Miracle-dz/UniFAR-FTUs huggingface dataset:
HDAC4 regulates the proliferation, migration, and invasion of trophoblasts in pre‐eclampsia through the miR‐134‐5p/FOXM1 axis

Epigenetics, including histone modifications and noncoding RNAs, affects abnormal placental function in pre‐eclampsia (PE). This study was conducted to explore the role of histone deacetylase 4 (HDAC4) in trophoblast invasion and migration. The expression levels of HDAC4, microRNA (miR)‐134‐5p, and forkhead box protein M1 (FOXM1) in placentas from PE patients and healthy controls and their correlations were examined. HTR8/SVneo cells were cultured and underwent gene intervention. Then, trophoblast proliferation, invasion, and migration were evaluated by 5‐ethynyl‐2ʹdeoxyuridine, Transwell, and scratch assays. The enrichments of HDAC4 and acetylated histone H3 at lysine 9 (H3K9Ac) on the miR‐134‐5p promoter were quantified by chromatin immunoprecipitation. The binding of miR‐134‐5p to FOXM1 was analyzed by dual‐luciferase assay. HDAC4 and FOXM1 were downregulated while miR‐134‐5p was upregulated in PE placentas. HDAC4 downregulation impaired trophoblast proliferation, invasion, and migration while HDAC4 overexpression played the opposite role. Mechanically, HDAC4 deacetylated H3K9Ac to repress miR‐134‐5p expression by erasing H3K9Ac, reduced the binding of miR‐134‐5p to FOXM1, and then promoted FOXM1 transcription. miR‐134‐5p overexpression or FOXM1 downregulation abrogated the promotive role of HDAC overexpression in trophoblast invasion and migration. Our study unraveled a novel mechanism of trophoblast proliferation, invasion, and migration and proposed that HDAC4 may be a promising target for the treatment of PE.
Glutamine regulates the cellular proliferation and cell cycle progression by modulating the mTOR mediated protein levels of β-TrCP

ABSTRACT The amino acid glutamine plays an important role in cell growth and proliferation. Reliance on glutamine has long been considered a hallmark of highly proliferating cancer cells. Development of strategies for cancer therapy that primarily target glutamine metabolism has been an active area of research. Glutamine depletion is associated with growth arrest and apoptosis-induced cell death; however, the molecular mechanisms involved in this process are not clearly understood. Here, we show that glutamine depletion activates the energetic stress AMPK pathway and inhibits mTORC1 activity. Furthermore, inhibition of mTORC1 reduces the protein levels of β-TrCP, resulting in aberrant cell cycle progression and reduced proliferation. In agreement with the role of β-TrCP in glutamine metabolism, knockdown of β-TrCP resulted in proliferation and cell cycle defects similar to those observed for glutamine depletion. In summary, our results provide mechanistic insights into the role of glutamine metabolism in regulation of cell growth and proliferation via β-TrCP, uncovering a previously undescribed molecular process involved in glutamine metabolism.
Soluble CD4 and low molecular weight CD4-mimetic compounds sensitize cells to be killed by anti-HIV cytotoxic immunoconjugates

