Miracle-dz/UniFAR-FTUs huggingface dataset:
Splicing with inverted order of exons occurs proximal to large introns.

Following our studies which showed that the alpha and beta exons of the chicken c‐ets‐1 gene are not conserved in the human homologue, we succeeded in identifying a novel human c‐ets‐1 transcript in which the normal order of exons is scrambled. By PCR and RNase protection assays, we demonstrated that while the order of exons is different from that in genomic DNA, splicing of these exons in aberrant order occurs in pairs and at the same conserved consensus splice sites used in the normally spliced transcript. The scrambled transcript is non‐polyadenylated and is expressed at much lower levels than the normal transcript. It is not the consequence of genomic rearrangement at the ets‐1 locus nor is it due to the transcription of any ets‐1 pseudogene. These results confirm previous observations of scrambled splicing.
Sclerostin: just one more player in renal bone disease?

Renal osteodystrophy (ROD) is one of the three components of chronic kidney disease–mineral and bone disorder (CKD-MBD) ([1][1]). Patients with CKD may develop various types of bone disease, spanning the spectrum of extreme situations such as severe osteitis fibrosa, osteomalacia, mixed osteopathy
Chronic Treatment with Anti-bipolar Drugs Down-Regulates Gene Expression of TRPC1 in Neurones

In the brain, TRPC1 channels are abundantly expressed in neurones virtually in all regions; these proteins function as receptor-activated ion channels and are implicated in numerous processes, being specifically important for neurogenesis. Primary cultures of mouse cerebellar granule cell, cerebral cortical neurones, and freshly isolated neurones from in vivo brains were used to study effects of chronic treatment with anti-bipolar drugs [carbamazepine (CBZ), lithium salts and valproic acid] on gene expression of TRPC1. Expression of TRPC1 mRNA was identified with reverse transcription-polymerase chain reaction, whereas protein content was determined by Western blotting. Store-operated plasmalemmal Ca2+ entry (SOCE) was measured with fura-2 based microfluorimetry. Chronic treatment with each of the three drugs down-regulated mRNA and protein expression in cultured cerebellar granule cells in a time- and concentration-dependent manner. Similar effect was also observed in cultured cerebral cortical neurones treated with CBZ, lithium salts and valproic acid and in freshly isolated neurones from the brains of CBZ-treated animals. The amplitude of SOCE was substantially decreased in cerebellar granule cells chronically treated with each of the three drugs. Our findings indicate that down-regulation of TRPC1 gene expression and function in neurones may be one of the mechanisms of anti-bipolar drugs action.
CD4+ T Cell Depletion during all Stages of HIV Disease Occurs Predominantly in the Gastrointestinal Tract

The mechanisms underlying CD4+ T cell depletion in human immunodeficiency virus (HIV) infection are not well understood. Comparative studies of lymphoid tissues, where the vast majority of T cells reside, and peripheral blood can potentially illuminate the pathogenesis of HIV-associated disease. Here, we studied the effect of HIV infection on the activation and depletion of defined subsets of CD4+ and CD8+ T cells in the blood, gastrointestinal (GI) tract, and lymph node (LN). We also measured HIV-specific T cell frequencies in LNs and blood, and LN collagen deposition to define architectural changes associated with chronic inflammation. The major findings to emerge are the following: the GI tract has the most substantial CD4+ T cell depletion at all stages of HIV disease; this depletion occurs preferentially within CCR5+ CD4+ T cells; HIV-associated immune activation results in abnormal accumulation of effector-type T cells within LNs; HIV-specific T cells in LNs do not account for all effector T cells; and T cell activation in LNs is associated with abnormal collagen deposition. Taken together, these findings define the nature and extent of CD4+ T cell depletion in lymphoid tissue and point to mechanisms of profound depletion of specific T cell subsets related to elimination of CCR5+ CD4+ T cell targets and disruption of T cell homeostasis that accompanies chronic immune activation.
Effect of Polymer/Organoclay Composition on Morphology and Rheological Properties of Polylactide Nanocomposites

