bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxytocin via oxytocin receptor excites neurons in the endopiriform nucleus of juvenile mice
Authors: Biggs Lindsey M. , Hammock Elizabeth A.D.
Published: March 2022

The neuropeptide oxytocin (OXT) modulates social behaviors across species and may play a developmental role for these behaviors and their mediating neural pathways. Despite having high, stable levels of OXT receptor (OXTR) ligand binding from birth, endopiriform nucleus (EPN) remains understudied. EPN integrates olfactory and gustatory input and has bilateral connections with several limbic areas. Because the role of OXTR signaling in EPN is unknown, we sought to provide anatomical and electrophysiological information about OXTR signaling in mouse EPN neurons. Using in situ hybridization, we found that most EPN neurons co-express Oxtr mRNA and the marker for VGLUT1 and are thus glutamatergic cells. Based on high levels of OXTR ligand binding in EPN, we hypothesized that oxytocin application would modulate activity in these cells as measured by whole-cell patch-clamp electrophysiology. Bath application of OXT and an OXTR specific ligand (TGOT) increased the excitability of EPN neurons in wild-type, but not in OXTR-knockout tissue. These results show an effect of OXT on a presumably glutamatergic cell population within EPN. Given the robust, relatively stable OXTR expression in EPN throughout life, OXTR in this multi-sensory and limbic integration area may be important for modulating activity in response to an array of social or other salient stimuli throughout the lifespan and warrants further study.

Significance statement

There is a high level of oxytocin receptor (OXTR) expression in the mouse endopiriform nucleus (EPN) throughout development, however little is known about the effect of oxytocin on these neurons. We show here that Oxtr mRNA co-expresses mainly with VGLUT1, a glutamatergic cell marker. Using OXTR-EGFP mice to identify EPN, we show that OXT has a mainly excitatory effect on EPN neurons. Thus, activity in EPN neurons may be modulated by OXT during exposure to salient or social stimuli throughout development and this could affect development of behavioral responses during social exposure.
Machine Learning–Informed Predictions of Nanoparticle Mobility and Fate in the Mucus Barrier
Authors: Kaler Logan , Joyner Katherine , Duncan Gregg A.
Published: March 2022

Diffusion and transport of nanomaterials through mucus, is of critical importance to many basic and applied areas of research such as drug delivery and infectious disease. However, it is often challenging to interpret the dynamics of nanoparticles within the mucus gel due to its inherently heterogeneous microstructure and biochemistry. In this study, we measured the diffusion of densely PEGylated nanoparticles (NP) in human airway mucusex vivousing multiple particle tracking and utilized machine learning to classify NP movement as either traditional Brownian motion (BM) or one of two different models of anomalous diffusion, fractional Brownian motion (FBM) and continuous time random walk (CTRW). Specifically, we employed a physics-based neural network model to predict the modes of diffusion experienced by individual NP in human airway mucus. We observed rapidly diffusing NP primarily exhibit BM whereas CTRW and FBM exhibited lower diffusion rates. Given the use of muco-inert nanoparticles, the observed transition from diffusive (BM) to sub-diffusive (CTRW/FBM) motion is likely a result of patient-to-patient variation in mucus network pore size. Using mathematic models that account for the mode of NP diffusion, we predicted the percentage of nanoparticles that would cross the mucus barrier over time in human airway mucus with varied total solids concentration. We also applied this approach to explore the transport modes and predicted fate of influenza A virus within human mucus. These results provide new tools to evaluate the extent of synthetic and viral nanoparticle penetration through mucus in the lung and other tissues.
Biological constraints on stereotaxic targeting of functionally-defined cortical areas
Authors: Narayanan Divya P , Tsukano Hiroaki , Kline Amber M , Onodera Koun , Kato Hiroyuki K
Published: March 2022

Understanding computational principles in hierarchically organized sensory systems requires functional parcellation of brain structures and their precise targeting for manipulations. Although brain atlases are widely used to infer area locations in the mouse neocortex, it has been unclear whether stereotaxic coordinates based on standardized brain morphology accurately represent functional domains in individual animals. Here, we used intrinsic signal imaging to evaluate the accuracy of area delineation in the atlas by mapping functionally-identified auditory cortices onto bregma-based stereotaxic coordinates. We found that auditory cortices in the brain atlas correlated poorly with the true complexity of functional area boundaries. Inter-animal variability in functional area locations predicted surprisingly high error rates in stereotaxic targeting with atlas coordinates. This variability was not simply attributed to brain sizes or suture irregularities but instead reflected differences in cortical geography across animals. Our data thus indicate that functional mapping in individual animals is essential for dissecting cortical area-specific roles with high precision.
Ultrasensitive Dopamine Detection with Graphene Aptasensor Multitransistor Arrays
Authors: Abrantes Mafalda , Rodrigues Diana , Domingues Telma , Nemala Siva S. , Monteiro Patricia , Borme Jérôme , Alpuim Pedro , Jacinto Luis
Published: March 2022

