Miracle-dz/UniFAR-FTUs huggingface dataset:
Analyse des PeBoW-Komplexes in der Ribosomenbiogenese

Wahrend der Zellproliferation mussen Zellwachstum und Zellteilung koordiniert werden. Die Kopplung erfolgt in der Hefe durch einen Komplex aus Nop7p, Erb1p und Ytm1p, der sowohl an der Ribosomenbiogenese als auch an der Kontrolle der DNA-Replikation beteiligt ist. Die homologen Proteine Pes1, Bop1 und WDR12 werden in Saugern von Zielgenen des Transkriptionsfaktors c-Myc, einem zellularen Onkoprotein, kodiert. In dieser Arbeit wurde die Existenz eines evolutionar konservierten Komplexes aus Pes1, Bop1 und WDR12 (PeBoW-Komplex) in Saugern belegt. Dabei wurde gezeigt, dass Bop1 als zentrales Protein des Komplexes agiert und die Interaktion von Pes1 und WDR12 vermittelt. Die Integritat des Komplexes ist wesentlich fur seine Funktion. Die Depletion einzelner Komponenten sowie die Uberexpression des integrierenden Proteins Bop1 hemmen die Reifung der Vorlaufer-rRNA der grosen ribosomalen Untereinheit sowie die Proliferation der Zellen. Bop1-Uberexpression fuhrt zur Ausbildung von zwei Subkomplexen aus Bop1 und Pes1 bzw. Bop1 und WDR12. Wahrend der Bop1/Pes1-Subkomplex als Teil der pre-Ribosomen im Nukleolus lokalisiert, wird WDR12 durch Bop1-Uberexpression im Zytoplasma gehalten und fehlt im Nukleolus zur Ausbildung eines funktionellen PeBoW-Komplexes. Pes1 und WDR12 konnen unabhangig in den Nukleolus translozieren, wahrend Bop1 dafur die Interaktion mit Pes1 benotigt. Untersuchungen zur Stabilitat der einzelnen PeBoW-Komponenten zeigten, dass monomeres Bop1 extrem instabil ist, durch Inkorporation in den PeBoW-Komplex aber vor Abbau geschutzt wird. Moglicherweise werden hierdurch interne PEST-Sequenzen in Bop1 maskiert. Die Menge an Bop1 ist somit abhangig von der Anwesenheit von Pes1 und WDR12. Die gegenseitige Abhangigkeit der Stabilitat aller drei PeBoW-Komponenten konnte in weitergehenden Experimenten gezeigt werden. Schlieslich wurde untersucht, ob der PeBoW-Komplex die Ribosomenbiogenese mit der DNA-Replikation uber Interaktion mit dem ORC-Komplex, wie in der Hefe beschrieben, koordiniert. Mit Hilfe der BiFC-Methode konnte eine Interaktion von Pes1 mit Orc6, eines Faktors des ORC-Komplexes, gezeigt werden. Die koordinierende Funktion des PeBoW-Komplexes fur Zellwachstum und Zellproliferation scheint von der Hefe bis zum Menschen stark konserviert zu sein.
Pathophysiological effects of low dietary phosphorus in pigs.

SUMMARY The homeostasis of inorganic phosphate (P(i)) is regulated by parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)(2)D), and P(i)itself in the intestine, kidney, and bone in all the mammalian species studied. Determinations of the serum concentrations of PTH, 1,25(OH)(2)D and osteocalcin were done in 82 southern Romanian Landrace pigs originating from three herds with dietary P(i)deficiency. Serum P(i)concentrations were negatively correlated with those of 1,25(OH)(2)D. In lactating animals and sucklings, the linear relationships between P(i)and 1,25(OH)(2)D were not present. Serum P(i)concentrations were positively correlated with those of PTH. In lactating animals and young pigs, the linear relationships between P(i)and PTH were not evident. PTH and 1,25(OH)(2)D concentrations were negatively correlated. The serum concentrations of 1,25(OH)(2)D and osteocalcin were positively correlated. Milk P(i)concentrations ranging from 3.10 to 7.49 mmol/L were correlated positively with urinary P(i)concentrations ranging from 0.26 to 11.37 mmol/L. In conclusion, similarly to other species, P(i)homeostasis is achieved in pigs by feedback mechanisms between P(i), PTH and 1,25(OH)(2)D and osteocalcin production is induced by 1,25(OH)(2)D. The effect of lactation on P(i)homeostasis remains to be explored.
Clinicopathological Evaluation Of Portal Hypertensive Colopathy In Cirrhotic Patients

