Miracle-dz/UniFAR-FTUs huggingface dataset:
Performance of pigs kept under different sanitary conditions affected by protein intake and amino acid supplementation1,2

ABSTRACT There is growing evidence that requirements for particular AA increase when pigs are kept under low sanitary conditions. The extent to which reduction in growth performance is related to these increased requirements is unclear. To evaluate this relationship, an experiment (2 × 2 × 2 factorial arrangement) was performed with 612 male pigs (9 per pen) kept under low sanitary conditions (LSC) or high sanitary conditions (HSC) and offered ad libitum access to either a normal CP concentration diet (NP; 17, 15, and 15% CP for the starter, grower, and finisher phase, respectively) or a low CP concentration diet (LP; 20% CP reduced relative to NP for each phase), each of which containing a basal AA profile (AA-B) or a supplemented AA profile (AA-S). The supplemented diet type contained 20% more Met, Thr, and Trp relative to Lys on an apparent ileal digestible basis compared with the basal diet type. Pigs were followed for a complete fattening period and slaughtered at a targeted pen weight of 110 kg. Haptoglobin concentrations in serum (0.92 g/L for LSC and 0.78 g/L for HSC) and IgG antibody titers against keyhole limpet hemocyanin (3.53 for LSC and 3.08 for HSC) collected in the starter, grower, and finisher phases and pleuritis scores at slaughter (0.51 for LSC and 0.20 for HSC) were greater for LSC pigs compared with HSC pigs (P ≤ 0.01), illustrating that sanitary conditions affected health conditions. The ADG and G:F were greater for HSC pigs compared with LSC pigs (P ≤ 0.01). The number of white blood cells (WBC) was higher in (AA-S)–fed pigs compared with (AA-B)–fed pigs when kept at LSC but not at HSC [SS (sanitary conditions) × AA interaction, P = 0.04]. Pigs fed NP had a lower number of WBC compared with pigs fed LP (P = 0.02). The number of platelets in pigs fed AA-S diets was higher compared with pigs fed AA-B diets (P ≤ 0.01). A 20% reduction in dietary supplementation of Met, Thr, and Trp relative to Lys decreased G:F more in LSC pigs than in HSC pigs (interaction, P = 0.03), illustrating that dietary requirements for these AA differ depending on sanitary conditions. This study, performed under practical conditions, shows that AA requirements are dependent on sanitary conditions. Furthermore, supplementation of diets with particular AA may improve performance, especially under poor hygienic conditions. Dietary protein concentration as well as Met, Thr, and Trp supplementation can modify immune status, which may influence resistance to subclinical and clinical diseases.
mRNA 3′ Tagging Is Induced by Nonsense-Mediated Decay and Promotes Ribosome Dissociation

ABSTRACT For a range of eukaryote transcripts, the initiation of degradation is coincident with the addition of a short pyrimidine tag at the 3′ end. Previously, cytoplasmic mRNA tagging has been observed for human and fungal transcripts. We now report that Arabidopsis thaliana mRNA is subject to 3′ tagging with U and C nucleotides, as in Aspergillus nidulans. Mutations that disrupt tagging, including A. nidulans cutA and a newly characterized gene, cutB, retard transcript degradation. Importantly, nonsense-mediated decay (NMD), a major checkpoint for transcript fidelity, elicits 3′ tagging of transcripts containing a premature termination codon (PTC). Although PTC-induced transcript degradation does not require 3′ tagging, subsequent dissociation of mRNA from ribosomes is retarded in tagging mutants. Additionally, tagging of wild-type and NMD-inducing transcripts is greatly reduced in strains lacking Upf1, a conserved NMD factor also required for human histone mRNA tagging. We argue that PTC-induced translational termination differs fundamentally from normal termination in polyadenylated transcripts, as it leads to transcript degradation and prevents rather than facilitates further translation. Furthermore, transcript deadenylation and the consequent dissociation of poly(A) binding protein will result in PTC-like termination events which recruit Upf1, resulting in mRNA 3′ tagging, ribosome clearance, and transcript degradation.
Inflammatory Myopathies With Anti-Ku Antibodies: A Prognosis Dependent on Associated Lung Disease