Dopamine is a neurotransmitter with critical roles in the human brain and body, and abnormal dopamine levels underlie brain disorders such as Parkinson’s Disease, Alzheimer’s Disease, and substance addiction. Herein, we present a novel high-throughput biosensor based on graphene multitransistor arrays (gMTAs) functionalized with a selective aptamer for robust ultrasensitive dopamine detection. The miniaturized biosensor integrates multiple electrolyte-gated graphene field-effect transistors (EG-gFETs) in an array configuration, fabricated by high-yield reproducible and scalable methodologies optimized at the wafer level. With these gMTA aptasensors, we reliably detected ultra-low dopamine concentrations in physiological buffers, including undiluted phosphate-buffered saline (PBS), artificial cerebral spinal fluid (aCSF), and high ionic strength complex biological samples. We report a record limit-of-detection (LOD) of 1 aM (10−18) for dopamine in both PBS, and dopamine-depleted brain homogenate samples spiked with dopamine. The gMTAs also display wide sensing ranges across all media, up to 100 μM (10−8), with a 22 mV/decade peak sensitivity in aCSF. Furthermore, we show that the gMTAs can detect minimal changes in dopamine concentrations in small working volume biological CSF samples obtained from a mouse model of Parkinson’s Disease.
SARS-CoV-2 remodels the Golgi apparatus to facilitate viral assembly and secretion
Authors: Zhang Jianchao , Kennedy Andrew , de Melo Jorge Daniel Macedo , Xing Lijuan , Reid Whitney , Bui Sarah , Joppich Joseph , Rose Molly , Ercan Sevval , Tang Qiyi , Tai Andrew W. , Wang Yanzhuang
Published: March 2022

The COVID-19 pandemic is caused by SARS-CoV-2, an enveloped RNA virus. Despite extensive investigation, the molecular mechanisms for its assembly and secretion remain largely elusive. Here, we show that SARS-CoV-2 infection induces global alterations of the host endomembrane system, including dramatic Golgi fragmentation. SARS-CoV-2 virions are enriched in the fragmented Golgi. Disrupting Golgi function with small molecules strongly inhibits viral infection. Significantly, SARS-CoV-2 infection down-regulates GRASP55 but up-regulates TGN46 protein levels. Surprisingly, GRASP55 expression reduces both viral secretion and spike number on each virion, while GRASP55 depletion displays opposite effects. In contrast, TGN46 depletion only inhibits viral secretion without affecting spike incorporation into virions. TGN46 depletion and GRASP55 expression additively inhibit viral secretion, indicating that they act at different stages. Taken together, we show that SARS-CoV-2 alters Golgi structure and function to control viral assembly and secretion, highlighting the Golgi as a potential therapeutic target for blocking SARS-CoV-2 infection.
Identification and evolutionary analysis of a Triticeae tribe specific novel non-autonomous DNA transposon in DREB related Dehydration Responsive Factor1 gene
Authors: Thiyagarajan K , Latini A , Cantale C , Porceddu E , Galeffi P
Published: March 2022

A non-autonomous DNA transposon was identified in the DRF1 gene, belonging to the DREB gene family, the presence of this element was initially assessed in the Triticum durum DRF1 gene and subsequently it was also identified in Aegilops speltoides and Triticum urartu DRF1 genes. The DRF1 gene consists of four exons and three introns, the transposon carrying core element is inserted between the first and the third introns. Our studies identified inverted repeats, target site duplications and the presence of many internal reverse and direct short tandem and long tandem repeats, that all represent signals of a transposable element. Based on transposon specific sequence and position of the terminal inverted repeats, a possible transposition mechanism was inferred. As the identified transposable element does not possess a sequence coding for a transposase enzyme, it represents a non-autonomous element. The transposon encompasses a core element with two small, transcribed regions (Exon 2 and Exon 3) that are combined by alternative splicing during gene expression and an intron (intron2). A possible role of this non-autonomous DNA transposon in the alternative splicing regulation was investigated by a genomics approach. Divergence time analysis supported the relatively recent evolution of this transposon in Triticeae comparing to other tribes and further there is no footprints or highly disrupted footprints sequence such as TIR, TSD in other earlier evolved Poaceae member species were observed, which revealed the novelty and well-preserved nature of these signals in Triticeae. While other monocots (apart from Poaceae) and dicots, including Arabidopsis thaliana, neither showed this transposon insertion and nor revealed the existence of alternative spliced gene transcripts. In Poaceae members the core element is well preserved with disturbed transposon and transposon signals, while the tribe Triticeae especially wheat, its progenitors have intact DRF1 transposon and its signals.
Cetacean “gas-bubble thromboembolic polycystic liver disease”: “Budd-Chiari like syndrome” in dolphins?
Authors: Fernandez Antonio , Jepson Paul D , Diaz-Delgado Josue , de Quiros Yara Bernaldo , Sierra Eva , Mompeo Blanca , Vela Ana Isabel , Di Guardo Giovanni , Suarez-Santana Cristian , de los Monteros Antonio Espinosa , Herraez Pedro , Andrada Marisa , Caballero Maria Jose , Rivero Miguel , Consoli Francesco , Castro Ayoze , Quesada Oscar , Arbelo Manuel
Published: March 2022