Aim: The aim of this study was to evaluate the colonoscopy findings in Patients with Cirrhosis Portal Hypertension and Histopathologic correlation of those colonoscopy lesions. The prevalence of portal hypertensive colopathy was evaluated, the lesions were biopsied and specimen sent for Histopathologicexamination. The prevalence of Portal Hypertensive colopathy were correlated with severity of Liver Disease. Methodology: Cases of Cirrhosis with Portal Hypertension presenting to the Medical Gastroenterology Department, were included in the study. Symptomatic Patients were subjected to White Light Colonoscopy. Lesions characteristic of Portal Hypertensive Colopathy were studied. Those lesions were biopsied and specimenwere subjected to Histopathological Examination. Results:In a study of 100 cases of cirrhosis, portal hypertensive colopathy was present in 61 patients (61%), including solitary vascular ectasia in 30 patients (30%) and diffuse vascular ectasia in 41 patients (41%). Histological study revealed a marked dilatation in the microcirculation at the level of the ascending colon and rectum. The Child Pugh class was correlated with a severity of portal hypertensive colopathy. Platelet count and history of Alcohol intake was significantly associated with portal hypertensive colopathy. Conclusion: A history of alcohol intake was the main cause of liver cirrhosis. As the Child – Pugh class worsens and platelet count decreases, the prevalence of portal hypertensive colopathy increases in patients with liver cirrhosis. Though the histopathologicevaluation had characteristiclesions, which correlated with Endoscopic findings.it did not correlate with the severity of Liver Disease. Hence acolonoscopy examination is indicated, especially those with worsening ChildPugh class and or decreasing platelet count but a routine Histopathological examination is not indicated.Other incidental findings in colonoscopy and histopathology was also made out during the study.
Desenvolvimento de ferramentas pedagógicas para identificação de escolares de risco para a dislexia

RESUMO – Objetivo: Elaborar e aplicar atividades pedagógicas coletivas, que avaliem as habilidades fonológicas em pré-leitores e leitores iniciantes e que sirvam como potenciais instrumentos de rastreamento para ajudar na identificação de escolares de risco para desenvolver dificuldades na leituraescrita. Método: As tarefas FAE (ferramentas alternativas do educador) basearam-se em tarefas fonológicas clássicas conhecidas como “categorização de sons” e no Protocolo de Habilidades Cognitivo-Linguísticas. As FAE consistiram basicamente no pareamento entre figuras e de figuras com palavras que apresentam similaridades fonológicas no início (aliteração) ou no final (rima) e foram aplicadas em 45 escolares, de ambos os gêneros, com idade média de 7 anos e 4 meses, juntamente com o referido protocolo. Resultados: O protocolo comprovou sua eficácia confirmando que a consciência fonológica, a memória de trabalho verbal e a nomeação rápida consistem nos principais fatores de risco para a dislexia e com as quais as FAE apresentaram suas mais fortes correlações, além da discriminação fonêmica. As tarefas FAE também foram fortemente correlacionadas com a leitura e a escrita. Conclusão: Escolares de risco para dislexia podem ser identificados por meio de ferramentas pedagógicas desenvolvidas, testadas e adaptadas para a realidade educacional brasileira, sendo este um promissor campo de pesquisa com potencial para ajudar a evitar o atual excessivo número de escolares equivocadamente considerados disléxicos e indevidamente encaminhados para os serviços públicos competentes, bem como indicar as abordagens teórico-empíricas mais adequadas para orientar nossa educação.
Interleukin-11 alters placentation and causes preeclampsia features in mice

Significance Preeclampsia is an insidious disease, unique to humans, affecting ∼8% of pregnancies. There are no early detection tests or pharmacological treatments. Impaired placentation is widely accepted to contribute to the pathogenesis. However, the mechanisms remain elusive, given the complications of studying first-trimester placental development in women. A major limitation for the study of new treatments is the lack of available animal models that recapitulate the full spectrum of preeclampsia features. We have developed a mouse model characterized by elevated levels of the cytokine Interleukin-11 (IL11). This study provides evidence of a novel pathway causative of preeclampsia features in vivo. It also provides a novel in vivo mouse model that is useful for preclinical studies to test potential therapeutics. Preeclampsia (PE) is a pregnancy-specific disorder characterized by hypertension and proteinuria after 20 wk gestation. Abnormal extravillous trophoblast (EVT) invasion and remodeling of uterine spiral arterioles is thought to contribute to PE development. Interleukin-11 (IL11) impedes human EVT invasion in vitro and is elevated in PE decidua in women. We demonstrate that IL11 administered to mice causes development of PE features. Immunohistochemistry shows IL11 compromises trophoblast invasion, spiral artery remodeling, and placentation, leading to increased systolic blood pressure (SBP), proteinuria, and intrauterine growth restriction, although nonpregnant mice were unaffected. Real-time PCR array analysis identified pregnancy-associated plasma protein A2 (PAPPA2), associated with PE in women, as an IL11 regulated target. IL11 increased PAPPA2 serum and placental tissue levels in mice. In vitro, IL11 compromised primary human EVT invasion, whereas siRNA knockdown of PAPPA2 alleviated the effect. Genes regulating uterine natural killer (uNK) recruitment and differentiation were down-regulated and uNK cells were reduced after IL11 treatment in mice. IL11 withdrawal in mice at onset of PE features reduced SBP and proteinuria to control levels and alleviated placental labyrinth defects. In women, placental IL11 immunostaining levels increased in PE pregnancies and in serum collected from women before development of early-onset PE, shown by ELISA. These results indicate that elevated IL11 levels result in physiological changes at the maternal–fetal interface, contribute to abnormal placentation, and lead to the development of PE. Targeting placental IL11 may provide a new treatment option for PE.
Randomised clinical trial to compare total contact casts, healing sandals and a shear‐reducing removable boot to heal diabetic foot ulcers

