Miracle-dz/UniFAR-FTUs huggingface dataset:
RORB and RORC associate with human islet dysfunction and inhibit insulin secretion in INS-1 cells

ABSTRACT Little is known about the expression and function of Retinoic acid-related orphan receptors (RORA, B, and C) in pancreatic β cells. Here in, we utilized cDNA microarray and RNA sequencing approaches to investigate the expression pattern of ROR receptors in normal and diabetic human pancreatic islets. Possible correlations between RORs expression and HbA1c levels as well as insulin secretory capacity in isolated human islets were evaluated. The impact of RORB and RORC expression on insulin secretion in INS-1 (832/13) cells was validated as well. While RORA was the highest expressed gene among the three RORs in human islet cells, RORC was the highest expressed in INS-1 cells (832/13) and while RORB was the lowest expressed gene in human islet cells, RORA was the highest expressed in INS-1 cells (832/13). The expression of RORB and RORC was significantly lower in diabetic/hyperglycemic donors as compared with non-diabetic counterparts. Furthermore, while the expression of RORB correlated positively with insulin secretion and negatively with HbA1c, that of RORC correlated negatively with HbA1c. The expression pattern of RORA did not correlate with either of the two parameters. siRNA silencing of RORB or RORC in INS-1 (832/13) cells resulted in a significant downregulation of insulin mRNA expression and insulin secretion. These findings suggest that RORB and RORC are part of the molecular cascade that regulates insulin secretion in pancreatic β cells; and insight that provides for further work on the potential therapeutic utility of RORB and RORC genes in β cell dysfunction in type 2 diabetes.
The role of putative human anterior intraparietal sulcus area in observed manipulative action discrimination

Although it has become widely accepted that the action observation network (AON) includes three levels (occipito‐temporal, parietal and premotor), little is known concerning the specific role of these levels within perceptual tasks probing action observation. Recent single cell studies suggest that the parietal level carries the information required to discriminate between two‐alternative observed actions, but do not exclude possible contributions from the other two levels.
Characterization, expression, and functional analysis of polyamine oxidases and their role in selenium-induced hydrogen peroxide production in Brassica rapa.

BACKGROUND Selenium (Se)-induced phytotoxicity has been linked to oxidative injury triggered by the accumulation of reactive oxygen species (ROS) due to the disturbance of anti-oxidative systems. However, the way Se stress induces hydrogen peroxide (H2 O2 ) production in plants is a long-standing question. Here we identified the role of polyamine oxidase (PAO) in H2 O2 production in the root of Brassica rapa upon Se stress. RESULTS Studying Se-induced growth inhibition, H2 O2 accumulation, and oxidative injury in the root of Brassica rapa, we found that excessive Se exposure resulted in a remarkable increase in PAO activity. Inhibition of PAO activity led to decreased H2 O2 content and alleviated oxidative injury in the Se-treated root. These results indicated that Se stress induced PAO-dependent H2 O2 production. A total of six BrPAO family members were discovered in the genome of B. rapa by in silico analysis. Se stress pronouncedly upregulated the expression of most BrPAOs and further transient expression analysis proved that it could lead to H2 O2 production. CONCLUSION These results suggest that Se stress upregulates the expression of a set of BrPAOs which further enhances PAO activity, contributing to H2 O2 generation in roots. © 2019 Society of Chemical Industry.
An Accelerated Linearly Convergent Stochastic L-BFGS Algorithm

The limited memory version of the Broyden–Fletcher–Goldfarb–Shanno (L-BFGS) algorithm is the most popular quasi-Newton algorithm in machine learning and optimization. Recently, it was shown that the stochastic L-BFGS (sL-BFGS) algorithm with the variance-reduced stochastic gradient converges linearly. In this paper, we propose a new sL-BFGS algorithm by importing a proper momentum. We prove an accelerated linear convergence rate under mild conditions. The experimental results on different data sets also verify this acceleration advantage.
Exercise initiated during pregnancy in rats born growth restricted alters placental mTOR and nutrient transporter expression

