bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial selection for predatory behaviour results in dietary niche differentiation in an omnivorous mammal
Authors: Hämäläinen Anni , Kiljunen Mikko , Koskela Esa , Koteja Pawel , Mappes Tapio , Rajala Milla , Tiainen Katariina
Published: March 2022

The diet of an individual is a result of the availability of dietary items and the individual's foraging skills and preferences. Behavioural differences may thus influence diet variation, but the evolvability of diet choice through behavioural evolution has not been studied. We used experimental evolution combined with a field enclosure experiment to test whether behavioural selection leads to dietary divergence. We analysed the individual dietary niche via stable isotope ratios of nitrogen (
δ
15
N) and carbon (
δ
13
C) in the hair of an omnivorous mammal, the bank vole, from four lines selected for predatory behaviour and four unselected control lines. Predatory voles had higher hair
δ
15
N values than control voles, supporting our hypothesis that predatory voles would consume a higher trophic level diet (more animal versus plant foods). This difference was significant in the early but not the late summer season. The
δ
13
C values also indicated a seasonal change in the consumed plant matter and a difference in food sources among selection lines in the early summer. These results imply that environmental factors interact with evolved behavioural tendencies to determine dietary niche heterogeneity. Behavioural selection thus has potential to contribute to the evolution of diet choice and ultimately the species' ecological niche breadth.
Climate change in the coastal ocean: shifts in pelagic productivity and regionally diverging dynamics of coastal ecosystems
Authors: Navarrete Sergio A. , Barahona Mario , Weidberg Nicolas , Broitman Bernardo R.
Published: March 2022

Climate change has led to intensification and poleward migration of the Southeastern Pacific Anticyclone, forcing diverging regions of increasing, equatorward and decreasing, poleward coastal phytoplankton productivity along the Humboldt Upwelling Ecosystem, and a transition zone around 31° S. Using a 20-year dataset of barnacle larval recruitment and adult abundances, we show that striking increases in larval arrival have occurred since 1999 in the region of higher productivity, while slower but significantly negative trends dominate poleward of 30° S, where years of recruitment failure are now common. Rapid increases in benthic adults result from fast recruitment–stock feedbacks following increased recruitment. Slower population declines in the decreased productivity region may result from aging but still reproducing adults that provide temporary insurance against population collapses. Thus, in this region of the ocean where surface waters have been cooling down, climate change is transforming coastal pelagic and benthic ecosystems through altering primary productivity, which seems to propagate up the food web at rates modulated by stock–recruitment feedbacks and storage effects. Slower effects of downward productivity warn us that poleward stocks may be closer to collapse than current abundances may suggest.
Gesture is the primary modality for language creation
Authors: Fay Nicolas , Walker Bradley , Ellison T. Mark , Blundell Zachary , De Kleine Naomi , Garde Murray , Lister Casey J. , Goldin-Meadow Susan
Published: March 2022

How language began is one of the oldest questions in science, but theories remain speculative due to a lack of direct evidence. Here, we report two experiments that generate empirical evidence to inform gesture-first and vocal-first theories of language origin; in each, we tested modern humans' ability to communicate a range of meanings (995 distinct words) using either gesture or non-linguistic vocalization. Experiment 1 is a cross-cultural study, with signal Producers sampled from Australia (
n
= 30,
M
age
= 32.63, s.d. = 12.42) and Vanuatu (
n
= 30,
M
age
= 32.40, s.d. = 11.76). Experiment 2 is a cross-experiential study in which Producers were either sighted (
n
= 10,
M
age
= 39.60, s.d. = 11.18) or severely vision-impaired (
n
= 10,
M
age
= 39.40, s.d. = 10.37). A group of undergraduate student Interpreters guessed the meaning of the signals created by the Producers (
n
= 140). Communication success was substantially higher in the gesture modality than the vocal modality (twice as high overall; 61.17% versus 29.04% success). This was true within cultures, across cultures and even for the signals produced by severely vision-impaired participants. The success of gesture is attributed in part to its greater universality (i.e. similarity in form across different Producers). Our results support the hypothesis that gesture is the primary modality for language creation.
JMM Profile: Actinobacillus pleuropneumoniae: a major cause of lung disease in pigs but difficult to control and eradicate
Authors: Stringer Oliver W. , Li Yanwen , Bossé Janine T. , Langford Paul R.
Published: March 2022

The Gram-negative bacterium

Actinobacillus pleuropneumoniae

is the causative agent of pleuropneumonia in pigs, its only known natural host. Typical symptoms of peracute disease include fever, apathy and anorexia, and time from infection to death may only be 6 h. Severe lung lesions result from presence of one or two of the ApxI-III toxins. Control is through good husbandry practice, vaccines and antibiotic use. Culture and presence of the species-specific apxIV gene by PCR confirms diagnosis, and identification of serovar, of which 19 are known, informs on appropriate vaccine use and epidemiology.
Familial Clustering and Genetic Analysis of Severe Thumb Carpometacarpal Joint Osteoarthritis in a Large Statewide Cohort
Authors: Gavile Catherine M. , Kazmers Nikolas H. , Novak Kendra A. , Meeks Huong D. , Yu Zhe , Thomas Joy L. , Hansen Channing , Barker Tyler , Jurynec Michael J.
Published: March 2022

Objectives

The objectives of this study are to 1) identify individuals that required surgery for thumb carpometacarpal osteoarthritis (CMCJ OA), 2) determine if CMCJ OA clusters in multigenerational families, 3) define the magnitude of familial risk of CMCJ OA, 4) identify risk factors associated with CMCJ OA and 5) identify rare genetic variants that segregate with familial CMCJ OA.

