Miracle-dz/UniFAR-FTUs huggingface dataset:
Simultaneous Requirements for Hes1 in Retinal Neurogenesis and Optic Cup–Stalk Boundary Maintenance

The bHLH transcription factor Hes1 is a key downstream effector for the Notch signaling pathway. During embryogenesis neural progenitors express low levels of Hes1 in an oscillating pattern, whereas glial brain boundary regions (e.g., isthmus) have high, sustained Hes1 levels that suppress neuronal fates. The bHLH transcription factor Hes1 is a key downstream effector for the Notch signaling pathway. During embryogenesis neural progenitors express low levels of Hes1 in an oscillating pattern, whereas glial brain boundary regions (e.g., isthmus) have high, sustained Hes1 levels that suppress neuronal fates. Here, we show that in the embryonic mouse retina, the optic nerve head and stalk express high Hes1, with the ONH constituting a boundary between the neural retina and glial cells that ultimately line the optic stalk. Using two Cre drivers with distinct spatiotemporal expression we conditionally inactivated Hes1, to delineate the requirements for this transcriptional repressor during retinal neurogenesis versus patterning of the optic cup and stalk. Throughout retinal neurogenesis, Hes1 maintains proliferation and blocks retinal ganglion cell formation, but surprisingly we found it also promotes cone photoreceptor genesis. In the postnatal eye, Hes1 inactivation with Rax-Cre resulted in increased bipolar neurons and a mispositioning of Müller glia. Our results indicate that Notch pathway regulation of cone genesis is more complex than previously assumed, and reveal a novel role for Hes1 in maintaining the optic cup–stalk boundary. SIGNIFICANCE STATEMENT The bHLH repressor Hes1 regulates the timing of neurogenesis, rate of progenitor cell division, gliogenesis, and maintains tissue compartment boundaries. This study expands current eye development models by showing Notch-independent roles for Hes1 in the developing optic nerve head (ONH). Defects in ONH formation result in optic nerve coloboma; our work now inserts Hes1 into the genetic hierarchy regulating optic fissure closure. Given that Hes1 acts analogously in the ONH as the brain isthmus, it prompts future investigation of the ONH as a signaling factor center, or local organizer. Embryonic development of the ONH region has been poorly studied, which is surprising given it is where the pan-ocular disease glaucoma is widely believed to inflict damage on RGC axons.
Voltage Sensing in Bacterial Protein Translocation

The bacterial channel SecYEG efficiently translocates both hydrophobic and hydrophilic proteins across the plasma membrane. Translocating polypeptide chains may dislodge the plug, a half helix that blocks the permeation of small molecules, from its position in the middle of the aqueous translocation channel. Instead of the plug, six isoleucines in the middle of the membrane supposedly seal the channel, by forming a gasket around the translocating polypeptide. However, this hypothesis does not explain how the tightness of the gasket may depend on membrane potential. Here, we demonstrate voltage-dependent closings of the purified and reconstituted channel in the presence of ligands, suggesting that voltage sensitivity may be conferred by motor protein SecA, ribosomes, signal peptides, and/or translocating peptides. Yet, the presence of a voltage sensor intrinsic to SecYEG was indicated by voltage driven closure of pores that were forced-open either by crosslinking the plug to SecE or by plug deletion. We tested the involvement of SecY’s half-helix 2b (TM2b) in voltage sensing, since clearly identifiable gating charges are missing. The mutation L80D accelerated voltage driven closings by reversing TM2b’s dipolar orientation. In contrast, the L80K mutation decelerated voltage induced closings by increasing TM2b’s dipole moment. The observations suggest that TM2b is part of a larger voltage sensor. By partly aligning the combined dipole of this sensor with the orientation of the membrane-spanning electric field, voltage may drive channel closure.
Sleep deprivation regulates availability of PrPC and Aβ peptides which can impair interaction between PrPC and laminin and neuronal plasticity