Anti-Ku antibodies have been reported in a wide spectrum of autoimmune diseases, sometimes in association with inflammatory myopathies (IM). We studied the clinical, laboratory, and muscle histologic features of all anti-Ku-positive patients detected in our hospital during the last 10 years, as well as their treatment and outcomes. Anti-Ku antibodies were found in 34 patients (0.46% of 20,600 sera positive for antinuclear antibodies), and complete data were available for 30 patients; 86.7% were female, mean age was 49 years (range, 20–73 yr). The most frequent clinical manifestations were arthralgia (77%) and Raynaud phenomenon (53%). Eleven (37%) patients had IM, 8 of them as part of an overlap syndrome defined as IM associated with connective autoimmune disease (5 systemic sclerosis [SSc], 2 Sjögren syndrome (SS), and 1 systemic lupus erythematosus [SLE]). Of 21 patients without IM, 19 had autoimmune diseases (including 6 SLE, 2 SSc, 2 SS, and 2 rheumatoid arthritis), 1 had bronchial neoplasia, and 1 had nephroangiosclerosis. Clinical features of the 9 patients with IM were myalgia (91%), proximal muscle weakness (89%), and dysphagia (36%). All had increased creatine kinase (median, 2210 U/L; range, 194–4073 U/L). Muscle biopsy showed necrosis, inflammation, and positive HLA class I immunostaining. Interstitial lung disease (ILD) was detected on computed tomography (CT) scan in 11 patients (37%) and was significantly more frequent in patients with IM (82% vs. 10.5%, p < 0.001). Fourteen (47%) patients required no immunosuppressive treatment or only a low corticosteroid dose (<15 mg/d, n = 3). A high dose of corticosteroids was more frequently administered in patients with IM (10/11 cases, 80% with associated ILD) than in patients without IM (4/19 cases, 0 with ILD). Complete muscle remission after steroids occurred in 73% of patients with IM. Lung disease was corticoresistant in 6 of 8 (75%) treated cases. Anti-Ku antibodies remain rarely detected, but their presence can be frequently associated with corticosensitive IM and severe, corticoresistant ILD. AbbreviationsANA = antinuclear antibodiesCT = computed tomographyENA = extractable nuclear antigenIBM = inclusion body myositisILD = interstitial lung diseaseIM = inflammatory myopathiesNSIP = nonspecific interstitial pneumoniaSLE = systemic lupus erythematosusSS = Sjögren syndromeSSc = systemic sclerosisUIP = usual interstitial pneumonia
Patient Compliance in Home-Based Self-Care Telehealth Projects

This paper presents the findings of a literature review on patient compliance in home-based self-care telehealth monitoring situations, intended to establish a knowledge base for this aspect which is often neglected alongside more conventional clinical, economic and service evaluations. A systematic search strategy led to 72 peer-reviewed published scientific papers being selected as most relevant to the topic, 58 of which appeared in the last 10 years. Patient conditions in which most evidence for compliance was found were blood pressure, heart failure and stroke, diabetes, asthma, chronic obstructive pulmonary disease and other respiratory diseases. In general, good compliance at the start of a study was found to drop off over time, most rapidly in the period immediately after the start. Success factors identified in the study included the extent of patient health education, telehealth system implementation style, user training and competence in system usage, active human support from the healthcare provider and maintaining strong participant motivation.
Cerebral microbleeds and cognitive functioning in the PROSPER study

Objectives: Cerebral microbleeds (MBs) are an important indicator of cerebral small-vessel disease, and their prevalence increases with increasing age. Little is known about the functional consequences of MBs in the aging population. In this study we investigated whether the presence and location of MBs are associated with cognition in the PROSPER study. Methods: For 439 subjects the number and location (cortico-subcortical, deep white matter, basal ganglia, and infratentorial) of the MBs was recorded. Difference in cognitive performance between subjects with and without MBs was calculated by entering the variables sex, age, white matter hyperintensity volume, infarction, and MBs in a linear mixed model. Differences in cognition between subjects with and without one or more MBs at different anatomic locations were assessed using the same model. Results: We found that after correction for sex, age, white matter hyperintensity volume, and infarction, subjects with infratentorial MBs had a significantly lower score on the Immediate Picture-Word Learning test, Delayed Picture-Word Learning, and Instrumental Activities of Daily Living. Conclusions: Our data demonstrate that in elderly individuals at increased vascular risk, infratentorial MBs are associated with loss in cognitive functioning.
Serotype-Specific Structural Differences in the Protease-Cofactor Complexes of the Dengue Virus Family