Fetal growth is dependent on effective placental nutrient transportation, which is regulated by mammalian target of rapamycin (mTOR) complex 1 modulation of nutrient transporter expression. These transporters are dysregulated in pregnancies affected by uteroplacental insufficiency and maternal obesity. Nutrient transporters and mTOR were altered in placentae of mothers born growth restricted compared to normal birth weight dams, with maternal diet‐ and fetal sex‐specific responses. Exercise initiated during pregnancy downregulated mTOR protein expression, despite an increase in mTOR activation in male associated placentae, and reduced nutrient transporter gene abundance, which was also dependent on maternal diet and fetal sex. Limited changes were characterized with exercise initiated before and continued throughout pregnancy in nutrient transporter and mTOR expression. Maternal exercise during pregnancy differentially regulated mTOR and nutrient transporters in a diet‐ and sex‐specific manner, which likely aimed to improve late gestational placental growth and neonatal survival.
Long noncoding RNA LINC00483/microRNA‐144 regulates radiosensitivity and epithelial–mesenchymal transition in lung adenocarcinoma by interacting with HOXA10

Lung adenocarcinoma (LAD) is the leading cause of cancer death worldwide. Long noncoding RNAs (lncRNAs) have been shown to play an important regulatory role in cancer biology, including that of LAD. The aim of this experiment was to explore the interaction of LINC00483, microRNA‐144 (miR‐144), and homeobox A10 (HOXA10), and their effects on radio sensitivity and epithelial–mesenchymal transition (EMT) of LAD. Initially, microarray analysis was used to screen out miRNAs and lncRNAs, as well as the differentially expressed genes related to LAD. Following the screening process, the targeting relationship of LINC00483, miR‐144, and that of miR‐144 and HOXA10 was determined. Following that, the expression of LINC00483, miR‐144, messenger RNA (mRNA), as well as protein expression of HOXA10, MMP‐2, MMP‐9, E‐cadherin, vimentin, and N‐cadherin that followed in cells was determined. Also, the effect of LINC00483 on cell migration and invasion ability, and cell tumorigenic ability was detected. LINC00483 and HOXA10 were found to be upregulated whereas miR‐144 was downregulated in LAD. Silencing of LINC00483 could competitively bind to miR‐144, thereby upregulating HOXA10. LINC00483 or HOXA10 silencing led to decreased HOXA10, MMP‐2, MMP‐9, vimentin, and N‐cadherin but elevated miR‐144 and E‐cadherin. Moreover, after being transfected with silenced LINC00483, the cell proliferation, migration, and invasion were inhibited with enhanced radiosensitivity. Consequently, the data of the study indicates that interference of LINC00483 weakens its competitive binding ability to miR‐144, thus reducing HOXA10 expression, and enhancing radiosensitivity in LAD.
Goal-Directed and Habitual Control in Smokers

Abstract Introduction Harmful behavior such as smoking may reflect a disturbance in the balance of goal-directed and habitual control. Animal models suggest that habitual control develops after prolonged substance use. In this study, we investigated whether smokers (N = 49) differ from controls (N = 46) in the regulation of goal-directed and habitual behavior. It was also investigated whether individual differences in nicotine dependence levels were associated with habitual responding. Methods We used two different multistage instrumental learning tasks that consist of an instrumental learning phase, subsequent outcome devaluation, and a testing phase to measure the balance between goal-directed and habitual responding. The testing phases of these tasks occurred after either appetitive versus avoidance instrumental learning. The appetitive versus aversive instrumental learning stages in the two different tasks modeled positive versus negative reinforcement, respectively. Results Smokers and nonsmoking controls did not differ on habitual versus goal-directed control in either task. Individual differences in nicotine dependence within the group of smokers, however, were positively associated with habitual responding after appetitive instrumental learning. This effect seems to be due to impaired stimulus-outcome learning, thereby hampering goal-directed task performance and tipping the balance to habitual responding. Conclusions The current finding highlights the importance of individual differences within smokers. For future research, neuroimaging studies are suggested to further unravel the nature of the imbalance between goal-directed versus habitual control in severely dependent smokers by directly measuring activity in the corresponding brain systems. Implications Goal-directed versus habitual behavior in substance use and addiction is highly debated. This study investigated goal-directed versus habitual control in smokers. The findings suggest that smokers do not differ from controls in goal-directed versus habitual control. Individual differences in nicotine dependence within smokers, however, were positively associated with habitual responding after appetitive instrumental learning. This effect seems to be due to impaired stimulus-outcome learning, thereby hampering goal-directed task performance and tipping the balance to habitual responding. These findings add to the ongoing debate on habitual versus goal-directed control in addiction and emphasize the importance of individual differences within smokers.
QUBEKit: Automating the Derivation of Force Field Parameters from Quantum Mechanics