In this work the relationships between system composition, polymer–organoclay interaction, morphology and rheological response, under shear, and elongational flow, of different melt compounded polylactic acid (PLA)/organoclay nanocomposites are investigated, with the aim to properly select the better organoclay for a well-specified PLA grade and processing technology. Polylactide nanocomposites are prepared using two commercial polylactide grades (PLA 4032D and PLA 2003D) and two different organomodified montmorillonites (Cloisite 30B and Nanofil SE3010). FTIR analysis evidences the occurrence of stronger polymer/organoclay interactions for the system PLA4032D1C30B, resulting in a higher clay dispersion and exfoliation levels. Moreover, rheological tests at low shear rates show that, if PLA 2003D is used as polymer matrix (differing from PLA4032D by the presence of a high molecular weight tail), a better dispersed nanomorphology can be obtained with Nanofil SE3010, characterized by a double d-spacing compared to Cloisite 30B, despite the higher polar character of this latter nanofiller. On the other hand, elongational rheological measurements evidence for NSE3010-based hybrids a marked extensional thickening, whilst the stronger polar interactions between the phases in both the polylactide grades filled with C30B, determine increments in elongational viscosity, but inhibit the strain hardening behavior. POLYM. COMPOS. , 00:000–000, 2015. V C 2015 Society of Plastics Engineers
SslE Elicits Functional Antibodies That Impair In Vitro Mucinase Activity and In Vivo Colonization by Both Intestinal and Extraintestinal Escherichia coli Strains

SslE, the Secreted and surface-associated lipoprotein from Escherichia coli, has recently been associated to the M60-like extracellular zinc-metalloprotease sub-family which is implicated in glycan recognition and processing. SslE can be divided into two main variants and we recently proposed it as a potential vaccine candidate. By applying a number of in vitro bioassays and comparing wild type, knockout mutant and complemented strains, we have now demonstrated that SslE specifically contributes to degradation of mucin substrates, typically present in the intestine and bladder. Mutation of the zinc metallopeptidase motif of SslE dramatically impaired E. coli mucinase activity, confirming the specificity of the phenotype observed. Moreover, antibodies raised against variant I SslE, cloned from strain IHE3034 (SslEIHE3034), are able to inhibit translocation of E. coli strains expressing different variants through a mucin-based matrix, suggesting that SslE induces cross-reactive functional antibodies that affect the metallopeptidase activity. To test this hypothesis, we used well-established animal models and demonstrated that immunization with SslEIHE3034 significantly reduced gut, kidney and spleen colonization by strains producing variant II SslE and belonging to different pathotypes. Taken together, these data strongly support the importance of SslE in E. coli colonization of mucosal surfaces and reinforce the use of this antigen as a component of a broadly protective vaccine against pathogenic E. coli species.
Visual Contrast Processing is Largely Unaltered during Saccades

Saccadic suppression refers to a reduction in visual sensitivity during saccadic eye movements. This reduction is conventionally regarded as mediated by either of two sources. One is a simple passive process of motion smear during saccades also accompanied by visual masking exerted by high-contrast pre- and post-saccadic images. The other is an active process exerted by a neural mechanism that significantly reduces visual processing so that the perception of a stable visual environment is not disrupted during saccades. Some studies have actually shown that contrast sensitivity is significantly lower during saccades than under fixation, but these experiments were not designed in a way that could weigh the differential contribution of active and passive sources of saccadic suppression. We report the results of measurements of psychometric functions for contrast detection using stimuli that are only visible during saccades, thus effectively isolating any visual processing that actually takes place during the saccades and also preventing any pre- and post-saccadic visual masking. We also report measurements of psychometric functions for detection under fixation for stimuli that are comparable in duration and spatio-temporal characteristics to the intrasaccadic retinal stimulus. Whether during saccades or under fixation, the psychometric functions for detection turned out to be very similar, leaving room only for a small amount of sensitivity reduction during saccades. This suggests that contrast processing is largely unaltered during saccades and, thus, that no neural mechanism seems to be actively involved in saccadic suppression.
Noticing Familiar Objects in Real World Scenes: The Role of Temporal Cortical Neurons in Natural Vision