Nearly two decades ago, pathologic examination results suggested acoustic factors, such as mid-frequency active naval military sonar (MFAS) could be the cause of acute decompression-like sickness in stranded beaked whales. Acute systemic gas embolism in these beaked whales was published together with enigmatic cystic liver lesions (CLL), characterized by intrahepatic encapsulated gas-filled cysts, tentatively interpreted as “gas-bubble” lesions in various cetacean species. Here we provide a pathologic reinterpretation of CLL in cetaceans. From 1,200 cetaceans necropsied, CLL were only observed in striped dolphins (Stenella coeruleoalba), with a low prevalence (2%), and recapitulated pathologic features of Budd-Chiari syndrome in humans. Our results strongly suggest that CLL are the result of the combination of pre-existing or concomitant hepatic vascular disorder (e.g., severe hepatobiliary trematodiasis) superimposed and exacerbated by gas bubbles, and clearly differ from acute systemic gas embolism in stranded beaked whales linked to MFAS.
Bessel-droplet foci enable high-resolution and high-contrast volumetric imaging of synapses and circulation in the brainin vivo
Authors: Chen Wei , Zhang Qinrong , Natan Ryan , Fan Jianglan , Ji Na
Published: March 2022

Bessel beam has long been utilized in physics for its ability to maintain lateral confinement during propagation. When used for two-photon fluorescence microscopy, Bessel foci have enabled high-speed volumetric imaging of the brain. At high numeric aperture (NA), however, the substantial energy in the side rings of Bessel foci reduces image contrast. Therefore, a compromise between resolution and contrast has to be made, limiting Bessel foci in microscopy to low NA. Here, we describe a method of generating axially extended Bessel-droplet foci with much suppressed side rings. Shaping the excitation wavefront with novel phase patterns, we generated Bessel-droplet foci of variable NAs at high power throughput and scanned them interferometrically along the axial direction for continuous volume imaging. More resistant to optical aberrations than Bessel foci, Bessel-droplet foci enabled high-resolution and high-contrast volumetric imaging of synaptic anatomy and function as well as lymphatic circulation in the mouse brainin vivo.
Revealing cell populations catching the early stages of the human embryo development in naïve pluripotent stem cells
Authors: Moya-Jódar Marta , Ullate-Agote Asier , Barlabé Paula , Rodríguez-Madoz Juan Roberto , Abizanda Gloria , Barreda Carolina , Carvajal-Vergara Xonia , Vilas-Zornoza Amaia , Romero Juan Pablo , Garate Leire , Agirre Xabier , Coppiello Giulia , Prósper Felipe , Aranguren Xabier L.
Published: March 2022

Naïve human pluripotent stem cells (hPSCs) are defined as the in vitro counterpart of the human preimplantation embryo’s epiblast and are used as a model system to study developmental processes. In this study, we report the discovery and characterization of distinct cell populations coexisting with epiblast-like cells in 5iLAF naïve human induced PSCs (hiPSCs) cultures. Noteworthily these populations closely resemble different cell types of the human embryo at early developmental stages. While epiblast-like cells represented the main cell population, interestingly we detected a cell population with gene and transposable element expression profile closely resembling the totipotent 8-Cell (8C) stage human embryo, and three cell populations analogous to trophectoderm (TE) cells at different stages of their maturation process: transition, early and mature stage. Thus, 5iLAF naïve hiPSCs cultures provide an excellent opportunity to model the earliest events of human embryogenesis, from the 8C stage to the peri-implantation period.

Graphical abstract
Downregulation of the secreted protein with an altered thrombospondin repeat (SPATR) impacts the infectivity of malaria sporozoites
Authors: Costa David Mendes , Sá Mónica , Teixeira Ana Rafaela , Pérez-Cabezas Begoña , Golba Sylvain , Sefiane-Djemaoune Hélèna , Formaglio Pauline , Franke-Fayard Blandine , Janse Chris J. , Amino Rogerio , Tavares Joana
Published: March 2022

The identification of surface proteins of the sporozoite stage of malaria parasites important for sporozoite infectivity could aid in the improvement of the efficacy of vaccines targeting pre-erythrocytic stages. Thus, we set out to disclose the role of the secreted protein with an altered thrombospondin repeat (SPATR), which is highly expressed in sporozoites. Previous studies showed an essential function in blood stages, while no role was detected in sporozoites despite high expression. To achieve downregulation of expression in sporozoites while maintaining blood stage expression, a promoter swap approach was used to generate a mutant where the Plasmodium berghei spatr gene was placed under transcriptional control of the hado gene promoter. Downregulation of expression in oocysts and sporozoites resulted in formation of sporozoites with impaired motility, strongly reduced capacity to invade salivary glands, and decreased infectivity to mice. In conclusion, we revealed a new role for SPATR in sporozoite infectivity, highlighting the importance to use complementary methods in studies on sporozoite biology.
Masculinizer-induced dosage compensation is achieved by transcriptional downregulation of both copies of Z-linked genes in the silkworm, Bombyx mori
Authors: Tomihara Kenta , Kawamoto Munetaka , Suzuki Yutaka , Katsuma Susumu , Kiuchi Takashi
Published: March 2022