Methods

We searched the Utah Population Database to identify a cohort of CMCJ OA patients that required a surgical procedure (CMC fusion or arthroplasty). Affected individuals were mapped to pedigrees to identify high-risk multigenerational families with excess clustering of CMCJ OA. Cox regression models were used to calculate familial risk of CMCJ OA in related individuals. Risk factors were evaluated using logistic regression models. Whole exome sequencing was used to identify a rare coding variant associated with familial CMCJ OA.

Results

We identified 550 pedigrees with excess clustering of severe CMCJ OA. The relative risk of developing CMCJ OA requiring surgical treatment was significantly elevated in first- and third-degree relatives of affected individuals, and significant associations with advanced age, female sex, obesity, and tobacco use were observed. A dominantly segregating, rare variant in CHSY3 was associated with familial CMCJ OA.

Conclusions

Familial clustering of severe CMCJ OA was observed in a statewide population. Identification of a candidate gene indicates a genetic contribution to the etiology of the disease. Our data indicate the genetic and environmental factors contribute to the disease process, further highlighting the multifactorial nature of the disease.

Key messages

We study a unique cohort of individuals requiring surgical management of CMCJ OA.

Severe CMCJ OA clusters in large, multigenerational families indicating a genetic contribution to the disease.

.We discovered a dominant coding variant in CHSY3 in a family with severe CMCJ OA.
SETBP1variants outside the degron disrupt DNA-binding and transcription independent of protein abundance to cause a heterogeneous neurodevelopmental disorder
Authors: Wong Maggie MK , Kampen Rosalie A , Braden Ruth O , Alagöz Gökberk , Hildebrand Michael S , Barnett Christopher , Barnett Meghan , Brusco Alfredo , Carli Diana , de Vries Bert BA , Dingemans Alexander JM , Elmslie Frances , Ferrero Giovanni B , Jansen Nadieh A , van de Laar Ingrid MBH , Moroni Alice , Mowat David , Murray Lucinda , Novara Francesca , Peron Angela , Scheffer Ingrid E , Sirchia Fabio , Turner Samantha J , Vignoli Aglaia , Vino Arianna , Weber Sacha , Chung Wendy K , Gerard Marion , López-González Vanessa , Palmer Elizabeth , Morgan Angela T , van Bon Bregje W , Fisher Simon E
Published: March 2022

Germlinede novo SETBP1variants cause clinically distinct and heterogeneous neurodevelopmental disorders. Heterozygous missense variants at a hotspot encoding a canonical degron lead to SETBP1 accumulation and Schinzel-Giedion syndrome (SGS), a rare severe developmental disorder involving multisystem malformations. Heterozygous loss-of-function variants result inSETBP1haploinsufficiency disorder which is phenotypically much milder than SGS. Following an initial description of four individuals with atypical SGS carrying heterozygous missense variants adjacent to the degron, a few individual cases of variants outside the degron were reported. Due to the lack of systematic investigation of genotype-phenotype associations of different types ofSETBP1variants, and limited understanding of the roles of the gene in brain development, the extent of clinical heterogeneity and how this relates to underlying pathophysiological mechanisms remain elusive, imposing challenges for diagnosis and patient care. Here, we present a comprehensive investigation of the largest cohort to-date of individuals carryingSETBP1missense variants outside the degron (n=18, including one in-frame deletion). We performed thorough clinical and speech phenotyping with functional follow-up using cellular assays and transcriptomics. Our findings suggest that such variants cause a clinically and functionally variable developmental syndrome, showing only partial overlaps with classical SGS andSETBP1haploinsufficiency disorder, and primarily characterised by intellectual disability, epilepsy, speech and motor impairment. We provide evidence of loss-of-function pathophysiological mechanisms impairing ubiquitination, DNA-binding and transcription. In contrast to SGS andSETBP1haploinsufficiency, these effects are independent of protein abundance. Overall, our study provides important novel insights into diagnosis, patient care and aetiology of SETBP1-related disorders.
Therapeutic effects of Rosa Canina, Urtica Dioica and Tanacetum Vulgare Herbal Combination in Treatment of Tinnitus Symptoms; A Double-blind Randomized Clinical Trial
Authors: Khosravi Mohammad Hossein , Atefi Amirhomayoun , Mehri Afsaneh , Sodeifian Fatemeh , Yousefi Jaleh , Hagh Ali Bagheri , Sohrabpour Saeed , Kazemi Fatemeh , Ajalloueian Mohammad , Saeedi Masoumeh
Published: March 2022

Background

Tinnitus is defined as the perception of sound in the ear or head in the absence of an external stimulus for which we have no definite treatment. Neurotec® is a medication of herbal origin with IFDA approval. Previous studies showed the neuroprotective effect of Neurotec®. In this study we evaluated the effectiveness of Neurotec in improving tinnitus symptoms.