ABSTRACT The reservoir of HIV-infected cells that persist in the face of effective anti-retroviral therapy (ART) is the barrier to curing HIV infection. These long-lived CD4+ cells carry a functional provirus that can become activated upon immune stimulation. When ART is stopped, this leads to a rapid rebound in viremia. A variety of approaches are proposed to eliminate these cells, many dependent upon the expression of virus proteins. We are examining the use of cytotoxic immunoconjugates targeting the HIV envelope protein (Env) as a method to eradicate cells producing virus and have demonstrated that soluble CD4 enhances the cytotoxic effect of gp41-targeted immunoconjugates. Mechanisms include increased antigen exposure and greater internalization of the immunoconjugate. Here we have tested different protein forms of CD4 and the small molecule CD4-mimetic BNM-III-170 for their effects on cells expressing cell-surface Env. Effects studied include sensitization to immunoconjugate killing, cell surface antigen expression, viability, and virus secretion. The CD4 proteins and BNM-III-170 produced comparable effects in these Env-expressing cell lines, each sensitizing cells to cytotoxicity by anti-gp41 immunoconjugates. The results provide further evidence that low molecular weight CD4 mimetics produce biologic effects similar to those caused by soluble CD4 itself and suggest additional therapeutic uses for these molecules. IMPORTANCE HIV infection can be effectively treated to prevent the development of AIDS, but it cannot be cured. We have attached poisons to anti-HIV antibodies to kill the infected cells that persist even after years of effective antiviral therapy. Here we show that the killing of infected cells can be markedly enhanced by the addition of soluble forms of the HIV receptor CD4 or by mimics of CD4. HIV infection can be effectively treated to prevent the development of AIDS, but it cannot be cured. We have attached poisons to anti-HIV antibodies to kill the infected cells that persist even after years of effective antiviral therapy. Here we show that the killing of infected cells can be markedly enhanced by the addition of soluble forms of the HIV receptor CD4 or by mimics of CD4.
El interés del alumnado de Educación Secundaria Obligatoria hacia la Educación Física The Interest of Compulsory High School Students in Physical Education

The way that the secondary education students see Physical Education is an issue of great interest to teachers. There are numerous variables that determine this view. In our research, we have analyzed how the student’s interest toward the subject influences different aspects related to Physical Education, i.e. the students’ gender, the importance attached to Physical Education, the student’s sports and physical activity, the context in which this activity is carried out, and the kind of qualification held by the Physical Education teacher. For this purpose, we have used a C.A. P.A. E.F. (Questionnaire for Analyzing Students’ Perceptions in Physical Education), specifically prepared for this research, on a sample of 1,499 students of the first and second cycles of Secondary Education of the Autonomous Region of Murcia. The main conclusions we have reached are the following: those students who show a great interest in Physical Education emphasize those objectives related to Health, Education and Competition, as well as Physical Condition and Health, and Games and Sports contents, with less value to SelfExpression Through Movement; they attach great importance to Physical Education, which is their favorite subject, and do not agree to reduce the number of lessons; they find Physical Education classes useful, easy and motivating, and find great support in their teachers as they are friendly, nice, understanding, cheerful and fair, and take a participative role in classes.
The impact of age‐relevant and generic infographics on knowledge, attitudes and intention to attend cervical screening: A randomized controlled trial

Abstract Objectives Cervical screening uptake in England is falling. Infographics could strengthen intention to attend, increase positive attitudes and improve knowledge. Age targeting could improve these outcomes further. We tested the impact of generic and age‐targeted infographics. Design A randomized controlled trial using an age‐stratified, parallel‐group design. Methods Women aged 25–64 (n = 2095) were recruited through an online panel and randomized to see one of the three infographics. We tested: (i) impact of a generic cervical screening infographic compared to a control infographic on an unrelated topic with all screening age women and (ii) impact of an age‐targeted infographic compared to a generic cervical screening infographic with older women (50–64 years). Intentions, knowledge and attitudes were measured. Results Women aged 25–64 years who viewed the generic infographic had significantly higher intentions [F(1, 1513) = 6.14, p = . 013, ηp2 = . 004], more accurate beliefs about the timeline of cervical cancer development (OR: 5.18, 95% CI: 3.86–6.95), more accurate social norms (OR: 3.03, 95% CI: 2.38–3.87) and more positive beliefs about screening benefits (OR: 2.23, 95% CI: 1.52–3.28) than those viewing the control infographic. In the older age group, there was no significant difference in intention between those viewing the generic versus age‐targeted versions [F(1, 607) = . 03, p = . 853, ηp2 < . 001], but the age‐targeted version was more engaging [F(1, 608) = 9.41, p = . 002, ηp2 = . 015]. Conclusions A cervical screening infographic can result in more positive attitudes and better knowledge and may have a small impact on intentions. Although age targeting did not affect intention, it had a positive impact on engagement and may therefore be useful in encouraging women to read and process materials.
Sedimentation in an actively tilting half‐graben: sedimentology and stratigraphy of Late Tournaisian–Viséan (Mississippian, Lower Carboniferous) carbonate rocks in south County Wexford, Ireland

