Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Expression of VGLUT2 in Mouse Mesopontine Cholinergic Neurons

Abstract Vesicular glutamate transporters (VGLUTs) mediate the synaptic uptake of glutamate from the cytosol into synaptic vesicles and are considered unambiguous neurochemical markers of glutamate neurons. However, many neurons not classically thought of as glutamatergic also express a VGLUT and co-release glutamate. Using a genetic fate-mapping strategy we found that most cholinergic neurons in the mouse mesopontine tegmentum express VGLUT2 at some point during development, including the pedunculopontine tegmental nucleus (PPTg), laterodorsal tegmental nucleus, and parabigeminal nucleus (PBG), but not the oculomotor nucleus. In contrast, very few of these cholinergic neurons displayed evidence of vesicular GABA transporter expression. Using multiplex fluorescent in situ hybridization, we determined that only PBG cholinergic neurons are also predominantly positive for VGLUT2 mRNA in the adult, with only small numbers of PPTg cholinergic neurons overlapping with VGLUT2 mRNA. Using Cre-dependent viral vectors we confirm these in situ hybridization data, and demonstrate projection patterns of cholinergic and glutamatergic populations. These results demonstrate that most mesopontine cholinergic neurons may transiently express VGLUT2, but that a large majority of PBG neurons retain VGLUT2 expression throughout adulthood, and support a growing body of literature indicating that distinct cholinergic populations have differing potential for GABA or glutamate co-release.
Contrasting effects of heat shock during in vitro maturation on development of in vitro-fertilized and parthenogenetic bovine embryos.

This study investigated the influence of heat shock during in vitro maturation on embryo development following in vitro fertilization (IVF) or parthenogenesis (Part). Immature bovine cumulus oocyte complexes were exposed to heat shock (41.0°C) during the first 12h of in vitro maturation (IVM), followed by 12h at 38.5°C. Control group consisted of in vitro maturation for 24h at 38.5°C. Oocytes were in vitro fertilized or activated with ionomycin and cultured in vitro for 192h post in vitro insemination or parthenogenetic activation (hpia). There was an interaction (P<0.01) between temperature of IVM and method of oocyte activation (IVF or Part) for cleavage at 48hpia. Heat shock had a negative impact (P<0.01) on cleavage of IVF embryos whereas no (P>0.05) effect was found in the Part embryos. Embryo development toward blastocyst stage at 168 and 192hpia decreased in both IVF and Part embryos derived from heat-shocked oocytes. Heat shock increased (P<0.05) the apoptotic index in Part blastocysts but no effect (P>0.05) was found in IVF counterparts. Heat shock also down-regulated the expression of AQP3 (P<0.01) and up-regulated the expression of HSP70.1 (P<0.01) in Part blastocysts whereas it down-regulated the expression of ATP1A1 (P<0.05) in IVF blastocysts. In conclusion, the effects of heat shock during IVM on early embryo cleavage and blastocysts apoptosis is influenced by the method of oocyte activation and expression of some genes can be disturbed in embryos derived from heat-shocked oocytes. This article is protected by copyright. All rights reserved.
Involvement of TRPV1 and TRPV4 Channels in Retinal Angiogenesis.

Purpose We investigate the contribution of TRPV1 and TRPV4 channels to retinal angiogenesis. Methods Primary retinal microvascular endothelial cells (RMECs) were used for RT-PCR, Western blotting, immunolabeling, Ca2+ signaling, and whole-cell patch-clamp studies while localization of TRPV1 also was assessed in retinal endothelial cells using whole mount preparations. The effects of pharmacologic blockers of TRPV1 and TRPV4 on retinal angiogenic activity was evaluated in vitro using sprout formation, cell migration, proliferation, and tubulogenesis assays, and in vivo using the mouse model of oxygen-induced retinopathy (OIR). Heteromultimerization of TRPV1 and TRPV4 channels in RMECs was assessed using proximity ligation assays (PLA) and electrophysiologic recording. Results TRPV1 mRNA and protein expression were identified in RMECs. TRPV1 labelling was found to be mainly localized to the cytoplasm with some areas of staining colocalizing with the plasma membrane. Staining patterns for TRPV1 were broadly similar in endothelial cells of intact vessels within retinal flat mounts. Functional expression of TRPV1 and TRPV4 in RMECs was confirmed by patch-clamp recording. Pharmacologic inhibition of TRPV1 or TRPV4 channels suppressed in vitro retinal angiogenesis through a mechanism involving the modulation of tubulogenesis. Blockade of these channels had no effect on VEGF-stimulated angiogenesis or Ca2+ signals in vitro. PLA and patch-clamp studies revealed that TRPV1 and TRPV4 form functional heteromeric channel complexes in RMECs. Inhibition of either channel reduced retinal neovascularization and promoted physiologic revascularization of the ischemic retina in the OIR mouse model. Conclusions TRPV1 and TRPV4 channels represent promising targets for therapeutic intervention in vasoproliferative diseases of the retina.
Quantitative and qualitative sensory testing results are associated with numbness rather than neuropathic pain in patients with post-implant trigeminal neuropathy: a cross-sectional pilot study