Methods

This double-blind randomized clinical trial was performed on patients with tinnitus. Patients received Neurotec 100 mg capsules (BID) or placebo for three months. Pure tone audiometry (PTA) was measured at 0.5, 1, 2, 4 and 6 KHz frequencies. Using a Tinnitus Handicap Inventory (THI) questionnaire, tinnitus loudness, daily annoyance, daily life or sleep disturbance, daily perception and mood alteration were evaluated.

Results

Finally, 103 (69 male and 34 female) patients with a mean age of 51.33±13.91 years were analyzed. There was no significant difference between the intervention (n=53) and the control group (n=50) regarding baseline symptoms before and one month after the intervention (P>0.05). While, they were significantly different three months after the intervention (P<0.05). The mean pure tone air and bone conduction were not significantly different between the control and the intervention group before and three months after the intervention at 0.5,1,2 and 4 kHz (P>0.05). The mean pure tone air conduction was not significantly different between the two groups before and three months after the intervention at 6 kHz (P>0.05).

Conclusion

A three-month treatment with Neurotec Capsules beside patient education can effectively control symptoms of patients with tinnitus.
Factors affecting zero-waste behaviors: Focusing on the health effects of microplastics
Authors: Choi Eun-Hi , Lee Hyunjin , Kang Mi-Jung , Nam Inwoo , Moon Hui-Kyeong , Sung Ji-Won , Eu Jae-Yun , Lee Hae-Bin
Published: March 2022

Microplastics harm human health. Therefore, the present study assessed the knowledge and attitude of university students towards reducing microplastic use and examined their zero-waste behaviors. Our results lay the foundation for program development aimed at promoting zero-waste activities. The study was conducted from August 20, 2021, to September 10, 2021, including students at a university in G metropolitan city. Questions were developed to verify how the use of disposables and the knowledge, attitude, and behaviors related to zero-waste were affected after the COVID-19 pandemic. A survey was conducted with 197 students, and the data of 196 students were analyzed. Family type (β=0.146, p=0.042) and usage of disposables (β=0.158, p=0.049) were the factors affecting zero-waste behavior in Model 1. In Model 2, which included the subcategory of zero-waste knowledge, the health effects of microplastics (β=0.197, p=0.008) and environmental preservation (β=0.236, p=0.001) were significant factors. In Model 3, which included the subcategory of zero-waste attitude, the health effects of microplastics (β=0.149, p=0.016), use of eco-friendly products (β=0.342, p<0.001), and environmental preservation (β=0.317, p<.001) were significant factors. Therefore, additional studies and education on the health effects of microplastics are warranted, and suitable alternatives for disposables must be developed.
Persistence of targetable lesions, predicted therapy sensitivity and proteomes through disease evolution in pediatric acute lymphoblastic leukemia
Authors: Lorentzian Amanda C. , Rever Jenna , Ergin Enes K. , Guo Meiyun , Akella Neha M. , Rolf Nina , Lim C. James , Reid Gregor S.D. , Maxwell Christopher A. , Lange Philipp F.
Published: March 2022

Childhood acute lymphoblastic leukemia (ALL) genomes show that relapses often arise from subclonal outgrowths. However, the impact of clonal evolution on the actionable proteome and response to targeted therapy is not known. Here, we present a comprehensive retrospective analysis of paired ALL diagnosis and relapsed specimen. Targeted next generation sequencing and proteome analysis indicated persistence of actionable genome variants and stable proteomes through disease progression. Paired viably-frozen biopsies showed high correlation of drug response to variant-targeted therapies butin vitroselectivity was low. Proteome analysis prioritized PARP1 as a new pan-ALL target candidate needed for survival following cellular stress; diagnostic and relapsed ALL samples demonstrated robust sensitivity to treatment with two PARP1/2 inhibitors. Together, these findings support initiating prospective precision oncology approaches at ALL diagnosis and emphasize the need to incorporate proteome analysis to prospectively determine tumor sensitivities, which are likely to be retained at disease relapse.

STATEMENT OF SIGNIFICANCE

We discover that disease progression and evolution in pediatric acute lymphoblastic leukemia is defined by the persistence of targetable genomic variants and stable proteomes, which reveal pan-ALL target candidates. Thus, personalized treatment options in childhood ALL may be improved with the incorporation of prospective proteogenomic approaches initiated at disease diagnosis.
Topical anticholinergic medications for primary hyperhidrosis: A protocol for a systematic review and meta-analysis
Authors: Wu Yang , Gao Wenli , Yan Jiao , Yang Min , Gao Dongyang
Published: March 2022

Background

Primary hyperhidrosis (PHH) is a chronic condition characterized by excessive sweating. Several topical anticholinergic agents have been developed, but the evidence for the efficacy and tolerability of changing medication pathways of anticholinergics for PHH is limited. We will review the available literature to derive information regarding the efficacy and safety of different medicines used for the topical treatment of patients with hyperhidrosis.

