Miracle-dz/UniFAR-FTUs huggingface dataset:
AUF1 and Hu proteins in the developing rat brain: Implication in the proliferation and differentiation of neural progenitors

Posttranscriptional events such as RNA stabilization are important for cell differentiation, but little is known about the impact of AU‐rich binding proteins (AUBPs) on the fate of neural cells. Expression of destabilizing AUBPs such as AUF1 and neuronal‐specific stabilizing proteins such as HuB, HuC and HuD was therefore analyzed in the developing central nervous system. Real‐time RT‐PCR indicated a specific developmental pattern in the postnatal cerebellum, with a progressive down‐regulation of AUF1 from P1, whereas HuB was strongly up‐regulated at about P7. These changes were accompanied by a progressive increase in AUF1p45 and the disappearance of one HuB isoform from P15, suggesting particular roles for these AUBPs in the developing cerebellum. AUF1 was detected in the three main cerebellar layers, whereas Hu proteins were found only in postmitotic neurons. A role for Hu proteins in the early stages of neuronal differentiation is further supported by arrest of cell proliferation following induction of HuB or HuD expression in a neural stem cell line. The decrease in nestin expression suggest that HuD, but not HuB, favors the transition of neural progenitors into early neuroblasts, but other factors are most probably required for their full differentiation into neurons, insofar as GAP‐43 was not detected in HuD‐transfected cells. These data suggest critical roles for HuB at the very earliest stages of neuronal differentiation, such as cell cycle exit, and HuD might also be involved in the transition of neural progenitors into early neuroblasts. Taken together, the present results strengthen the importance of AUBPs in brain ontogenesis. © 2008 Wiley‐Liss, Inc.
Intraepidermal nerve fiber density and its application in sarcoidosis

Background: Intraepidermal nerve fiber density (IENFD) is considered a good diagnostic tool for small fiber neuropathy (SFN). Objectives: To assess stratified normative values for IENFD and determine the reliability and validity of IENFD in sarcoidosis. Methods: IENFD was assessed in 188 healthy volunteers and 72 patients with sarcoidosis (n = 58 with SFN symptoms, n = 14 without SFN symptoms). Healthy controls were stratified (for age and sex), resulting in 6 age groups (20–29, 30–39, … up to ≥70 years) containing at least 15 men and 15 women. A skin biopsy was taken in each participant 10 cm above the lateral malleolus and analyzed in accordance with the international guidelines using bright-field microscopy. Interobserver/intraobserver reliability of IENFD was examined. In the patients, a symptoms inventory questionnaire (SIQ; assessing SFN symptoms) and the Vickrey Peripheral Neuropathy Quality-of-Life Instrument-97 (PNQoL-97) were assessed to examine the discriminative ability of normative IENFD values. Results: There was a significant age-dependent decrease of IENFD values in healthy controls, with lower densities in men compared with women. Good interobserver/intraobserver reliability scores were obtained (κ values ≥0.90). A total of 21 patients with sarcoidosis had a reduced IENFD score (<5th percentile; 19 [32.8%] in patients with SFN symptoms, 2 [14.3%] in patients without SFN symptoms). The validity of the normative IENFD values was demonstrated by distinguishing between the SIQ scores and various PNQoL-97 values for the different patient groups. Conclusion: This study provides clinically applicable distal intraepidermal nerve fiber density normative values, showing age- and sex-related differences.
Physical basis of some membrane shaping mechanisms