During natural vision, the brain efficiently processes views of the external world as the eyes actively scan the environment. To better understand the neural mechanisms underlying this process, we recorded the activity of individual temporal cortical neurons while monkeys looked for and identified familiar targets embedded in natural scenes. We found a group of visual neurons that exhibited stimulus-selective neuronal bursts just before the monkey's response. Most of these cells showed similar selectivity whether effective targets were viewed in isolation or encountered in the course of exploring complex scenes. In addition, by embedding target stimuli in natural scenes, we could examine the activity of these stimulus-selective cells during visual search and at the time targets were fixated and identified. We found that, during exploration, neuronal activation sometimes began shortly before effective targets were fixated, but only if the target was the goal of the next fixation. Furthermore, we found that the magnitude of this early activation varied inversely with reaction time, indicating that perceptual information was integrated across fixations to facilitate recognition. The behavior of these visually selective cells suggests that they contribute to the process of noticing familiar objects in the real world.
Work-related asthma among professional cleaning women

ABSTRACT The job of cleaning has developed dynamically as a working service, and women constitute the majority of all professional cleaning workers. Cleaners are at an increased risk of work-related asthma (WRA). This study characterizes work-related respiratory symptoms reported by female cleaners, evaluates any associated factors of WRA, and shows diagnostic management of medical certification. The study group comprised 50 professional cleaning women referred to our Occupational Diseases Department due to suspicion of occupational asthma (OA). A questionnaire, skin prick tests, serum specific IgE antibodies, and specific inhalant challenge were performed in all of the participants. Work-related asthma was recognized in 46% of symptomatic cleaners, of whom 15 were considered as having work-exacerbated asthma (WEA) and 8 as having OA. Sensitization to latex and disinfectants played an important role as a causative agent in OA of cleaners.
Neuroplasticity in mood disorders

Neuroimaging and neuropathological studies of major depressive disorder (MDD) and bipolar disorder (BD) have identified abnormalities of brain structure in areas of the prefrontal cortex, amygdala, striatum, hippocampus, parahippocampal gyrus, and raphe nucleus. These structural imaging abnormalities persist across illness episodes, and preliminary evidence suggests they may in some cases arise prior to the onset of depressive episodes in subjects at high familial risk for MDD. In other cases, the magnitude of abnormality is reportedly correlated with time spent depressed. Postmortem histopathological studies of these regions have shown abnormal reductions of synaptic markers and glial cells, and, in rare cases, reductions in neurons in MDD and BD. Many of the regions affected by these structural abnormalities show increased glucose metabolism during depressive episodes. Because the glucose metabolic signal is dominated by glutamatergic transmission, these data support other evidence that excitatory amino acid transmission is elevated in limbic-cortical-striatal-pallidal-thalamic circuits during depression. Some of the subject samples in which these metabolic abnormalities have been demonstrated were also shown to manifest abnormally elevated stressed plasma cortisol levels. The co-occurrence of increased glutamatergic transmission and Cortisol hypersecretion raises the possibility that the gray matter volumetric reductions in these depressed subjects are partly accounted for by processes homologous to the dendritic atrophy induced by chronic stress in adult rodents, which depends upon interactions between elevated glucocorticoid secretion and N-meihyl-D-aspartate (NMDA)-glutamate receptor stimulation. Some mood-stabilizing and antidepressant drugs that exert neurotrophic effects in rodents appear to reverse or attenuate the gray matter volume abnormalities in humans with mood disorders. These neurotrophic effects may be integrally related to the therapeutic effects of such agents, because the regions affected by structural abnormalities in mood disorders are known to play major roles in modulating the endocrine, autonomic, behavioral, and emotional experiential responses to stressors.
Interest rate liberalization and economic growth in Zambia: a dynamic linkage