Methods

PubMed, Cochrane Library, Embase, Web of Science, and Cochrane Central Register of Controlled Trials will be searched from inception to May 2023 for studies that may be eligible for inclusion. Randomized controlled trials (RCTs) of PHH treated with topical anticholinergic drugs will be included in the analysis. The primary outcomes will include the severity of hyperhidrosis measured quantitatively, the Hyperhidrosis Disease Severity Scale (HDSS) score, or the proportion of subjects with a minimum 2-grade improvement from baseline in HDSS, the Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) score, and Dermatology Life Quality Index (DLQI). The secondary outcomes will focus on safety and tolerability. Study selection, data extraction, and assessment of the risk of bias will be independently performed by two investigators. Data synthesis will be performed using Review Manager 5.4 software.

Results

The results will be published as a peer-reviewed article.

Conclusions

This review will systematically evaluate the existing evidence on the efficacy and safety of topical anticholinergic agents in the treatment of PHH. These conclusions will provide supporting evidence for the current guidelines and more reliable evidence-based medicine references for clinical practitioners and researchers.

PROSPERO registration number

CRD42022312316
Post COVID-19 Condition in South Africa: 3-month follow-up after hospitalisation with SARS-CoV-2
Authors: Dryden Murray , Mudara Caroline , Vika Caroline , Blumberg Lucille , Mayet Natalie , Cohen Cheryl , Tempia Stefano , Parker Arifa , Nel Jeremy , Perumal Rubeshan , Groome Michelle J. , Conradie Francesca , Ndjeka Norbert , Sigfrid Louise , Merson Laura , Jassat Waasila
Published: March 2022

Background

Post COVID-19 Condition (PCC) as defined by WHO refers to a wide range of new, returning, or ongoing health problems experienced by COVID-19 survivors, and represents a rapidly emerging public health priority. We aimed to establish how this developing condition has impacted patients in South Africa and which population groups are at risk.

Methods

In this prospective cohort study, participants ≥18 years who had been hospitalised with laboratory-confirmed SARS-CoV-2 infection during the second and third wave between December 2020 and August 2021 underwent telephonic follow-up assessment up at one-month and three-months after hospital discharge. Participants were assessed using a standardised questionnaire for the evaluation of symptoms, functional status, health-related quality of life and occupational status. Multivariable logistic regression models were used to determine factors associated with PCC.

Findings

In total, 1,873 of 2,413 (78%) enrolled hospitalised COVID-19 participants were followed up at three-months after hospital discharge. Participants had a median age of 52 years (IQR 41-62) and 960 (51.3%) were women. At three-months follow-up, 1,249 (66.7%) participants reported one or more persistent COVID-related symptom(s), compared to 1,978/2,413 (82.1%) at one-month post-hospital discharge. The most common symptoms reported were fatigue (50.3%), shortness of breath (23.4%), confusion or lack of concentration (17.5%), headaches (13.8%) and problems seeing/blurred vision (10.1%). On multivariable analysis, factors associated with new or persistent symptoms following acute COVID-19 were age ≥65 years [adjusted odds ratio (aOR) 1.62; 95%confidence interval (CI) 1.00-2.61]; female sex (aOR 2.00; 95% CI 1.51-2.65); mixed ethnicity (aOR 2.15; 95% CI 1.26-3.66) compared to black ethnicity; requiring supplemental oxygen during admission (aOR 1.44; 95% CI 1.06-1.97); ICU admission (aOR 1.87; 95% CI 1.36-2.57); pre-existing obesity (aOR 1.44; 95% CI 1.09-1.91); and the presence of ≥4 acute symptoms (aOR 1.94; 95% CI 1.19-3.15) compared to no symptoms at onset.

Interpretation

The majority of COVID-19 survivors in this cohort of previously hospitalised participants reported persistent symptoms at three-months from hospital discharge, as well as a significant impact of PCC on their functional and occupational status. The large burden of PCC symptoms identified in this study emphasises the need for a national health strategy. This should include the development of clinical guidelines and training of health care workers, in identifying, assessing and caring for patients affected by PCC, establishment of multidisciplinary national health services, and provision of information and support to people who suffer from PCC.
A multi-phenotype analysis reveals 19 novel susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma
Authors: Seviiri Mathias , Law Matthew H. , Ong Jue-Sheng , Gharahkhani Puya , Fontanillas Pierre ,   23andMe Research Team, Olsen Catherine M. , Whiteman David C. , MacGregor Stuart
Published: March 2022

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common forms of skin cancer. There is genetic overlap between skin cancers, pigmentation traits, and autoimmune diseases. We use linkage disequilibrium score regression to identify 20 traits (melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers) with a high genetic correlation (rg > 10%, P < 0.05) with BCC (20,791 cases and 286,893 controls in the UK Biobank) and SCC (7,402 cases and 286,892 controls in the UK Biobank), and use a multi-trait genetic analysis to identify 78 and 69 independent genome-wide significant (P < 5 × 10-8) susceptibility loci for BCC and SCC respectively; 19 BCC and 15 SCC loci are both novel and replicated (P < 0.05) in a large independent cohort; 23andMe, Inc (BCC: 251,963 cases and 2,271,667 controls, and SCC: 134,700 cases and 2,394,699 controls. Novel loci are implicated in BCC/SCC development and progression (e.g. CDKL1), pigmentation (e.g. DSTYK), cardiometabolic pathways (e.g. FADS2), and immune-regulatory pathways including; innate immunity against coronaviruses (e.g. IFIH1), and HIV-1 viral load modulation and disease progression (e.g. CCR5). We also report a powerful and optimised BCC polygenic risk score that enables effective risk stratification for keratinocyte cancer in a large prospective Canadian Longitudinal Study of Aging (794 cases and 18139 controls); e.g. percentage of participants reclassified; MTAGPRS = 36.57%, 95% CI = 35.89-37.26% versus UKBPRS= 33.23%, 95% CI=32.56-33.91%).
Reprogrammed Schwann Cells Organize into Dynamic Tracks that Promote Pancreatic Cancer Invasion
Authors: Deborde Sylvie , Gusain Laxmi , Powers Ann , Marcadis Andrea , Yu Yasong , Chen Chun- Hao , Frants Anna , Kao Elizabeth , Tang Laura , Vakiani Efsevia , Calo Annalisa , Omelchenko Tatiana , Jessen Kristian R. , Reva Boris , Wong Richard J.
Published: March 2022