The objective of this study was to evaluate the efficacy of three off‐loading techniques to heal diabetic foot wounds: total contact casts (TCCs), healing sandals (HSs) and a removable boot with a shear‐reducing foot bed (SRB). This was a 12‐week, single‐blinded randomised clinical trial with three parallel treatment groups of adults with diabetes and a foot ulcer (n = 73). Ulcer healing was defined as full reepithelialisation with no drainage. Diabetic patients with grade UT1A or UT2A forefoot ulcers on the sole of the foot were enrolled. Patients with malignancy, immune‐compromising diseases, severe peripheral vascular disease (ankle‐brachial index < 0·60 or transcutaneous oxygen < 25 mm/Hg), alcohol or substance abuse within 6 months, untreated osteomyelitis or Charcot arthropathy with residual deformity that would not fit the HS or boot were excluded. In the intent‐to‐treat analysis, significantly higher proportion of patients were healed in the TCC group (69·6%) compared to those treated with the SRB (22·2%, P < 0·05). There was no difference in the rate of healed ulcers in the HS (44·5%) and TCC groups. Ulcers in the TCC group healed faster than those in the HS group (5·4 ± 2·9 versus 8·9 ± 3·5 weeks, P < 0·02). However, there was no difference in the time to healing in the TCC and SRB groups (6·7 ± 4·3 weeks, P = 0·28). Patients who used HS were significantly more active (4022 ± 4652 steps per day, P < 0·05) than those treated with TCCs (1447 ± 1310) or SRB (1404 ± 1234). It is concluded that patients treated with TCCs had the highest proportion of healed wounds and fastest healing time. The novel shear‐reducing walker had the lowest healing and highest rate of attrition during the study.
Bone mineral density of eating disorder subgroups.

OBJECTIVE We tested nine hypotheses among eating disorder subgroups and a control group on spinal bone density and investigated the relationship of their spinal bone density with a critical fracture threshold and five clinical variables--age of onset, years ill, percentage of ideal body weight (IBW), months of amenorrhea, and hours per week of exercise. METHOD Dual photon absorptiometry measured spinal bone density. RESULTS Anorectic patients had significantly less spinal bone mass than bulimic patients with no history of anorexia nervosa or control patients. Eating disordered patients with past or present anorexia nervosa had significantly more spinal bone density values below a critical fracture threshold. Duration of amenorrhea and exercise significantly predicted spinal bone density. DISCUSSION Anorectic women were unlikely to reach their peak bone density, thus possibly developing osteoporosis later in life, and were likely to be at risk for nontraumatic spinal fractures. Predicting spinal bone density of anorectic women could be done by knowing their duration of amenorrhea and exercise.
Sporidial mating and infection process of the smut fungus, Ustilago hordei, in susceptible barley

Ustilago hordei (Pers.) Lagerh. causes covered smut of barley and oats. Sporidial mating and the infection process on compatible barley plants, cv. Hannchen, were investigated using light microscopy and scanning and trans- mission electron microscopy. Within 2 h after mixing of sporidia of opposite mating types on water agar, polar conju- gation tubes emerged that subsequently fused, producing infection hyphae at the junctions. Similar events occurred on germinated barley shoots, although sporidia regularly produced several conjugation tubes, of which only one was involved in mating. Tubes emerging from the sides of cells were also observed. Infection hyphae emerged from either the conjugation tube or conjugated cell body. Hyphae elongated along the shoot surface until characteristic crook and appressorium-like structures were formed. An invading hypha emerged beneath this structure and directly penetrated the underlying epidermal cell. Hyphae extended both intra- and inter-cellularly into tissues, without much branching, before becoming established in the shoot meristematic region. Plant plasma membranes remained intact during pathogen ingress and an electron-dense matrix of unknown origin appeared in the interface between plant plasma membrane and invading hypha. A large fungal biomass was generated in the host spike tissue at 42-63 days postinoculation during the development of the floral meristem.
Vascular-derived TGF-β increases in the stem cell niche and perturbs neurogenesis during aging and following irradiation in the adult mouse brain

