Miracle-dz/UniFAR-FTUs huggingface dataset:
Neurobehavioral Correlates of Surprisal in Language Comprehension: A Neurocomputational Model

Expectation-based theories of language comprehension, in particular Surprisal Theory, go a long way in accounting for the behavioral correlates of word-by-word processing difficulty, such as reading times. An open question, however, is in which component(s) of the Event-Related brain Potential (ERP) signal Surprisal is reflected, and how these electrophysiological correlates relate to behavioral processing indices. Here, we address this question by instantiating an explicit neurocomputational model of incremental, word-by-word language comprehension that produces estimates of the N400 and the P600—the two most salient ERP components for language processing—as well as estimates of “comprehension-centric” Surprisal for each word in a sentence. We derive model predictions for a recent experimental design that directly investigates “world-knowledge”-induced Surprisal. By relating these predictions to both empirical electrophysiological and behavioral results, we establish a close link between Surprisal, as indexed by reading times, and the P600 component of the ERP signal. The resultant model thus offers an integrated neurobehavioral account of processing difficulty in language comprehension.
Prediction of Lymph-Node Metastasis in Cancers Using Differentially Expressed mRNA and Non-coding RNA Signatures

Accurate prediction of lymph-node metastasis in cancers is pivotal for the next targeted clinical interventions that allow favorable prognosis for patients. Different molecular profiles (mRNA and non-coding RNAs) have been widely used to establish classifiers for cancer prediction (e.g., tumor origin, cancerous or non-cancerous state, cancer subtype). However, few studies focus on lymphatic metastasis evaluation using these profiles, and the performance of classifiers based on different profiles has also not been compared. Here, differentially expressed mRNAs, miRNAs, and lncRNAs between lymph-node metastatic and non-metastatic groups were identified as molecular signatures to construct classifiers for lymphatic metastasis prediction in different cancers. With this similar feature selection strategy, support vector machine (SVM) classifiers based on different profiles were systematically compared in their prediction performance. For representative cancers (a total of nine types), these classifiers achieved comparative overall accuracies of 81.00% (67.96–92.19%), 81.97% (70.83–95.24%), and 80.78% (69.61–90.00%) on independent mRNA, miRNA, and lncRNA datasets, with a small set of biomarkers (6, 12, and 4 on average). Therefore, our proposed feature selection strategies are economical and efficient to identify biomarkers that aid in developing competitive classifiers for predicting lymph-node metastasis in cancers. A user-friendly webserver was also deployed to help researchers in metastasis risk determination by submitting their expression profiles of different origins.
Myocardial Iron Overload in an Experimental Model of Sudden Unexpected Death in Epilepsy

Uncontrolled repetitive generalized tonic-clonic seizures (GTCS) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). GTCS can be observed in models such as Pentylenetetrazole kindling (PTZ-K) or pilocarpine-induced Status Epilepticus (SE-P), which share similar alterations in cardiac function, with a high risk of SUDEP. Terminal cardiac arrhythmia in SUDEP can develop as a result of a high rate of hypoxic stress-induced by convulsions with excessive sympathetic overstimulation that triggers a neurocardiogenic injury, recently defined as “Epileptic Heart” and characterized by heart rhythm disturbances, such as bradycardia and lengthening of the QT interval. Recently, an iron overload-dependent form of non-apoptotic cell death called ferroptosis was described at the brain level in both the PTZ-K and SE-P experimental models. However, seizure-related cardiac ferroptosis has not yet been reported. Iron overload cardiomyopathy (IOC) results from the accumulation of iron in the myocardium, with high production of reactive oxygen species (ROS), lipid peroxidation, and accumulation of hemosiderin as the final biomarker related to cardiomyocyte ferroptosis. Iron overload cardiomyopathy is the leading cause of death in patients with iron overload secondary to chronic blood transfusion therapy; it is also described in hereditary hemochromatosis. GTCS, through repeated hypoxic stress, can increase ROS production in the heart and cause cardiomyocyte ferroptosis. We hypothesized that iron accumulation in the “Epileptic Heart” could be associated with a terminal cardiac arrhythmia described in the IOC and the development of state-potentially in the development of SUDEP. Using the aforementioned PTZ-K and SE-P experimental models, after SUDEP-related repetitive GTCS, we observed an increase in the cardiac expression of hypoxic inducible factor 1α, indicating hypoxic-ischemic damage, and both necrotic cells and hemorrhagic areas were related to the possible hemosiderin production in the PTZ-K model. Furthermore, we demonstrated for the first time an accumulation of hemosiderin in the heart in the SE-P model. These results suggest that uncontrolled recurrent seizures, as described in refractory epilepsy, can give rise to high hypoxic stress in the heart, thus inducing hemosiderin accumulation as in IOC, and can act as an underlying hidden mechanism contributing to the development of a terminal cardiac arrhythmia in SUDEP. Because iron accumulation in tissues can be detected by non-invasive imaging methods, cardiac iron overload in refractory epilepsy patients could be treated with chelation therapy to reduce the risk of SUDEP.
ER-PM Contact Sites – SNARING Actors in Emerging Functions