Abstract Purpose: This study aimed to characterize the sensory profile of patients with post-implant trigeminal neuropathy and identify the association between subjective symptoms and objective signs including psychophysical testing and radiographic imaging. This study further evaluated to the association between quantitative sensory testing (QST)/qualitative sensory testing (QualST) and the severity of nerve injury graded by radiographic imaging. Materials and methods: This retrospective study included 34 patients diagnosed with post-implant trigeminal neuropathy. Data on the neuropathic pain symptom inventory (NPSI), thermal and electric QST, bedside QualST, and cone beam computed tomography (CBCT) was collected and the association between these variables were analysed. Results: Numbness was the most common subjective symptom and evoked pain was the most frequent neuropathic pain. There was no significant correlation between negative and positive symptoms. Spearman’s rank correlation analyses indicated that objective findings including QST/QualST correlated with a sensory loss profile rather than a gain of function profile. Moderate positive correlations between some positive symptoms and the score of QualST were observed. The Mann–Whitney U test showed that subjective symptoms did not differ according to the severity of nerve damage according to CBCT, but the electric QST and QualST was discriminative. Conclusions: This study suggests that QST/QualST associated with the severity of nerve damage according to CBCT might be useful in assessing numbness in patients with negative and positive symptoms after implant surgery, but may be of marginal utility in the evaluation of neuropathic pain within the limitation of this cross-sectional study with small sample size.
Translation and cultural adaptation of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer Module for quality of life assessment in patients with lung cancer in Brazil

ABSTRACT Objective: To translate the European Organisation for Research and Treatment of Cancer (EORTC) 29-item Quality of Life Questionnaire-Lung Cancer Module (QLQ-LC29, developed for the assessment of quality of life in patients with lung cancer) to Portuguese, conducting a pilot study of the Portuguese-language version and adapting it for use in Brazil. Methods: For the translation, cultural adaptation, and pilot testing of the QLQ-LC29, we followed the guidelines established by the EORTC. The translation (English → Portuguese) and back-translation (Portuguese → English) were both carried out by translators, working independently, who were native speakers of one language and fluent in the other. After review, a draft version was created for pilot testing in lung cancer patients in Brazil. Results: A total of 15 patients diagnosed with lung cancer completed the Portuguese-language version of the questionnaire. At the end of the process, we conducted a structured interview to identify any patient difficulty in understanding any of the questions. The final versions were sent to the EORTC and were approved. Conclusions: The Portuguese-language version of the EORTC QLQ-LC29 appears to be a useful, important, reliable questionnaire that is a valid tool for assessing quality of life in patients with lung cancer in Brazil.
Authors’ Reply to the Letter to the Editor from Filho et al.

We thank for the opportunity to respond to Fernandez et al. concerns that readers may have been misguided about the reasonable likelihood of a "false positive" result from the 3-year follow-up of our trial (Vibe Fersum et al., 2019). While we agree, and had highlighted in the manuscript, that there is risk of bias of the 3-year treatment effect due to missing data, we strongly disagree that we have misguided readers. Rather, we have been as explicit as possible about the missing data and the subsequent implications for risk of bias, and performed numerous sensitivity analyses so readers can reasonably judge if a different statistical approach would markedly change the results. This article is protected by copyright. All rights reserved.
Beta-band Motor Unit Coherence and Nonlinear Surface EMG Features of the First Dorsal Interosseous Muscle Vary with Force.