PrPC is a glycoprotein capable to interact with several molecules and mediates diverse signaling pathways. Among numerous ligands, laminin (LN) is known to promote neurite outgrowth and memory consolidation, while amyloid‐beta oligomers (Aβo) trigger synaptic dysfunction. In both pathways, mGluR1 is recruited as co‐receptor. The involvement of PrPC/mGluR1 in these opposite functions suggests that this complex is a key element in the regulation of synaptic activity. Considering that sleep‐wake cycle is important for synaptic homeostasis, we aimed to investigate how sleep deprivation affects the expression of PrPC and its ligands, laminin, Aβo, and mGluR1, a multicomplex that can interfere with neuronal plasticity. To address this question, hippocampi of control (CT) and sleep deprived (SD) C57BL/6 mice were collected at two time points of circadian period (13 hr and 21 hr). We observed that sleep deprivation reduced PrPC and mGluR1 levels with higher effect in active state (21 hr). Sleep deprivation also caused accumulation of Aβ peptides in rest period (13 hr), while laminin levels were not affected. In vitro binding assay showed that Aβo can compete with LN for PrPC binding. The influence of Aβo was also observed in neuritogenesis. LN alone promoted longer neurite outgrowth than non‐treated cells in both Prnp+/+ and Prnp0/0 genotypes. Aβo alone did not show any effects, but when added together with LN, it attenuated the effects of LN only in Prnp+/+ cells. Altogether, our findings indicate that sleep deprivation regulates the availability of PrPC and Aβ peptides, and based on our in vitro assays, these alterations induced by sleep deprivation can negatively affect LN–PrPC interaction, which is known to play roles in neuronal plasticity.
Pregnancy outcomes in anti-NMDA receptor encephalitis

Objective To report the effects of anti-NMDA receptor (NMDAR) encephalitis in pregnant patients and their babies. Methods We studied a retrospective cohort of patients who developed anti-NMDAR encephalitis during pregnancy or became pregnant while recovering from the encephalitis. In addition, we reviewed the English literature between 2010 and 2019 related to this topic. Results We studied 11 patients; 6 developed anti-NMDAR encephalitis during pregnancy, and 5 became pregnant while recovering. There were no obstetrical complications, but 6 (55%) babies were premature. Ten newborns were healthy, and 1 (9%) developed transient respiratory distress. Nine infants had assessable follow-up (median 18 months; range, 7–96 months), and all showed normal development. We identified 21 cases in the English literature. Obstetrical complications occurred in 7 (33%) pregnancies. Two patients died of septic shock (1 baby successfully delivered), another 2 had miscarriages, and in 2, the pregnancy was terminated. Sixteen babies (76%) were delivered, 9 (56%) premature. At birth, 13/16 (81%) newborns were healthy, 2/16 (13%) had transient neurologic or respiratory symptoms, and 1 (6%) died of brain edema. Follow-up (median 12 months; range, 6–36 months) was reported for 8 children: 7 (88%) showed normal development and behavior, and 1 (13%) cortical dysplasia. Immunotherapy was used during pregnancy in 7 (64%) of our patients and 18 (86%) of the reported cases, including rituximab in 4 cases, without adverse effects. Conclusions Patients who develop anti-NMDAR encephalitis during pregnancy or become pregnant during recovery often have obstetrical complications, but most of the newborns are healthy and appear to have normal development.
Increasing the Medium Osmolarity Reduces the Inflammatory Status of Human OA Chondrocytes and Increases Their Responsiveness to GDF-5

The environment surrounding chondrocytes changes drastically in osteoarthritis (OA). For instance, the osmolarity in cartilage (ranging from 350 to 460 mOsm in healthy tissue) decreases during the progression of OA, reaching 270 mOsm. The objective of this study was to evaluate how osmolarity influences human OA chondrocytes. For this purpose, the osmolarity of the culture medium (340 mOsm) was increased to 380, 420 or 460 mOsm and its effect on the phenotype, matrix production, protease expression, cytokine release and growth and differentiation factor-5 (GDF-5) receptor expression in human OA chondrocytes was evaluated in a monolayer. Afterwards, the same parameters, as well as the responsiveness to GDF-5, were evaluated in 3D culture at 340 and 380 mOsm. Our results revealed that increasing the medium osmolarity increased matrix production but also reduced cytokine release, type I collagen and protease expression. It was also demonstrated that at 380 mOsm, the response to GDF-5 in 3D culture was more robust than at 340 mOsm. For the first time, it was established that a decreased osmolarity plays a role in sustaining inflammation and catabolic activities in OA chondrocytes and decreases their responsiveness to GDF-5. This indicates that osmolarity is a critical aspect of OA pathobiology.
The Effect of the Tumor Microenvironment and Tumor-Derived Metabolites on Dendritic Cell Function