The compartmentalisation achieved by confining cytoplasm into membrane-enclosed organelles in eukaryotic cells is essential for maintaining vital functions including ATP production, synthetic and degradative pathways. While intracellular organelles are highly specialised in these functions, the restricting membranes also impede exchange of molecules responsible for the synchronised and responsive cellular activities. The initial identification of contact sites between the ER and plasma membrane (PM) provided a potential candidate structure for communication between organelles without mixing by fusion. Over the past decades, research has revealed a far broader picture of the events. Membrane contact sites (MCSs) have been recognized as increasingly important actors in cell differentiation, plasticity and maintenance, and, upon dysfunction, responsible for pathological conditions such as cancer and neurodegenerative diseases. Present in multiple organelles and cell types, MCSs promote transport of lipids and Ca2+ homoeostasis, with a range of associated protein families. Interestingly, each MCS displays a unique molecular signature, adapted to organelle functions. This review will explore the literature describing the molecular components and interactions taking place at ER-PM contact sites, their functions, and implications in eukaryotic cells, particularly neurons, with emphasis on lipid transfer proteins and emerging function of SNAREs.
Descriptive Analysis of Heavy Metals Content of Beef From Eastern Uganda and Their Safety for Public Consumption

In this study, we initiated an effort to generate information about beef safety in Uganda. Our entry point was to assess by atomic absorption spectrophotometry the levels of essential elements copper (Cu), cobalt (Co), iron (Fe) and zinc (Zn), and non-essential elements lead (Pb), chromium (Cr), nickel (Ni), and cadmium (Cd) in 40 beef samples collected from within and around Soroti (Uganda). The information was used to evaluate the safety of consuming such beef against the World Health Organization (WHO) limits. The latter was accomplished by (i) estimating the daily intake (EDI) of each metal in the study area, (ii) modeling the non-cancer health risk using the target hazard quotient (THQ) and (iii) modeling the cancer risk using the incremental lifetime cancer risk (ILCR). The study finds that the mean concentrations (±95% CI) and EDI were in the order of Fe > Zn > Cr > Ni > Pb > Co > Cu > Cd. Cancer risk was found to be due to Ni > Cr > Cd > Pb and significantly higher in children than adults. The latter particularly demonstrates the importance of Ni poisoning in the study area. Overall, while essential elements in our beef samples were below WHO limits (hence no health risks), non-essential elements had high health and cancer risks due to higher levels of Cr and Ni.
MiR-132-3p Modulates MEKK3-Dependent NF-κB and p38/JNK Signaling Pathways to Alleviate Spinal Cord Ischemia-Reperfusion Injury by Hindering M1 Polarization of Macrophages