Motor unit (MU) firing times are weakly coupled across a range of frequencies during voluntary contractions. Coherent activity within the beta-band (15-35 Hz) has been linked to oscillatory cortical processes, providing evidence of functional connectivity between the motoneuron pool and motor cortex. The aim of this study was to investigate whether beta-band MU coherence is altered with increasing abduction force in the first dorsal interosseous muscle. Coherence between MU firing times, extracted from decomposed surface EMG signals, was investigated in 17 subjects at 10%, 20%, 30% and 40% of maximum voluntary contraction. Corresponding changes in nonlinear surface EMG features, specifically sample entropy and determinism which are sensitive to MU synchronization, were also examined. A reduction in beta-band and alpha-band coherence was observed as force increased (F(3, 151) = 32, p < . 001 and F(3, 151) = 27, p < . 001, respectively), accompanied by corresponding changes in nonlinear surface EMG features. A significant relationship between the nonlinear features and MU coherence was also detected (r = -0.43 ± 0.1 and r = 0.45 ± 0.1, for sample entropy and determinism, respectively, both p < .001). The reduction in beta-band coherence suggests a change in the relative contribution of correlated and uncorrelated pre-synaptic inputs to the motoneuron pool, and/or a decrease in the responsiveness of the motoneuron pool to synchronous inputs at higher forces. The study highlights the importance of considering muscle activation when investigating changes in MU coherence or nonlinear EMG features, and examines other factors that can influence coherence estimation.
Pru p 3-glycodendropeptides based on mannoses promote changes in the immunological properties of dendritic and T-cells from LTP-allergic patients.

SCOPE Glycodendropeptides (GDPs) functionalized with mannose can enhance allergen interaction with dendritic cells (DCs) via C-type lectin receptors (CLRs), modulating the immune response. They can present multiple peptides and have potential applications for diagnosis and treatment of food allergy (FA). We analysed the immune response induced by GDPs with mannose and Pru p 3 peptides (mono/tetravalent) with ester (D1 ManPrup3/D4 ManPrup3) or ether linkers (D1 Man-O- Prup3/D4 Man-O- Prup3) in LTP-allergic patients and tolerant controls. METHODS AND RESULTS The immunological response induced by GDPs was studied by assessing monocyte-derived-DC maturation, lymphocyte proliferation, cytokine production and basophil response by flow cytometry. Dn ManPrup3 was recognised by DCs via CLRs inducing DC maturation in all subjects. However, CCR7 expression was significantly upregulated in allergic patients compared to tolerant controls. These changes correlated with lymphocyte proliferation and specific production of Th2/Th1 cytokines in allergic patients. Moreover, D1 ManPrup3 did not induce basophil activation. CONCLUSION Dn ManPrup3 induces changes in DC maturation and lymphocyte proliferation, indicating specific recognition via CLRs. Prup3-GDPs are recognised by immune cells, inducing a specific immune response and modulating the immunological response in FA patients. The specific geometry of D1 ManPrup3 in particular makes it a potential candidate for specific immunotherapy development. This article is protected by copyright. All rights reserved.
Impact of Two High-Volume Set Configuration Workouts on Resistance Training Outcomes in Recreationally Trained Men.