ABSTRACT With an estimated 40% of the world population at risk, dengue poses a significant threat to human health, especially in tropical and subtropical regions. Preventative and curative efforts, such as vaccine development and drug discovery, face additional challenges due to the occurrence of four antigenically distinct serotypes of the causative dengue virus (DEN1 to -4). Complex immune responses resulting from repeat assaults by the different serotypes necessitate simultaneous targeting of all forms of the virus. One of the promising targets for drug development is the highly conserved two-component viral protease NS2B-NS3, which plays an essential role in viral replication by processing the viral precursor polyprotein into functional proteins. In this paper, we report the 2.1-Å crystal structure of the DEN1 NS2B hydrophilic core (residues 49 to 95) in complex with the NS3 protease domain (residues 1 to 186) carrying an internal deletion in the N terminus (residues 11 to 20). While the overall folds within the protease core are similar to those of DEN2 and DEN4 proteases, the conformation of the cofactor NS2B is dramatically different from those of other flaviviral apoprotease structures. The differences are especially apparent within its C-terminal region, implicated in substrate binding. The structure reveals for the first time serotype-specific structural elements in the dengue virus family, with the reported alternate conformation resulting from a unique metal-binding site within the DEN1 sequence. We also report the identification of a 10-residue stretch within NS3pro that separates the substrate-binding function from the catalytic turnover rate of the enzyme. Implications for broad-spectrum drug discovery are discussed.
Data mining of motor patterns recorded with wearable technology

Discusses utilizing self-organizing maps to manage large data sets gathered in the field. Dramatic advances in wearable technology suggest that wearable sensors and systems are close to deployment in the clinical field environment. Miniature, wireless sensors are becoming readily available due to the tremendous research efforts focused on this area as well as the great interest demonstrated by the private sector for the associated potential market of these devices. Wearable systems, including base stations and hand-held units, are becoming less cumbersome, with an ever-increasing capacity to receive and store vast amounts of data for extensive periods of time. Further, the growing availability of wireless LANs makes it possible to envision wearable systems from which data can be continuously uploaded, while hand-held units provide a means to communicate with the patient when needed.
RBM4-MEF2C network constitutes a feed-forward circuit that facilitates the differentiation of brown adipocytes

Myocyte enhancer factor 2c (MEF2C) is the MADS-box type transcription factor involved in the differentiation of cardiac and skeletal muscle and synaptic formation. Alternatively spliced transcripts of the MEF2C gene were proven to encode isoforms which exert distinct functions in transcriptional regulation. During the differentiation of brown adipocytes, upregulated RBM4 enhanced skipping of the MEF2Cγ region which functions as a transcriptional repressor. The presence of an overexpressed MEF2Cγ- isoform in turn induced transcriptional activity of the RBM4 promoter, constituting a positive feedback circuit in differentiating brown adipocytes. The RBM4-MEF2Cγ- network induced the expression of "myogenic" miR-1 to a greater extent than did PRDM17, BMP7 C/EBPβ, or UCP1 transcripts in C3H10T1/2 cells. Overexpression of miR-1 independently exerted the same activity as RBM4 and the MEF2Cγ- isoform of upregulating brown adipocyte-specific factors in C3H10T1/2 cells, which suggests a potential effect of miR-1 on brown adipocytes. These results indicated that the RBM4-MEF2C-miR-1 network constitutes a novel mechanism which programs the gene expression profile toward the development of brown adipocytes.
Aurora‐A activation, correlated with hypoxia‐inducible factor‐1α, promotes radiochemoresistance and predicts poor outcome for nasopharyngeal carcinoma

