Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of orexin‐1 receptors in the ventrolateral periaqueductal grey matter (vlPAG) modulates pulpal nociception and the induction of substance P in vlPAG and trigeminal nucleus caudalis

AIM To characterize the role of orexin-1 receptors (OX1Rs) in ventrolateral periaqueductal grey matter (vlPAG) on modulation of capsaicin-induced pulpal nociception in rats. METHODOLOGY Sixty-six adult male Wistar rats (2 months old) weighing between 230 and 260 g were used. The animals were cannulated for microinjection of drugs into the vlPAG matter. Pulpalgia was induced by intradental application of capsaicin solution (100 μg) into the incisor teeth of the rats. Ten min prior to capsaicin application, orexin-A (50, 100 and 150 pmol L-1 per rat) was administered. Orexin-A (150 pmol L-1 ) was also co-administrated with SB-334867 (40 nmol L-1 per rat), an OX1Rs antagonist; or bicuculline (1 μg per rat), a GABAA receptors antagonist. Moreover, treatment effects on the release of pro-nociceptive modulator substance P (SP) in vlPAG and trigeminal nucleus caudalis (Vc) of rats were explored using an immunofluorescence technique. One-way analysis of variance was used for the statistical analysis. RESULTS Orexin-A dose-dependently decreased capsaicin-induced nociceptive behaviour. However, SB-334867 (40 nmol L-1 per rat) pretreatment (P < 0.05), but not bicuculline (1 μg per rat), attenuated the analgesic effect of orexin-A (150 pmol L-1 ). The level of SP was significantly increased in Vc and decreased in vlPAG of capsaicin-treated rats (P < 0.05). Capsaicin-induced changes in SP levels, however, were prohibited by orexin-A treatment (150 pmol L-1 ) (P < 0.05). CONCLUSIONS Orexin-A administration into the vlPAG was associated with an inhibitory effect on capsaicin-induced pulpal nociception and bidirectional effects on the induction of SP in vlPAG and Vc of rats. Central activation of OX1Rs is a potential therapeutic tool for pulpalgia.
Arabidopsis Protein Kinase D6PKL3 Is Involved in the Formation of Distinct Plasma Membrane Aperture Domains on the Pollen Surface[OPEN]

Screening of natural Arabidopsis accessions reveals a membrane-associated protein kinase involved in pollen aperture development and the formation of distinct membrane domains in microspores. Certain regions on the surfaces of developing pollen grains exhibit very limited deposition of pollen wall exine. These regions give rise to pollen apertures, which are highly diverse in their patterns and specific for individual species. Arabidopsis thaliana pollen develops three equidistant longitudinal apertures. The precision of aperture formation suggests that, to create them, pollen employs robust mechanisms that generate distinct cellular domains. To identify players involved in this mechanism, we screened natural Arabidopsis accessions and discovered one accession, Martuba, whose apertures form abnormally due to the disruption of the protein kinase D6PKL3. During pollen development, D6PKL3 accumulates at the three plasma membrane domains underlying future aperture sites. Both D6PKL3 localization and aperture formation require kinase activity. Proper D6PKL3 localization is also dependent on a polybasic motif for phosphoinositide interactions, and we identified two phosphoinositides that are specifically enriched at the future aperture sites. The other known aperture factor, INAPERTURATE POLLEN1, fails to aggregate at the aperture sites in d6pkl3 mutants, changes its localization when D6PKL3 is mislocalized, and, in turn, affects D6PKL3 localization. The discovery of aperture factors provides important insights into the mechanisms cells utilize to generate distinct membrane domains, develop cell polarity, and pattern their surfaces.
Geometric Features-Based Parking Slot Detection

In this paper, we propose a parking slot markings detection method based on the geometric features of parking slots. The proposed system mainly consists of two steps, namely, separating line detection and parking slot entrance detection. First, in the separating line detection stage, we propose a line-clustering method based on the line segment detection (LSD) algorithm. Our detecting and line-clustering algorithm can detect the separating lines that contain a pair of parallel lines with a fixed distance in a bird’s eye view (BEV) image under diverse lighting and ground conditions. Consequently, parking slot candidates are generated by pairing the separating lines according to the width of the parking slots. In the parking slot entrance detection process, we propose a multiview fusion-based learning approach that can increase the number of training samples by performing a perspective transformation on the acquired BEV images. The proposed method was evaluated using 353 BEV images covering diverse parking slot markings. Experiments show that the proposed method can recognize typical perpendicular and parallel rectangular parking slots, and a precision of 97.4% and recall of 96.6% are achieved.
The plant pathogen Pseudomonas aeruginosa triggers a DELLA-dependent seed germination arrest in Arabidopsis