Dosage compensation balances the expression of sex-chromosome-linked genes with autosome-linked genes in the heterogametic sex. The silkworm (Bombyx mori), a lepidopteran model insect, uses the female heterogametic WZ sex determination system. In B. mori, a Z-linked gene, Masculinizer (Masc), is the primary determinant of maleness and dosage compensation. However, it remains unknown whether one of the two Z chromosomes is inactivated or both Z chromosomes are suppressed in B. mori males. Hence, we performed transcriptome analysis using hybrids between two B. mori strains and analyzed the allele-specific expression (ASE) to solve the problem. The ASE analysis revealed that the genes located on the maternal and paternal Z chromosomes are transcriptionally upregulated in Masc knocked down males. Also, our results revealed that two Z chromosomes are transcriptionally downregulated in B. mori males as observed in Caenorhabditis elegans.
Paired single-cell host profiling with multiplex-tagged bacterial mutants reveals intracellular virulence-immune networks
Authors: Heyman Ori , Yehezkel Dror , Blumberger Neta , Rosenberg Gili , Mattioli Camilla Ciolli , Solomon Aryeh , Hoffman Dotan , Ben-Moshe Noa Bossel , Avraham Roi
Published: March 2022

Encounters between host cells and intracellular bacterial pathogens lead to complex phenotypes that determine the outcome of infection. Single-cell RNA-sequencing (scRNA-seq) are increasingly used to study the host factors underlying diverse cellular phenotypes. But current approaches do not permit the simultaneous unbiased study of both host and bacterial factors during infection. Here, we developed scPAIR-seq, an approach to analyze both host and pathogen factors during infection by combining multiplex-tagged mutant bacterial library with scRNA-seq to identify mutant-specific changes in host transcriptomes. We applied scPAIR-seq to macrophages infected with a library of Salmonella Typhimurium secretion system effector mutants. We developed a pipeline to independently analyze redundancy between effectors and mutant-specific unique fingerprints, and mapped the global virulence network of each individual effector by its impact on host immune pathways. ScPAIR-seq is a powerful tool to untangle bacterial virulence strategies and their complex interplay with host defense strategies that drive infection outcome.
A comprehensive analysis of immune landscape of Indian triple negative breast cancer
Authors: Korlimarla Aruna , Hari PS , Prabhu Jyoti , Ragulan Chanthirika , Patil Yatish , Snijesh VP , Desai Krisha , Mathews Aju , Appachu Sandhya , Diwakar Ravi B. , Srinath BS , Cheang Maggie , Sadanandam Anguraj
Published: March 2022

Background

Triple-negative breast cancer (TNBC) is a heterogeneous disease with a significant clinical challenge. TNBC alarmingly comprises 25-30% of breast cancers in India compared with only 10-15% in the West. However, immunotherapy was approved for high-risk early-stage TNBCs in the West. Hence, a long-standing question is whether Indian TNBCs immunologically and clinically resemble Western TNBCs such that they respond similarly to immunotherapies. Here we sought to elucidate the immune landscape of Indian TNBCs for the first time, compare them to Western disease and associate them with clinical parameters, cellular types/signaling, and immunotherapy response.

Methods

We profiled 730 immune genes in 88 retrospective Indian TNBC samples using NanoString platform, clustered them into subtypes using a machine-learning approach, and compared them with Western TNBCs (n=422; public datasets). Subtype-specific gene signatures were identified, followed by clinicopathological, immune cell type, and pathway (multiomics) analyses. We also assessed responses to (cross-cancer) immunotherapy. Tumor-infiltrating lymphocytes (TILs) and pan-macrophage marker were evaluated using hematoxilin-eosin staining and immunohistochemistry, respectively.

Results

We identified three robust and similarly distributed TNBC immune transcriptome subtypes (Subtypes-1-3) in Indian women, and they are represented correspondingly in Western TNBCs and associated with well-known TNBC subtypes. Irrespective of the ethnicity, Subtype-1 harbored tumor microenvironmental and anti-tumor immune events associated with smaller tumors, younger age, and a better prognosis. Subtype-1 mainly represented basal-like/claudin-low breast cancer and immunomodulatory TNBC subtypes. Subtype-1 showed an increase in a cascade of events, including damage-associated molecular patterns, acute inflammation, Th1 responses, T-cell receptor-related and chemokine-specific signaling, antigen presentation, and viral-mimicry pathways. Subtype-1 was significantly (p<0.05) associated with pre-menopausal women, dense TILs and responses and/or improved prognosis to anti-PD-L1 and MAGEA3 immunotherapies. Subtype-2 was enriched for Th2/Th17 responses, CD4+ regulatory cells, basal-like/mesenchymal subtypes, and an intermediate prognosis. Subtype-3 patients expressed innate immune genes/proteins, including those representing macrophages and neutrophils, and had poor survival.

Conclusion

We identified three immune-specific TNBC subtypes in Indian patients with differential clinical and immune behaviors, which largely overlapped with the Western TNBC cohorts. This study suggests cancer immunotherapy in TNBC may work similarly in both populations. Hence, this may expedite pharmaceutical adoption of immunotherapy to Indian TNBC patients.
A Genomically and Clinically Annotated Patient Derived Xenograft (PDX) Resource for Preclinical Research in Non-Small Cell Lung Cancer
Authors: Woo Xing Yi , Srivastava Anuj , Mack Philip C. , Graber Joel H. , Sanderson Brian J. , Lloyd Michael W. , Chen Mandy , Domanskyi Sergii , Gandour-Edwards Regina , Tsai Rebekah A. , Keck James , Cheng Mingshan , Bundy Margaret , Jocoy Emily L. , Riess Jonathan W. , Holland William , Grubb Stephen C. , Peterson James G. , Stafford Grace A. , Paisie Carolyn , Neuhauser Steven B. , Karuturi R. Krishna Murthy , George Joshy , Simons Allen K. , Chavaree Margaret , Tepper Clifford G. , Goodwin Neal , Airhart Susan D. , Lara Primo N. , Openshaw Thomas H. , Liu Edison T. , Gandara David R. , Bult Carol J.
Published: March 2022