Dendritic cells (DCs) have a critical effect on the outcome of adaptive immune responses against growing tumors. Recent studies on the metabolism on DCs provide new insights on the functioning of these critical controllers of innate and adaptive immunity. DCs within the tumor microenvironment (TME) often exist in an inactive state, which is thought to limit the adaptive immune response elicited by the growing tumor. Tumor-derived factors in the TME are known to suppress DC activation and result in functional alterations in DC phenotype. We are now beginning to appreciate that many of these factors can also induce changes in immune cell metabolism. In this review, we discuss the functional alternation of DC phenotype by tumor metabolites.
Combined Src/EGFR Inhibition Targets STAT3 Signaling and Induces Stromal Remodeling to Improve Survival in Pancreatic Cancer

Lack of durable response to cytotoxic chemotherapy is a major contributor to the dismal outcomes seen in pancreatic ductal adenocarcinoma (PDAC). Extensive tumor desmoplasia and poor vascular supply are two predominant characteristics which hinder the delivery of chemotherapeutic drugs into PDAC tumors and mediate resistance to therapy. Previously, we have shown that STAT3 is a key biomarker of therapeutic resistance to gemcitabine treatment in PDAC, which can be overcome by combined inhibition of the Src and EGFR pathways. Although it is well-established that concurrent EGFR and Src inhibition exert these antineoplastic properties through direct inhibition of mitogenic pathways in tumor cells, the influence of this combined therapy on stromal constituents in PDAC tumors remains unknown. In this study, we demonstrate in both orthotopic tumor xenograft and Ptf1acre/+;LSL-KrasG12D/+;Tgfbr2flox/flox (PKT) mouse models that concurrent EGFR and Src inhibition abrogates STAT3 activation, increases microvessel density, and prevents tissue fibrosis in vivo. Furthermore, the stromal changes induced by parallel EGFR and Src pathway inhibition resulted in improved overall survival in PKT mice when combined with gemcitabine. As a phase I clinical trial utilizing concurrent EGFR and Src inhibition with gemcitabine has recently concluded, these data provide timely translational insight into the novel mechanism of action of this regimen and expand our understanding into the phenomenon of stromal-mediated therapeutic resistance. Implications: These findings demonstrate that Src/EGFR inhibition targets STAT3, remodels the tumor stroma, and results in enhanced delivery of gemcitabine to improve overall survival in a mouse model of PDAC.
Usability of Clinical Information in Discharge Summary Data in the Diagnosis Procedure Combination Survey for Cancer Patients

Valid data are required to monitor and measure the quality of cancer treatment. This study aims to assess the usability of diagnosis procedure combination (DPC) survey discharge summary data. DPC survey data were analyzed by linking them to the hospital-based cancer registries (HBCR) from 231 hospitals. We focused on patients who were aged 20 years or older and diagnosed in 2013 with stomach, colorectal, liver, lung, or breast cancer. We assessed the percentage of unknown/missing values in supplementary data for patients with five common cancers and compared DPC cancer stage information to that of HBCR. In total, 279,451 discharge data sets for 180,399 patients were analyzed. The percentages of unknown data for smoking index and height/weight were 10.5% and 2.3%, respectively, and varied from 0.0% to 93.0% between hospitals. In the activity of daily living component, the rates of missing data for climbing stairs (3.6%) and bathing (2.9%) at admission were slightly higher than for other elements. Unexpectedly low concordance rate of tumor, node, and metastasis classification between DPC survey and HBCR data was observed as 80.6%, which means 20.4% of the data showed discrepancies. The usability of DPC survey discharge summary data is generally acceptable, but some variables had substantial amounts of missing values.
Naringenin protects AlCl3/D-galactose induced neurotoxicity in rat model of AD via attenuation of acetylcholinesterase levels and inhibition of oxidative stress