Nerves are a component of the tumor microenvironment contributing to cancer progression, but the role of cells from nerves in facilitating cancer invasion remains poorly understood. Here we show that Schwann cells (SCs) activated by cancer cells collectively function as Tumor Activated Schwann cell Tracks (TASTs) that promote cancer cell migration and invasion. Non-myelinating SCs form TASTs and have cell gene expression signatures that correlate with diminished survival in patients with pancreatic ductal adenocarcinoma. In TASTs, dynamic SCs form tracks that serve as cancer pathways and apply forces on cancer cells to enhance cancer motility. These SCs are activated by c-Jun, analogous to their reprogramming during nerve repair. This study reveals a mechanism of cancer cell invasion that co-opts a wound repair process and exploits the ability of SCs to collectively organize into tracks. These findings establish a novel paradigm of how cancer cells spread and reveal therapeutic opportunities.

SIGNIFICANCE

How the tumor microenvironment participates in pancreatic cancer progression is not fully understood. Here, we show that Schwann cells are activated by cancer cells and collectively organize into tracks that dynamically enable cancer invasion in a c-Jun dependent manner.
Self-cleaving 2A peptides allow for expression of multiple genes in Dictyostelium discoideum
Authors: Zhu Xinwen , Ricci-Tam Chiara , Sgro Allyson E.
Published: March 2022

The social amoeba Dictyostelium discoideum is a model for a wide range of biological processes including chemotaxis, cell-cell communication, phagocytosis, and development. Interrogating these processes with modern genetic tools often requires the expression of multiple transgenes. While it is possible to transfect multiple transcriptional units, the use of separate promoters and terminators for each gene leads to large plasmid sizes and possible interference between units. In other eukaryotic systems this challenge has been addressed through polycistronic expression mediated by 2A viral peptides, permitting efficient, co-regulated gene expression. Here, we screen the most commonly used 2A peptides, porcine teschovirus-1 2A (P2A), Thosea asigna virus 2A (T2A), equine rhinitis A virus 2A (E2A), and foot-and-mouth disease virus 2A (F2A), for activity in D. discoideum. We find that these 2A sequences are effective but that, unexpectedly, combining the coding sequences of two proteins into a single transcript leads to notable decreases in expression level with strain-dependent magnitudes, suggesting unexplored constraints of gene expression in D. discoideum that merit further investigation. Our results show that P2A is the optimal sequence for polycistronic expression, opening up new possibilities for genetic engineering in this model system.
Dynamic changes of gut microbiota associated with blood glucose levels in sows from pregnancy through lactation
Authors: Wang Mingjun , Li Jiaju , Chen Bo , Li Haitao , Ren Jun
Published: March 2022

Gut microbiota plays important roles in metabolism and physiological homeostasis throughout the lifespan of mammals, including in pregnancy. To evaluate the effects of practically adopted restricted feeding during gestation on blood glucose level and fecal microbiota composition, 31 sows were used to identify the shifts in bacterial assemblages by 16S rRNA sequencing in their early pregnancy, late pregnancy and late lactation stages. We find that the blood glucose was elevated significantly (p < 0.001) in sows offered abundant feed in the late lactation as compared with those of the same cohort in the pregnancy stages when on limited feed. Five bacterial genera were differentially abundant among three stages, and the abundances of Streptococcus (padj < 0.001) and unclassified_f_Lachnospiraceae (padj < 0.001) were increased, whereas the abundances of Lactobacillus (padj = 0.035) and Escherichia-Shigella (padj< 0.001) were decreased in the latter two stages. The genus Prevotellaceae_NK3B31_group (padj = 0.026) displayed higher abundance in the late lactation stage. A significant correlation in the Pearson’s analysis indicates that three out of these five differentially abundant genera were related to blood glucose change. Our data show that restricted-fed gestating sows have aberrant blood glucose level and may affect the intestinal microbiota.
Activation of the cGAS-STING innate immune response in cells with deficient mitochondrial topoisomerase TOP1MT
Authors: Khatib Iman Al , Deng Jingti , Lei Yuanjiu , Torres-Odio Sylvia , Rojas Gladys R. , Newman Laura E. , Chung Brian K. , Symes Andrew , Zhang Hongliang , Huang Shar-yin N. , Pommier Yves , Khan Aneal , Shadel Gerald S. , West A. Phillip , Gibson William T. , Shutt Timothy E.
Published: March 2022