In vesicular transport pathways, membrane proteins and lipids are internalized, externalized or transported within cells, not by bulk diffusion of single molecules, but embedded in the membrane of small vesicles or thin tubules. The formation of these ‘transport carriers’ follows sequential events: membrane bending, fission from the donor compartment, transport and eventually fusion with the acceptor membrane. A similar sequence is involved during the internalization of drug or gene carriers inside cells. These membrane-shaping events are generally mediated by proteins binding to membranes. The mechanisms behind these biological processes are actively studied both in the context of cell biology and biophysics. Bin/amphiphysin/Rvs (BAR) domain proteins are ideally suited for illustrating how simple soft matter principles can account for membrane deformation by proteins. We review here some experimental methods and corresponding theoretical models to measure how these proteins affect the mechanics and the shape of membranes. In more detail, we show how an experimental method employing optical tweezers to pull a tube from a giant vesicle may give important quantitative insights into the mechanism by which proteins sense and generate membrane curvature and the mechanism of membrane scission. This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.
Matrigel‐Induced Tubular Morphogenesis of Human Eccrine Sweat Gland Epithelial Cells

Human eccrine sweat glands are tubule‐structured glands of the skin that are vital in thermoregulation, secretion, and excretion of water and electrolytes. A study of tubular morphogenesis in vitro would facilitate the development of a tissue engineering model for eccrine sweat glands and other tubule‐structured glands. Matrigel, a basement membrane matrix, has been shown to promote differentiation and morphogenesis of many different cell types, including tubular cells. This study investigated the growth, differentiation, and tubular morphogenesis of human eccrine sweat gland epithelial cells cultured in Matrigel. Human eccrine gland epithelial cells were isolated and cultured in vitro. The cell growth in Matrigel was evidenced by the formation of cell clusters, which were observed under an inverted microscope. The internal structure of the cell clusters was further investigated by hematoxylin–eosin (HE) staining and confocal laser scanning microscopy (CLSM) of propidium iodide‐stained nuclei. The results demonstrated that although on a plastic surface or in a collagen gel the cells could not form tubular structures, they formed tubular structures when cultured in Matrigel. Consequently, we conclude that Matrigel can promote tubular morphogenesis of human eccrine sweat gland epithelial cells. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.
Comparative intraosseal growth of human prostate cancer cell lines LNCaP and PC-3 in the nude mouse.

BACKGROUND More than 75% of patients with advanced prostate carcinoma have skeletal involvement, which is the principal metastatic site and the major complication of this disease. The goal of this work was to compare the osseous metastasis of androgen-sensitive and insensitive prostate cancers in the nude mouse. MATERIALS AND METHODS Androgen-sensitive LNCaP or -insensitive PC-3 human prostate carcinoma cells were injected directly into the femur medullas of male nude Beige mice, the animals were then sacrificed at successive time intervals to study the gross and microscopic characteristics of the established tumors. RESULTS LNCaP and PC-3 both colonized in the bone marrow within a week, then gradually expanded to the entire bone medulla followed by osseous infiltration to produce obvious symptoms in the affected extremities. Based on the morphology, both osteoblastic and osteolytic changes occurred during the course of tumor progression. In addition, PC-3 tumors eventually broke through the bone cortex, invaded the surrounding tissues, and metastasized to the regional lymph nodes. In contrast, LNCaP remained localized within the bone, and appeared to eventually regress and die after displacing the normal bone marrow cells. Immunohistochemically, LNCaP tumors were consistently positive for prostate-specific antigen in bone metastasis, while PC-3 tumors were negative. Tumor cell nuclei of both PC-3 and LNCaP hybridized to a human repeated sequence DNA probe indicating that the proliferating malignant cells were of human origin. CONCLUSIONS These cancer cell lines produced a high incidence of growth in the bone that differed in histogenesis. The relative malignancy of these cell lines was demonstrated in this model.
Suicidal Behaviour in Mood Disorders—Who, When, and Why?

