dL in women), we classified patients with Hb ≥ 7 g/dL, <10 d/dL as moderate anemia, other cases classified as mild anemia. Among patients with normal hemoglobin levels, we classified those with Hb > 16.5 g/dL in men, and > 16.0 g/dL in women, as having high hemoglobin. We examined the relationship between anemia with all-cause mortality and secondary outcomes – including cardiovascular mortality, myocardial infarction, stroke, and repeat revascularization. We classified 3.3%, 21.5%, and 5.3% of patients as moderate anemia, mild anemia, and high hemoglobin, respectively. During a median follow-up of 67.2 (interquartile range; 46.8–88.5) months, 74 (3.8%) patients died. Compared with patients with normal hemoglobin, we detected a significantly increased risk for all-cause mortality in patients with anemia (adjusted hazard ratios for moderate and mild anemia, respectively: 8.26 [95% confidence interval: 3.98–17.15], P < .001 and 2.60 [1.54–4.40], P < .001). Among patients with ACS, anemia is prevalent and is strongly associated with increased mortality and cardiovascular events. Clinical trials will prospectively evaluate the efficacy of treatment for anemia on the outcomes of patients with ACS.
Large gastroduodenal artery pseudoaneurysm, arterioportal fistula and portal vein stenosis in chronic pancreatitis treated using combined transarterial embolization and transportal stenting: A case report
Authors: Lim Sung Gong , Park Sung Eun , Nam In Chul , Choi Ho Cheol , Won Jung Ho , Jo Sa Hong , Baek Hye Jin , Moon Jin Il , Cho Eun , Jang Jae Yool
Published: December 2022

Rationale:

Chronic pancreatitis is an ongoing fibroinflammatory disease of the pancreas characterized by irreversible damage to the pancreatic parenchyma and ductal system. Besides, chronic pancreatitis can present with a variety of life-threatening complications.

Patient concerns:

The patients visited our hospital due to abdominal pain and anemia, and had chronic pancreatitis as an underlying disease.

Diagnoses:

Computed tomography showed a large gastroduodenal artery pseudoaneurysm, arterioportal vein fistula, and portal vein stenosis.

Interventions:

We would like to report the successful use of the coils, and N-butyl cyanoacrylate glue for the therapeutic embolization of the pseudoaneurysm and fistula between the gastroduodenal artery and the portal vein, and stenting for portal vein stenosis.

Outcomes:

On the day following the endovascular management, the patient reported remission of abdominal pain, and hemoglobin level returned to normal after transfusion. It was confirmed that it was still well maintained in the follow-up examination after 1 month.

Lessons:

Although chronic pancreatitis causes many vascular complications, simultaneous occurrence of these lesions is extremely rare. Herein, we share our experience with a unique case of an extrahepatic arterioportal fistula induced by the rupture of gastroduodenal artery pseudoaneurysm with concomitant portal vein stenosis. In these complex cases, combined transarterial embolization and transportal stenting can be helpful.
Landscape of lipidomics in cardiovascular medicine from 2012 to 2021: A systematic bibliometric analysis and literature review
Authors: Wang Wenting , Song Lei
Published: December 2022

Lipidomics has shaped our knowledge of how lipids play a central role in cardiovascular diseases (CVD), whereas there is a lack of a summary of existing research findings. This study performed a bibliometric analysis of lipidomics research in cardiovascular medicine to reveal the core countries, institutions, key researchers, important references, major journals, research hotspots and frontiers in this field. From 2012 to 2021, a total of 761 articles were obtained from the Web of Science Core Collection database. There is a steady increase of publications yearly. The United States and China are on the top of the list regarding article output. The institutions with the most publications were the Baker Heart and Diabetes Institute, the Chinese Academy of Sciences and Harvard Medical School. Peter J Meikle was both the most published and most co-cited author. The major journal in this field is Journal of lipid research. Keyword co-occurrence analysis indicated that coronary heart disease, mass spectrometry, risk, fatty acid, and insulin resistance have become hot topics in this field and keyword burst detection suggests that metabolomics, activation, liver, low density lipoprotein are the frontiers of research in recent years. Collectively, lipidomics in CVD is still in its infancy with a steady increase yearly. More in-depth studies in this area are warranted in the future.
Behavioral Management of Children With Autism in the Emergency Department
Authors: Wolpert Katherine H. , Kodish Ian , Kim Soo-Jeong , Uspal Neil G.
Published: December 2022

Autism spectrum disorder (ASD) is characterized by impaired social communication in conjunction with patterned behaviors. Often associated with emotional dysregulation, irritability, aggression, depression, and suicidality, ASD youth frequently present to the emergency department for behavioral and mental health evaluation. Psychiatric comorbidities, agitation, and depression are commonly encountered. During these visits, practitioners must thoughtfully consider organic etiologies for presenting symptoms, formulate plans to address risk of agitation, and understand how to effectively formulate disposition options in this patient population.
Applying Genomics to Unravel Health Disparities in Organ Transplantation: Paul I. Terasaki State-of-the-art Lecture; American Transplant Congress 2021
Authors: Valantine Hannah A.
Published: December 2022