This paper examines the dynamic impact of interest rate reforms on economic growth in Zambia—using two models in a stepwise fashion. In the first model, the efficacy of interest rate liberalization is examined by regressing the interest rate on the level of financial deepening. In the second model, the causal relationship between financial depth and economic growth is examined by incorporating savings as an intermittent variable in the bivariate setting, thereby creating a simple trivariate model. Using the cointegration-based error correction model, the study finds strong support for the positive impact of interest rate liberalization on financial deepening.Inaddition,thestudyfindsthatfinancialdeepening,whichresults frominterestrateliberalization,Grangercauseseconomicgrowth.Theresults apply irrespective of whether the causality is estimated in the short run or in the long run. Other results show that: (1) lagged financial depth leads to further financial deepening; (2) savings and economic growth Granger cause each other; and (3) financial development Granger causes savings in the long run.
Development of novel PEGylation approaches based on non-covalent interactions

Biopharmaceuticals hold important value for the treatment of severe diseases. However, stability concerns remain one of the main obstacles for their successful market authorization. Generally, physical instabilities (in particular aggregation), in vivo immunogenicity, and short circulation half-lifes due to enzymatic degradation and fast renal elimination pose major challenges. After PEGylation, the covalent conjugation of poly(ethylene glycol) to biopharmaceuticals, decreased enzymatic degradation, prolonged plasma half-lifes, reduced in vivo immunogenicity, and improved formulation stability have been reported. However, several challenges remain for covalent PEGylation: i) the chemical processing and subsequent purification needed to attach the PEG may represent further stress on the protein, resulting in increased aggregation and possible loss of activity, ii) heterogeneous products are obtained requiring separation and characterization, and iii) an observed reduced in vivo bioactivity resulting from decreased interactions of the drug with its receptor due to steric shielding by the PEG. As described in this thesis, we addressed the need for alternative PEGylation approaches by development of novel techniques based on non-covalent interactions.
THE GISMO TWO-MILLIMETER DEEP FIELD IN GOODS-N

We present deep continuum observations using the GISMO camera at a wavelength of 2 mm centered on the Hubble Deep Field in the GOODS-N field. These are the first deep field observations ever obtained at this wavelength. The 1σ sensitivity in the innermost ∼4′ of the 7′ diameter map is ∼135 μJy beam−1, a factor of three higher in flux/beam sensitivity than the deepest available SCUBA 850 μm observations, and almost a factor of four higher in flux/beam sensitivity than the combined MAMBO/AzTEC 1.2 mm observations of this region. Our source extraction algorithm identifies 12 sources directly, and another 3 through correlation with known sources at 1.2 mm and 850 μm. Five of the directly detected GISMO sources have counterparts in the MAMBO/AzTEC catalog, and four of those also have SCUBA counterparts. HDF850.1, one of the first blank-field detected submillimeter galaxies, is now detected at 2 mm. The median redshift of all sources with counterparts of known redshifts is . Statistically, the detections are most likely real for five of the seven 2 mm sources without shorter wavelength counterparts, while the probability for none of them being real is negligible.
How River Beds Move

Insights into sediment transport at river beds can come from experiments in granular physics. The transport of sediment through river channels has major consequences for public safety, management of water resources, and environmental sustainability. Most studies of sediment transport in rivers have focused on mass flux and its relation to water flow. Yet, after more than a century of work, there is no satisfactory theory for bedload, the component of the sediment load transported in contact with the stream bed. Bedload transport formulae often overpredict the actual rate by orders of magnitude (1). It is therefore difficult to predict, for example, the impact of disturbances such as extreme floods on the channel. Better insight may come from viewing bedload as a granular phenomenon.
Minding the body.

As we continue to elucidate relationships between neural structures and cognitive functioning in this Decade of the Brain, it is important not to lose sight of the larger context. The brain is but one component of the complex system that is the body. We take in information and interact with the world through our bodies, and our bodies change with--and in some cases change--cognitive and emotional processing. In this introductory paper, we present an overview of a broad range of psychophysiological techniques: electroencephalography, event-related potentials, magnetoencephalography, positron emission tomography, optical imaging, functional magnetic resonance imaging, electromyograms, eye tracking, pupillometry, cardiovascular measures, and electrodermal activity. These techniques not only differ in their temporal and spatial resolutions but also in the physiological and psychological processes to which they are sensitive. With respect to the system as a whole, these techniques are thus complementary. Combining measures--old and new, central and peripheral--ultimately provides the most inferential power for attacking the questions we hope to answer with all psychophysiological measures in our quest to understand the nature of the relationship between the mind and the body.
ELUCIDATION OF THE RATE-LIMITING STEP IN NOREPINEPHRINE BIOSYNTHESIS IN THE PERFUSED GUINEA-PIG HEART.