Karsten, DB, Fu, Y, Larumbe-Zabala, DE, Seijo, DM, and Naclerio, DF. Impact of two high-volume set configuration workouts on resistance training outcomes in recreationally trained men. J Strength Cond Res XX(X): 000-000, 2019-This study compared the effects of 2 weekly equalized by volume, loading zone and frequency resistance training designs using repetition to failure (RTF) or not to failure (NTF), on body composition, strength, and mechanical power. Based on individual baseline maximal strength, 18 recreationally resistance-trained men were pair-matched and consequently randomly assigned to an RTF (n = 9) or an NTF (n = 9) protocol. Subjects trained for 6 weeks using 2 different routines performed once per week (2 workouts per week). The RTF protocol comprised 4 sets of 10 repetitions per exercise with 2-minute rest and the NTF involved 8 sets of 5 repetitions per exercise with 1-minute rest. Subjects were tested pre- and post-intervention for maximal strength, upper- and lower-body power, fat-free mass, limb circumferences, and muscle thickness. Compared to baseline, both groups improved (p < 0.01) the maximal loads lifted in the bench press (RTF +9.44 ± 3.00 kg; NTF +7.22 ± 4.41 kg) and the squat (RTF +9.44 ± 4.64 kg; NTF +11.1 ± 10.33 kg) exercises, but only the NTF group increased (p < 0.05) upper-body power (+15.73 ± 12.59 W). Conversely, only the RTF group showed significant (p < 0.05) increase of the elbow flexors (+3.44 ± 5.11 mm) and vastus medialis (+3.28 ± 2.32 mm) thickness, whereas both groups enhanced anterior deltoid thickness (RTF +1.84 ± 1.68 mm, p < 0.05; NTF +2.76 ± 2.63 mm, p < 0.01). Although both training strategies improved strength, the RTF group elicited superior hypertrophic outcomes, whereas the NTF protocol resulted in more favorable improvements for upper-body power.
Brazilin Treatment Produces Antidepressant- and Anxiolytic-Like Effects in Mice.

Increasing evidence shows depression relevant to oxidative stress and inflammation. Anti-inflammatory strategies or antioxidants have led to the development of new antidepressants. Brazilin is a natural product from the Chinese traditional medicine Caesalpinia sappan L. , exerting anti-inflammatory, antioxidant, anti-platelet concentration, and anti-cancer effects. While the antidepressant effect of brazilin is largely unknown. In present study, we investigated the effects of brazilin on H2O2-induced oxidative injury in PC12 cells and on depression- and anxiety-like behaviors of chronically mild stressed (CMS)-induced depression mice. It was found that brazilin pre-treatment (both 10 and 20 µM) significantly increased cell viability and decreased cell apoptosis in H2O2-treated PC12 cells. Furthermore, repetitive administration of brazilin to CMS-induced depression mice by intraperitoneal injection (10 mg/kg) made the mice significantly lose their latency of feeding in novelty-suppressed feeding test (NSF), have more the sucrose preference in sucrose preference test (SPT), and more time spent in the central zone without affecting their crossing activity in open field test (OFT). These results suggested that brazilin can play a role in antidepressant and anxiolytic-like behaviors for CMS-induced depression mice probably through inhibiting the oxidative stress. Therefore, brazilin is worth to be further explored for treating depressive and anxiety disorders.
mRNA-Sequencing Identifies Liver as a Potential Target Organ for Triphenyl Phosphate in Embryonic Zebrafish.

Triphenyl phosphate (TPHP) is a commonly used organophosphate flame retardant and plasticizer in the United States. Using zebrafish as a model, the overall objective of this study was to identify potential organs that might be targeted by TPHP during embryonic development. Based on mRNA-sequencing, TPHP exposure from 24 to 30 h post fertilization (hpf) and 24 to 48 hpf significantly affected the abundance of 305 and 274 transcripts, respectively, relative to vehicle (0.1% DMSO) controls. In addition to minor effects on cardiotoxicity- and nephrotoxicity-related pathways, Ingenuity Pathway Analysis (IPA) of significantly affected transcripts within 30- and 48-hpf embryos revealed that hepatotoxicity-related pathways were strongly affected following exposure to TPHP alone. Moreover, while pre-treatment with fenretinide (a retinoic acid receptor agonist) mitigated TPHP-induced pericardial edema and liver enlargement at 72 hpf and 128 hpf, respectively, IPA revealed that fenretinide was unable to block TPHP-induced effects on cardiotoxicity-, nephrotoxicity-, and hepatotoxicity-related pathways at 48 hpf, suggesting that TPHP-induced effects on the transcriptome were not associated with toxicity later in development. In addition, based on Oil Red O staining, we found that exposure to TPHP nearly abolished neutral lipids from the embryonic head and trunk and, based on metabolomics, significantly decreased the total abundance of metabolites - including betaine, a known osmoprotectant - at 48 and 72 hpf. Overall, our data suggest that, in addition to the heart, TPHP exposure during early development results in adverse effects on the liver, lipid utilization, and osmoregulation within embryonic zebrafish.
Factors influencing countries on their path to sustainable development: implications for organizations