An extensive body of research about team science provides empirical evidence that diverse teams outperform homogenous teams in creating more innovative solutions to complex problems. At the core of diverse and inclusive teams is a rich diversity of perspectives, experiences, and backgrounds that invite new questions and broaden the scope of research. Diverse perspectives are especially relevant for biomedicine, which seeks to find solutions for challenging problems affecting the human condition. It is essential that diversity and inclusion in biomedicine is prioritized as a key driver of innovation, both through the people who conduct the research and the science itself. Key questions have been articulated as important drivers for funding research: (1) Who is doing the science and who is building the tools? (2) What science and technology is being done and how? and (3) Who has access to the knowledge and benefits of scientific innovation? I will briefly review the empirical evidence supporting diversity as a powerful enhancer of the quality and outputs of research and clinical care. I offer my own research as a case study of incorporating a framework of diversity, equity, and inclusion into research that uses new emerging genomic tools for earlier and more precise diagnosis of organ transplant rejection. I will demonstrate how these same tools hold great promise for accelerating the discovery of hitherto unexplored mechanisms that drive the poor outcomes for African ancestry organ transplant recipients, which in turn will identify new diagnostics and therapeutic targets that benefit transplant recipients across all ancestries.
Multi-scale tissue fluorescence mapping with fibre optic ultraviolet excitation and generative modelling
Authors: Ang Joel Lang Yi , Tan Ko Hui , Yong Alexander Si Kai , Tan Chiyo Wan Xuan , Kng Jessica Sze Jia , Tan Cyrus Jia Jun , Soh Rachael Hui Kie , Tan Julian Yi Hong , Liang Kaicheng
Published: December 2022

Cellular imaging of thick samples requires physical sectioning or laser scanning microscopy, generally incompatible with high-throughput requirements. We developed fibre optic microscopy with ultraviolet (UV) surface excitation (FUSE), a portable, quantitative fluorescence imaging platform for thick tissue that substantially advances prior UV excitation approaches with illumination engineering and computational methods. Optic fibres delivered <300nm light with directional control, enabling unprecedented 50X widefield imaging on thick tissue with sub-nuclear clarity, and 3D topography of surface microstructure. Generative modelling of high-magnification images using our normalising flow architecture FUSE-Flow (open-source) enhanced low-magnification imaging by variational inference. Comprehensive validation comprised multi-scale fluorescence histology compared with standard H&E, and quantitative analyses of senescence, antibiotic toxicity, and nuclear DNA content in tissue models via efficient sampling of entire murine organs by thick slices up to 0.4×8×12mm and 1.3 million cells per surface. This technology addresses long-standing laboratory gaps for high-throughput studies for rapid cellular insights.

Teaser

Large-field functional cellular insights into thick tissue with generative AI enables accelerated decision-making
Redesigning methionyl-tRNA synthetase forβ-methionine activity with adaptive landscape flattening and experiments
Authors: Opuu Vaitea , Nigro Giuliano , Lazennec-Schurdevin Christine , Mechulam Yves , Schmitt Emmanuelle , Simonson Thomas
Published: December 2022

Amino acids (AAs) with a noncanonical backbone would be a valuable tool for protein engineering, enabling new structural motifs and building blocks. To incorporate them into an expanded genetic code, the first, key step is to obtain an appropriate aminoacyl-tRNA synthetase (aaRS). Currently, directed evolution is not available to optimize such AAs, since an appropriate selective pressure is not available. Computational protein design (CPD) is an alternative. We used a new CPD method to redesign MetRS and increase its activity towardsβ-Met, which has an extra backbone methylene. The new method considered a few active site positions for design and used a Monte Carlo exploration of the corresponding sequence space. During the exploration, a bias energy was adaptively learned, such that the free energy landscape of the apo enzyme was flattened. Enzyme variants could then be sampled, in the presence of the ligand and the bias energy, according to theirβ-Met binding affinities. Eleven predicted variants were chosen for experimental testing; all exhibited detectable activity forβ-Met adenylation. Top predicted hits were characterized experimentally in detail. Dissociation constants, catalytic rates, and Michaelis constants for bothα-Met andβ-Met were measured. The best mutant retained a preference forα-Met overβ-Met; however, the preference was reduced, compared to the wildtype, by a factor of 29. For this mutant, high resolution crystal structures were obtained in complex with bothα-Met andβ-Met, indicating that the predicted, active conformation ofβ-Met in the active site was retained.