The Wexford Basin (south‐eastern Ireland) is a NE–SW‐trending sedimentary basin containing carbonates and evaporites deposited during the Late Tournaisian and Viséan. Two separate depositional areas are defined on the basis of facies and facies associations. Sediments were deposited in inner ramp, lagoonal and peritidal environments near Rosslare, and in a more open‐marine, shallow‐ to moderately deep‐water, mid to outer ramp environment in the western area around Duncormick. Thick breccia deposits that occur in the Wexford Basin formed as a result of (i) fault movement that produced syn‐sedimentary debris flows in the Late? Chadian (Breccia type I); (ii) dissolution of anhydrite/gypsum and subsequent collapse of sedimentary strata (Breccia type II); and (iii) fracturing and brecciation of porous rock caused by the movement of high temperature, late diagenetic fluids along fault planes (Breccia type III). The NE–SW facies polarity displayed by both sedimentary successions was the result of NW–SE extension and the reactivation of the NE–SW‐trending Wexford Boundary Fault during the Chadian. Extension at the SE margin of the basin with downthrow to the NNW gave the basin a half‐graben character. Thickening of the debris flow deposits to the SW suggests that while the half‐graben was being tilted it also underwent a NE–SW block rotation due to an axial component of that normal fault.
Happy Family, Healthy Kids

Background Substantial effort has been invested to combat childhood obesity, but overall effects are disappointing, especially in low-income racial minority children. One possible reason is a lack of focus on the important stress–eating connection. Stress can negatively influence eating behaviors, leading to an increased appetite for high-fat and energy-dense foods. Objective This study aimed to evaluate the preliminary effects of a healthy eating and stress management program targeting multiple theoretical variables on improving eating behavior (dyads’ fruit/vegetable intake, emotional eating), food insecurity, anthropometric characteristics (dyads’ body mass index, % body fat), cardiovascular health (dyads’ blood pressure), and mental well-being (parental stress). Methods A one-group, quasi-experimental pilot study was conducted among 107 low-income parent–preschooler dyads. The 14-week program included a parent component, a parent–preschooler learning component, and a day care-based preschooler component. Results The program had positive effects on improving dyads’ fruit/vegetable intake, food insecurity, body mass index, and blood pressure and parents’ nutrition knowledge, self-efficacy, support, food resource management behavior, problem-focused coping, and home eating environment. The overall satisfaction rate was 95.2%, and 88.1% stated that the program assisted their families with having a healthy lifestyle. Discussion Results support the preliminary effects of the program on improving health outcomes in rural and urban low-income families. Although warranting further investigation with a more rigorous randomized controlled trial, the healthy eating and stress management program provides a potential solution to the current coexistence of an obesity epidemic and mental health crisis.
Granularity in disease classification impacts survival prediction in advanced systemic mastocytosis: A single institution study of 329 informative cases

The World Health Organization (WHO) classification system categorizes advanced systemic mastocytosis (SM‐Adv) into aggressive SM (ASM), mast cell leukemia (MCL), and SM with associated hematological neoplasm (SM‐AHN). By contrast, the International Consensus Classification (ICC) requires “immature” MC cytomorphology for the diagnosis of MCL and limits SM‐AHN to myeloid neoplasms (SM‐AMN). The current study includes 329 patients with SM‐Adv (median age 65 years, range 18–88; males 58%): WHO subcategories SM‐AHN (N = 212; 64%), ASM (N = 99; 30%), and MCL (N = 18; 6%); ICC subcategories SM‐AMN (N = 190; 64%), ASM (N = 99; 33%), and MCL (N = 9; 3%); WHO‐defined MCL with “mature” MC cytomorphology and SM‐AHN associated with lymphoid neoplasms were operationally labeled as “MCL‐mature” (N = 9) and SM‐ALN (N = 22), respectively, and distinguished from ICC‐defined MCL and SM‐AMN. Multivariable analysis that included the Mayo alliance risk factors for survival in SM (age >60 years, anemia, thrombocytopenia, increased alkaline phosphatase) revealed more accurate survival prediction with the ICC versus WHO classification order: (i) survival was significantly worse with MCL‐immature versus MCL‐mature (hazard ratio [HR] 15; p < .01), (ii) prognostic distinction between MCL and SM‐AHN/AMN was confirmed in the context of ICC (HR 9.3; p < .01) but not WHO classification order (p = .99), (iii) survival was similar between MCL‐mature and SM‐AMN (p = .18), and (iv) SM‐AMN (HR 1.7; p < .01) but not SM‐ALN (p = .37) was prognostically distinct from ASM. The current study provides evidence for the independent prognostic contribution of both the ICC system for SM‐Adv and the Mayo alliance risk factors for survival in SM.
Calderite-rich garnets from metamorphosed manganese silicate rocks of the Sausar Group, India, and their derivation