Spinal cord ischemia-reperfusion (SCIR) injury is a serious complication of open surgical and endovascular aortic procedures. MicroRNA-132-3p (miR-132-3p) has been reported to be involved in the progression of various diseases, but its role in SCIR injury is unclear. Thus, we aimed in this study to investigate the mechanism of miR-132-3p in SCIR injury and explore its pathway as a therapeutic target for SCIR injury. We first constructed a SCIR injury rat model and documented motor function in the model. Reverse transcription quantitative polymerase chain reaction (RT-qPC)R and Western blot analysis were used to detect the expression of miR-132-3p and mitogen-activated protein kinase kinase kinase 3 (MEKK3) in SCIR injury rats. The interaction between miR-132-3p and MEKK3 was identified by dual-luciferase reporter gene assay. Then, the effects of miR-132-3p and MEKK3 on macrophage M1 polarization were evaluated in vitro and in vivo by altering their expression in macrophages of SCIR injury rats, with treatments altering the nuclear factor-kappaB (NF-κB) and c-Jun N-terminal kinase (JNK)/p38 signaling pathways using SP600125, SB203580, or PDTC. The SCIR injury rats had a high Tarlov score and low miR-132-3p expression along with high MEKK3 expression. miR-132-3p could directly bind to MEKK3, and that macrophage M1 polarization and inflammation could be inhibited by overexpression of miR-132-3p through downregulating MEKK3 and inactivating the NF-κB and p38/JNK signaling pathways. Besides, increased miR-132-3p expression could decrease the injured rat Tarlov score. Overall, our study demonstrated that miR-132-3p can suppress M1 polarization of macrophages and alleviate SCIR injury by blocking the MEKK3-dependent activation of the NF-κB and p38/JNK signaling pathway. Thus, miR-132-3p and its downstream pathways may be useful targets to alleviate the symptoms of SCIR injury.
Immunomodulatory Effects of Rhinovirus and Enterovirus Infections During the First Year of Life

Early childhood infections have been implicated in the development of immune-mediated diseases, such as allergies, asthma, and type 1 diabetes. We set out to investigate the immunomodulatory effects of early viral infections experienced before the age of one year on the peripheral regulatory T cell population (Treg) and circulating cytokines in a birth-cohort study of Estonian and Finnish infants. We show here a temporal association of virus infection with the expression of FOXP3 in regulatory T cells. Infants with rhinovirus infection during the preceding 30 days had a higher FOXP3 expression in Treg cells and decreased levels of several cytokines related to Th1 and Th2 responses in comparison to the children without infections. In contrast, FOXP3 expression was significantly decreased in highly activated (CD4+CD127−/loCD25+FOXP3high) regulatory T cells (TregFOXP3high) in the infants who had enterovirus infection during the preceding 30 or 60 days. After enterovirus infections, the cytokine profile showed an upregulation of Th1- and Th17-related cytokines and a decreased activation of CCL22, which is a chemokine derived from dendritic cells and associated with Th2 deviation. Our results reveal that immunoregulatory mechanisms are up-regulated after rhinovirus infections, while enterovirus infections are associated with activation of proinflammatory pathways and decreased immune regulation.
Plant Hormone-Mediated Regulation of Heat Tolerance in Response to Global Climate Change

Agriculture is largely dependent on climate and is highly vulnerable to climate change. The global mean surface temperatures are increasing due to global climate change. Temperature beyond the physiological optimum for growth induces heat stress in plants causing detrimental and irreversible damage to plant development, growth, as well as productivity. Plants have evolved adaptive mechanisms in response to heat stress. The classical plant hormones, such as auxin, abscisic acid (ABA), brassinosteroids (BRs), cytokinin (CK), salicylic acid (SA), jasmonate (JA), and ethylene (ET), integrate environmental stimuli and endogenous signals to regulate plant defensive response to various abiotic stresses, including heat. Exogenous applications of those hormones prior or parallel to heat stress render plants more thermotolerant. In this review, we summarized the recent progress and current understanding of the roles of those phytohormones in defending plants against heat stress and the underlying signal transduction pathways. We also discussed the implication of the basic knowledge of hormone-regulated plant heat responsive mechanism to develop heat-resilient plants as an effective and efficient way to cope with global warming.
Biologics During Pregnancy and Breastfeeding Among Women With Rheumatic Diseases: Safety Clinical Evidence on the Road

Females are generally more affected by autoimmune diseases, a fact that underlines the relationship with pregnancy and the safety of anti-rheumatic drugs in pregnancy and lactation. Biologic therapies are increasingly prescribed to treat and maintain remission in a significant number of systemic autoimmune rheumatic diseases. The experience with the use of biologics during gestation is extremely lacking because of the observational nature of the available studies and the difficulty in designing proper clinical trials in pregnancy. Among the studied biologics, more information was published on TNFα inhibitors and, in particular, on their potential passage through the placenta and impact on the fetus. Currently, a fragment of anti-TNFα monoclonal IgG, certolizumab pegol, is considered safe with almost no placental transfer. Subsequent observations are suggesting a comparable safety for the soluble TNFα receptor etanercept. Another biologic, eculizumab, the anti-C5a antibody used to treat complement-mediated microangiopathies, is also considered safe due to the unique engineered IgG2/4κ formulation that limits its passage through the placental barrier. Still, long-term data about children born to women treated with biologics in pregnancy are not attainable. Data on breastfeeding are currently available for several biologics. This article reviews the literature available about which drugs are considered safe during pregnancy and lactation, which are not, and on future prospects.
The Mysterious Island: Insula and Its Dual Function in Sleep and Wakefulness