Author summary

Amino acids (AAs) with a noncanonical backbone would be valuable for protein engineering, enabling new structural motifs. To incorporate them into an expanded genetic code, the key step is to obtain an appropriate aminoacyl-tRNA synthetase (aaRS). Currently, directed evolution is not available to optimize such AAs. Computational protein design is an alternative. We used a new method to redesign MetRS and increase its activity towardsβ-Met, which has an extra backbone methylene. The method considered a few active site positions for design and used a Monte Carlo exploration of sequence space, during which a bias energy was adaptively learned, such that the free energy landscape of the apo enzyme was flattened. Enzyme variants could then be sampled, in the presence of the ligand and the bias energy, according to theirβ-Met binding affinities. Eleven predicted variants were chosen for experimental testing; all exhibited detectableβ-Met adenylation activity. Top hits were characterized experimentally in detail. The best mutant had its preference forα-Met overβ-Met reduced by a factor of 29. Crystal structures indicated that the predicted, active conformation ofβ-Met in the active site was retained.
PKA regulatory subunit Bcy1 couples growth, lipid metabolism, and fermentation during anaerobic xylose growth inSaccharomyces cerevisiae
Authors: Wagner Ellen R. , Nightingale Nicole M. , Jen Annie , Overmyer Katherine A. , McGee Mick , Coon Joshua J. , Gasch Audrey P.
Published: December 2022

Organisms have evolved elaborate physiological pathways that regulate growth, proliferation, metabolism, and stress response. These pathways must be properly coordinated to elicit the appropriate response to an ever-changing environment. While individual pathways have been well studied in a variety of model systems, there remains much to uncover about how pathways are integrated to produce systemic changes in a cell, especially in dynamic conditions. We previously showed that deletion of Protein Kinase A (PKA) regulatory subunitBCY1can decouple growth and metabolism inSaccharomyces cerevisiaeengineered for anaerobic xylose fermentation, allowing for robust fermentation in the absence of division. This provides an opportunity to understand how PKA signaling normally coordinates these processes. Here, we integrated transcriptomic, lipidomic, and phosphor-proteomic responses upon a glucose to xylose shift across a series of strains with different genetic mutations promoting either coupled or decoupled xylose-dependent growth and metabolism. Together, results suggested that defects in lipid homeostasis limit growth in thebcy1Δstrain despite robust metabolism. To further understand this mechanism, we performed adaptive laboratory evolutions to re-evolve coupled growth and metabolism in thebcy1Δparental strain. Genetic mutations in PKA subunitTPK1and lipid regulatorOPI1, among other genes underscored a role for lipid homeostasis, which was further supported by evolved changes in lipid profiles and gene expression. We suggest several models for how cells coordinate growth, metabolism, and other responses in budding yeast and how restructuring these processes enables anaerobic xylose utilization.

Author Summary

All organisms utilize an energy source to generate the cellular resources needed to grow and divide. These individual processes have been well study, but the coordination and crosstalk between the process is not well understood. To study growth and metabolism coupling, we used a yeast strain that was genetically engineered to ferment the sugar xylose but lacked growth on the sugar. The decoupled growth and metabolism was caused by a single gene deletion in a highly conserved signaling pathway found in all eukaryotes. While our work is focused on xylose metabolism, we address the fundamental question of how cells coordinate growth with metabolism under non-ideal conditions. We identified vast changes in gene expression that implicated altered regulatory mechanisms involved in lipid metabolism correlating with decouple growth and metabolism. Our work highlights the complexity of engineering new cellular functions and that global regulatory modifications, rather than altering individual pathways, may be required for broad cellular changes.
Forces driving transposable element load variation during Arabidopsis range expansion
Authors: Jiang Juan , Xu Yong-Chao , Zhang Zhi-Qin , Chen Jia-Fu , Niu Xiao-Min , Hou Xing-Hui , Li Xin-Tong , Wang Li , Zhang Yong , Ge Song , Guo Ya-Long
Published: December 2022

Genetic load refers to the accumulated and potentially life-threatening deleterious mutations in populations. Understanding the mechanisms underlying genetic load variation of transposable elements (TEs), one major large-effect mutations, during range expansion is an intriguing question in biology. Here, we used 1,115 globally natural accessions ofArabidopsis thaliana, to study the driving forces of TE load variation during its range expansion. The TE load increased with range expansion, especially in the recently established Yangtze River basin population. The effective population size explained 62.0% of the variance in TE load, and high transposition rate and positive selection or hitch-hiking effect contributed to the accumulation of TEs in the expanded populations. We genetically mapped the candidate causal genes or TEs and revealed the genetic architecture of TE load. Overall, this study reveals the variation in the genetic load of TEs during Arabidopsis expansion and highlights the causes of TE load variation.
Human TRMT2A methylates tRNA and contributes to translation fidelity
Authors: Witzenberger Monika , Burczyk Sandra , Settele David , Mayer Wieland , Welp Luisa M. , Heiss Matthias , Wagner Mirko , Monecke Thomas , Janowski Robert , Carell Thomas , Urlaub Henning , Hauck Stefanie M. , Voigt Aaron , Niessing Dierk
Published: December 2022

