An atlas of RNA-dependent proteins in cell division reveals the riboregulation of mitotic protein-protein interactions.

Ribonucleoprotein complexes are dynamic assemblies of RNA with RNA-binding proteins (RBPs), which can modulate the fate of the RNA molecules from transcription to degradation. Vice versa, RNA can regulate the interactions and functions of the associated proteins. Dysregulation of RBPs is linked to diseases such as cancer and neurological disorders.

Adenovirus small E1A directs activation of Alu transcription at YAP/TEAD- and AP-1-bound enhancers through interactions with the EP400 chromatin remodeler.

Alu retrotransposons, which form the largest family of mobile DNA elements in the human genome, have recently come to attention as a potential source of regulatory novelties, most notably by participating in enhancer function. Even though Alu transcription by RNA polymerase III is subjected to tight epigenetic silencing, their expression has long been known to increase in response to various types of stress, including viral infection. Here we show that, in primary human fibroblasts, adenovirus small e1a triggered derepression of hundreds of individual Alus by promoting TFIIIB recruitment by Alu-bound TFIIIC.

Time-course transcriptome analysis of a double challenge bleomycin-induced lung fibrosis rat model uncovers ECM homoeostasis-related translationally relevant genes.

Background: Idiopathic pulmonary fibrosis (IPF) is an irreversible disorder with a poor prognosis. The incomplete understanding of IPF pathogenesis and the lack of accurate animal models is limiting the development of effective treatments. Thus, the selection of clinically relevant animal models endowed with similarities with the human disease in terms of lung anatomy, cell biology, pathways involved and genetics is essential.

Time-resolved transcriptomic profiling of the developing rabbit's lungs: impact of premature birth and implications for modelling bronchopulmonary dysplasia.

Background: Premature birth, perinatal inflammation, and life-saving therapies such as postnatal oxygen and mechanical ventilation are strongly associated with the development of bronchopulmonary dysplasia (BPD); these risk factors, alone or combined, cause lung inflammation and alter programmed molecular patterns of normal lung development. The current knowledge on the molecular regulation of lung development mainly derives from mechanistic studies conducted in newborn rodents exposed to postnatal hyperoxia, which have been proven useful but have some limitations.

Methods: Here, we used the rabbit model of BPD as a cost-effective alternative model that mirrors human lung development and, in addition, enables investigating the impact of premature birth per se on the pathophysiology of BPD without further perinatal insults (e.

A necrotising fasciitis: case report.

Necrotizing fasciitis is one of the most common soft tissue infections, with a high risk of major amputation and a mortality ranging from 6 to 33% which has not changed in the past 20 years. Early surgical resection of necrotic tissue plays a key role in determining the prognosis. Nawijn et al.

Interpreting and integrating big data in non-coding RNA research.

In the last two decades, we have witnessed an impressive crescendo of non-coding RNA studies, due to both the development of high-throughput RNA-sequencing strategies and an ever-increasing awareness of the involvement of newly discovered ncRNA classes in complex regulatory networks. Together with excitement for the possibility to explore previously unknown layers of gene regulation, these advancements led to the realization of the need for shared criteria of data collection and analysis and for novel integrative perspectives and tools aimed at making biological sense of very large bodies of molecular information. In the last few years, efforts to respond to this need have been devoted mainly to the regulatory interactions involving ncRNAs as direct or indirect regulators of protein-coding mRNAs.

RNA Modulates the Expression of Cell Cycle Genes in Human Fibroblasts.

retroelements, whose retrotransposition requires prior transcription by RNA polymerase III to generate RNAs, represent the most numerous non-coding RNA (ncRNA) gene family in the human genome. transcription is generally kept to extremely low levels by tight epigenetic silencing, but it has been reported to increase under different types of cell perturbation, such as viral infection and cancer. RNAs, being able to act as gene expression modulators, may be directly involved in the mechanisms determining cellular behavior in such perturbed states.

Referral Decision Making of General Practitioners: A Signal Detection Study.

Background: Signal detection theory (SDT) describes how respondents categorize ambiguous stimuli over repeated trials. It measures separately "discrimination" (ability to recognize a signal amid noise) and "criterion" (inclination to respond "signal" v. "noise").

The effect of rTMS over the inferior parietal lobule on EEG sensorimotor reactivity differs according to self-reported traits of autism in typically developing individuals.