Abstract Manganiferous garnets occur in metamorphosed Mn silicate-oxide and silicate-carbonate-oxide rocks of the Sausar Group, India. The garnets of the carbonatic rock show maximum calderite content (∼50 mole%). Increased Ca content in the bulk has been observed to be sympathetically related to the concentration of calderite, rather than the expected andradite component of the garnets. This is the consequence of the preferential partitioning of Ca in coexisting pyroxmangite and/or carbonate. Petrochemical characteristics of the diverse assemblages in response to the physical conditions of metamorphism show that the calderite solubility in manganiferous garnet is not only a function of pressure. Such characteristics only indicate that the mobile components in the bulk influenced the mineralogy of the assemblages at the ambient physical conditions of metamorphism, and this in turn controlled the calderite solubility in garnet.
The design and testing of a free-fall device for recording seismic activity beneath the ocean floor

For the last thirty years ocean bottom seismometers (OBSs) have been used to survey the oceans. However, the quality of the data they produce is often degraded due to poor coupling or high levels of ambient noise. In contrast, sensors placed beneath the seafloor avoid many of these problems. For the last two decades burials have relied on Ocean Drilling Program (ODP) boreholes. This approach is expensive and demands numerous human resources. In addition, the locations of these boreholes, determined by the ODP, are rarely desirable for monitoring seismic activity. In this paper a sub-bottom seismic acquisition system is presented that uses free-fall devices, or deep ocean seismic penetrators (DOSP), to place sensors several tens of metres beneath the seafloor. The DOSPs weigh approximately 1800 kg, achieve terminal velocities between 30-50 m/s and penetrate to depths of 20-30 metres in soft sea sediments. Once buried, they record seismic activity and transmit data back to the surface using a frequency shift keyed (FSK) modulation technique. The results of an experiment conducted in the Mediterranean using this system are presented. These confirm the predicted dynamic and kinematic behaviour of the DOSP and allow an assessment of the ambient seismic noise level at a depth of /spl ap/30 metres beneath the seafloor. In conclusion this paper discusses the potential use of free-fall devices to increase our understanding of processes in the deep oceans, with particular emphasis on their applicability to future deep ocean seismology.
Traumatic spinal injury patterns of on vs. off-road motorcycle crashes

Abstract Objective Two wheel motorized vehicles used in both street transportation and recreation are a common cause of severe injury in the United States (US). To date, there has been limited data describing the spinal injury patterns among these motorcycle injury patients in the US. The goal of this study is to characterize and compare differences in specific injury patterns of patients sustaining traumatic spinal injuries after motocross (off-road) and street bike (on-road) collisions in the southwestern US at a Level I Trauma Center. Methods Trauma registry data was queried for patients sustaining a spinal injury after motorcycle collision from 2010 to 2019 at a single Level I Trauma Center. Computed tomography (CT) scan and magnetic imaging resonance imaging (MRI) reports from initial trauma evaluation were reviewed and data was manually obtained regarding injury morphology and location. Results A total of 1798 injuries were identified in 549 patients who sustained a motorcycle collision, specifically 67 off-road and 482 on-road motorcycle patients. Off-road motorcycle patients were found to be significantly younger (34.75 vs. 42.66, p = 0.00015). A total of 46.2% of the off-road injuries were determined to be from compression mechanisms, compared to 32.9% in the on-road cohort (p = 0.0027). The on-road cohort was more likely to have an injury classified as insignificant, such as transverse and spinous process fractures (60.1% vs. 42.5%, p = 00.25). There was no significant difference in regards to junctional, mobile, and semirigid spine segments between the two cohorts. Conclusions Different fracture patterns were seen between the off-road and on-road motorcycle cohorts. Off road motorcyclists experienced significantly more compression and translational injuries, while on road motorcyclists experienced more frequent insignificant injury patterns. Data on the different fracture patterns may help professionals develop safety equipment for motorcyclists.
Neuronal aging is associated with declined autophagy caused by reduced functionality of cGAS-STING signaling