Methyl-5-uridine (m5U) is one of the most abundant RNA modifications found in cytosolic tRNA. tRNA methyltransferase 2 homolog A (hTRMT2A) is the dedicated mammalian enzyme of m5U formation at tRNA position 54. However, its RNA binding specificity and functional role in the cell are not well understood. Here we dissected structural and sequence requirements for binding and methylation of its RNA targets. Specificity of tRNA modification by TRMT2A is achieved by a combination of modest binding preference and presence of a uridine in position 54 of tRNAs. Mutational analysis together with crosslinking experiments identified a large hTRMT2A-tRNA binding surface. Furthermore, complementing hTRMT2A interactome studies revealed that TRMT2A interacts with proteins involved in RNA biogenesis. Finally, we addressed the question of the importance of TRMT2A function by showing that its knockdown reduces translation fidelity. These findings extend the role of hTRMT2A beyond tRNA modification towards a role in translation.
High Field Asymmetric Waveform Ion Mobility Spectrometry-Mass Spectrometry to Enhance Cardiac Muscle Proteome Coverage
Authors: Ai Lizhuo , Binek Aleksandra , Kreimer Simion , Ayres Matthew , Stotland Aleksandr , Van Eyk Jennifer E.
Published: December 2022

Heart tissue sample preparation for mass spectrometry (MS) analysis that includes pre-fractionation reduces the cellular protein dynamic range and increases the relative abundance of non-sarcomeric proteins. We previously described “IN-Sequence” (IN-Seq) where heart tissue lysate is sequentially partitioned into three subcellular fractions to increase the proteome coverage than a single direct tissue analysis by mass spectrometry. Here, we report an adaptation of the high-field asymmetric ion mobility spectrometry (FAIMS) coupled to mass spectrometry, and the establishment of a simple one step sample preparation coupled with gas-phase fractionation. FAIMS approach substantially reduces manual sample handling, significantly shortens MS instrument processing time, and produces unique protein identification and quantification approximating the commonly used IN-Seq method in for less time requirement.
Annexin A6 mediates calcium-dependent secretion of exosomes
Authors: Williams Justin Krish , Ngo Jordan Matthew , Schekman Randy
Published: December 2022

Exosomes are a subtype of extracellular vesicles (EV) that are secreted upon fusion of multivesicular bodies (MVBs) with the plasma membrane. In order to identify proteins responsible for this fusion event, we developed sensitive cellular and cell-free assays to measure exosome secretion. Our results suggest that exosome secretion is coupled to Ca2+-dependent plasma membrane repair. Using a targeted proteomics approach, we identify annexin A6 (ANXA6), a well-known plasma membrane repair protein, as a MVB binding protein and demonstrate that it is required for Ca2+-dependent exosome secretion both in intact and in permeabilized cells. Our results suggest that cells employ MVBs as a membrane source for plasma membrane lesion repair during physiological mechanical stress or treatment with a bacterial pore-forming toxin, and that this repair process results in the coincident secretion of exosomes. We propose that this unconventional secretion process may contribute significantly to the heterogeneity of EVs in biological fluids.
Sex and age specific effects on the development of addiction and compulsive-like drinking in rats
Authors: Foo Jerome C. , Skorodumov Ivan , Spanagel Rainer , Meinhardt Marcus W.
Published: December 2022

Biological factors are known to influence disease trajectories and treatment effectiveness in alcohol addiction. One important biological factor influencing disease dynamics in alcohol use disorder is sex, as preclinical and clinical evidence suggests that gender influences disease trajectories in subjects with alcohol use disorder. Another critical factor is age at first intoxicating drink, which has been identified as a risk factor for later alcohol binging. Preclinical research allows prospective monitoring of rodents throughout the lifespan, providing very detailed information that cannot be acquired in humans. Lifetime monitoring in rodents can be conducted under highly controlled conditions, during which one can systematically introduce multiple biological and environmental factors that impact behaviors of interest.

Here, we used the alcohol deprivation effect (ADE) rat model of alcohol addiction in a computerized drinkometer system to study disease dynamics and transition points of addictive behavior in cohorts of adolescent vs. adult as well as male vs. female rats in direct comparison. Early age of onset of drinking (postnatal day 40) in male rats had surprisingly little impact on the development of drinking behavior and compulsivity (quinine taste adulteration) when compared to rats that started drinking during early adulthood (postnatal day 72). However, female rats showed a stronger resistance to quinine taste adulteration after a history of ADEs, indicative of more pronounced compulsive behavior in females as compared to male rats. Specifically, female rats exhibit during quinine taste adulteration a higher frequency of drinking events and a larger access size, especially from the 20% alcohol solution, resulting in fast intoxication despite taste aversion in a relapse-like situation. Our results suggest that drinking patterns, and specifically solution preference as well as access size, provide a valuable indication into determining compulsive drinking. These findings provide a better understanding of sex and age factors involved in the development of drinking behavior that are important in preclinical development of models of addiction, drug development and exploration options for new treatments.
MOPD I patient-derived cerebral organoids model microcephaly showing premature neurogenesis due to disrupted mitotic spindle orientation
Authors: Singh Jagjit , Daniels Noah J. , Pirozzi Filomena , Wynshaw-Boris Anthony , Lopez-Gonzalez Rodrigo , Padgett Richard A.
Published: December 2022

Mutations in the single-copy RNU4ATAC gene, which encodes U4atac snRNA of the minor spliceosome are linked to the developmental disorder microcephalic osteodysplastic primordial dwarfism type I (MOPD I). Partial loss-of-function mutations of U4atac snRNA lead to a poor prognosis, with less than three year survival. The most prominent characteristic of MOPD I is disrupted central nervous system development resulting in severe microcephaly and lissencephaly.