Patient-derived xenograft models (PDXs) are an effective preclinical in vivo platform for testing the efficacy of novel drug and drug combinations for cancer therapeutics. Here we describe a repository of 79 genomically and clinically annotated lung cancer PDXs available from The Jackson Laboratory that have been extensively characterized for histopathological features, mutational profiles, gene expression, and copy number aberrations. Most of the PDXs are models of non-small cell lung cancer (NSCLC), including 37 lung adenocarcinoma (LUAD) and 33 lung squamous cell carcinoma (LUSC) models. Other lung cancer models in the repository include four small cell carcinomas, two large cell neuroendocrine carcinomas, two adenosquamous carcinomas, and one pleomorphic carcinoma. Models with both de novo and acquired resistance to targeted therapies with tyrosine kinase inhibitors are available in the collection. The genomic profiles of the LUAD and LUSC PDX models are consistent with those observed in patient tumors of the same tumor type from The Cancer Genome Atlas (TCGA) and to previously characterized gene expression-based molecular subtypes. Clinically relevant mutations identified in the original patient tumors were confirmed in engrafted tumors. Treatment studies performed for a subset of the models recapitulated the responses expected based on the observed genomic profiles.

Significance

The collection of lung cancer Patient Derived Xenograft (PDX) models maintained at The Jackson Laboratory retain both the histologic features and treatment-relevant genomic alterations observed in the originating patient tumors and show expected responses to treatment with standard-of-care agents. The models serve as a valuable preclinical platform for translational cancer research. Information and data for the models are freely available from the Mouse Models of Human Cancer database (MMHCdb, http://tumor.informatics.jax.org/mtbwi/pdxSearch.do).
Low expression of EXOSC2 protects against clinical COVID-19 and impedes SARS-CoV-2 replication
Authors: Moll Tobias , Odon Valerie , Harvey Calum , Collins Mark O , Peden Andrew , Franklin John , Graves Emily , Marshall Jack N.G. , Santos Souza Cleide dos , Zhang Sai , Azzouz Mimoun , Gordon David , Krogan Nevan , Ferraiuolo Laura , Snyder Michael P , Shaw Pamela J , Rehwinkel Jan , Cooper-Knock Johnathan
Published: March 2022

New therapeutic targets are a valuable resource in the struggle to reduce the morbidity and mortality associated with the COVID-19 pandemic, caused by the SARS-CoV-2 virus. Genome-wide association studies (GWAS) have identified risk loci, but some loci are associated with co-morbidities and are not specific to host-virus interactions. Here, we identify and experimentally validate a link between reduced expression of EXOSC2 and reduced SARS-CoV-2 replication. EXOSC2 was one of 332 host proteins examined, all of which interact directly with SARS-CoV-2 proteins; EXOSC2 interacts with Nsp8 which forms part of the viral RNA polymerase. Lung-specific eQTLs were identified from GTEx (v7) for each of the 332 host proteins. Aggregating COVID-19 GWAS statistics for gene-specific eQTLs revealed an association between increased expression of EXOSC2 and higher risk of clinical COVID-19 which survived stringent multiple testing correction. EXOSC2 is a component of the RNA exosome and indeed, LC-MS/MS analysis of protein pulldowns demonstrated an interaction between the SARS-CoV-2 RNA polymerase and the majority of human RNA exosome components. CRISPR/Cas9 introduction of nonsense mutations within EXOSC2 in Calu-3 cells reduced EXOSC2 protein expression, impeded SARS-CoV-2 replication and upregulated oligoadenylate synthase (OAS) genes, which have been linked to a successful immune response against SARS-CoV-2. Reduced EXOSC2 expression did not reduce cellular viability. OAS gene expression changes occurred independent of infection and in the absence of significant upregulation of other interferon-stimulated genes (ISGs). Targeted depletion or functional inhibition of EXOSC2 may be a safe and effective strategy to protect at-risk individuals against clinical COVID-19.
Dietary Lipid Oxidization Products Alter Growth, Adiposity and Gut Microbial Ecology in Prepubertal Porcine Model
Authors: Arowolo Folagbayi K. , Willis Kent A. , Karabayir Ibrahim , Akbiligic Oguz , Blaser Morgan , Booth Jeffrey , Pierre Joseph F. , Shanmuganayagam Dhanansayan
Published: March 2022