Neurogenesis decreases during aging and following cranial radiotherapy, causing a progressive cognitive decline that is currently untreatable. However, functional neural stem cells remained present in the subventricular zone of high dose‐irradiated and aged mouse brains. We therefore investigated whether alterations in the neurogenic niches are perhaps responsible for the neurogenesis decline. This hypothesis was supported by the absence of proliferation of neural stem cells that were engrafted into the vascular niches of irradiated host brains. Moreover, we observed a marked increase in TGF‐β1 production by endothelial cells in the stem cell niche in both middle‐aged and irradiated mice. In co‐cultures, irradiated brain endothelial cells induced the apoptosis of neural stem/progenitor cells via TGF‐β/Smad3 signalling. Strikingly, the blockade of TGF‐β signalling in vivo using a neutralizing antibody or the selective inhibitor SB‐505124 significantly improved neurogenesis in aged and irradiated mice, prevented apoptosis and increased the proliferation of neural stem/progenitor cells. These findings suggest that anti‐TGF‐β‐based therapy may be used for future interventions to prevent neurogenic collapse following radiotherapy or during aging.
The clinical relevance of circulating tumor necrosis factor-alpha in acute decompensated chronic heart failure without cachexia.

STUDY OBJECTIVE To evaluate the clinical relevance of circulating tumor necrosis factor-alpha (TNF alpha) in subjects with advanced acutely decompensated congestive heart failure (CHF) and to determine the modulatory effect of clinical interventions on short-term elaboration of this cytokine. DESIGN Prospective, case-controlled study. SETTING Inpatient and outpatient (hospital and clinic), at regional academic medical center. PATIENT INTERVENTIONS: Plasma concentrations of TNF alpha were determined in 25 healthy, normal control subjects and in 29 noncachectic patients with advanced CHF (mean ejection fraction = 16 +/- 6%) who required hospitalization for i.v. diuretic and/or inotropic therapy despite optimization of oral medical regimens. CHF patients were divided into two groups: diuretic responsive (group A; n = 6) and diuretic resistant requiring inotropic support (group B; n = 23). Group B was randomly allocated to receive either i.v. dobutamine (n = 13) or milrinone (n = 10) for 72 h. TNF alpha levels in CHF patients were measured serially at baseline, at 6 h, at 48 h, at 72 h, and at 1-week follow-up after hospital discharge. RESULTS Plasma TNF alpha levels at baseline in CHF patients were 4.0 +/- 1.1 pg/mL (range, 0.5 to 6.5 pg/ mL) and 2.5 +/- 0.6 pg/mL (range, 0.5 to 6.8 pg/mL) in groups A and B, respectively, which were significantly different (p < 0.002) from normal subjects (0.89 +/- 0.40 pg/mL; range, 0.5 to 9.7 pg/mL). Despite clinically successful therapy with i.v. diuretics, dobutamine, or milrinone, plasma levels of this cytokine remained unchanged. Plasma TNF alpha in CHF patients measured in recovery (1 week after hospital discharge) was 5.1 +/- 1.2 pg/mL (range, 1.0 to 9.9 pg/mL) and 3.9 +/- 0.8 pg/mL (range, 0.5 to 8.7 pg/mL) in groups A and B, respectively. CONCLUSION These findings suggest that although noncachectic patients with chronic heart failure who suffer acute decompensation elaborate significantly higher circulating levels of TNF alpha compared with healthy control subjects, no significant reduction or alteration in circulating TNF alpha is noted in the short-term follow-up despite clinical improvement.
Gamma knife radiosurgery for intralabyrinthine schwannomas.