To anticipate potential seedling damage, plants block seed germination under unfavorable conditions. Previous studies investigated how seed germination is controlled in response to abiotic stresses through gibberellic and abscisic acid signaling. However, little is known about whether seeds respond to rhizosphere bacterial pathogens. We found that Arabidopsis seed germination is blocked in the vicinity of the plant pathogen Pseudomonas aeruginosa. We identified L-2-amino-4-methoxy-trans-3-butenoic acid (AMB), released by P. aeruginosa, as a biotic compound triggering germination arrest. We provide genetic evidence that in AMB-treated seeds DELLA factors promote the accumulation of the germination repressor ABI5 in a GA-independent manner. AMB production is controlled by the quorum sensing system IQS. In vitro experiments show that the AMB-dependent germination arrest protects seedlings from damage induced by AMB. We discuss the possibility that this could serve as a protective response to avoid severe seedling damage induced by AMB and exposure to a pathogen.
Association of Elevated Serum GM-CSF, IFN-γ, IL-4, and TNF-α Concentration with Tobacco Smoke Induced Chronic Obstructive Pulmonary Disease in a South Indian Population

Background Chronic obstructive pulmonary disease (COPD) is a devastating condition with limited pharmacotherapeutic options and exceptionally high public-health burden globally as well as in India. Tobacco smoking is the primary cause for COPD among men in India. Systemic inflammation involving altered regulation of cytokines controlling the host defense mechanism is a hallmark of COPD pathogenesis. However, biomarker discovery studies are limited among Indian COPD patients. Methods We assessed the serum concentrations [median (25th-75th percentile) pg/ml] of interleukin (IL)-2,4,6,8,10, granulocyte macrophage colony stimulating factor (GM-CSF), interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α) using a multiplexed immunoassay. Our study cohort consisted of 30 tobacco smokers with COPD (TS COPD) and 20 tobacco smokers without COPD (TS CONTROL) from South India. The study population was matched for age, sex (male), and tobacco consumption (pack-years). COPD was diagnosed according to the global initiative for chronic obstructive lung disease (GOLD) criteria of persistent airflow obstruction determined by the ratio of postbronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) of <0.7. A validated structured questionnaire-based survey [Burden of Obstructive Lung Disease (BOLD) study] and spirometry were performed during house to house visit of the field study. Statistical analysis included nonparametric (two-tailed) Mann–Whitney U and Spearman rank test, as appropriate (significance: p<0.05). Results Serum GM-CSF [69.64 (46.67, 97.48); 36.78 (30.07, 53.88), p=0.014], IFN-γ [51.06 (17.00, 84.86); 11.70 (3.18, 32.81), p=0.017], IL-4 [9.09 (1.8, 19.9); 1.8 (1.8, 4.46); p=0.024], and TNF-α [20.68 (5.5, 29.26); 3.5 (3.5, 4.5); p<0.001] concentrations (pg/ml) were increased in TS COPD subjects compared to TS CONTROL. A weak correlation between lung function parameters and cytokine concentrations was detected. Conclusion Our pilot study reveals GM-CSF, IFN-γ, IL-4, and TNF-α as plausible COPD susceptibility biomarkers within the investigated South Indian population that needs to be validated in a larger cohort.
β-Cell DNA Damage Response Promotes Islet Inflammation in Type 1 Diabetes

Type 1 diabetes (T1D) is an autoimmune disease where pancreatic β-cells are destroyed by islet-infiltrating T cells. Although a role for β-cell defects has been suspected, β-cell abnormalities are difficult to demonstrate. We show a β-cell DNA damage response (DDR), presented by activation of the 53BP1 protein and accumulation of p53, in biopsy and autopsy material from patients with recently diagnosed T1D as well as a rat model of human T1D. The β-cell DDR is more frequent in islets infiltrated by CD45+ immune cells, suggesting a link to islet inflammation. The β-cell toxin streptozotocin (STZ) elicits DDR in islets, both in vivo and ex vivo, and causes elevation of the proinflammatory molecules IL-1β and Cxcl10. β-Cell–specific inactivation of the master DNA repair gene ataxia telangiectasia mutated (ATM) in STZ-treated mice decreases the expression of proinflammatory cytokines in islets and attenuates the development of hyperglycemia. Together, these data suggest that β-cell DDR is an early event in T1D, possibly contributing to autoimmunity.
Postoperative Pain Assessment Indices Based on Photoplethysmography Waveform Analysis