In this study, we used self-organizing 3D cerebral organoids from patient-derived induced pluripotent stem cells (iPSCs) to investigate defective cellular events that disturb the laminar organization of the cortex and influence brain topology. We analyzed organoids from iPSCs homozygous for the partial loss-of-function U4atac snRNA 51G>A mutation and compared them to isogenic organoids obtained from iPSCs expressing wild-type U4atac snRNA, using immunostaining and 10X Genomics single-cell RNA sequencing. In our MOPD I organoids, we observed: a) reduced proliferation accompanied by premature neurogenesis depleting the neuro-progenitor pool due to an increased frequency of horizontal cell divisions in the ventricular zone; b) reduced numbers of intermediate progenitor and outer radial glial cells in the outer sub-ventricular zone; and c) defective radial neuronal migration, which is critical for cortical expansion in humans. Our findings therefore provide insight into MOPD I cellular pathogenesis and underline the value of these cerebral organoids as model systems for human neurodevelopmental disorders.
Ketamine modulates a norepinephrine-astroglial circuit to persistently suppress futility-induced passivity
Authors: Duque Marc , Chen Alex B. , Hsu Eric , Narayan Sujatha , Rymbek Altyn , Begum Shahinoor , Saher Gesine , Cohen Adam Ezra , Olson David E. , Prober David A , Bergles Dwight E , Fishman Mark C , Engert Florian , Ahrens Misha B
Published: December 2022

Mood-altering compounds hold promise for the treatment of many psychiatric disorders, such as depression, but connecting their molecular, circuit, and behavioral effects has been challenging. Here we find that, analogous to effects in rodent learned helplessness models, ketamine pre-exposure persistently suppresses futility-induced passivity in larval zebrafish. While antidepressants are thought to primarily act on neurons, brain-wide imaging in behaving zebrafish showed that ketamine elevates intracellular calcium in astroglia for many minutes, followed by persistent calcium downregulation post-washout. Calcium elevation depends on astroglial α1-adrenergic receptors and is required for suppression of passivity. Chemo-/optogenetic perturbations of noradrenergic neurons and astroglia demonstrate that the aftereffects of glial calcium elevation are sufficient to suppress passivity by inhibiting neuronal-astroglial integration of behavioral futility. Imaging in mouse cortex reveals that ketamine elevates astroglial calcium through conserved pathways, suggesting that ketamine exerts its behavioral effects by persistently modulating evolutionarily ancient neuromodulatory systems spanning neurons and astroglia.
Systematic mapping of neural signals in the periphery reveals a rich and specific alphabet for immune cell communication
Authors: Berman Karen Regev , Milman Neta , Segev Meital , Stratovsky Elina , Shen-Orr Shai S.
Published: December 2022

Accumulating evidence indicate a strong link between neural signals and the immune system. Given neural signals constitute a large family that may be leveraged for communication, we systematically explored the neuro-immune regulation network in the periphery and uncovered a broad yet lineage selective expression of neuro-receptors on immune cells. We constructed a rich social immune network map showing the neural molecular pathways supporting the regulation of the immune system at steady state. Our results emphasize neuro-receptors role in the commitment and differentiation of B and T cells along their developmental process. We identified the immune cells’ functionality in the specific tissue is extensively shaped by the communication with the microenvironment and nervous systems via a rich alphabet of neural mediators. Collectively, our findings suggest neural genes are an integral part of the immune regulatory system and provide clear testable new avenues of experimental follow up for neuroimmunologists and immunologists alike.

Abstract Figure

Highlights

160 neural genes potentially active in immune cells in the periphery with high specificity to lineage

Neuro-receptors co-expressed in immune lineages are enriched for biological functions

Changes in neuro-receptors expression influence the HCS differentiation and commitment

Immune-microenvironment neural signaling architecture reflects tissue biological role
A high-throughput machine vision-based univariate scale for pain and analgesia in mice
Authors: Sabnis Gautam S. , Hession Leinani E. , Kim Kyungin , Beierle Jacob A. , Kumar Vivek
Published: December 2022