Modern molecular mechanics force fields are widely used for modeling the dynamics and interactions of small organic molecules using libraries of transferable force field parameters. However, for molecules outside the training set, the parameters are potentially inaccurate and it may be preferable to derive molecule-specific parameters. Here we present an intuitive parameter derivation toolkit, QUBEKit (QUantum mechanical BEspoke Kit), which enables the automated generation of system-specific small molecule force field parameters directly from quantum mechanics. QUBEKit is written in python and combines bond, angle, torsion, charge, and Lennard-Jones parameter derivation methodologies alongside a method for deriving the positions and charges of off-center virtual sites from the partitioned quantum mechanical electron density. As a proof of concept, we have rederived a complete set of parameters for 109 small organic molecules and assessed the accuracy by comparing computed liquid properties with experiments. QUBEKit gives competitive results when compared to standard transferable force fields, with mean unsigned errors of 0.024 g/cm3, 0.79 kcal/mol, and 1.17 kcal/mol for the liquid density, heat of vaporization, and free energy of hydration, respectively. This indicates that the derived parameters are suitable for molecular modeling applications, including computer-aided drug design.
Capacitively Coupled Electrical Impedance Tomography (CCEIT) for Brain Imaging

—Electrical impedance tomography (EIT) is considered as a potential candidate for brain stroke imaging due to its compactness and potential use in bedside and in emergency settings. The electrode-skin contact impedance and low conductivity of skull pose some major practical challenges in EIT head imaging. This work studies the use of capacitively coupled electrical impedance tomography (CCEIT), a new contactless EIT technique for brain imaging. CCEIT uses voltage excitation without direct contact with the skin, as oppose to direct current injection in EIT. Because the safety issue of a new technique should be strictly treated, simulation work based on a simplified head model was carried out to investigate the safety aspects of CCEIT. By comparing with standard EIT excited by a typical safe current level used in brain imaging, the safe excitation reference of CCEIT is obtained. This is done by comparing the maximum level of internal electrical fields of EIT and CCEIT and hence internal current density. Simulation results provide useful knowledge concerning the level of excitation signal in CCEIT and also a critical comparison with traditional EIT. Experiments were carried out with a twelve-electrode CCEIT phantom to study its performance for stroke imaging. Experimental results show the feasibility and potential of CCEIT on stroke imaging with an anomaly diameter resolution of 10 mm, which is 1/18 of the phantom diameter showing small volume stroke could be detected. This is achieved by an excitation voltage of 1V, much lower than safe level of excitation, with possibility of even better performance when higher level of excitation voltages is used.
Fecal Microbiota Analysis in Patients Going through a Depressive Episode during Treatment in a Psychiatric Hospital Setting