Previously, we and others showed that hypoxia‐inducible factor‐1α (HIF‐1α) and transcriptionally upregulated Aurora‐A were required for disease progression in several tumors. Here, we address the clinicopathologic value of Aurora‐A and HIF‐1α in locally advanced nasopharyngeal carcinoma (NPC). Aurora‐A and HIF‐1α expression was semiquantitatively evaluated by immunohistochemistry staining in 144 cases from a randomized controlled trial. Of these patients, 69 received neoadjuvant chemotherapy plus concurrent chemoradiotherapy, and acted as the training set, and 75 cases treated with neoadjuvant chemotherapy plus radiotherapy were used as the testing set to validate the prognostic effect of Aurora‐A and HIF‐1α. We found that Aurora‐A and HIF‐1α were highly expressed in NPC, but were deficient in normal adjacent epithelia. In the testing set, Aurora‐A overexpression predicted a shortened 5‐year overall survival (59.1% vs 82.5%, P = 0.024), progression‐free survival (44.8% vs 79.8%, P = 0.004), and distant metastasis‐free survival (43.0% vs 17.3%, P = 0.016). Multivariate regression analysis confirmed that Aurora‐A was indeed an independent prognostic factor for death, recurrence, and distant metastasis both in the testing set and overall patients. Moreover, a positive correlation between Aurora‐A and HIF‐1α was detected (P = 0.037). Importantly, although HIF‐1α did not show any prognostic effect for patient outcome, the subset with Aurora‐A and HIF‐1α co‐overexpression had the poorest overall, progression‐free, and distant metastasis‐free survival (all P < 0.05). Our results confirmed that Aurora‐A was an independent prognostic factor for NPC. Aurora‐A combined with HIF‐1α refined the risk definition of the patient subset, thus potentially directing locally advanced NPC patients for more selective therapy. (Cancer Sci, doi: 10.1111/j.1349‐7006.2012.02332.x, 2012)
Evidence for Distinct Substrate Specificities of Importin α Family Members in Nuclear Protein Import

ABSTRACT Importin α plays a pivotal role in the classical nuclear protein import pathway. Importin α shuttles between nucleus and cytoplasm, binds nuclear localization signal-bearing proteins, and functions as an adapter to access the importin β-dependent import pathway. In contrast to what is found for importin β, several isoforms of importin α, which can be grouped into three subfamilies, exist in higher eucaryotes. We describe here a novel member of the human family, importin α7. To analyze specific functions of the distinct importin α proteins, we recombinantly expressed and purified five human importin α’s along with importin α from Xenopus andSaccharomyces cerevisiae. Binding affinity studies showed that all importin α proteins from humans or Xenopus bind their import receptor (importin β) and their export receptor (CAS) with only marginal differences. Using an in vitro import assay based on permeabilized HeLa cells, we compared the import substrate specificities of the various importin α proteins. When the substrates were tested singly, only the import of RCC1 showed a strong preference for one family member, importin α3, whereas most of the other substrates were imported by all importin α proteins with similar efficiencies. However, strikingly different substrate preferences of the various importin α proteins were revealed when two substrates were offered simultaneously.
Interaction between Microglia and Oligodendrocyte Cell Progenitors Involves Golli Proteins

Abstract: Multiple sclerosis (MS) is an autoimmune and chronic inflammatory disease characterized by plaques, areas of destroyed myelin sheaths in the CNS, which results in multiple disabilities for patients. In addition to demyelinated plaques, pathophysiological studies have shown “shadow plaques” that represent areas of partial remyelination. New myelin can be made by oligodendrocytes (OLs) generated from oligodendrocyte progenitor cells (OPCs) that pre‐exist in the demyelinated area or recruited from surrounding areas. To successfully repopulate the demyelinated area, OPCs have to proliferate, migrate, and differentiate into mature OLs capable of forming myelin. Identifying factors that influence remyelination is a current topic in developmental neurobiology. Previously, we showed that Golli proteins, which have a broad distribution in the nervous and immune systems, are present both in OPCs and activated microglia around MS lesions. We hypothesized that in response to inflammation, Golli proteins may promote proliferation of OPCs through microglial cells. To test this, we established neonatal mouse brain slice and cell cultures and used lipopolysaccharide (LPS) to induce inflammation. In LPS‐treated brain slices, Golli proteins displayed increased expression in the cortical subventricular zone. Furthermore, Golli proteins were demonstrated only in the conditioned medium from LPS‐treated microglial cell cultures (LPS‐MCM), and were absent in either conditioned medium from LPS‐treated astrocytes or control media. Finally, proliferation of purified OPCs was promoted with LPS‐MCM or Golli proteins, but not with LPS alone. In summary, these results demonstrate that activated microglia are beneficial for proliferation of OPCs and suggest possible involvement of Golli proteins as one of mediators in this process.
Extracellular activation and membrane conductances of neurones in the guinea‐pig deep cerebellar nuclei in vitro.