1

Treatment of acute and chronic pain represent a widespread clinical challenge with poor therapeutic options. While rodents are an invaluable model to study pain, scoring nociceptive responses in clinically relevant paradigms and at high-throughput remains an unmet challenge. Therefore, there is a need for automated, high-throughput methods that sensitively and accurately assess pain and analgesia. Such objective and scalable technologies will enable the discovery of novel analgesics and yield mechanistic insights into the neural and genetic mechanisms of pain. Here, we adopt the open field arena to build a univariate scale for the formalin injection model of inflammatory pain by using a machine learning approach that incorporates 82 behavioral features. This tool outperforms traditional measures of licking and shaking in detection of formalin dose, and was validated using 4 diverse mouse strains. We also detected previously unreported differences in formalin induced nocifensive behaviors that were strain and sex specific. This model also reliably identifies morphine induced antinociception. This novel, sensitive, and inexpensive tool provides a method for quantifying voluntary nociceptive responses to facilitate genetic mapping and analgesic compound screening in a high throughput manner.
Sparse and stereotyped encoding implicates a core glomerulus for ant alarm behavior
Authors: Hart Taylor , Frank Dominic , Lopes Lindsey E. , Olivos-Cisneros Leonora , Lacy Kip D. , Trible Waring , Ritger Amelia , Valdés-Rodríguez Stephany , Kronauer Daniel J. C.
Published: December 2022

Ants communicate via large arrays of pheromones and possess expanded, highly complex olfactory systems, with antennal lobes in the brain comprising ~500 glomeruli. This expansion implies that odors could activate hundreds of glomeruli, which would pose challenges for higher order processing. To study this problem, we generated the first transgenic ants, expressing the genetically encoded calcium indicator GCaMP6s in olfactory sensory neurons. Using two-photon imaging, we mapped complete glomerular responses to four ant alarm pheromones. Alarm pheromones robustly activated ≤6 glomeruli, and activity maps for the three pheromones inducing panic-alarm in our study species converged on a single glomerulus. These results demonstrate that, rather than using broadly tuned combinatorial encoding, ants employ precise, narrowly tuned, and stereotyped representation of alarm pheromone cues. The identification of a central sensory hub glomerulus for alarm behavior suggests that a simple neural architecture is sufficient to translate pheromone perception into behavioral outputs.
Electrophysiological Activity of Primary Cortical Neuron-Glia Mixed Cultures
Authors: Goshi Noah , Kim Hyehyun , Girardi Gregory , Gardner Alexander , Seker Erkin
Published: December 2022

Background

We have previously described a tri-culture of neurons, astrocytes, and microglia that accurately mimics thein vivoneuroinflammatory response (both neurotoxic and neuroprotective) to a wide range of neuroinflammatory stimuli. Electrophysiological activity is an essential measure of neuronal function, which is influenced by neuroinflammation. Microelectrode array (MEA) technology is a versatile tool to non-invasively studyin vitroneural networks by simultaneously recording electrophysiological activity from multiple sites. In this study, we used extracellular recordings to determine the effect of microglia on neural network formation and stability in primary cortical cultures and monitor the changes in neural activity in response to neuroinflammatory stimuli.

Methods

Primary neonatal rat cortical tri-cultures of neurons, astrocytes, and microglia or co-cultures of neurons and astrocytes were cultured on custom MEAs and the neural activity was monitored for 21 daysin vitroto assess culture maturation and network formation. Quantification of synaptic puncta and averaged spike waveforms were used to determine the difference in excitatory to inhibitory neuron ratio (E/I ratio) of the neurons in tri- and co-cultures. The electrophysiological response to lipopolysaccharide (LPS) treatment of both culture types were compared.

Results

The tri- and co-culture showed minimal difference in electrophysiological markers of neural network formation and stability with the exception of a significant increase in spike frequency in the tri-culture at later timepoints (DIV 17 and 21). Additionally, there was no significant difference in the density of either post-synaptic or excitatory pre-synaptic puncta between the culture types. However, characterization of the average spike waveforms revealed that the tri-culture had an E/I ratio much closer to that found in the rat cortex. Finally, only the tri-culture displayed a significant decrease in both the number of active channels and spike frequency following LPS exposure.

Conclusions

This study demonstrates that the microglia in the tri-culture do not disrupt neural network formation and stability as quantified using extracellular recordings and may be a better representation of thein vivocortex due to the closer E/I ratio than more traditional isolated neuron and neuron-astrocyte co-cultures. Additionally, the tri-culture is better able to mimic the neuroinflammatory response to LPS, which was quantified via changes in neural electrophysiological activity.
The Role of Polyglutamine in Inter- and Intra-molecular Interactions in Med15-dependent Regulation
Authors: Cooper David G. , Fassler Jan S.
Published: December 2022

Med15 is a general transcriptional regulator and member of the tail module of the RNA Pol II Mediator complex. TheS. cerevisiaeMed15 protein has a well-structured N-terminal KIX domain, three Activator Binding Domains (ABDs) and several naturally variable polyglutamine (poly-Q) tracts (Q1, Q2, Q3) embedded in an intrinsically disordered central region, and a C-terminal Mediator Association Domain (MAD). We investigated how the presence of ABDs and changes in length and composition of poly-Q tracts influences Med15 activity and function using phenotypic, gene expression, and transcription factor interaction assays of truncation, deletion, and synthetic alleles. We found that individual Med15 activities were influenced by the number of activator binding domains (ABDs) and adjacent polyglutamine composition. We also observed that distant glutamine tracts and Med15 phosphorylation affected the activities of the KIX domain, suggesting that intramolecular interactions may be required for KIX domain interactions with transcription factors. We conclude that robust Med15 activity required at least the Q1 tract and that the length of that tract modulates activity in a context-dependent manner. We speculate that the glutamine tract provides a degree of intramolecular flexibility that is needed for Med15 function. Finally, we found that loss of Msn2-dependent transcriptional activation in Med15 Q1 tract variants correlates well with a reduction in Msn2:Med15 interaction strength.
The deubiquitinase Ubp3/Usp10 constrains glucose-mediated mitochondrial repression via phosphate budgeting
Authors: Vengayil Vineeth , Niphadkar Shreyas , Adhikary Swagata , Varahan Sriram , Laxman Sunil
Published: December 2022