Object To analyze indications and technical specificities of treatment of intralabyrinthine schwannoma (ILS) by Gamma Knife radiosurgery. Methods Six patients were treated by Gamma Knife irradiation for a schwannoma arising from the cochleo-vestibular structures. Patients presented hearing worsening at different stages, tinnitus, imbalance and/or vertigo. Results ILS was intravestibular/intracochlear/intravestibulocochlear/ transmacular in respectively 2/1/2/1 patients. We cover the entire tumor volume with a margin prescription dose of 12-Gy. The tumor volume remained unchanged at last follow-up in all cases; for 4 patients with functional hearing still present before treatment, the audiological status remained stable in 2 patients, worsened moderately in 1 patientand worsened to cophosis in 1 patient. No patient experienced worsening of tinnitus, imbalance or vertigo after irradiation. Conclusions Gamma Knife treatment of ILS is technically feasible without risk thanks to the precision of current robotized Gamma Knife devices. Patients treated radiosurgically avoid some of the risks of microsurgery, could in some cases maintain useful hearing and prevent further symptoms worsening.
Association of human herpesvirus 6 reactivation with the flaring and severity of drug‐induced hypersensitivity syndrome

Background Drug‐induced hypersensitivity syndrome (DIHS) is an adverse reaction with clinical signs of fever, rash and internal organ involvement. In the vast majority of patients in Japan, the causative drugs for DIHS are limited to the following eight: carbamazepine, phenytoin, phenobarbital, zonisamide, mexiletine, dapsone, salazosulfapyridine and allopurinol. The association of human herpesvirus (HHV)‐6 reactivation with DIHS has been reported by various groups.
Aging enhances pressure-induced arterial superoxide formation.

The purpose of this study was to investigate the mechanisms that regulate superoxide (O(2)(*-)) production as a function of an acute elevation of intravascular pressure and age. Mesenteric arteries isolated from young (6 mo) and aged (24 mo) male Fischer 344 rats were used. O(2)(*-) production in vessels in response to 80 (normal pressure, NP) and 180 (high pressure, HP) mmHg was determined by the superoxide dismutase-inhibitable nitroblue tetrazolium (NBT) reduction assay. In vessels exposed to NP, O(2)(*-) production was significantly higher in aged than in young vessels (32.7 +/- 7.0 vs. 15.4 +/- 2.4 nmol.mg(-1). 30 min(-1)). HP enhanced O(2)(*-) production in vessels of both groups, but the enhancement was significantly greater in aged than in young vessels (63.4 +/- 6.7 vs. 32.7 +/- 4.3 nmol.mg(-1). 30 min(-1)). Apocynin (100 micromol/l) attenuated HP-induced increases in O(2)(*-) production in both groups, whereas allopurinol (100 micromol/l) and N(omega)-nitro-L-arginine methyl ester (100 mumol/l) inhibited the response only in aged vessels. Confocal microscopy showed increases in O(2)(*-) in response to HP in endothelial and smooth muscle layers of both groups, with much greater fluorescent staining in aged than in young rats and in the endothelium than in smooth muscle cells. No significant changes in NAD(P)H oxidase gene and protein expressions were observed in vessels of the two groups. Upregulation of protein expression of xanthine oxidase was detected in aged vessels. We conclude that NAD(P)H oxidase contributes importantly to HP-induced enhanced O(2)(*-) production in vessels of both young and aged rats, whereas xanthine oxidase and nitric oxide synthase-dependent O(2)(*-) production also contribute to the enhancement in mesenteric arteries of aged rats.
The impact behaviour of silk cocoons

SUMMARY Silk cocoons, constructed by silkmoths (Lepidoptera), are protective structural composites. Some cocoons appear to have evolved towards structural and material optimisation in order to sustain impact strikes from predators and hinder parasite ingress. This study investigates the protective properties of silk cocoons with different morphologies by evaluating their impact resistance and damage tolerance. Finite element analysis was used to analyse empirical observations of the quasi-static impact response of the silk cocoons, and to evaluate the separate benefits of the structures and materials through the deformation and damage mechanism. We use design principles from composite engineering in order to understand the structure–property–function relationship of silkworm cocoons. Understanding the highly evolved survival strategies of the organisms building natural cocoons will hopefully lead to inspiration that in turn could lead to improved composite design.
Could Spirituality and Religion Promote Stress Resilience in Survivors of Childhood Trauma?

Trauma is a precursor to many mental health conditions that greatly impact victims, their loved ones, and society. Studies indicate that neurobiological associations with adverse childhood experiences are mediated by interpersonal relationships and play a role in adult behavior, often leading to cycles of intergenerational trauma. There is a critical need to identify cost effective community resources that optimize stress resilience. Faith-based communities may promote forgiveness rather than retaliation, opportunities for cathartic emotional release, and social support, all of which have been related to neurobiology, behavior, and health outcomes. While spirituality and religion can be related to guilt, neurotic, and psychotic disorders, they also can be powerful sources of hope, meaning, peace, comfort, and forgiveness for the self and others. This article provides an overview of religion and spirituality as they relate to the neurobiology of resilience in victims of childhood trauma.