Browse Articles

Immune mechanisms affected by cyclooxygenase inhibition combined with antiviral treatment in calves infected with bovine respiratory syncytial virus

Bovine respiratory syncytial virus (BRSV) infection is a part of the bovine respiratory disease complex. This is one of the most significant problems in both the dairy and beef production sector, inflicting severe economic damage to the industry. BRSV manifests clinically as a respiratory syndrome, affecting both upper and lower respiratory tract, including bronchiolitis with dyspnea and wheezing. It has been shown previously that these symptoms caused by IL-4/IL-13 domination in the immune response are associated with an antibody isotype switch to IgE. Prostaglandin production, such as PGE2 is another factor contributing to the pathogenesis of the disease. In this work we demonstrated the effects of ibuprofen and antiviral fusion protein inhibitor (FPI) separately and combined. We showed the synergistic effect of ibuprofen in combination with FPI on antiviral effects and suppression of PGE2, resulting in improved cytoplasmic toll-like receptor recognition and humoral immune responses mediated by antimicrobial peptide in lungs. We also demonstrated a Th1/Th2 balance shift towards a Th2 response in lungs and mediastinal lymph nodes, favorable to IL-4/IL-13 responses. This shift may explain the factors contributing to higher viral loads and the lack of histopathological improvement with ibuprofen administered without FPI. Additionally, we demonstrated that endocannabinoids may play a crucial role as natural regulators of the inflammation, adaptive immune response, and resolution of the inflammatory process.

Impact of visual stimulus complexity on associative learning and associated reaction times in migraine patients

Abstract The semantic complexity and verbalizability of visual stimuli can influence associative learning. The Rutgers Acquired Equivalence Test (RAET) uses semantically rich stimuli (faces and colored fish) to assess associative learning and generalization, while a modified version, the Polygon test, employs simpler stimuli with reduced semantic content (grayscale circles and geometric shapes). Although cognitive alterations are well-documented in migraine patients during interictal periods, the impact of visual stimulus complexity on associative learning and reaction times has not been studied. Forty-one migraine patients without aura completed both the RAET and Polygon tests. Performance metrics included acquisition error ratios, retrieval and generalization error ratios, and reaction times. The two tests were compared using non-parametric statistical methods. Migraine patients demonstrated comparable acquisition performance on the RAET and Polygon test. However, reaction times were significantly longer in the Polygon test across both acquisition and test phases. Retrieval and generalization performance were also similar between tests, despite longer reaction times with semantically reduced stimuli. Migraine patients showed consistent learning performance across visual stimuli of varying semantic complexity. Prolonged reaction times with simpler stimuli suggest increased cognitive demands, potentially mitigated by cortical compensatory mechanisms that maintain learning ability under challenging conditions.

Iconicity as an organizing principle of the lexicon

The view that words are arbitrary is a foundational assumption about language, used to set human languages apart from nonhuman communication. We present here a study of the alignment between the semantic and phonological structure (systematicity) of American Sign Language (ASL), and for comparison, two spoken languages—English and Spanish. Across all three languages, words that are semantically related are more likely to be phonologically related, highlighting systematic alignment between word form and word meaning. Critically, there is a significant effect of iconicity (a perceived physical resemblance between word form and word meaning) on this alignment: words are most likely to be phonologically related when they are semantically related and iconic. This phenomenon is particularly widespread in ASL: half of the signs in the ASL lexicon are iconically related to other signs, i.e., there is a nonarbitrary relationship between form and meaning that is shared across signs. Taken together, the results reveal that iconicity can act as a driving force behind the alignment between the semantic and phonological structure of spoken and signed languages, but languages may differ in the extent that iconicity structures the lexicon. Theories of language must account for iconicity as a possible organizing principle of the lexicon.

Effect of different origins on genes encoding key enzymes involved in the polysaccharide biosynthetic pathway in Hedysarum polybotrys Hand.-Mazz.