The recognition that cytosolic mtDNA activates cGAS-STING innate immune signaling has unlocked novel disease mechanisms. Here, an uncharacterized variant predicted to affect TOP1MT function, P193L, was discovered in a family with multiple early-onset autoimmune diseases, including Systemic Lupus Erythematosus (SLE). Although there was no previous genetic association betweenTOP1MTand autoimmune disease, the role of TOP1MT as a regulator of mtDNA led us to investigate whether TOP1MT could mediate the release of mtDNA to the cytosol, where it could then activate the cGAS-STING innate immune pathway known to be activated in SLE and other autoimmune diseases. Through analysis of cells with reduced TOP1MT expression, we show that loss of TOP1MT results in release of mtDNA to the cytosol, which activates the cGAS-STING pathway. We also characterized the P193L variant for its ability to rescue several TOP1MT functions when expressed inTOP1MTknockout cells. We show that the P193L variant is not fully functional, as its re-expression at high levels was unable to rescue mitochondrial respiration deficits, and only showed partial rescue for other functions, including repletion of mtDNA replication following depletion, nucleoid size, steady state mtDNA transcripts levels, and mitochondrial morphology. Additionally, expression of P193L at endogenous levels was unable to rescue mtDNA release-mediated cGAS-STING signaling. Overall, we report a link between TOP1MT and mtDNA release leading to cGAS-STING activation. Moreover, we show that the P193L variant has partial loss of function that may contribute to autoimmune disease susceptibility via cGAS-STING mediated activation of the innate immune system.
Nucleotide augmentation for machine learning-guided protein engineering
Authors: Minot Mason , Reddy Sai T.
Published: March 2022

Machine learning-guided protein engineering is a rapidly advancing field. Despite major experimental and computational advances however, collecting protein genotype (sequence) and phenotype (function) data remains time and resource intensive. As a result, the quality and quantity of training data is often a limiting factor in developing machine learning models. Data augmentation techniques have been successfully applied to the fields of computer vision and natural language processing, however, there is a lack of such augmentation techniques for biological sequence data. Towards this end we develop nucleotide augmentation (NTA), which leverages natural nucleotide codon degeneracy to augment protein sequence data in a biologically meaningful way. As a proof of concept for protein engineering, we apply NTA to train machine learning models with benchmark data sets of protein genotype and phenotype, revealing performance gains on par and surpassing benchmarks models, even when only using a fraction of the training data. NTA also enables substantial improvements for classification tasks under heavy class imbalance.

Availability and implementation

The code to use NTA and to reproduce the analyses in this study is publicly available at https://github.com/minotm/NTA
Superoxide Dismutase 1 translocates to the nucleus in spinal cord mixed cells from newborn rats
Authors: Santos Nathália V. , Machado Camila M. L. , Cerchiaro Giselle
Published: March 2022

Superoxide dismutase 1 (SOD1) catalyzes the superoxide conversion to oxygen and hydrogen peroxide in general. SOD1 can translocate to the cell nucleus in response to oxidative stress in yeast and human fibroblasts. Here, we report the translocation of sod1 to the cell nucleus in primary co-cultures of neurons and astrocytes derived from newborn rats explants even in the absence of oxidative stress stimuli. The successful tissue explants from rats allowed simplistic and clean modeling of Amyotrophic lateral sclerosis (ALS)-simile tissue microenvironment. This mixed-cells-population was responsive to H2O2 (100 μM) oxidative stress with a progressive dying process up to 6 h after stimuli. However, no differences in SOD1 nucleus translocation were observed in rat amyotrophic lateral sclerosis (ALS)-simile tissue microenvironment up to 6 hours under oxidative stress. These results altogether point to a robust cellular collaboration between neurons and astrocytes so that the tissue can equilibrate this SOD1 translocation during the oxidative stress response and in the early animal development.
Distinct phospho-variants of STAT3 regulate naïve pluripotency and developmental pacein vivo
Authors: Azami Takuya , Kraunsoe Sophie , Martello Graziano , Pei Yihan , Boroviak Thorsten , Nichols Jennifer
Published: March 2022

STAT3 has been studied extensively in the context of self-renewal of naïve pluripotent mouse embryonic stem cells. We uncovered acute roles for STAT3 and its target, TFCP2L1, in maintenance of epiblast and primitive endoderm duringin vivodiapause. On an outbred genetic background, we observed consistent developmental retardation from implantation until embryonic day 11.5, beginning with significant reduction of epiblast cells at implantation inStat3null embryos. Remarkably, mutants closely resemble non-affected embryos from the previous day at all postimplantation stages examined. We attribute this phenotype to loss of the active serine phosphorylated form of STAT3 required for neural differentiation and implicated in growth defects in mice and humans. Bulk RNA-sequencing analysis of isolated epiblasts revealed compromised lipid metabolism inStat3null embryos by embryonic day 6.5. Furthermore, we demonstrate that gastruloids generated fromStat3null ESCs failed to extend the posterior axis or maintain BRACHYURY expression and were underrepresented in this region when mixed with wild type cells in chimaeric gastruloids. Our study implicates a role for STAT3 in temporal control of embryonic progression and metabolic mechanisms.
Rescue by gene swamping as a gene drive deployment strategy
Authors: Harris Keith D. , Greenbaum Gili
Published: March 2022