Rationale: There is a worldwide prevalence of generalized anxiety and major depressive disorders (MDD). Gut–brain axis dysfunction, antibacterial activity, and modulatory effects of antidepressants toward intestinal bacteria have been shown both in vitro and in vivo. Objectives: In this study, we aimed to investigate the effects of hospital stay, including escitalopram administration, on gut microbiota in patients with depressive episodes. Methods: After admission to the hospital and 7-days washout from all medications the composition of fecal microbiota samples was evaluated at baseline (W0) and after 6 weeks (W6), using 16S rRNA sequencing. The study was conducted on 17 inpatients (52.9% females), who followed the same daily hospital routine, including a standard diet and received 5–20 mg daily doses of escitalopram. Results: At the end of treatment (W6), no change was observed in the Chao1 index. However, Shannon (median (Q1–Q3): W0 2.78 (2.67–3.02) vs. W6 3.11 (2.80–3.30)), and inverse Simpson (median (Q1–Q3): W0 9.26 (7.26–13.76) vs. W6 12.13 (9.17–15.73)) indices increased significantly compared to baseline values (False Discovery Rate p (q) = 0.031 and q = 0.011, respectively). We also found that between-subject W0 Bray–Curtis dissimilarities were significantly higher than W0–W6 within-subject dissimilarities (median (Q1–Q3): 0.68 (0.56–0.77) vs. 0.38 (0.35–0.52), two sided Mann–Whitney test p < 0.00001. The within-subject dissimilarities did not depend on sex, age, BMI, illness duration and a daily dose of escitalopram. No significant differences between taxa levels, at the studied time points, were observed when adjusted for multiple hypotheses testing procedures. Conclusions: We conclude that a six-week treatment in a psychiatric hospital setting resulted in increased alpha biodiversity in fecal microbiota, however its causal relationship with patients’ mental health was not proved. We have also found that individual microbiome stability was not affected by hospitalization.
RESEARCH Integrative Cardiovascular Physiology and Pathophysiology Sex differences in cerebral autoregulation are unaffected by menstrual cycle phase in young, healthy women

Favre Serrador JM. Sex differences in cerebral autoregulation are unaffected by menstrual cycle phase in young, healthy women. Am Physiol 2019. is known to affect the prevalence of conditions such as stroke. However, effects of sex on cerebral blood ﬂow regulation are still not well understood. Critical to this understanding is how ﬂuctuations in hormones across the menstrual cycle affect cerebral autoregulation. We measured autoregulation in the early follicular, late follicular, and midluteal phases during spontaneous and induced blood pressure oscillations in 26 young, healthy individuals (13 women and 13 men, age: 26 (cid:2) 4 yr). Men participated three times, ~1–3 wk apart. Beat-by-beat blood pressure, heart rate, end-tidal CO 2 , and transcranial Doppler ultrasonography of the middle (MCA) and anterior (ACA) cerebral arteries were obtained. We did not ﬁnd a difference in cerebral autoregulation across the menstrual cycle in women but found signiﬁcantly improved autoregulation in the MCA and ACA of women compared with men. Women demonstrated signiﬁcantly lower MCA gain (0.97 (cid:2) 0.13 vs. 1.17 (cid:2) 0.14%/mmHg, P (cid:3) 0.001), higher MCA phase (46.1 (cid:2) 12.6 vs. 35.8 (cid:2) 7.9°, P (cid:3) 0.019), and higher ACA phase (40.5 (cid:2) 10.8 vs 31.5 (cid:2) 8.5°, P (cid:3) 0.040) during repeated squat-to-stand maneuvers. Women also had lower MCA gain (1.50 (cid:2) 0.11 vs. 1.72 (cid:2) 0.30%/mmHg, P (cid:3) 0.029) during spontaneous ﬂuctuations in pressure while standing and less of a decrease in MCA ﬂow velocity ( (cid:4) 18.7 (cid:2) 2.7 vs. (cid:4) 23.2 (cid:2) 6.0%, P (cid:3) 0.014) during sit-to-stand maneuvers. Our results suggest that young women have improved cerebral autoregulation compared with young men regardless of menstrual cycle phase and that autoregulation is relatively robust to acute ﬂuctuations in female sex hormones.
Giant Hogweed phytophotodermatitis