Previous research suggested that EEG markers of mirror neuron system activation may differ, in the normal population as a function of different levels of the autistic spectrum quotient; (AQ). The present study aimed at modulating the EEG sensorimotor reactivity induced by hand movement observation by means of repetitive transcranial magnetic stimulation (rTMS) applied to the inferior parietal lobule. We examined how the resulting rTMS modulation differed in relation to the self-reported autistic traits in the typically developing population.

Object-guided spatial selection in touch without concurrent changes in the perceived location of the hands.

In an endogenous cueing paradigm with central visual cues, observers made speeded responses to tactile targets at the hands, which were either close together or far apart, and holding either two separate objects or one common object between them. When the hands were far apart, the response time costs associated with attending to the wrong hand were reduced when attention had to be shifted along one object jointly held by both hands compared to when it was shifted over the same distance but across separate objects. Similar reductions in attentional costs were observed when the hands were placed closer together, suggesting that processing at one hand is less prioritized over that at another when the hands can be "grouped" by virtue of arising from the same spatial location or from the same object.

Measuring the effects of manipulating stimulus presentation time on sensorimotor alpha and low beta reactivity during hand movement observation.

The present study addresses three methodological questions that have been ignored in previous research on EEG indices of the human mirror neuron system (hMNS), particularly in regard to autistic individuals. The first question regards how to elicit the EEG indexed hMNS during movement observation: Is hMNS activation best elicited using long stimulus presentations or multiple short repetitions? The second question regards what EEG sensorimotor frequency bands reflect sensorimotor reactivity during hand movement observation? The third question regards how widespread is the EEG reactivity over the sensorimotor cortex during movement observation? The present study explored sensorimotor alpha and low beta reactivity during hand movement versus static hand or bouncing balls observation and compared two experimental protocols (long exposure vs. multiple repetitions) in the same participants.

Low fasting serum triglyceride level as a precocious marker of autoimmune disorders.

The authors recently reported the occurrence of low fasting serum triglyceride (TG) and high free fatty acid (FFA) levels in idiopathic pulmonary fibrosis. TG estimation in diverse groups of patients with autoimmune disease or hyperactive immune response confirmed the occurrence of a similar decrease of TG. In some patients, serum FFA level was also evaluated.

A clinical variant of familial Hermansky-Pudlak syndrome.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive inherited disease consisting of (1) partial oculocutaneous albinism (with nystagmus, strabism, and visual acuity loss), (2) platelet storage pool deficiency (with bleeding diathesis), and (3) disorder of "ceroid" metabolism with a multisystem tissue lysosomal ceroid deposition. HPS is less uncommon in Puerto Rico, where the most important studies have been performed, but is a very rare disease in Europe. HPS basic defect remains unknown, even if an HPS-causing gene was identified in chromosome segment 10q23-q23.

Rheumatoid syndrome associated with lung interstitial disorder in a dental technician exposed to ceramic silica dust. A case report and critical literature review.

Exposure to silica minerals is associated with silicosis and autoimmune disorders, especially systemic scleroderma. Evidence of this association has been increasingly reported in the last decade. The aim of this paper is to discuss, on the basis of a literature review, the case of a 28-year-old female dental technician who suffered from episodes of weakness, arthralgia, pain, swelling and stiffness of the fingers, dyspnoea with cough, a positive Waaler-Rose reaction, increased rheumatoid factor and normal ESR.

Automatic volumetric capillary cytometry in the routine of an apheresis unit involved in multicomponent collection.

In apheresis, leukodepletion by secondary filtration of the platelet components or by the primary use of special high efficiency apparatuses is widely used to meet current clinical practice. Leukodepletion of RBC is mandatory for hematooncological patients and new filters for plasma are progressively being introduced in the routine of European blood banks. However, since the monitoring of leukodepletion efficiency continues to be carried out manually using the Nageotte or the microdroplet fluorescence assay (MFA), inaccuracy and labour-intensity of counting will limit the possibility of satisfying the increasing demand for leukodepletion monitoring.

Autoreactive lymphocytotoxic IgM antibodies in highly sensitized dialysis patients waiting for a kidney transplant: identification and clinical relevance.