Gene drives are genetic constructs that can spread deleterious alleles with potential application to population suppression of harmful species. Given that a gene drive can potentially spill over to other populations or even other species, control measures and fail-safes strategies must be considered. Gene drives are designed to generate a rapid demographic decline, while at the same time generating a dynamic change in the population’s genetics. Since these evolutionary and demographic processes are linked and are expected to occur at a similar time-scale during gene drive spread, feedback between these processes may significantly affect the outcome of deployment. To study this feedback and to understand how it affects gene drive spillovers, we developed a gene drive model that combines evolutionary and demographic dynamics in a two-population setting. The model demonstrates how feedback between evolutionary and demographic dynamics can generate additional outcomes to those generated by the evolutionary dynamics alone. We identify an outcome of particular interest, where the short-term suppression of the target population is followed by gene swamping and loss of the gene drive. This outcome could be useful for designing gene drive deployments that temporarily suppress the population, but ultimately do not remain in the population. Using our model, we demonstrate the robustness of this outcome to spillover and to the evolution of resistance, and suggest that it could be used as a fail-safe strategy for gene drive deployment.
Comparative Genomic Analysis of Salmonella enterica serovar Typhimurium from Passerines Reveals Two Lineages Circulating in Europe, New Zealand, and the United States
Authors: Fu Yezhi , M’ikanatha Nkuchia M. , Dudley Edward G.
Published: March 2022

Salmonella enterica serovar Typhimurium from passerines have caused wild bird mortality and human salmonellosis outbreaks in Europe, Oceania, and North America. Here, we performed comparative genomic analysis to explore the emergence, genetic relationship, and evolution of geographically dispersed passerine isolates. We found that passerine isolates from Europe and the United States clustered to form two lineages (EU and US passerine lineages), which were distinct from major S. Typhimurium lineages circulating in other diverse hosts (e.g., humans, cattle, pigs, chicken, other avian hosts such as pigeons and ducks). Further, passerine isolates from New Zealand clustered to form a sublineage (NZ passerine lineage) of the US passerine lineage. We inferred that the passerine isolates mutated at a rate of 3.2 × 10-7 substitutions/site/year, and the US, EU, and NZ passerine lineages emerged in ca. 1952, 1970, and 1996, respectively. Isolates from the three lineages presented genetic similarity such as lack of antimicrobial resistance genes and accumulation of same virulence pseudogenes. In addition, genetic diversity due to microevolution existed in the three passerine lineages. Specifically, pseudogenization in type 1 fimbrial gene fimC (deletion of G at position 87) was only detected in the US and NZ passerine isolates, while a single-base deletion in type 3 secretion system effector genes (i.e., gogB, sseJ, and sseK2) solely concurred in the EU passerine isolates. These findings provide insights into evolution, host adaptation, and epidemiology of S. Typhimurium in passerines.

IMPORTANCE

Passerine-associated S. Typhimurium have been linked to human salmonellosis outbreaks in recent years. Here we investigated the phylogenetic relationship of globally distributed passerine isolates and profiled their genomic similarity and diversity. Our study reveals two passerine-associated S. Typhimurium lineages circulating in Europe, Oceania, and North America. Isolates from the two lineages presented phylogenetic and genetic signatures that were distinct from isolates of other hosts. The findings shed light on host adaptation of S. Typhimurium in passerines and are important for source attribution of S. Typhimurium to avian hosts. Further, we found S. Typhimurium definitive phage type (DT) 160 from passerines that caused decade-long human salmonellosis outbreaks in New Zealand and Australia formed a sublineage of the US passerine lineage, suggesting that DT160 may have originated from passerines outside Oceania. Our study demonstrates the importance of whole-genome sequencing and genomic analysis of historical microbial collections to modern day epidemiologic surveillance.
Application of decision support tool in design-build projects: a quasi-experiment with novice decision makers
Authors: Lee Zheng Ping , Rahman Rahimi A. , Doh Shu Ing
Published: March 2022

Purpose

Design-Build (DB) is known as the alternative for Design-Bid-Build in the Malaysian construction industry. For DB projects, it is critical to adopt effective decision support tool to ensure the execution of a systematic decision-making technique. This study aimed to examine the impact of a decision support tool for novice decision makers to reject or adopt DB for their construction projects.

Design/methodology/approach

Literature review and qualitative input from experts identified several key-selection factors pertaining to critical success factors and design-build drivers. This resulted in the development of Decision Support Tool for Design-Build (DST-DB). A quasi-experiment, which involved 382 novice decision makers in the construction industry, was conducted to test the DST-DB quantitatively. The participants were required to compare two construction projects using DST-DB and traditional decision-making methods. Multivariate analysis was performed to analyse all collected data.

Findings

The quasi-experiment data suggests that DST-DB enables significantly higher usability, likelihood, precision, confidence and satisfaction rate when compared to the traditional decision-making process. The pre- and post-surveys indicated that the DST-DB is effective in improving decision-making performance through selection factors of client-briefing, maximised resources and sharing expertise. The participants also agreed that DST-DB is easy to use and helps them to gain better understanding of the decision-making process for construction projects.