Guinea-pig hearts were perfused with varying concentrations of the norepinephrine precursors, tyrosine, 3,4-dihydroxyphenylalanine (dopa) and 3,4-dihydroxyphenethylamine (dopamine). With all three precursors the rate of norepinephrine synthesis increased as the concentration in the perfusion fluid increased. However, only with tyrosine were maximal rates achieved (0.2 µg/g/hr) at concentrations below 5 x 10 -4 M. The apparent Km for the overall reaction (tyrosine → norepinephrine) was found to be comparable to that observed for conversion of tyrosine to dopa by purified tyrosine hydroxylase ( 2 x 10 -5 M). These and other factors indicate that conversion of tyrosine to dopa is the rate-limiting step in the formation of norepinephrine in the sympathetic nervous system. Although ascorbic acid has been shown to be a requirement for purified dopamine-β-oxidase activity severe seurvy did not diminish the ability of isolated heart to form norepinephrine from tyrosine or dopamine.
A structural numerical model for the optimization of double pelvic osteotomy in the early treatment of canine hip dysplasia

Summary Background: Double pelvic osteotomy (DPO) planning is usually performed by hip palpation, and on radiographic images which give a poor representation of the complex three-dimensional manoeuvre required during surgery. Furthermore, bone strains which play a crucial role cannot be foreseen. Objective: To support surgeons and designers with biomechanical guidelines through a virtual model that would provide bone stress and strain, required moments, and three-dimensional measurements. Methods: A multibody numerical model for kinematic analyses has been coupled to a finite element model for stress/strain analysis on deformable bodies. The model was parametrized by the fixation plate angle, the iliac osteotomy angle, and the plate offset in ventro-dorsal direction. Model outputs were: acetabular ventro-version (VV) and lateralization (L), Norberg (NA) and dorsal acetabular rim (DAR) angles, the percentage of acetabular coverage (PC), the peak bone stress, and moments required to deform the pelvis. Results: Over 150 combinations of cited parameters and their respective outcome were analysed. Curves reporting NA and PC versus VV were traced for the given patient. The optimal VV range in relation to NA and PC limits was established. The 25° DPO plate results were the most similar to 20° TPO. The output L grew for positive iliac osteotomy inclinations. The 15° DPO plate was critical in relation to DAR, while very large VV could lead to bone failure. Clinical significance: Structural models can be a support to the study and optimization of DPO as they allow for foreseeing geometrical and structural outcomes of surgical choices. ORCID iD ALA: http://orcid.org/0000-0002-4877-3630 AV: http://orcid.org/0000-0003-2837-7822 CB: http://orcid.org/0000-0002-7065-2552 EZ: http://orcid.org/0000-0003-4121-6126 MT: http://orcid.org/0000-0002-5699-6009
Control plane handoff analysis for IP mobility

Seamless host mobility is vital to future network mobility, and has been an active research area for a long time. Much research focuses on the performance of the data plane. In this paper, we present comprehensive analyses on the control (signalling) plane in the IETF Mobile IPv6, and compare it with the IRTF Identifier-Locator Network Protocol (ILNP). The control plane behaviour is important in order to assess the robustness and scalability of the mobility protocol. ILNP has a different mobility model from Mobile IPv6: it is a host-based, end-to-end architecture and does not require additional network-layer entities. Hence, the control signals are exchanged only between the end systems. We provide model-based analyses for handoff signalling, and show that ILNP is more efficient than MIPv6 in terms of robustness and scalability. The analytical models we present could also be adapted for other mobility solutions, for comparative assessment.