The contribution of different families of lymphocytotoxic antibodies in the serologic reactivity of 45 highly sensitized dialysis patients (HSDP) (panel reactivity antibody value-PRA greater than 80%) was assessed by analyzing patients' sera for the presence of auto- and alloreactive IgM and alloreactive IgG antibodies. A total of 220 sera was screened at different incubation temperatures, before and after treatment with the reducing agent dithiothreitol, against a large variety of cell targets by means of complement dependent cytotoxicity (CDC) and antiglobulin augmented (AHG) CDC assays. The results allowed to subdivide the HSDP under study into four groups: Group 1 consisted of 13 untransplanted patients and 14 patients with a prior failed graft whose PRA values did not change following DTT treatment.

Effect of monophosphoryl lipid A on the in vitro function of peritoneal leukocytes from uremic patients on continuous ambulatory peritoneal dialysis.

We analyzed the effects of monophosphoryl lipid A (MPL), a relatively nontoxic immunostimulant derived from bacterial endotoxin, on the depressed in vitro immune function of leukocytes derived from six patients undergoing continuous ambulatory peritoneal dialysis and who had histories of recurrent bacterial peritonitis. MPL was also tested for its capacity to stimulate the proliferation of peritoneal fibroblasts, as determined by [3H]thymidine incorporation. In vitro incubation of peritoneal lymphocytes and macrophages (PM phi) with increasing amounts of MPL, up to 5 micrograms/ml, resulted in a dose-dependent enhancement of gamma interferon and interleukin-2 production by peritoneal lymphocytes and interleukin-1 release by PM phi.

Effect of monophosphoryl lipid A (MPLA) on peritoneal leukocyte function.

We analyzed the in vitro effects of monophosphoryl lipid A (MPLA), a nontoxic bacterial endotoxin-derived immunomodulant, on the depressed immune functions of peritoneal lymphocytes (PLy) and macrophages (PMO) of 6 CAPD patients with relapsing bacterial peritonitis. MPLA was also tested for its capacity to stimulate the peritoneal fibroblast proliferation as determined by 3H-thymidine incorporation. In vitro incubation of PLy and PMO with escalating doses of MPLA up to 5 micrograms/ml, resulted in a dose-dependent enhancement of Gamma-Interferon (Gamma-IFN) and Interleukin-2 (IL-2) production by PLy, and Interleukin-1 (IL-1) by PMO.

Response of CAPD patients with a high incidence of peritonitis to intraperitoneal immunoglobulin therapy.

This study has demonstrated that in the majority of high-peritonitis-incidence (PI) CAPD patients the defective opsonic activity levels in the peritoneal dialysis effluent (PDE) are restored for 3 weeks by a 12 g IP injection of immunoglobulins (Ig). Further studies showed that in a minority of high-PI CAPD patients who also had low PDE IgG and opsonic activity levels, IP Ig therapy did not significantly reduce the PI. To evaluate this phenomenon we utilized this therapy in 20 high-PI CAPD patients undergoing IP Ig therapy for an average of 24 months daily for 3 weeks (12 g every 3 weeks) and analyzed: 1) PDE IgG levels; 2) PDE opsonic activity; 3) peritoneal macrophage (PM0) membrane-bound IgG; 4) PDE Interleukin-1 (IL-1) levels; 5) PM0 membrane Fc receptor number.

Detection of parasite related antigens associated with conglutinin binding immune complexes in patients with Schistosoma haematobium.

An ELISA assay was designed to detect the presence of parasite related antigens associated with circulating immune complexes in patients affected by urinary schistosomiasis. The assay makes use of bovine conglutinin as the immune complex recognition unit and of human anti-Schistosoma antibody as the antigen recognition unit. Using this method we showed that 10 of 15 (67%) patients with a positive polyethylene glycol assay had circulating immune complexes in which parasite antigens could be detected.

The serum capacity to solubilize immune complexes (ICSC) measured by an enzyme-anti-enzyme complex probe.

The capacity to solubilize immune complexes can be readily measured by incubating the test serum with a suspension of an immune precipitate formed by beta-galactosidase and anti-beta-galactosidase antibody, and then reading the enzyme units (EU) liberated in the clear supernatant. Our method is rapid and inexpensive; it can be performed in plates and read in scanning colorimeters. Although on large numbers of observations the ICSC is significantly correlated with the CH50, a few discordant cases suggest that solubilization and haemolysis are functions of the alternative and classical pathways of complement respectively.