The purpose of this study was to derive parameters that might reflect postoperative pain from photoplethysmography (PPG) and verify the derived parameters in postoperative pain assessment. We obtained preoperative and postoperative PPG and 100-mm visual analog scale (VAS) from 65 surgical patients and extracted a total of 51 PPG morphology-based parameters and their normalized parameters from these PPGs obtained. Pain discrimination performances of these derived parameters were assessed by statistical analyses, including Wilcoxon signed rank test with Bonferroni correction, classification accuracy based on logistic regression, and 4-fold cross validation. After comparing these parameters derived from PPG in pre- and post-operative conditions, statistically significant difference was found in 36 of the 51 parameters. Using logistic classification, dynamic between-pulse parameters such as normalized systolic amplitude variation and normalized diastolic amplitude variation showed better pain classification performance than the static within-pulse parameters. VAS score was 0 in every pre-operation condition, but >60 VAS was observed in the post-operative condition. Systolic peak amplitude variation normalized by PPG AC amplitude showed the best performance in classifying post-operative pain, with accuracy, sensitivity, specificity, and positive predictivity values of 79.5, 74.0, 86.0, and 84.5%, respectively. These results are superior to those of the surgical pleth index (SPI, GE Healthcare, Chicago, IL, United States) at 65.9, 65.9, 66.5, and 66.5%, respectively.
A multicenter study to evaluate pulmonary function in osteogenesis imperfecta

Pulmonary complications are a significant cause for morbidity and mortality in osteogenesis imperfecta (OI). However, to date, there have been few studies that have systematically evaluated pulmonary function in individuals with OI. We analyzed spirometry measurements, including forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1), in a large cohort of individuals with OI (n = 217) enrolled in a multicenter, observational study. We show that individuals with the more severe form of the disease, OI type III, have significantly reduced FVC and FEV1 which do not follow the expected trends of the normal population. We also show that “normalization” of FVC and FEV1 using general population data to generate percent predicted values underestimates the pulmonary involvement in OI. Within each subtype of OI, we used linear mixed models to find potential correlations between FEV1 and FVC with the clinical variables including mobility, bisphosphonate use, and scoliosis. Our results are an important step in understanding the extent of pulmonary involvement in individuals with OI and for developing pulmonary endpoints for use in the routine patient care as well as in the investigation of new therapies.
Sanhuang Xiexin Tang Ameliorates Type 2 Diabetic Rats via Modulation of the Metabolic Profiles and NF-κB/PI-3K/Akt Signaling Pathways

Sanhuang Xiexin Tang (SXT), a classic prescription, has been clinically used to cure diabetes for thousands of years, but its mechanism remains unclear. Here, a systematic in-depth research was performed to unravel how it worked by the signaling pathway and metabonomics analysis. Our studies were conducted using high-fat diets (HFD) and streptozocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats. The blood glucose was measured by a glucose-meter. Protein contents were determined by western blotting or ELISA and mRNA expression was identified by RT-PCR analysis. The pathological status of pancreas was assessed by histopathological analysis. Furthermore, Ultra Performance Liquid Chromatography-Quadrupole-Time of Flight/Mass Spectrometry (UPLC-Q-TOF/MS) coupled with multivariate statistical analysis was performed to discover potential biomarkers and the associated pathways. Hyperglycaemia, insulin resistance, dyslipidemia and inflammation in T2DM rats were significantly ameliorated after 7-week oral administration of SXT. The expressions of phosphatidylinositol-3-kinase (PI-3K), protein kinase B (Akt), glucose transporters-4 (GLUT4) Mrna, and p-PI-3K, p-Akt, GLUT4 protein involved in the PI-3K/Akt signaling pathway of T2DM were markedly up-regulated. Further investigation indicated that the perturbance of metabolic profiling in T2DM rats was obviously reversed by SXT and 38 potential biomarkers were screened and identified. Our study might help clarify the mechanism of SXT and provide some evidences for its clinical application in the future.
Turnip Mosaic Virus Uses the SNARE Protein VTI11 in an Unconventional Route for Replication Vesicle Trafficking