Currently prescribed medications for the treatment of Alzheimer’s disease (AD) that are based on acetylcholinesterase inhibition only offer symptomatic relief but do not provide protection against neurodegeneration. There appear to be an intense need for the development of therapeutic strategies that not only improve brain functions but also prevent neurodegeneration. The oxidative stress is one of the main causative factors of AD. Various antioxidants are being investigated to prevent neurodegeneration in AD. The objective of this study was to investigate the neuroprotective effects of naringenin (NAR) against AlCl3+D-gal induced AD-like symptoms in an animal model. Rats were orally pre-treated with NAR (50 mg/kg) for two weeks and then exposed to AlCl3+D-gal (150 mg/kg + 300 mg/kg) intraperitoneally for one week to develop AD-like symptoms. The standard drug, donepezil (DPZ) was used as a stimulator of cholinergic activity. Our results showed that NAR pre-treatment significantly protected AD-like behavioral disturbances in rats. In DPZ group, rats showed improved cognitive and cholinergic functions but the neuropsychiatric functions were not completely improved and showed marked histopathological alterations. However, NAR not only prevented AlCl3+D-gal induced AD-like symptoms but also significantly prevented neuropsychiatric dysfunctions in rats. Results of present study suggest that NAR may play a role in enhancing neuroprotective and cognition functions and it can potentially be considered as a neuroprotective compound for therapeutic management of AD in the future.
Attitudes of Polish Nurses Toward Selected National Groups

Introduction: Opening up to global migration processes has contributed to increasing the cultural diversity of Polish society. The diagnosis of nurses’ attitudes toward cultural differences is important in the assessment of training needs and in providing professional care. Method: Cross-sectional studies, was carried out in 2018 among 1,271 nurses. In the research, the following scales and questionnaire were used: Bogardus Social Distance and Social Dominance Orientation Scales; Social Approbation Questionnaire and author’s questionnaire. Results: The respondents showed the highest social distance toward Russians, Vietnamese, and Chechens. There was a significant dependence of the level of social distance of respondents from age, job seniority, place of residence, education, frequency of contact with representatives of other nationalities, living abroad, care for a person of other nationality, training on transcultural nursing, participation in cultural events regarding representatives of other nationalities. Conclusions: The results of the research indicate the need to train nurses in the field of transcultural nursing.
Nanotip Contacts for Electric Transport and Field Emission Characterization of Ultrathin MoS2 Flakes

We report a facile approach based on piezoelectric-driven nanotips inside a scanning electron microscope to contact and electrically characterize ultrathin MoS2 (molybdenum disulfide) flakes on a SiO2/Si (silicon dioxide/silicon) substrate. We apply such a method to analyze the electric transport and field emission properties of chemical vapor deposition-synthesized monolayer MoS2, used as the channel of back-gate field effect transistors. We study the effects of the gate-voltage range and sweeping time on the channel current and on its hysteretic behavior. We observe that the conduction of the MoS2 channel is affected by trap states. Moreover, we report a gate-controlled field emission current from the edge part of the MoS2 flake, evidencing a field enhancement factor of approximately 200 and a turn-on field of approximately 40 V/μm at a cathode–anode separation distance of 900 nm.
Low FODMAP Diet: Evidence, Doubts, and Hopes

Food is often considered to be a precipitating factor of irritable bowel syndrome (IBS) symptoms. In recent years, there has been a growing interest in FODMAPs (Fermentable Oligo-, Di-, Mono-saccharides, And Polyols), which can be found in many common foods. A low FODMAP diet (LFD) is increasingly suggested for IBS treatment. However, long-term, large, randomized controlled studies are still lacking, and certainties and doubts regarding LFDs have grown, often in a disorderly and confused manner. Some potential LFD limitations and concerns have been raised, including nutritional adequacy, cost, and difficulty in teaching the diet and maintaining it. Most of these limitations can be solved with the involvement of a skilled nutritionist, who can clearly explain the different phases of the LFD and ensure nutritional adequacy and compliance. Further studies should focus on new methods of teaching and learning the LFD and on predictors of response. Moreover, particular interest should be focused on the possible use of LFD in gastrointestinal diseases other than functional disorders and, possibly, also in non-gastrointestinal diseases. The aim of the present review was to clarify the effective and appropriate indications and limitations of an LFD and to discuss its possible future uses.
Built and Natural Environmental Correlates of Parental Safety Concerns for Children’s Active Travel to School