Many cells in high glucose repress mitochondrial respiration, as observed in the Crabtree and Warburg effects. Our understanding of biochemical constraints for mitochondrial activation is limited. Using aSaccharomyces cerevisiaescreen, we identified the conserved deubiquitinase Ubp3 (Usp10), as necessary for mitochondrial repression. Ubp3 mutants have increased mitochondrial activity despite abundant glucose, along with decreased glycolytic enzymes, and a rewired glucose metabolic network with increased trehalose production. UtilizingΔubp3cells, along with orthogonal approaches, we establish that the high glycolytic flux in glucose continuously consumes free Pi. This restricts mitochondrial access to inorganic phosphate (Pi), and prevents mitochondrial activation. Contrastingly, rewired glucose metabolism with enhanced trehalose production and reduced GAPDH (as inΔubp3cells) restores Pi. This collectively results in increased mitochondrial Pi and derepression, while restricting mitochondrial Pi transport prevents activation. We therefore suggest that glycolytic-flux dependent intracellular Pi budgeting is a key constraint for mitochondrial repression.
Order and disorder in the evolution of online knowledge community: an investigation of the chaotic behavior in social tagging systems with evidence of stack overflow
Authors: Shi Yanqing , Cao Hongye , Chen Si
Published: December 2022

Purpose

Online question-and-answer (Q&A) communities serve as important channels for knowledge diffusion. The purpose of this study is to investigate the dynamic development process of online knowledge systems and explore the final or progressive state of system development. By measuring the nonlinear characteristics of knowledge systems from the perspective of complexity science, the authors aim to enrich the perspective and method of the research on the dynamics of knowledge systems, and to deeply understand the behavior rules of knowledge systems.

Design/methodology/approach

The authors collected data from the programming-related Q&A site Stack Overflow for a ten-year period (2008–2017) and included 48,373 tags in the analyses. The number of tags is taken as the time series, the correlation dimension and the maximum Lyapunov index are used to examine the chaos of the system and the Volterra series multistep forecast method is used to predict the system state.

Findings

There are strange attractors in the system, the whole system is complex but bounded and its evolution is bound to approach a relatively stable range. Empirical analyses indicate that chaos exists in the process of knowledge sharing in this social labeling system, and the period of change over time is about one week.

Originality/value

This study contributes to revealing the evolutionary cycle of knowledge stock in online knowledge systems and further indicates how this dynamic evolution can help in the setting of platform mechanics and resource inputs.
The mediating role of social dynamics in the influence of absorptive capacity and tacit knowledge sharing on project performance
Authors: Boamah Fredrick Ahenkora , Zhang Jianhua , Shehzad Muhammad Usman , Ahmad Mubashir
Published: December 2022

Purpose

This research aims to establish a comprehensive approach that integrates the aspects to describe how knowledge is focused, developed, reassigned, and implemented to increase project effectiveness. This study examines the interaction of social factors that influences tacit knowledge sharing, absorptive capacity, and project site performance.

Design/methodology/approach

The data were collected from Chinese project-based organizations and examined using structural equation modeling (SEM) to test the model and evaluate the hypothesis.

Findings

The findings reveal that good knowledge governance and tacit knowledge sharing are essential prerequisites to boost the project’s absorptive capability. Furthermore, social dynamics favorably modify the link between absorptive capacity, tacit knowledge sharing, and project results. The findings are supportive of the proposed model in general.

Originality/value

This research addresses the critical issue of project knowledge management systems and presents a comprehensive framework that broadens the technical and interpretative bounds of current models designed to achieve project success.
Regression trees for hospitality data analysis
Authors: Tsionas Mike , Assaf A. George
Published: December 2022

Purpose

The purpose of this note is to describe the concept of regression trees (RTs) for hospitality data analysis.

Design/methodology/approach

RT is an effective non-parametric predicting modelling approach that would free researchers from the need to force a certain functional form. The method does not require normalization or scaling of data.

Findings

The authors illustrate how RTs can be used to find a model that would result in the best prediction.

Research limitations/implications

A common challenge facing hospitality researchers is to estimate a regression model with the correct specification. RTs can help researchers identify the best explanatory model for prediction.