Elevated levels of dietary fats in westernized diets, associated with increased risk of obesity and other chronic diseases, are increasingly consumed by children in the United States. Cooking practices such as high heat frying and increased use of oxidizable sources of fats have introduced high levels of lipid oxidation products (LOPs) into these diets. The effects of these highly reactive dietary compounds on human biology are largely unstudied, especially in the gut where these compounds are likely present at higher concentrations. Given that the gut microbiome can be influenced by dietary components and then in turn have a systemic impact, we investigated the effects of consuming LOPs on gut bacterial and fungal communities and on growth and body composition during the prepubertal period in a porcine model. The presence of LOPs in the high fat diet reduced growth and body fat gain in the model. The gut microbiome was uniquely altered by both high fat and the presence of LOPs, with notable changes in the abundances ofTuricibacterales, Spriochaetales, RF39, Lactobacillales and Erysipelotrichales. The mycobiome was dominated byKazachstania, a porcine specific yeast, which was only minimally influenced by the dietary regimen. Application of machine learning identified dietary fat and LOPs as strong predictors of body fat. The genusMethanobrevibacterwas the key microbial predictor of body fat. This study highlights the need for further studies on the biological effects of LOPs which have become ubiquitous in human, livestock and pet diets in developed countries.
The neural code for ‘face cells’ is not face specific
Authors: Vinken Kasper , Prince Jacob S. , Konkle Talia , Livingstone Margaret
Published: March 2022

1

‘Face cells’ are visual neurons that respond more to faces than other objects. Clustered together in inferotemporal cortex, they are thought to carry out face processing specifically and are thus studied using faces almost exclusively. Analyzing neural responses in and around macaque face patches to hundreds of objects, we found graded response profiles for non-faces that were predictive of the degree of face selectivity and provided information on face-cell tuning that could not be characterized with actual faces. This relationship between non-face and face responses was not predicted by color and simple shape properties, but by information encoded in deep neural networks trained on general object classification rather than face identification. These findings contradict the long-standing assumption that face cells owe their category selectivity to face-specific features, instead providing evidence for the notion that category-selective neurons are best understood as tuning directions in an integrated, domain-general object space.
Individual stochasticity in the life history strategies of animals and plants
Authors: Varas-Enríquez Pablo José , van Daalen Silke , Caswell Hal
Published: March 2022

The life histories of organisms are expressed as rates of development, reproduction, and survival. However, individuals may experience differential outcomes for the same set of rates. Such individual stochasticity generates variance around familiar mean measures of life history traits, such as life expectancy and the reproductive number R0. By writing life cycles as Markov chains, we calculate variance and other indices of variability for longevity, lifetime reproductive output (LRO), age at offspring production, and age at maturity for 83 animal and 332 plant populations from the Comadre and Compadre matrix databases. We find that the magnitude within and variability between populations in variance indices in LRO, especially, are surprisingly high. We furthermore use principal components analysis to assess how the inclusion of variance indices affects life history constraints. We find that these indices, to a similar or greater degree than the mean, explain the variation in life history strategies among plants and animals.
PTEN is required for human Treg suppression of costimulation
Authors: Lam Avery J. , Haque Manjurul , Ward-Hartstonge Kirsten A. , Uday Prakruti , Wardell Christine M. , Gillies Jana K. , Speck Madeleine , Mojibian Majid , Geltink Ramon I. Klein , Levings Megan K.
Published: March 2022

Regulatory T cell (Treg) therapy is under clinical investigation for the treatment of transplant rejection, autoimmune disease, and graft-versus-host disease. With the advent of genome editing, attention has turned to reinforcing Treg function for therapeutic benefit. A hallmark of Tregs is dampened activation of PI3K-AKT signalling, of which PTEN is a major negative regulator. Loss-of-function studies of PTEN, however, have not conclusively shown a requirement for PTEN in upholding Treg function and stability. Using CRISPR-based genome editing in human Tregs, we show that PTEN ablation does not cause a global defect in Treg function and stability; rather, it selectively blocks their ability to suppress antigen-presenting cells. PTEN-KO Tregs exhibit elevated glycolytic activity, upregulate FOXP3, maintain a Treg phenotype, and have no discernable defects in lineage stability. Functionally, PTEN is dispensable for human Treg-mediated inhibition of T cell activity in vitro and in vivo but is required for suppression of costimulatory molecule expression by antigen-presenting cells. These data are the first to define a role for a signalling pathway in controlling a subset of human Treg activity. Moreover, they point to the functional necessity of PTEN-regulated PI3K-AKT activity for optimal human Treg function.
Newly synthesized mRNA escapes translational repression during the acute phase of the mammalian unfolded protein response
Authors: Alzahrani Mohammed R. , Guan Bo-Jhih , Zagore Leah L. , Wu Jing , Licatalosi Donny D. , Baker Kristian E. , Hatzoglou Maria
Published: March 2022

Endoplasmic Reticulum (ER) stress, caused by the accumulation of misfolded proteins in the ER, elicits a homeostatic mechanism known as the Unfolded Protein Response (UPR). The UPR reprograms gene expression to promote adaptation to chronic ER stress. The UPR comprises an acute phase involving inhibition of bulk protein synthesis and a chronic phase of transcriptional induction coupled with the partial recovery of protein synthesis. However, the role of transcriptional regulation in the acute phase of the UPR is not well understood. Here we analyzed the fate of newly synthesized mRNA encoding the protective and homeostatic transcription factor X-box binding protein 1 (XBP1) during this acute phase. We have previously shown that global translational repression induced by the acute UPR was characterized by decreased translation and increased stability of XBP1 mRNA. We demonstrate here that this stabilization is independent of new transcription. In contrast, we show XBP1 mRNA newly synthesized during the acute phase accumulates with long poly(A) tails and escapes translational repression. Inhibition of nascent RNA polyadenylation during the acute phase decreased cell survival with no effect in unstressed cells. Furthermore, during the chronic phase of the UPR, levels of XBP1 mRNA with long poly(A) tails decreased in a manner consistent with co-translational deadenylation. Finally, additional pro-survival, transcriptionally-induced mRNAs show similar regulation, supporting the broad significance of the pre-steady state UPR in translational control during ER stress. We conclude that the biphasic regulation of poly(A) tail length during the UPR represents a previously unrecognized pro-survival mechanism of mammalian gene regulation.
A review of recent clinical measures that can be used to support psychological therapies with adults with intellectual disabilities
Authors: Gourley Thomas Richard , Yates Luke
Published: March 2022