The lifelong maintenance of cognitive abilities in an increasingly aging human society is one of the major challenges of future research and medical services. For this, a better understanding of the cellular aging processes in the mammalian brain is a fundamental requirement. In particular, the functioning of postmitotic neurons, which require special strategies for lifelong functionality, is still elusive in many details. Among many other hallmarks of neuronal aging, the impairment of autophagy as an essential element of cellular homeostasis is of particular importance. However, the mechanisms for regulating these processes have not yet been fully elucidated. Establishing an in vitro model from primary cortical cells of the mouse brain, which shows the characteristic features of cellular senescence that are also observed in the total brain, we found the accumulation of dsDNA in the cytosol of neurons. Since dsDNA is a trigger for the activation of the cGAS-STING signaling and its primordial function is a non-canonical activation of autophagy, we analyzed its impact on aging neurons. We were able to demonstrate that the age-dependent downregulation of cGAS- STING signaling in neurons leads to an inhibition of autophagy at different levels. In contrast, activation of STING led to a complete rescue of autophagy in old neurons. Additionally, we found no evidence for age dependent cGAS-STING mediated IFN-I production. Hence, we propose that the primary function of cGAS-STING signaling in neurons is to maintain autophagy rather than contribute to age-related inflammation, and thus represents a target for therapeutic intervention.
Identifying the cortical face network with dynamic face stimuli: A large group fMRI study

Functional magnetic resonance imaging (fMRI) studies have identified a network of face-selective regions distributed across the human brain. In the present study, we analyzed data from a large group of gender-balanced participants to investigate how reliably these face-selective regions could be identified across both cerebral hemispheres. Participants (N=52) were scanned with fMRI while viewing short videos of faces, bodies, and objects. Results revealed that five face-selective regions: the fusiform face area (FFA), posterior superior temporal sulcus (pSTS), anterior superior temporal sulcus (aSTS), inferior frontal gyrus (IFG) and the amygdala were all larger in the right than in the left hemisphere. The occipital face area (OFA) was larger in the right hemisphere as well, but the difference between the hemispheres was not significant. The neural response to moving faces was also greater in face-selective regions in the right than in the left hemisphere. An additional analysis revealed that the pSTS and IFG were significantly larger in the right hemisphere compared to other face-selective regions. This pattern of results demonstrates that moving faces are preferentially processed in the right hemisphere and that the pSTS and IFG appear to be the strongest drivers of this laterality. An analysis of gender revealed that face-selective regions were typically larger in females (N=26) than males (N=26), but this gender difference was not statistically significant.
Diet-induced obesity impacts influenza disease severity and transmission dynamics in ferrets

Obesity, and the associated metabolic syndrome, is a risk factor for increased disease severity with a variety of infectious agents, including influenza virus. Yet the mechanisms are only partially understood. As the number of people, particularly children, living with obesity continues to rise, it is critical to understand the role of host status on disease pathogenesis. In these studies, we use a novel diet-induced obese ferret model and new tools to demonstrate that like humans, obesity resulted in significant changes to the lung microenvironment leading to increased clinical disease and viral spread to the lower respiratory tract. The decreased antiviral responses also resulted in obese animals shedding higher infectious virus for longer making them more likely to transmit to contacts. These data suggest the obese ferret model may be crucial to understanding obesity’s impact on influenza disease severity and community transmission, and a key tool for therapeutic and intervention development for this high-risk population. Teaser A new ferret model and tools to explore obesity’s impact on respiratory virus infection, susceptibility, and community transmission.