A 17 year old male was performing outdoor work and cut down a “tall weed with flowers like a cauliflower head. ” The plant’s flowers brushed across his left face as it fell. Six hours later, while showering, he noted the development of vesicles and sloughing of the skin of his left face. He was brought to our facility for treatment of phytophotodermatitis, secondary to the Giant Hogweed (Heracleum mantegazzianum). The Giant Hogweed is an invasive “noxious weed” with an expanding distribution in parts of the Northeast, MidAtlantic, and Pacific Northwest of the United States. The sap of the plant contains the psoralens, 5-methoxypsoralen and 8-methylpsoralen; linear furanocoumarins that are phytotoxic [1]. Sap concentrations of furanocoumarins are thought to be highest in the plant’s fruits and leaves. In the presence of ultraviolent (UV) light, these psoralens cross-link with skin cell DNA, thereby damaging the DNA, and resulting in partial, or even full thickness burns. Most published reports on the management of Giant Hogweed phytophotodermatitis originate from mainland Europe, with more recent reports originating from the plant’s expansion into the United Kingdom [2]. Management of exposure includes immediate decontamination of the exposed skin with soap and water, ideally within 15min. UV light should be avoided for 48–72 h to prevent psoralen photoactivation. If partialor full-thickness burns develop, they should be managed at, or in conjunction with, a burn center as per standard burn center referral criteria. Indeed, delayed treatment of full thickness burns resulting from the Giant Hogweed have required surgical debridement and skin grafting in some cases [3]. Patients should be made aware that affected skin may become hyperor hypo-pigmented in the first two months of healing, and that skin may remain photosensitive for as much as six months following exposure. Protection from additional damaging UV light during this time is paramount [4]. This patient was treated supportively for two days in our burn center. Topical bacitracin and collagenase were applied to wounds for two weeks following discharge. At 2 week follow-up, the patient’s wound were healing well. High SPF (sun protection factor over 50) sunscreen was recommended for 12 months. Image 1. 20 Hours post-exposure.
The antagonistic effect of tamoxifen against d-galactosamine/lipopolysaccharide-induced acute liver failure is associated with reactivation of hepatic nuclear factor-κB

Abstract Context: Tamoxifen (TAM) ameliorates D-galactosamine/lipopolysaccharide (Gal/LPS)-induced acute liver failure (ALF) through its antioxidative effect; thus, this study was designed to determine whether the effectiveness of TAM is related to nuclear factor-κB (NF-κB) reactivation. Materials and methods: Experimental mice were injected with TAM once daily for 3 consecutive days intraperitoneally (i.p). Twelve hours after pretreatment, Gal/LPS was given to mice (i.p) for ALF induction. In the positive control group, N-acetylcysteine (NAC) was administered immediately after ALF establishment. Except for survival observation, other animals were sacrificed 7 h after Gal/LPS treatment. Survival and hepatic failure were evaluated. For the oxidation assessment, the reduced/oxidized glutathione (GSH/GSSG) ratio and hepatic superoxide dismutase (SOD) activity were analyzed using both colorimetry and Western blotting. Lastly, hepatic NF-κB activation was measured through Western blot analysis of p65 and IκBα. Results: The results indicated that pretreatment with TAM dramatically attenuated Gal/LPS-induced ALF, as demonstrated by improved survival (70%), decreased transaminase levels, and reversed histopathological manifestation. In addition, the hepatic GSH/GSSG ratio and SOD activity were decreased in the ALF model. However, to some degree, TAM and NAC effectively prevented this undesirable phenomenon in contrast to the ALF model. Western blotting revealed that compared with mice in the ALF model group, mice treated with TAM or NAC showed reactivation of hepatic NF-κB. Conclusions: Taking the results together with those of other studies, we conclude that TAM may attenuate Gal/LPS-induced ALF by antagonizing oxidative stress through NF-κB reactivation.
Integrity under stress: Host membrane remodelling and damage by fungal pathogens

Membrane bilayers of eukaryotic cells are an amalgam of lipids and proteins that distinguish organelles and compartmentalise cellular functions. The mammalian cell has evolved mechanisms to sense membrane tension or damage and respond as needed. In the case of the plasma membrane and phagosomal membrane, these bilayers act as a barrier to microorganisms and are a conduit by which the host interacts with pathogens, including fungi such as Candida, Cryptococcus, Aspergillus, or Histoplasma species. Due to their size, morphological flexibility, ability to produce long filaments, secrete pathogenicity factors, and their potential to replicate within the phagosome, fungi can assault host membranes in a variety of physical and biochemical ways. In addition, the recent discovery of a fungal pore‐forming peptide toxin further highlights the importance of membrane biology in the outcomes between host and fungal cells. In this review, we discuss the apparent “stretching” of membranes as a sophisticated biological response and the role of vesicular transport in combating membrane stress and damage. We also review the known pathogenicity factors and physical properties of fungal pathogens in the context of host membranes and discuss how this may contribute to pathogenic interactions between fungal and host cells.