Turnip mosaic virus replication vesicles bypass the Golgi and take an alternative, nonconventional pathway involving VTI11 in order to reach prevaculolar compartments/multivesicular bodies. Infection of plant cells by RNA viruses leads to the generation of organelle-like subcellular structures that contain the viral replication complex. During Turnip mosaic virus (TuMV) infection of Nicotiana benthamiana, the viral membrane protein 6K2 plays a key role in the release of motile replication vesicles from the host endoplasmic reticulum (ER). Here, we demonstrate that 6K2 contains a GxxxG motif within its predicted transmembrane domain that is vital for TuMV infection. Replacement of the Gly with Val within this motif inhibited virus production, and this was due to a relocation of the viral protein to the Golgi apparatus and the plasma membrane. This indicated that passage of 6K2 through the Golgi apparatus is a dead-end avenue for virus infection. Impairing the fusion of transport vesicles between the ER and the Golgi apparatus by overexpression of the SNARE Sec22 protein resulted in enhanced intercellular virus movement. Likewise, expression of nonfunctional, Golgi-located synaptotagmin during infection enhanced TuMV intercellular movement. 6K2 copurified with VTI11, a prevacuolar compartment SNARE protein. An Arabidopsis thaliana vti11 mutant was completely resistant to TuMV infection. We conclude that TuMV replication vesicles bypass the Golgi apparatus and take an unconventional pathway that may involve prevacuolar compartments/multivesicular bodies for virus infection.
Microbial Community and Potential Pathogen Shifts Along an Ornamental Fish Supply Chain

There is broad interest in disease spread through the pet trade, but empirical research on hosts and pathogens in transit along actual trade routes is notably absent. Using next-generation DNA sequencing, and partnering with the ornamental fish industry, we tracked shifts in microbial community and potential pathogen structure associated with Sailfin Tang (Zebrasoma desjardinii) along the United States (U.S.) leg of an international supply chain. We observed striking changes in microbial diversity and composition of potential pathogens, including increased dominance of vibrios of fishes in transit. Our pilot findings suggest that high investment in fishes early in the supply chain may not matter to their long-term health depending on end destination conditions.
PARP inhibitors synergize with gemcitabine by potentiating DNA damage in non‐small‐cell lung cancer

Poly (ADP‐ribose) polymerase (PARP) inhibitors have demonstrated great promise in the treatment of patients with deficiencies in homologous recombination (HR) DNA repair, such as those with loss of BRCA1 or BRCA2 function. However, emerging studies suggest that PARP inhibition can also target HR‐competent cancers, such as non‐small‐cell lung cancer (NSCLC), and that the therapeutic effect of PARP inhibition may be improved by combination with chemotherapy agents. In our study, it was found that PARP inhibitors talazoparib (BMN‐673) and olaparib (AZD‐2281) both had synergistic activity with the common first‐line chemotherapeutic gemcitabine in a panel of lung cancer cell lines. Furthermore, the combination demonstrated significant in vivo antitumor activity in an H23 xenograft model of NSCLC compared to either agent as monotherapy. This synergism occurred without loss of HR repair efficiency. Instead, the combination induced synergistic single‐strand DNA breaks, leading to accumulation of toxic double‐strand DNA lesions in vitro and in vivo. Our study elucidates the underlying mechanisms of synergistic activity of PARP inhibitors and gemcitabine, providing a strong motivation to pursue this combination as an improved therapeutic regimen.
Direct Gaze Blurs Self-Other Boundaries

Abstract Self-other merging can arise not only between acquainted people but also between strangers. To date, the factors determining self-other merging between strangers remain to be elucidated. We investigate whether strangers’ facial appearance (i.e. gaze direction) modulates such initial processes of self-other merging. In the two experiments, participants viewed strangers’ faces whose gaze either directed to or averted from them. The extent of self-other merging was measured in terms of perception of face resemblance, Inclusion of the Other in the Self (IOS) scale, and correlations of personality judgments. We found that direct gaze blurred the self-other boundaries at both facial and conceptual levels. Participants felt a stranger who directly gazed at them to be closer and more similar to themselves about face and personality.
Spinal cord involvement in adult-onset metabolic and genetic diseases