Radix Hedysari (HP) is a traditional Chinese medicine that has gained widespread attention for its tonic effects. Environmental factors significantly influence the active components in HP, notably Radix Hedysari polysaccharides (HPS), which are the principal active constituents. To date, no studies have reported on the environmental impact on the accumulation and biosynthesis of HPS. This research aims to evaluate the HPS accumulation and its biosynthetic pathways across different environments. We measured the HPS levels in samples from the core geographic area (geo-authentic product region) in Wudu, Gansu Province (WD), and a non-core geographic area (non-geo-authentic product region) in Tanchang, Gansu Province (TC), and conducted transcriptomic analyses. The HPS content in HP from WD (HP-WD, 12.14 ± 0.17 mg/g) was significantly higher than that in HP from TC (HP-TC, 5.48 ± 0.29 mg/g). Our investigation into the biosynthetic pathways of HPS showed that 21 enzymes, encoded by 198 unigenes, are involved. We identified 50 unigenes encoding 15 enzymes as differentially expressed genes (DEGs), indicating that approximately 71.4% of these enzymes are substantially affected by environmental factors. Heat map analysis of these 50 DEGs clearly differentiates HP-WD from HP-TC. Pearson correlation analysis revealed that the regulatory genes for 11 key enzymes have a significant positive correlation with HPS content (P <  0.05, r >  0.8). Consequently, the HP-WD is more likely to accumulate polysaccharides than HP-TC, potentially due to the activity of the aforementioned 11 key enzymes. This study provides theoretical support for the enhanced HPS content and quality assessment of HP sourced from the geo-authentic product region.

Biocatalytic production of 3-hydroxypropionic acid precursors using a regioselective Baeyer-Villiger monooxygenase

Daily briefing: Potato pangenome reveals the complex genetics of the humble spud

European Neolithic farmers interbred their domestic pigs with wild boar

Proof of concept study of the posterior quadratus lumborum block for laparoscopic myomectomy: A randomized controlled trial

In the United States, 65,000 myomectomies are performed annually to treat uterine fibroids. The quadratus lumborum block (QLB) is an effective block for laparoscopic pelvic surgery, urologic surgery, hip surgery and cesarean sections, with limited data for laparoscopic myomectomies. We evaluated the posterior QLB in reducing MME consumption and numeric rating scale (NRS) pain scores in patients undergoing laparoscopic myomectomies. Twenty-two subjects were enrolled in this single-center, randomized, controlled study between March 28, 2019 and June 16, 2020 and were randomized to either the QLB or control group. Seven subjects were excluded from the final analysis, 5 after being lost to follow-op and 2 for not meeting the inclusion criteria. Recipients in the QLB group received bilateral posterior QLBs, with 30 mL of 0.25% ropivacaine per injection. The primary outcome of MME use at 24 hours was not significant between the QLB group and the control group (23.3 ± 8.5 mg vs. 25.7 ± 14.4 mg, p = 0.859). The secondary outcome of NRS pain scores was also not significant between groups (p > 0.05). While this study did not provide evidence that QLB may be useful in reducing opioid consumption or pain scores in patients undergoing laparoscopic myomectomies, further studies with a larger sample size will be valuable to determine the effectiveness of this block for laparoscopic myomectomy.

Exploring the association between SNPs and facial morphology in a Spanish population

The multifaceted roles of the transcriptional coactivator TAZ in extravillous trophoblast development of the human placenta

Insights into the molecular processes that drive early development of the human placenta is crucial for our understanding of pregnancy complications such as preeclampsia and fetal growth restriction, since defects in maturation of its epithelial cell, the trophoblast, have been detected in the severe forms of these diseases. However, key regulators specifying the differentiated trophoblast subtypes of the placenta are only slowly emerging. By using diverse trophoblast cell models, we herein show that the transcriptional coactivator of HIPPO signaling, TAZ, plays a pivotal role in the development of invasive extravillous trophoblasts (EVTs), cells that are essential for decidual vessel remodeling and adaption of maternal blood flow to the placenta. Ribonucleic acid sequencing (RNA-seq) or protein analyses upon TAZ gene silencing or CRISPR-Cas9-mediated knockout in differentiating trophoblast stem cells, organoids, primary EVTs, choriocarcinoma cells, or villous explant cultures unraveled that the coactivator promoted expression of genes associated with EVT identity, motility, and survival. Accordingly, depletion or chemical inhibition of TAZ, interacting with TEA domain family member 1 (TEAD1), impaired EVT differentiation, invasion, and migration and triggered apoptosis in the different trophoblast models. Notably, the coactivator also suppressed cell cycle genes and regulators of trophoblast self-renewal and prevented EVTs from cell fusion in organoids and primary cultures. Moreover, TAZ promoted human leukocyte antigen G (HLA-G) surface expression and increased NUAK1 kinase in EVTs thereby maintaining its own expression. In summary, the transcriptional coactivator TAZ plays a multifaceted role in the development of the EVT cell lineage by controlling different biological processes that initiate and preserve differentiation.