Originality/value

This research contributes to the existing body of knowledge through the impact of DST on the decisions of novices. The novice decision makers found that DST-DB is practically adaptable and comparatively effective for decision-making process than traditional decision-making methods. This contributes to the practical application of construction companies to provide DST-DB training to the fresh graduate employees to enhance their competencies in the decision-making process.
Hybrid nanoliquid flow through a microchannel with particle shape factor, slip and convective regime
Authors: Sindhu S. , B.J. Gireesha , Sowmya G. , Makinde Oluwole Daniel
Published: March 2022

Purpose

This study aims to portray the systematic study of hybrid nanofluid with particle shape effect on significant heat transfer enhancement. The steady flow of hybrid nanoliquid in a microchannel with the aid of porous medium has been considered. The dispersion of copper and Al2O3 in water is taken as hybrid mixture. The impact of thermal radiation, slip length and convective conditions on flow and thermal features are examined numerically.

Design/methodology/approach

The modelled equations are made dimensionless by means of nondimensional entities. The solutions are computed numerically by the implementation of Runge–Kutta-based shooting technique. The results depict that the shape of hybrid mixtures plays a significant role in convective heat transfer. Relevant results on flow velocity, temperature, Nusselt number and friction factor for various physical constraints have been perused. The obtained outcomes are displayed graphically.

Findings

The acquired results depict that Nusselt number augments with Eckert number and solid volume fraction of hybrid nanoparticles, which has a vibrant role in enriching the heat transfer coefficient. Also, it is emphasized that the Nusselt number is larger for blade-shaped nanoparticle compared to other shapes.

Originality/value

The analysis of individual effect of thermal radiation, Joule heating, viscous dissipation and magnetic field on the flow of Cu and Al2O3 hybrid nanofluid through microchannel has vivacious role in augmenting heat transmission. Along with this, the impact of porous medium, shape factor, slip and convective peripheral conditions are also emphasized.
Online branding strategies of family SME wineries: a Hungarian-German comparative study
Authors: Paunovic Ivan , Obermayer Nóra , Kovari Edit
Published: March 2022

Purpose

Both Hungary and Germany belong to the old-world wine-producing countries and have long winemaking traditions. This paper aims at exploring and comparing online branding strategies of family SME (small and medium sized enterprises) wineries at Lake Balaton (Hungary) and Lake Constance (Germany), as two wine regions with similar geographic characteristics.

Design/methodology/approach

This paper, based on a total sample of 37 family wineries, 15 at Lake Balaton and 22 at Lake Constance, investigates the differences in brand identity on the website, brand image in social media and online communication channels deployed in both wine regions. The study applies a qualitative methodology using MaxQDA software for conducting content analysis of texts in websites and social media. Descriptive statistics and t-test were conducted to compare the usage of different communication channels and determine statistical significance.

Findings

At Lake Balaton, the vineyard, the winery and the family, while at Lake Constance, the lake itself and the grape are highlighted regarding family winery brand identity. The customer-based brand image of Hungarian family wineries emphasizes wine, food and service, with the predominant use of Facebook. In the German family wineries, the focus of brand identity is on wine, friendliness and taste and includes more extensive usage of websites.

Originality/value

The paper deploys a novel methodology, both in terms of tools used as well as geographic focus to uncover online branding patterns of family wineries, thereby providing implications for wine and tourism industries at lake regions. It compares the share of selected most-used words in the overall text in websites and in social media, and presents the key findings from this innovative approach.
IFRS adoption and accounting-based performance measures: evidence from an emerging capital market
Authors: Ebaid Ibrahim El-Sayed
Published: March 2022

Purpose

This study aims to examine the economic consequences of the adoption of International Financial Reporting Standards (IFRS) in Saudi Arabia. More specifically, the study examines the impact of the mandatory adoption of IFRS on the accounting-based performance measures.

Design/methodology/approach

Data on study variables were obtained manually from the published financial statements of 67 of listed companies in the Saudi stock market during the period 2014–2019. The study addressed the research hypotheses by comparing the accounting-based performance measures computed under the Saudi accounting standards for three years (2014–2016) before the mandatory adoption of IFRS and the corresponding three years (2017–2019) after the mandatory adoption of IFRS. The Mann–WhitneyUTest was used to investigate the significance of differences between the values of performance measures in the pre- and post-mandatory adoption periods.

Findings

The findings of the study revealed that there were no significant differences between the values of accounting-based performance measures related to the three performance categories (i.e. profitability, liquidity and leverage) in the post-mandatory adoption period (IFRS) compared to the values of these measures in the pre-mandatory adoption period (Saudi accounting standards).

Research limitations/implications

The results of the study indicated that there is a good convergence between the Saudi accounting standards that were implemented before 2017 and the IFRS that began to be applied starting from 2017. This convergence resulted in a low significant impact of IFRS on the financial statements of companies and then on the accounting-based performance measures calculated from them. However, this study suffers from some limitations, the most important of which is the small sample size as a result of the small number of listed companies in the Saudi market during the study period.

Originality/value

Although the impact of the adoption of IFRS have always been a subject of intense research in developed countries, the study of the impact of the adoption of IFRS in developing countries still limited. This study contributes to the literature by examining the economic consequences of adopting IFRS in Saudi Arabia as one of developing countries.