In the recent sleep studies, it was shown that afferentation of many cortical areas switches during sleep to the interoceptive one. However, it was unclear whether the insular cortex, which is often considered as the main cortical visceral representation, maintains the same effective connectivity in both states of vigilance, or processes interoceptive information predominantly in one state. We investigated neuronal responses of the cat insular cortex to electrical stimulations of the intestinal wall delivered during wakefulness and natural sleep. Marked increase was observed in the number of insular neurons responding to this stimulation in sleep comparing to wakefulness, and enlarged amplitudes of evoked local field potentials were found as well. Moreover, most of the cells responding to intestinal stimulation in wakefulness never responded to identical stimuli during sleep and vice versa. It was also shown that applied low intensity intestinal stimulations had never compromised sleep quality. In addition, experiments with microstimulation of the insular cortex and recording of intestinal myoelectric activity demonstrated that effective insula-to-gut propagation also happened only during sleep. On the other hand, the same insular stimulations in wakefulness led to contractions of orofacial muscles. The evoked face movements gradually disappeared in the course of sleep development. These findings demonstrate that pattern of efficient afferent and efferent connections of the insular cortex changes with transition from wakefulness to sleep.
Arthroscopic Guided Synovial Biopsies

Synovial tissue can be safely and reliably collected for research and clinical purposes using arthroscopy. This technique offers the obvious advantage of allowing direct visualization, and targeted biopsy of specific areas of interest within the joint, as well as for the collection of tissue which will include a lining layer. Much has been learnt by studying the synovium retrieved using this technique concerning the pathobiology of inflammatory arthritis. Furthermore, recent evidence suggests that the tissue retrieved may enable the identification of unique pathotypes that will allow for a precise approach to treatment selection in individual patients. Although ultrasound guided techniques for sampling synovial tissue have gained in popularity over the last decade, both methodologies are expected to compliment each other, each having unique benefits and drawbacks. We present here a detailed description of the arthroscopy technique reporting on our collective experience at two centers in Europe.
MicroRNA-142-3p Inhibits Tumorigenesis of Colorectal Cancer via Suppressing the Activation of Wnt Signaling by Directly Targeting to β-Catenin

Background Altered expression profile of microRNAs (miRNAs) was reported to be associated with colorectal cancer (CRC). The aims of this study are to identify the changed miRNAs in the plasma of CRC patients and explore the underlying mechanism of these miRNAs during tumorigenesis. Methods Plasma miRNA expression profiles were compared between healthy people and CRC patients. MiRNA expression was measured using quantitative real-time PCR. Colony formation and MTT assays were used to test cell proliferation. Luciferase assay, immunohistochemistry and Western blotting were employed to explore the molecular mechanism. Results MiR-142-3p level was found as the most significantly repressed miRNA in CRC patients. Overexpression of miR-142-3p dramatically repressed colony formation and cell proliferation of both HT29 and HCT116 cells while inhibition of miR-142-3p promoted those of the cells. Interestingly, overexpression of miR-142-3p reduced the level and nuclear accumulation of β-catenin. We further observed that miR-142-3p remarkably inhibited the transcriptional activity of β-catenin gene (CTNNB1). However, mutations in the predicted binding sites blocked this inhibition, suggesting that miR-142-3p may directly bind to the mRNA of β-catenin. Conclusion In conclusion, we identified miR-142-3p exerts its function as a tumor suppressor through blocking the activation of Wnt signaling by directly targeting to CTNNB1.
Cholinergic and α-Adrenergic Stimulation of Prostaglandin Release by Dog Thyroid in Vitro*