Correction: The use of dance to improve the health and wellbeing of older adults: A global scoping review of research trials

Sensorless anti-control and synchronization of chaos of brushless DC motor driver

A rare variant in <i>GPR156</i> associated with depression in a Mennonite pedigree causes habenula hyperactivity and stress sensitivity in mice

Major depressive disorder (MDD) is a leading cause of disability worldwide. Risk for MDD is heritable, and the genetic structure of founder populations enables investigation of rare susceptibility alleles with large effect. In an extended Old Order Mennonite family cohort, we identified a rare missense variant in GPR156 (c.1599G&gt;T, p.Glu533Asp) associated with a two-fold increase in the relative risk of MDD. GPR156 is an orphan G protein–coupled receptor localized in the medial habenula, a region implicated in mood regulation. Insertion of a human sequence containing c.1599G&gt;T into the murine Gpr156 locus induced medial habenula hyperactivity and abnormal stress-related behaviors. This work reveals a human variant that is associated with depression, implicates GPR156 as a target for mood regulation, and introduces informative murine models for investigating the pathophysiology and treatment of affective disorders.

“Support for my dad would have benefited me because I was the one looking after him”: A qualitative analysis of the support needs of young people exposed to Adverse Childhood Experiences

Background Adverse childhood experiences (ACEs) are associated with negative health and wellbeing outcomes. Ensuring young people receive timely and appropriate support after experiencing ACEs could improve these outcomes. Objective This study aimed to explore what works to support young people living with ACEs; what support do they receive, and what are the characteristics of valuable help? Participants and Setting Young people living in Wales aged 16–18 years (n = 559) completed an online survey about their ACEs and the help they did or did not receive with these experiences. Methods Free text responses were analysed using reflexive thematic analysis. Public involvement workshops with young people were utilised to guide the analytic process. Results Few participants reported accessing enough support. Five themes were developed: “Help me by helping my family”, “Talking to a trusted adult is helpful… until it’s not”, “Being informed: ‘I was kept in the loop’”, “Schools and colleges as sites of support” and “Loneliness and peer support”. Conclusions More support is needed for young people with ACEs. Young people find it helpful when their whole family is supported in times of adversity, not blamed. People who provide support should be empathic and non-judgmental. Young people would rather be spoken to about ACEs and ‘kept in the loop’ than have them treated as a taboo or sensitive subject. Experiencing ACEs can be lonely in the absence of peer support. Schools and colleges are acceptable sites of support and may be well placed to provide opportunities for peer support.

Advanced leukocyte classification using attention mechanisms and dual channel U-Net architecture

Abstract Leukocytes or white blood cells plays an important role in protecting the body from various contagious diseases and infectious agents. Different conventional leukocyte analysis approaches often face several problems like inaccuracies, demanding the need for sophisticated approaches to improve diagnostic precision. Therefore, a holistic structure namely a novel Attention-based Dual Channel U-shaped Network (ADCU-Net) utilizing three datasets is introduced in this paper for effective leukocyte classification. The image quality is boosted in the preprocessing phase through noise reduction, contrast enhancement, and background removal, significantly improving clarity. Then, the Dung Beetle Optimization (DBO) algorithm enhanced with Levy flight optimization is implemented for effective image segmentation processes. A dung beetle with a levy flight strategy assists in streamlined exploration of the search space thereby the detection and delineation of specific regions within images are improved, which results in higher boundary detection accuracy. The evaluation of major quantitative measures such as standard deviation, mean and entropy is comprised in the feature extraction process which offers crucial insights into the structural characteristics of leukocytes. Finally, a novel ADCU-Net model is utilized for the effective classification process. This ADCU-Net model is particularly selected to effectively capture various features and preserve spatial data, achieving98.4% accuracy. Overall, this paper highlights the performance of integrated sophisticated deep-learning structures for accurate leukocyte classification and segmentation, enabling the path for improved diagnostic tools in clinical settings.

Temperature thresholds induce abrupt shifts in biodiversity and ecosystem services in montane ecosystems worldwide

Montane ecosystems are crucial for maintaining global biodiversity and function that sustain life on our planet. Yet, these ecosystems are highly vulnerable to changing temperatures and may undergo critical transitions under ongoing climate change. What we do not know is to what extent montane biodiversity and ecosystem services will respond to local temperature variations in a gradual versus abrupt manner across global environments. To fill this knowledge gap, we conducted a global synthesis, including 4,462 observations from 290 elevation gradients, to investigate how biodiversity (spanning animals and plants) and ecosystem services (including plant production, soil carbon, and fertility) respond to local temperature variations along elevation gradients. We found that nearly one-third of these gradients exhibited abrupt shifts in multiple biodiversity and ecosystem services in response to local variations in temperature along elevation gradients. More specifically, we showed that once a particular local temperature level (~10 °C for mean annual temperature) was reached, even small increases in temperature resulted in dramatic variations in biodiversity and ecosystem services. We further showed that those abrupt shifts in response to local temperature increases were commonly positive for plant and animal diversity, as well as plant production, while soil carbon and fertility more commonly exhibit negative abrupt trends. Our work, based on the most comprehensive empirical evidence available so far, reveals the pervasive abrupt responses of biodiversity and ecosystem services to local temperature variations in montane ecosystems worldwide, highlighting the highly sensitive nature of montane ecosystems in the context of climate change.