Objective: About one-half to two-thirds of all suicides are by people who suffer from mood disorders; preventing suicides among those who suffer from them is thus central for suicide prevention. Understanding factors underlying suicide risk is necessary for rational preventive decisions. Method: The literature on risk factors for completed and attempted suicide among subjects with depressive and bipolar disorders (BDs) was reviewed. Results: Lifetime risk of completed suicide among psychiatric patients with mood disorders is likely between 5% and 6%, with BDs, and possibly somewhat higher risk than patients with major depressive disorder. Longitudinal and psychological autopsy studies indicate suicidal acts usually take place during major depressive episodes (MDEs) or mixed illness episodes. Incidence of suicide attempts is about 20- to 40-fold, compared with euthymia, during these episodes, and duration of these high-risk states is therefore an important determinant of overall risk. Substance use and cluster B personality disorders also markedly increase risk of suicidal acts during mood episodes. Other major risk factors include hopelessness and presence of impulsive–aggressive traits. Both childhood adversity and recent adverse life events are likely to increase risk of suicide attempts, and suicidal acts are predicted by poor perceived social support. Understanding suicidal thinking and decision making is necessary for advancing treatment and prevention. Conclusion: Among subjects with mood disorders, suicidal acts usually occur during MDEs or mixed episodes concurrent with comorbid disorders. Nevertheless, illness factors can only in part explain suicidal behaviour. Illness factors, difficulty controlling impulsive and aggressive responses, plus predisposing early exposures and life situations result in a process of suicidal thinking, planning, and acts.
A comparison of four diagnostic criteria for lymphedema in a post-breast cancer population.

BACKGROUND Breast cancer survivors are at life-time risk of developing lymphedema (LE). The goal of this research was to describe LE incidence over time among women treated for breast cancer. METHODS AND RESULTS Limb volume changes (LVC) were evaluated by two measurement methods, circumferences and perometry, among 118 participants followed preoperative to 12 months postdiagnosis. Four diagnostic criteria were used: 200 mL perometry LVC; 10% perometry LVC; 2 cm circumferential increase; and report of heaviness or swelling, either "now" or "in the past year. " Using 200 mL, the estimated LE rate was 24% (95% CI = 17%-32%) at 6 months, and 42% (31%-53%) at 1 year. Using 10% LVC, the estimated LE rate was 8% (2%-13%) at 6 months, and 21% (12%-30%) at 1 year. Using 2 cm, the estimated LE rate was 46% (36%-56%) at 6 months, and 70% (60%-79%) at 1 year. Based on reported symptoms of heaviness or swelling, the estimated LE rate was 19% (11%-26%) at 6 months, and 40% (30-59%) at 1 year. CONCLUSIONS In the absence of a gold standard, we can only say that the different LE definitions are not equivalent, but cannot say which is "best". From this data, it appears that 10% LVC corresponds to a more conservative definition, whereas the 2 cm difference corresponds to a more liberal definition. These preliminary findings also document the importance of baseline (preoperative) anthropometric and symptom data and monitoring of changes over time. Further investigation of LE occurrence over an extended time period is warranted.
Method of renal mass reduction is a critical modulator of subsequent hypertension and glomerular injury.

The hypertension, proteinuria, and glomerulosclerosis that develop in the remnant kidney model (uninephrectomy plus infarction of approximately 2/3 of the other kidney) have been generally considered to represent the adverse consequences of a severe reduction in nephron number. To differentiate the blood pressure (BP) responses to infarction from those of reduced renal mass per se, BP was continuously monitored radiotelemetrically in rats whose total renal mass was reduced by 2/3 (infarction) and by 5/6 (infarction or surgical excision of both poles) and in sham-operated controls. Hypertension only developed in the two infarcted groups. Overall averages of systolic BP monitored every 10 min over 6 wk were 144 +/- 8 and 156 +/- 5 mm Hg in the 2/3 and 5/6 infarction groups (N = 10 each), respectively, as compared with 120 +/- 2 mm Hg (N = 12) in the approximately 5/6 surgical excision group (P < 0.01) and 117 +/- 5 mm Hg (N = 8) in controls. Changes in kidney weights, glomerular volumes, RBF, GFR, and renal autoregulatory ability after renal mass reduction by the two methods were qualitatively similar in additional animals from each group monitored for 2, 4, or 6 wk without radiotelemetry. Significant proteinuria and glomerulosclerosis only developed in the two infarction (hypertensive) groups. At 6 wk, 18 +/- 4 and 19 +/- 3% of the glomeruli exhibited injury in the 2/3 (N = 22) and the 5/6 infarction groups (N = 21), respectively, in contrast to 3 +/- 1% glomerular injury in the 5/6 surgical excision group (N = 24) (P < 0.01). (ABSTRACT TRUNCATED AT 250 WORDS)
Neutralization of Gamma Interferon Augments Borreliacidal Antibody Production and Severe Destructive Lyme Arthritis in C3H/HeJ Mice