Dog thyroid slices released in their incubation medium prostaglandins E2 (PGE2), F2 alpha (PGF2 alpha), 15-keto-13,14-dihydro-F2 alpha, and thromboxane B2 (TxB2), as measured by direct RIA. This release could be inhibited by indomethacin and naproxen, indicating that it corresponded to a neosynthesis. Carbamylcholine (2--100 microns) stimulated the release of PGE2, PGF2 alpha, and TxB2, whereas epinephrine (20 microns to 1 nM) enhanced the release of PGE2 and PGF2 alpha but had no effect on TxB2. These stimulations were inhibited by atropine and dihydroergocryptine, respectively, suggesting that a muscarinic and an alpha-adrenergic receptor were involved. The ionophore A23187 reproduced these stimulations, and the stimulatory effects of carbamylcholine and epinephrine were inhibited in the absence of exogenous Ca++ and after EGTA depletion. Ca++ thus appears as a major regulator of PG production in the thyroid. TSH (0.06--10 MU/ml) and dibutyryl cAMP had no effect on the release of PGE2, PGF2 alpha, or TxB2 by dog thyroid in vitro.
Increased Abundance of Tumour-Associated Neutrophils in HPV-Negative Compared to HPV-Positive Oropharyngeal Squamous Cell Carcinoma Is Mediated by IL-1R Signalling

The incidence of human papillomavirus (HPV)-associated cancer is increasing and HPV is now implicated in the aetiology of more than 60% of all oropharyngeal squamous cell carcinomas (OPSCC). In OPSCC, innate immune cells such as neutrophils and macrophages generally correlate with poor prognosis, whilst adaptive immune cells, such as lymphocytes, tend to correlate with improved prognosis. This may, in part, be due to differences in the immune response within the tumour microenvironment leading to the recruitment of specific tumour-associated leukocyte sub-populations. In this study, we aimed to examine if differences exist in the levels of infiltrated leukocyte sub-populations, with particular emphasis on tumour-associated neutrophils (TAN), and to determine the mechanism of chemokine-induced leukocyte recruitment in HPV-positive compared to HPV-negative OPSCC. Immunohistochemical analysis showed that HPV-negative OPSCC contained significantly more neutrophils than HPV-positive tumours, whilst levels of CD68+ macrophages and CD3+ lymphocytes were similar. Using a 3D tissue culture model to represent tumour-stromal interactions, we demonstrated that HPV-negative tumour-stromal co-cultures expressed significantly higher levels of CXCL8, leading to increased neutrophil recruitment compared to their HPV-positive counterparts. HPV-negative OPSCC cells have previously been shown to express higher levels of IL-1 than their HPV-positive counterparts, indicating that this cytokine may be responsible for driving increased chemokine production in the HPV-negative 3D model. Inhibition of IL-1R in the tumour-stromal models using the receptor-specific antagonist, anakinra, dramatically reduced chemokine secretion and significantly impaired neutrophil and monocyte recruitment, suggesting that this tumour-stromal response is mediated by the IL-1/IL-1R axis. Here, we identify a mechanism by which HPV-negative OPSCC may recruit more TAN than HPV-positive OPSCC. Since TAN are associated with poor prognosis in OPSCC, our study identifies potential therapeutic targets aimed at redressing the chemokine imbalance to reduce innate immune cell infiltration with the aim of improving patient outcome.
Phenotypic Variation in an Asexual-Sexual Fish System: Visual Lateralization

Sexual reproduction is nearly ubiquitous in the vertebrate world, yet its evolution and maintenance remain a conundrum due to the cost of males. Conversely, asexually reproducing species should enjoy a twofold population increase and thus replace sexual species all else being equal, but the prevalence of asexual species is rare. However, stable coexistence between asexuals and sexuals does occur and can shed light on the mechanisms asexuals may use in order to persist in this sex-dominated world. The asexual Amazon molly (Poecilia formosa) is required to live in sympatry with one of its sexual sperm hosts –sailfin molly (Poecilia latipinna) and Atlantic molly (Poecilia mexicana)—and are ecological equivalents to their host species in nearly every way except for reproductive method. Here, we compare the visual lateralization between Amazon mollies and sailfin mollies from San Marcos, Texas. Neither Amazon mollies nor sailfin mollies exhibited a significant eye bias. Additionally, Amazon mollies exhibited similar levels of variation in visual lateralization compared to the sailfin molly. Further investigation into the source of this variation –clonal lineages or plasticity—is needed to better understand the coexistence of this asexual-sexual system.