Purpose

Psychometrically sound measures are essential for clinical practice to provide appropriate therapeutic input. Vlissideset al.(2016) reviewed measures used in psychological therapies with people who have intellectual disabilities (ID). This paper aims to review the evidence for the psychometric properties of recent clinical measures published since/overlooked by Vlissideset al.(2016).

Design/methodology/approach

A literature search was conducted to identify relevant clinical measures. Experts in the field also were contacted. Twenty papers were identified, relating to five novel clinical measures: psychological therapies outcome scale – intellectual disabilities, clinical outcome in routine evaluation – learning disabilities scale 30, quality of early relatedness rating scale, scale of emotional development – short and the Frankish assessment of the impact of trauma.

Findings

Evidence was found supporting a proportion of the psychometric properties of each measure, and some measures were found to be useful in directing interventions and informing clinical decisions. None of the measures identified, however, are yet to be fully psychometrically investigated, requiring further research.

Originality/value

To the best of the authors’ knowledge, this paper is the first to review the evidence of psychometric properties for these five emerging clinical measures and as such contributes an original perspective on their current state and requirements for future development.
Who shares wins? Understanding barriers to information sharing in managing supply chain risk
Authors: Hannibal Claire , Rowan Jack , Durowoju Olatunde , Bryde David , Holloway Jake , Adeyemi Omolola , Shamim Saira
Published: March 2022

Purpose

Currently there is no universally accepted approach to supply chain risk management and assurance. To begin to shed more light on the practical operational challenges presented when considering supply chain risk mitigation through the sharing of information, this paper discusses the results of an empirical study conducted with manufacturing supply chain professionals. The study examines state-of-the-art challenges to managing risk in today's supply chains by reporting on data collected in 2021.

Design/methodology/approach

To develop a rich picture of the challenges of information sharing in multi-tier supply chains, the authors adopted a qualitative research design. The authors conducted 14 interviews with supply chain professionals and ran two focus groups that were industry specific: one focused on the nuclear industry and the other on automotive.

Findings

The study identifies contemporary practical challenges to information sharing in supply chains – specifically challenges related to data quality and the acceptance of sub-optimal normative supply chain practices, which have consequences for supplier assurance fatigue and supply chain transparency.

Originality/value

The topical and contemporary study shows how an acceptance of the normative practices of a supply chain can have a cumulative effect on the likelihood of supply chain disruption due to shortcomings in approaches to information sharing. The notion of the acceptance of the status quo in this context has received limited research attention, and hence offers an extension to current discourse on supply chain risk and resilience.
Employees' reactions to supervisors' fulfillment/non-fulfillment of psychological contract promises: an experimental field study
Authors: Ababneh Khaldoun I. , Dedousis Evangelos , Braendle Udo
Published: March 2022

Purpose

Drawing upon social exchange theory and psychological contract (PC) research, this study aims to examine the impact of supervisors' fulfillment/non-fulfillment of transactional psychological contract (TPC) and relational psychological contract (RPC) promises on employees' reactions (e.g. feelings of violation, trust in the supervisor and organizational commitment) in a non-Western context, namely, the United Arab Emirates (UAE).

Design/methodology/approach

An experimental field design was used with a sample of employees (N = 234) from a wide range of nationalities and work backgrounds. Four conditions were developed by manipulating the fulfillment of three TPC promises (e.g. competitive salary) and three RPC promises (e.g. sufficient power and responsibility). Participants were randomly assigned to the four conditions and asked to complete the study materials as if they were experiencing a real employment situation with a real organization. Hypotheses were tested using multivariate analysis of covariance and follow-up univariate analysis with Bonferronipost hoccomparisons.

Findings

This study demonstrated that a supervisor's failure to fulfill promises pertinent to both TPC and RPC, or one of them, generated negative reactions among participants. Based on a comparison of means analysis, this study also established that breach of TPC promises produced a higher negative impact than breach of RPC promises on perceptions of breach, feelings of violation, trust in the supervisor, organizational perceptions, organizational commitment and recommendation intentions. Furthermore, these findings revealed that a supervisor's breach of RPC promises has no significant incremental (additive) effect above a supervisor's breach of TPC promises. On the other hand, a supervisor's breach of TPC promises has a significant incremental (additive) effect above a supervisor's breach of RPC promises.