ABSTRACT Development of a high level of sustained borreliacidal antibody is paramount for maintaining protection against infection with Borrelia burgdorferi. We show that production of borreliacidal antibody can be enhanced by preventing the effects of gamma interferon (IFN-γ). When lymph node cells capable of producing borreliacidal antibody were cultured with anti-murine IFN-γ, an eightfold increase in borreliacidal antibody production was obtained. However, anti-IFN-γ treatment of these cells also enhanced their ability to adaptively induce arthritis. When anti-IFN-γ-treated lymph node cells producing borreliacidal antibody were infused into C3H/HeJ mice and the mice were then challenged with B. burgdorferi, the mice developed severe destructive Lyme arthritis. Additional studies are needed to delineate the immune response responsible for the induction of arthritis and production of borreliacidal antibody. These studies are needed to ensure an effective and safe vaccine against infection with B. burgdorferi.
Human natural killer cells: their origin, receptors and function

The term of "natural killer" (NK) cells was originally assigned on a merely functional basis to lymphoid cells capable of lysing certain tumors in the absence of prior stimulation. However, both their origin and the molecular mechanism(s) involved in their function remained a mystery for many years 1 . Regarding their origin, clear evidence has now been provided both inmouse and in man that NK and T cells may derive from a common precursor 2 – 5 . Thus, mature NK cells can be obtained in vitro from CD34+ cells isolated from umbilical cord blood, bone marrow (BM) and even human thymus 6 when cultured in the presence of appropriate feeder cells or IL‐15. The molecular mechanism allowing NK cells to discriminate between normal and tumor cells, predicted by the "missing self hypothesis" 7 , has been clarified only in recent years. Thus, NK cells recognize MHC class I molecules through surface receptors delivering signals that inhibit, rather than activate, NK cells. As a consequence, NK cells lyse target cells that have lost (or express insufficient amounts of) MHC class I molecules, as frequently occurs in tumors and in cells infected by certain viruses.
Reprogramming of tau alternative splicing by spliceosome-mediated RNA trans-splicing: Implications for tauopathies

Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) is caused by mutations in the gene encoding the microtubule-associated protein, tau. Some FTDP-17 mutations affect exon 10 splicing. To correct aberrant exon 10 splicing while retaining endogenous transcriptional control, we evaluated the feasibility of using spliceosome-mediated RNA trans-splicing (SMaRT) to reprogram tau mRNA. We designed a pre-trans-splicing molecule containing human tau exons 10 to 13 and a binding domain complementary to the 3′ end of tau intron 9. A minigene comprising tau exons 9, 10, and 11 and minimal flanking intronic sequences was used as a target. RT-PCR analysis of SH-SY5Y cells or COS cells cotransfected with a minigene and a pre-trans-splicing molecule using primers to opposite sides of the predicted splice junction generated products containing exons 9 to 13. Sequencing of the chimeric products showed that an exact exon 9–exon 10 junction had been created, thus demonstrating that tau RNA can be reprogrammed by trans-splicing. Furthermore, by using the same paradigm with a minigene containing full-length intronic sequences, we show that cis-splicing exclusion of exon 10 can be by-passed by trans-splicing and that conversion of exon 10– tau RNA into exon 10+ tau RNA could be achieved with ≈34% efficiency. Our results demonstrate that an alternatively spliced exon can be replaced by trans-splicing and open the way to novel therapeutic applications of SMaRT for tauopathies and other disorders linked to aberrant alternative splicing.
Hydroxynonenal inactivates cathepsin B by forming Michael adducts with active site residues