Nowadays sustainable development is a central concept for our age. It is both a way ofunderstanding the world and a method for solving global problems. It is currently a crucial concept for the world to understand and to implement. This research study focuses on examining the foundations of achieving sustainable development and main factors influencing this process at a national level. The aim is to characterize those factors which influence this implementation process mainly from the economic point of view. However, other noneconomic factors related to human well-being and orga- nizational development are not omitted. Countries’ political and legislative environment are also evaluated since they can have significant implications for development of individual organizations conducting their business activities within countries’ borders. The focus of examining the topic of countries’ sustainable development is on the cross- country comparison. Values of some important indicators are also provided in terms of comparison among selected countries which enables us to explain the reasons for dif- ferences in countries’ development, as well as predictions for the future. Historical perspective provides data which enable to evaluate influence of selected factors in terms of countries’ path to achieving sustainable development.
MicroRNA-383-5p inhibits the progression of gastric carcinoma via targeting HDAC9 expression

MicroRNAs (miRNAs), as post-transcriptional regulators, have been reported to be involved in the initiation and progression of various types of cancer, including gastric cancer (GC). The present study aimed to investigate the role of miR-383-5p in gastric carcinogenesis. Cell viability was analyzed using CCK-8 kit. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to evaluate cell apoptosis. The expression levels of miR-383-5p and histone deacetylase 9 (HDAC9) mRNA in GC tissues and cell lines were analyzed using RT-qPCR. The protein expression of HDAC9 was detected by western blotting. We found that HDAC9 was up-regulated and miR-383-5p was down-regulated in GC tissues and cell lines. High HDAC9 expression or low miR-383-5p expression was closely related to poor prognosis and metastasis in GC patients. HDAC9 knockout or miR-383-5p mimics led to growth inhibition and increased apoptosis in AGS and SGC-7901 cells. More importantly, we validated that miR-383-5p as a post-transcriptional regulator inhibited HDAC9 expression and was inversely correlated with HDAC9 expression in GC tissues. miR-383-5p had the opposite effects to HDAC9 in gastric carcinogenesis. miR-383-5p played an important role in gastric carcinogenesis, and it is one of the important mechanisms to regulate oncogenic HDAC9 in GC, which might be helpful in the development of novel therapeutic strategies for the treatment of GC.
Thyroid Peroxidase Activity is Inhibited by Phenolic Compounds—Impact of Interaction

The aim of this study was to estimate the mode of thyroid peroxidase (TPO) inhibition by polyphenols: Chlorogenic acid, rosmarinic acid, quercetin, and rutin. All the tested polyphenols inhibited TPO; the IC50 values ranged from 0.004 mM to 1.44 mM (for rosmarinic acid and rutin, respectively). All these pure phytochemical substances exhibited different modes of TPO inhibition. Rutin and rosmarinic acid showed competitive, quercetin—uncompetitive and chlorogenic acid—noncompetitive inhibition effect on TPO. Homology modeling was used to gain insight into the 3D structure of TPO and molecular docking was applied to study the interactions of the inhibitors with their target at the molecular level. Moreover, the type and strength of mutual interactions between the inhibitors (expressed as the combination index, CI) were analyzed. Slight synergism, antagonism, and moderate antagonism were found in the case of the combined addition of the pure polyphenols. Rutin and quercetin as well as rutin and rosmarinic acid acted additively (CI = 0.096 and 1.06, respectively), while rutin and chlorogenic acid demonstrated slight synergism (CI = 0.88) and rosmarinic acid with quercetin and rosmarinic acid with chlorogenic acid showed moderate antagonism (CI = 1.45 and 1.25, respectively). The mixture of chlorogenic acid and quercetin demonstrated antagonism (CI = 1.79). All the polyphenols showed in vitro antiradical ability against 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid), ABTS. The highest ability (expressed as IC50) was exhibited by rosmarinic acid (0.12 mM) and the lowest value was ascribed to quercetin (0.45 mM).