Correction: Age and political leaning predict COVID-19 vaccination status at a large, multi-campus, public university in Pennsylvania: A cross-sectional survey

Modeling the effect of scale deposition on heat transfer in injection molding

Abstract The advent of additive manufacturing technologies has revolutionized the design and application of injection molds with conformal cooling systems. These mold inserts, manufactured directly from metal powder, feature complex geometries that align with the part contours, enabling more efficient and uniform heat extraction than traditional cooling methods. However, over time, even the most efficient cooling circuits degrade due to corrosion, limescale, and other deposition on the cooling channel walls, significantly decreasing heat transfer. We developed finite element models to simulate various deposition scenarios to address the complexity of modeling these depositions and their impact on heat transfer. Our study evaluates the thermal conductivity and thickness of deposit layers in conventional and conformal cooling channels. The resulting universal model accurately predicts the cooling efficiency of injection molds produced of various mold material, considering arbitrary deposition characteristics, e.g. limescale and corrosion. This model makes optimizing cooling systems for injection molds easier, thus providing crucial information on the time limit of the predictive maintenance and the mold performance change.

SNX10 deficiency impairs sensitivity to anti-HER2 antibody–drug conjugates via altering HER2 trafficking in HER2-positive breast cancer

Antibody–drug conjugates (ADCs) are a rapidly developing therapeutic approach in cancer treatment that has shown remarkable efficacy in breast cancer. Despite the promising efficacy of anti-HER2 ADCs, many patients are still experiencing disease progression under treatment. Here, by analyzing the transcriptome data from patient-derived organoid models, I-SPY2 trial, and resistant cell lines, we identified that SNX10 deficiency conferred anti-HER2 ADCs resistance in HER2-positive breast cancer. Low levels of SNX10 attenuated HER2 recycling and promoted HER2 trafficking into lysosomes. Furthermore, we found the underlying mechanism of SNX10 in HER2 traffic by regulating the endosomal RAB11A. We propose that SNX10 deficiency contributes to the inhibition of HER2 recycling as well as the decrease of cell-surface HER2 and causes anti-HER2 ADC resistance.

Analysis of structural and metabolic changes in surface microorganisms following powdery mildew infection in wheat and assessment of their potential function in biological control

Powdery mildew is a highly destructive disease that greatly reduces both the yield and quality of wheat. As there is limited research on changes in microorganism community caused by powdery mildew infection in different tissue parts, especially after spike infection, this study aimed to examine surface microorganisms in infected and healthy wheat plants. Samples were collected from the leaves and spikes, and the number of operational taxonomic units (OTUs), diversity index, abundance, and metabolic changes of the surface microbial community were analysed using 16S rRNA amplicon sequencing technology. Through the identification of surface microbial community in different tissues, 24 phyla were identified in the leaves, and 20 phyla were identified in the spikes. The dominant bacterial phyla observed were Proteobacteria and Bacteroidetes. At the genus level, 19 genera were detected in the leaves, and 11 genera were detected in the spikes. Notably, the total number of genera in the leaves exceeded that in the spikes. The dominant genera were Pseudomonas, Sphingomonas, and Pantoea. At the species level, there were 37 types identified in leaves and 35 types in spikes. The dominant bacterial species identified included Pedobacterium panaciterrae, Pseudomonas baetica, Pseudomonas rhizophaerae, and Sphingomonas aerolata. The analysis conducted in this study revealed that the incidence of powdery mildew was greater in plots situated closer to obstacles than in other plots. Notably, when wheat was infected with powdery mildew, the results indicated that surface microorganisms on both leaves and spikes were significantly impacted, with the response of surface microorganisms on the spikes being more pronounced than that on the leaves. Different from the response of microorganisms on the leaf surface, after infection with powdery mildew, the pathway changes of microorganisms on the spike surface are mainly metabolic regulation. These research results provide theoretical support for the prevention and control of powdery mildew in wheat crops.