Originality/value

This paper describes the concept of RTs for the modelling of hospitality data.
Magnetohydrodynamic hybrid nanofluid flow over a decelerating rotating disk with Soret and Dufour effects
Authors: Vijay Neha , Sharma Kushal
Published: December 2022

Purpose

The investigation of fluid flow over a rotating disk has been increasing due to the spread of machine technology. Because of this development, we scrutinized the Magnetohydrodynamic (MHD) flow of hybrid nanofluid caused by a decelerating rotating disk with Ohmic heating, Soret and Dufour effects. The disk's angular velocity is taken to be an inversely time-dependent linear function. Moreover, the temperature-dependent viscosity of hybrid nanofluid is incorporated in the present investigation. Methanol is considered as base fluid, while copper oxide (CuO) and magnesium oxide (MgO) are nanoparticles.

Design/methodology/approach

Estimated fundamental partial differential equations of flow problems are altered as a dimensionless system of ordinary differential equations using appropriate similarity transformation and solved using a numerical technique: BVP Midrich scheme in Maple software. The impression of emerging non-dimensional parameters is portrayed graphically. All outcomes are shown in the velocity, temperature and concentration profiles.

Findings

The developed flow problem involves a non-dimensional parameter (A) that reveals the deceleration of the disk. For larger values of A, the disk decelerates faster and for some fixed time, the fluid surrounding the disk revolves more rapidly than the disk itself. The radial velocity of fluid diminishes and axial velocity becomes uniform when the disk is subjected to wall suction velocity (B).

Originality/value

This analysis is significant in biomedical engineering, cancer therapeutic, manufacturing industries and nano-drug suspension in pharmaceuticals. The novelty of the current study is the hybrid nanofluid flow with Ohmic heating, Soret and Dufour effects on a decelerating rotating disk. To the best of the author's knowledge, no such consideration has been published in the literature.
Challenges and opportunities in IT transformation of public service delivery: case of India Post
Authors: Sinha Shekhar Kumar , Mukhopadhyay Sandip , Upadhyay Parijat , Dwivedi Yogesh K. , Bhattacharyya Subhajit , Paul Manas , Bhattacharyy Amrita K.
Published: December 2022

Purpose

Legacy organizations, particularly government departments, have always remained focused on technology acquisition at a low cost. However, they must balance their quest for better financial performance with a commitment to social obligations and inclusiveness. This study aims to analyze the issues faced by a public sector department, India Post, in its digitization process.

Design/methodology/approach

This study takes a case-based approach to analyze India Post’s digitization journey through the theoretical prism of the technology, organization and environment framework.

Findings

The organization’s ability to benefit from innovative technology is constrained by its outdated structure and business processes. The other constraints include the limited technological know-how within the organization and the lack of intricate organizational process knowledge of today’s vendors.

Practical implications

This study portends important implications for policymakers and provides a base for several inquiries for future research. This study attempted to identify the facilitators and inhibitors of digitization initiatives of a legacy government organization with extensive outreach in rural economy which policymakers can consider while rolling out digitization initiatives for public sector organizations.

Originality/value

There are very few studies available as published literature which examined the digitization journey of a legacy government organization in a developing economy. To the best of the authors’ knowledge, there was no published literature available on India Post’s digital transformation process.
An integrated QFD and fuzzy TOPSIS approach for supplier evaluation and selection
Authors: Sharma Jitendra , Tripathy Bibhuti Bhusan
Published: December 2022

Purpose

Supplier evaluation and selection is an essential (multi-criteria decision-making) MCDM process that considers qualitative and quantitative factors. This research work attempts to use a MCDM technique based on merging fuzzy Technique for Order Preference by Similarity to Ideal Solution (F-TOPSIS) and Quality Function Deployment (QFD) ideas. The study attempts to find the supplier's attributes (HOWs) to accomplish its goals after determining the product's characteristics to suit the company's needs (WHATs).

Design/methodology/approach

The proposed research methodology comprises the following four steps: Step 1: Determine the product purchase requirements (“WHATs”) and those pertinent to supplier evaluation (“HOWs”). In Step 2, the relative importance of the “WHAT-HOW” correlation scores is determined and also the resulting weights of “HOWs”. In Step 3, linguistic evaluations of possible suppliers in comparison to subjective criteria are given to the decision-makers. Step 4 combines the QFD and F-TOPSIS techniques to select suppliers.

Findings

A fuzzy MCDM method based on fusing and integrating fuzzy information and QFD is presented to solve the drawbacks of conventional decision-making strategies used in supplier selection. Using the F-TOPSIS method, fuzzy positive ideal solution (FPIS) and fuzzy negative ideal solution (FNIS), the relative closeness coefficient values for all alternatives are computed. The suppliers are ranked by relating the closeness of coefficient values. This method permits the combination of ambiguous and subjective data expressed as fuzzy-defined integers or linguistic variables.

Originality/value

QFD and TOPSIS, two widely used approaches, are combined in this article to rank and evaluate suppliers based on the traits that the suppliers choose to prioritize. This study demonstrates that the method employed could address multiple-criteria decision-making scenarios in a computationally efficient manner. The effectiveness and applicability of the method are illustrated using an example.