The responses of cerebellar nuclear cells to extracellular stimulation in a slice preparation were studied and the ionic basis of their electroresponsiveness was investigated with blockers of membrane conductances and with ion substitutions in the extracellular medium. The cells could be activated antidromically from the cerebellar cortex and the white matter surrounding the nuclei. The dominating response to orthodromic stimulation was an inhibitory synaptic potential presumably produced by activation of Purkinje cell fibres. The action potentials and the subthreshold spikelets were shown to be Na+ dependent and are presumably generated by a voltage‐dependent inactivating Na+ conductance. Plateau potentials with a low threshold were also Na+ dependent, but these long‐lasting potentials are probably produced by activation of a voltage‐dependent non‐inactivating Na+ conductance. Plateau potentials with a high threshold and high‐threshold spikelets were Ca2+ dependent and seem to be generated by non‐inactivating and possibly inactivating Ca2+ conductances. The spike after‐hyperpolarizations had an early voltage‐dependent K+ component and a late Ca2+‐dependent K+ component. They are therefore produced by voltage‐sensitive and Ca2+‐dependent K+ conductances. By analogy with the distribution of conductances in Purkinje cells it is proposed that the Na+ conductances are mainly located in the somatic and axonal membrane and that the Ca2+ conductances are located in the dendrites. The functional implications of the complex electroresponsive properties of cerebellar nuclear cells are discussed.
Relationship of NEO-PI to personality styles and severity of trauma in chronic PTSD victims.

The relationship of the NEO-PI to personality disorders was evaluated in a clinical population. Eighty subjects with post-traumatic stress disorder (PTSD) were given this measure, along with the MCMI-II and PTSD and combat scales. Two questions were addressed: (1) What is the relationship of NEO-PI domains and facets to personality disorders? ; and (2) What is this scale's relationship to PTSD problems? Results support previous studies that employed a clinical population, but with lower correlation coefficients. For the most part, then, the NEO-PI domains and facets correlated in expected ways with the MCMI-II. On PTSD measures, N accounted for the majority of the variance, but other domains were entered when independent regression equations were calculated to account for different personality disorders.
Educating Pakistan's daughters : the intersection of schooling, unequal citizenship and violence

The purpose of this thesis is to explore how education in one girls’ government school teaches understandings of citizenship and to identify potential links to the reproduction of identity-based violence in Pakistan. This in-depth qualitative case study was conducted in a girls’ government model school. This study focuses on curriculum and school practices of the secondary school section. Data was collected through interviews with staff, a participatory workshop with teachers, focus groups with students, classroom observation, and informal discussions. I also analyzed the Pakistan Studies textbook used in the secondary section of the school. Using theories of critical education, intersectionality, and Galtung’s violence triangle, I argue that despite recent political and curricular reform attempts, education in Pakistan reproduces a homogeneous concept of a legitimate citizen (male Sunni Muslim). While this evolved to unite an ethnically diverse Pakistan, it has contributed to identity-based violence (direct, structural, and cultural) against those that do not fit within this conception. In this school, the Pakistan Studies textbooks create an official discourse that promotes this gendered and exclusionary citizenship. I show how the Pakistan studies textbook uses history and constitutional lessons to promote citizenship that is based in a masculine Islam meant to oppose the Hindu ‘other’ as well as to promote the exclusion of women and minorities from full citizenship. I also found that teachers own understandings of citizenship, which closely reflect the text, are deeply rooted in their understanding of their notions of the ideal Muslim woman. I find that the school rewards gendered behavior in both students and teachers. I then explore the extent to which the school reproduces other social divisions including religious, ethnicity, and class. I find that the school simultaneously reproduces, mitigates, and exacerbates these tensions. I then argue that the teachers’ and students’ understandings of the role of women to counter violence is rooted in the notions of middle class women’s roles as mothers and supporters of men that are reproduced through school practice. This study furthers the knowledge on the links between education and violence by showing that promoting a homogeneous ideal of a citizen through education, while intended as a nation building project, can contribute to structural, cultural and direct violence against women and minorities, limiting their agency to engage in social transformation.