This cross-sectional study examines built and natural environmental correlates of parental safety concerns for children’s active travel to school (ATS), controlling for socio-demographic, attitudinal, and social factors. Questionnaire surveys (n = 3291) completed by parents who had 1st–6th grade children were collected in 2011 from 20 elementary schools in Austin, Texas. Objectively-measured built and natural environmental data were derived from two software programs: Geographic Information Systems (GIS) and Environment for Visualizing Images (ENVI). Ordinal least square regressions were used for statistical analyses in this study. Results from the fully adjusted final model showed that bike lanes, the presence of highway and railroads, the presence of sex offenders, and steep slopes along the home-to-school route were associated with increased parental safety concerns, while greater intersection density and greater tree canopy coverage along the route were associated with decreased parental safety concerns. Natural elements and walking-friendly elements of the built environment appear important in reducing parental safety concerns, which is a necessary step toward promoting children’s ATS.
The psychometric properties of a version of the Treatment Self-Regulation Questionnaire for assessing motivations for responsible drinking

Abstract Objective The aim of the present studies was to provide a psychometric evaluation of a version of the Treatment Self-Regulation Questionnaire (TSRQ) for assessing motivations derived from self-determination theory for responsible drinking among college students. Methods: A convenience sample of 308 college student drinkers (71.7% female) were recruited for Study 1 and a random sample of 192 college student drinkers (58.9% female) were recruited for Study 2. Participants completed the TSRQ and other self-report measures in both studies. Results: In Study 1, confirmatory factor analyses supported a revised four-factor structure of the TSRQ. In Study 2, correlation analyses generally provided support for the concurrent validity of the TSRQ subscales. Conclusion: The present studies provide some initial support for the TSRQ for assessing motivations for responsible drinking. Directions for future research and implications of a measure for assessing motivations for responsible drinking among college students are discussed.
The Singularity of the Drosophila Male Germ Cell Centriole: The Asymmetric Distribution of Sas4 and Sas6

Drosophila spermatocytes have giant centrioles that display unique properties. Both the parent centrioles maintain a distinct cartwheel and nucleate a cilium-like region that persists during the meiotic divisions and organizes a structured sperm axoneme. Moreover, the parent centrioles are morphologically undistinguishable, unlike vertebrate cells in which mother and daughter centrioles have distinct structural features. However, our immunofluorescence analysis of the parent centrioles in mature primary spermatocytes revealed an asymmetric accumulation of the typical Sas4 and Sas6 proteins. Notably, the fluorescence intensity of Sas4 and Sas6 at the daughter centrioles is greater than the intensity found at the mother ones. In contrast, the centrioles of wing imaginal disc cells display an opposite condition in which the loading of Sas4 and Sas6 at the mother centrioles is greater. These data underlie a subtle asymmetry among the parent centrioles and point to a cell type diversity of the localization of the Sas4 and Sas6 proteins.
Classical human astroviruses in symptomatic and asymptomatic children of Goiás, Brazil: Positivity rates, viral loads, and molecular characterization

Classical human astroviruses (HAstV) are agents of nonbacterial acute gastroenteritis (AGE), being predominant among children. There are only a few studies reporting HAstV loads in samples from patients with AGE, data are even scarcer regarding asymptomatic patients. The aim of this study was to evaluate the occurrence and estimate the viral load of HAstV and to perform molecular characterization of positive samples obtained from children, up to 6 years old, with and without AGE. One fecal sample was obtained from each of the 250 children enrolled in the study, from May 2014 to April 2015. Real‐time reverse transcription‐polymerase chain reaction (RT‐qPCR TaqMan) was performed, followed by a conventional RT‐PCR directed to ORF2, region C, of the positive samples. Then, these amplicons were sequenced and a phylogenetic analysis was performed to determine the HAstV‐1 lineages. A global positivity index of 3.2% (8 of 250) was observed for HAstV with a similar frequency (50%) in both symptomatic and asymptomatic group. Viral loads ranged from 2.8 × 105 to 1.6 × 1011 genome copy/mL Four samples were characterized as HAstV‐1, lineage 1a and two as HAstV‐4, lineage 4c. Our findings show similar HAstV positivity rates for children with and without AGE, providing evidence of HAstV‐1a and HAstV‐4c lineage cocirculation in the Central West region of Brazil. Data contributes to the molecular epidemiology of these agents in the region.