Originality/value

This study is one of the very few studies that examined and established, under a controlled setting, the differential effects of fulfillment/non-fulfillment of both TPC and RPC promises on employees' breach perceptions, emotions, attitudes and behavioral intentions.
Systems thinking approach for disaster resilient and climate smart agriculture in Bangladesh
Authors: Islam Sheikh Tawhidul , Akand Md. Kamruzzaman , Islam Md. Nurul , Samad Soumic , Rishal Faiyad H.
Published: March 2022

Purpose

Linear and narrow focus of climate change and disaster impact assessments on agriculture turns out as a limiting factor to understand how impact conditions trigger changes in the whole system resulting to make problems complicated. The paper aims to identify the micro-level challenges of the agriculture sector and then shows how macro-level planning could be developed and may help the rural peasants of Bangladesh to better cope with the adverse conditions generated as a result of disaster impacts and/or climate change-induced threats.

Design/methodology/approach

The paper, based on a secondary literature review and primary data generated by the author, shows that agriculture happens as a system where many microelements and processes contribute and benefits from it do not only confine into the final product generation. Using both the primary and secondary data, the paper shows how simplistic approaches to assess disaster impacts on agriculture in Bangladesh are taking place and thus leaving scopes to read properly the more complex and cyclic forms of hazard impacts in the sector by using the systems thinking approach and complex systems methodology.

Findings

The paper finally suggests how a better and comprehensive understanding of disaster and climate change impacts on agriculture would provide arguments for mainstreaming climate change adaptation and disaster risk reduction actions into regular development planning of the government.

Originality/value

The authors declare that this submission is their own work, and, to the best of the authors’ knowledge, it contains no materials previously published or written by another person or substantial proportions of material which have been accepted for the award of anywhere else.
Work and active aging: is there a relationship between health and meaning in life?
Authors: Torres Isabel , Gaspar Tânia , Rodrigues Paula
Published: March 2022

Purpose

This study aims to explain the health impact of work demands and organization, job content, leadership and values in the workplace. It also explores the extent to which health conditions influence the meaning in life in late career.

Design/methodology/approach

The sample consisted of 1,330 Portuguese-based individuals aged 55–75 years. The structural equation modeling (SEM) was used for the data analysis and to test the research questions.

Findings

The results showed that stress and burnout are influenced by work demands and organization, job content, leadership and values in the workplace. Employment status had no influence. Health status affects the meaning in life.

Research limitations/implications

Although participants were asked to answer the questionnaire bearing in mind their last work experience, retirees could have had difficulty reporting on their last work; therefore, in future research, the use of a qualitative methodology could also be equated as to complement richer information regarding past experiences in the work context.

Practical implications

Considering the main goals of the United Nations 2030 Agenda for sustainable development, this study contributes, namely, to the third one – Ensure healthy lives and promote well-being for all at all ages. In fact, directing a look at the condition in which older people work and at their health contributes not only to more productive organizations, to less spending of public money on health, but also to a more inclusive society. Bearing in mind workers are progressively retiring later and that the exposure to certain work conditions during the late career is problematic for organizations and for society in general, this study has practical and social implication.

Originality/value

Considering demographic changes and the aging of the active population in Portugal and the scarce studies carried out in the country concerning this relevant theme, the authors believe that the conclusions may constitute an important input for workplace policies regarding older workers. In addition, little research has focused on the effect of health in meaning in life.
Investigating the role of technostress, cognitive appraisal and coping strategies on students' learning performance in higher education: a multidimensional transactional theory of stress approach
Authors: Sharma Shwadhin , Gupta Babita
Published: March 2022

Purpose

COVID-19 has galvanized educational institutions to rapidly adopt technology-enhanced learning (TEL) environment where students are required to use and manage a diverse set of information and communication technologies (ICTs). Using the Transactional Theory of Stress, the authors investigate the impact of a TEL environment on students' stress, cognitive appraisal and coping. The authors also explore how the TEL environment impacts students' learning satisfaction and performance.

Design/methodology/approach

A survey using Qualtrics was developed to collect the data from 275 undergraduate students. The authors used the Partial Least Squares (PLS) through SmartPLS for instrument validation and testing of the structural model. The reflective-formative model was applied as the measures used to evaluate the first-order constructs are unidimensional, and the second-order construct has a formative measurement.

Findings

Students experienced technology-related stress due to ICT use. The negative appraisal such as harm and threat leads to emotion-focused coping among students, while the constructive appraisal such as positive and challenge leads to problem-focused coping. Emotion-focused coping was found to negatively impact learning satisfaction, while problem-focused coping was found to positively impact satisfaction. The authors also found that students with a higher level of experience with online and hybrid classes, higher confidence in computer usage and lower anxiety are better equipped to deal with technostress.

Research limitations/implications

This study provides the first comprehensive technostress model in the IS literature that uses formative modeling to explain technostress creators and inhibitors and emotion-focused coping and problem-focused coping, as was intended by the Transactional Theory of Stress. The result allows for rethinking TEL environment by drawing attention to strategies that can reduce technological complexity and uncertainty. For future research, it may be helpful to perform a longitudinal or experimental study to obtain rigorous causal inference.

Originality/value

There is limited research on the impact of technostress in the field of higher education. Also, technostress has been used inconsistently in Information Systems research, with the majority of research focusing on technostress creators and inhibitors only. This research incorporates all the constructs of the original theory adding new knowledge to the IS literature about the nature and causes of stress created by the use of technology.