Oxidation of plasma low‐density lipoprotein (oxLDL) generates the lipid peroxidation product 4‐hydroxy‐2 nonenal (HNE) and also reduces proteolytic degradation of oxLDL and other proteins internalized by mouse peritoneal macrophages in culture. This leads to accumulation of undegraded material in lysosomes and formation of ceroid, a component of foam cells in atherosclerotic lesions. To explore the possibility that HNE contributes directly to the inactivation of proteases, structure‐function studies of the lysosomal protease cathepsin B have been pursued. We found that treatment of mouse macrophages with HNE reduces degradation of internalized maleyl bovine serine albumin and cathepsin B activity. Purified bovine cathepsin B treated briefly with 15 μM HNE lost ∼76% of its protease activity and also developed immunoreactivity with antibodies to HNE adducts in Western blot analysis. After stabilization of the potential Michael adducts by sodium borohydride reduction, modified amino acids were localized within the bovine cathepsin B protein structure by mass spectrometric analysis of tryptic peptides. Michael adducts were identified by tandem mass spectrometry at cathepsin B active site residues Cys 29 (mature A chain) and His 150 (mature B chain). Thus, covalent interaction between HNE and critical active site residues inactivates cathepsin B. These results support the hypothesis that the accumulation of undegraded macromolecules in lysosomes after oxidative damage are caused in part by direct protease inactivation by adduct formation with lipid peroxidation products such as HNE.
Body image and weight status of children from rural areas of Valparaíso, Chile.

OBJECTIVE To determine the relation between the perceived and the real nutritional status in children from rural areas. PARTICIPANTS The study comprehends 206 students from first to eighth year of primary school from rural institutions of the Valparaiso region, Chile (43% females). METHODS The real nutritional status was measured using the Body Mass Index (BMI), and the perceived status by means of corporeal figures. The Socioeconomic Status (SES) was determined using the modified Graffar scale. The analysis was carried out using the concordance correlation coefficient kappa, and the chi-square test was used for the association of variables. RESULTS The subjects are concentrated in the low SES (82% male; 72% female). 49.5% of the students present overweight and obesity. Boys show higher prevalence of obesity (29%) than girls (20%). 62.5% of the females underestimate their weight, which surpasses the percentage of males (52.5%). 98.10% of the obese individuals underestimate their weight, as well as the 100% of the evaluated children with an overweight condition. CONCLUSIONS Boys and girls from rural areas in conditions of overweight and obesity present a higher prevalence rate of an inappropriate perception of body image (underestimation), which has an important impact when recognizing their own condition of over nutrition. This status can have significant repercussions in public health, since it can be maintained to adult life and develop non-transmissible chronic diseases.
Physical occupational exposures during working life and quality of life after labour market exit: results from the GAZEL study

Objective: To investigate variations in quality of life at older ages, we take a life course perspective to analyse long-term effects of physical working conditions upon quality of life after retirement. In doing so, we study to what extent these associations are explained by individuals’ health at older ages. Method: We use administrative data and self-administered questionnaire responses from the French GAZEL cohort. Quality of life was assessed with CASP-19 in 2009 and related to three types of physical working conditions during previous working life: (1) ergonomic strain, (2) physical danger and (3) exposures to chemicals. Health was assessed in 2007 with the SF-36 Health Survey. Multiple regressions were calculated in retired men only, controlling for important confounders including social position. Results: In contrast to men, few women were exposed to strenuous and dangerous working conditions in this cohort and were not included in subsequent analyses. Negative effects on retired men's quality of life were found for the physical occupational exposures of ergonomic strain and physical danger, but not for chemical exposures. Effects were attenuated after the introduction of physical and mental health to the models, indicating an indirect effect of physical working conditions upon quality of life via health. Conclusion: Adverse physical working conditions have long-term consequences for health and quality of life at older ages. Improvements to physical working conditions may improve individuals’ quality of life over the long term.