In adulthood, spinal cord MRI abnormalities such as T2-weighted hyperintensities and atrophy are commonly associated with a large variety of causes (inflammation, infections, neoplasms, vascular and spondylotic diseases). Occasionally, they can be due to rare metabolic or genetic diseases, in which the spinal cord involvement can be a prominent or even predominant feature, or a secondary one. This review focuses on these rare diseases and associated spinal cord abnormalities, which can provide important but over-ridden clues for the diagnosis. The review was based on a PubMed search (search terms: ‘spinal cord’ AND ‘leukoencephalopathy’ OR ‘leukodystrophy’; ‘spinal cord’ AND ‘vitamin’), further integrated according to the authors’ personal experience and knowledge. The genetic and metabolic diseases of adulthood causing spinal cord signal alterations were identified and classified into four groups: (1) leukodystrophies; (2) deficiency-related metabolic diseases; (3) genetic and acquired toxic/metabolic causes; and (4) mitochondrial diseases. A number of genetic and metabolic diseases of adulthood causing spinal cord atrophy without signal alterations were also identified. Finally, a classification based on spinal MRI findings is presented, as well as indications about the diagnostic work-up and differential diagnosis. Some of these diseases are potentially treatable (especially if promptly recognised), while others are inherited as autosomal dominant trait. Therefore, a timely diagnosis is needed for a timely therapy and genetic counselling. In addition, spinal cord may be the main site of pathology in many of these diseases, suggesting a tempting role for spinal cord abnormalities as surrogate MRI biomarkers.
Comparing CNN and LSTM character-level embeddings in BiLSTM-CRF models for chemical and disease named entity recognition

We compare the use of LSTM-based and CNN-based character-level word embeddings in BiLSTM-CRF models to approach chemical and disease named entity recognition (NER) tasks. Empirical results over the BioCreative V CDR corpus show that the use of either type of character-level word embeddings in conjunction with the BiLSTM-CRF models leads to comparable state-of-the-art performance. However, the models using CNN-based character-level word embeddings have a computational performance advantage, increasing training time over word-based models by 25% while the LSTM-based character-level word embeddings more than double the required training time.
Elevated methylation of OPRM1 and OPRL1 genes in Alzheimer's disease

Previous studies have suggested that increased opioid receptor κ1 (OPRK1) and opioid receptor δ1 (OPRD1) methylation levels are involved in Alzheimer's disease (AD). In the present study, the methylation levels of two opioid receptor genes, opioid receptor µ1 (OPRM1) and opioid related nociceptin receptor 1 (OPRL1), were analyzed for their association with AD. Gene methylation levels were measured using bisulfite pyrosequencing in DNA samples derived from blood samples of 51 AD patients and 63 controls. The results indicated that there were significantly elevated promoter methylation levels of OPRM1 and OPRL1 in AD (OPRM1: P=0.007; OPRL1: P=2.987×10−6). Dual-luciferase reporter gene assays demonstrated that the promoter fragments of these two genes were able to promote gene expression (OPRM1: Fold-change=2.616, P=0.003; OPRL1: Fold change=11.395, P=0.007). In addition, receiver operating characteristic analyses further indicated that a methylation panel of four opioid receptor genes (area under the curve=0.848, sensitivity=0.723, and specificity=0.879) performed well in the prediction of AD. These results suggested that opioid receptor genes may be used as potential methylation biomarkers for the diagnosis of AD.
Effective Improvement of Under-Modeling Frequency-Domain Kalman Filter

The frequency-domain Kalman filter (FKF) has been utilized in many audio signal processing applications due to its fast convergence speed and robustness. However, the performance of the FKF in under-modeling situations has not been investigated. This letter presents an analysis of the steady-state behavior of the commonly used diagonalized FKF and reveals that it suffers from a biased solution in under-modeling scenarios. An effective improvement of the FKF is proposed, having the benefits of the guaranteed optimal steady-state behavior at the cost of a very limited increase of computational burden. The convergence behavior of the proposed algorithm is also analyzed. Computer simulations are conducted to validate the improved performance of the proposed method.