Miracle-dz/UniFAR-FTUs huggingface dataset:
Production of experimental models of foetal growth retardation by inhibition of DNA or protein synthesis.

Foetal growth retardation was induced in the rat by administration of hydroxyurea, an inhibitor of DNA synthesis, or cycloheximide, an inhibitor of protein synthesis. Each drug was given at 2 stages of pregnancy, either at 15 or at 18 days. Body and organ weights were studied at term (21 days) and DNA, RNA and protein estimations performed on brain and liver, with additional measurements of carbohydrate in the liver. Inhibition of DNA synthesis (hydroxyurea) caused reduction in organ cell population whether given early or late in pregnancy but the effect on the brain was more marked in early pregnancy. Haemopoietic cells in the liver were destroyed by repeated dosage on day 18. Inhibition of protein synthesis (cycloheximide) caused reduction in mean cell weight, but little reduction in cell population whether given early or late. With both drugs the effects on cell population were more severe with administration early in pregnancy. The results indicate that timing, mode of action and severity of stimulus are all important in determining the effect of any particular stress on foetal growth. The implications for studies on human intra-uterine growth retardation are discussed.
25-Hydroxyvitamin D status, arterial stiffness and the renin–angiotensin system in healthy humans

Abstract Vitamin D deficiency is associated with increased arterial stiffness. We sought to clarify the influence of vitamin D in modulating angiotensin II-dependent arterial stiffness. Thirty-six healthy subjects (33 ± 2 years, 67% female, mean 25-hydroxyvitamin D 69 ± 4 nmol/L) were studied in high salt balance. Arterial stiffness, expressed as brachial pulse wave velocity (bPWV) and aortic augmentation index (AIx), was measured by tonometry at baseline and in response to angiotensin II infusion (3 ng/kg/min × 30 min then 6 ng/kg/min × 30 min). The primary outcome was change in bPWV after an angiotensin II challenge. Results were analyzed according to plasma 25-hydroxyvitamin D status: deficient (<50 nmol/L) and sufficient (≥50 nmol/L). There were no differences in baseline arterial stiffness between vitamin D deficient (25-hydroxyvitamin D 40 ± 2 nmol/L) and sufficient (25-hydroxyvitamin D 80 ± 4 nmol/L) groups. Compared with sufficient vitamin D status, vitamin D deficiency was associated with a decreased arterial response to angiotensin II challenge (Δbrachial pulse wave velocity: 0.48 ± 0.44 m/s versus 1.95 ± 0.22 m/s, p = 0.004; Δaortic augmentation index: 9.4 ± 3.4% versus 14.2 ± 2.7%, p = 0.3), which persisted for brachial pulse wave velocity response after adjustment for covariates (p = 0.03). Vitamin D deficiency is associated with increased arterial stiffness in healthy humans, possibly through an angiotensin II-dependent mechanism.
Covalent crosslinking between molecules of type I and type III collagen. The involvement of the N-terminal, nonhelical regions of the alpha 1 (I) and alpha 1 (III) chains in the formation of intermolecular crosslinks.

Several peptides containing intermolecular crosslinks were isolated from tryptic digests of the insoluble matrix of human leiomyoma and calf aorta. From leiomyoma type III collagen, two crosslinked peptides were isolated. The peptide [TN(III)]2, is a dimer which contains the 73 amino-terminal residues of two, zero-D staggered, crosslinked α1(III) chains (D being the distance by which molecules or chains are staggered relative to each other). After de-blocking with pyroglutamate aminopeptidase, its amino-terminal amino acid sequence was determined to be < Glu-Tyr-Asp-Ser-Tyr-Asp-Val-Xaa-Ser-Gly-Val-Ala-Val-Gly-Gly-Leu-Ala-Gly-Tyr-Hyp-Gly-. The involvement of [TN(III)]2 in the formation of 4D-staggered intermolecular bonds was demonstrated by sequence analysis of [TN(III)2]×T(III). For this three-chained peptide, a double sequence which corresponded to TN(III) and T(III), a nine-residue peptide from the carboxy-terminal helical crosslinking site of type III collagen, was found. Crosslinks between type I and type III collagens were identified by isolating a peptide TN(III)×TN(I) from leiomyoma. This peptide was characterized, first by digesting it with collagenase giving rise to ColN(III)×ColN(I) and then chymotrypsin giving C(III) and C(I). C(I) and C(III) are peptides characteristic for type I and type III collagens, respectively. Further, three-component crosslink-containing peptides, from both type I and type III collagen, were isolated from aorta and leiomyoma. The peptides ColN(III)× ColN(I)× T(III) from leiomyoma and Col×N(III) ColN(I)× T(I) from aorta are crosslinked amino-terminal regions of 0D-staggered type I and type III molecules, joined either to an adjacent 4D-staggered type III or type I molecule. Crosslinked peptides involving only type III collagen molecules were also isolated from calf aorta [colN(III)]2 and [CoIN(III)2]×T(III)]. As intramolecular bonds between type I and III collagens can be excluded the isolation of these crosslinked peptides demonstrated that type I and type III collagen molecules are present within the same collagen fibrit with OD stagger, bound by intermolecular crosslinks. The significance of these findings with respect to the proposed models for collagen fibres and the physiological properties of the extracellular matrix, are discussed.
Sonographic variations in common bile duct dimensions

Introduction: Biliary diseases such as cholelithiasis, cholecystitis, hepatitis, cirrhosis and pancreatitis are common in Nepal. Cholelithiasis was present in 8 percent of the emergency patients, second to acute appendicitis. Acute cholecysistitis was present in 25 percent of these patients. 1 The most common operation in a district hospital was cholecystectomy (31%]). 2 Ultrasound plays an integral part in evaluation of biliary system. The aim of the study was also to determine whether the size of the CBD increases with age. Methods: We prospectively collected data on 100 patients aged 15 years or older who underwent abdominal sonography. The subjects had no history of biliary and pancreatic disease or operation. The CBD was measured in porta hepatis, in the distal aspect of head of pancreas and midway between these points. Linear regression was used to correlate age with the dimension. Results: There were 30 males and 70 females in the study. The subjects ranged from 15 to 80 years. The mean diameters were as follows: 3.76mm in proximal, 4.26 mm in middle, 4.90mm in distal portion of CBD. The overall measurement was 4.23mm. Conclusions: There was a significant correlation between CBD size and age. Correlation with age was best observed for the distal segment. Keywords : Biliary diseases, CBD, ultrasound. DOI: 10.3126/joim.v31i3. 2993 Journal of Institute of Medicine, December, 2009; 31(3) 27-29
Cotransplantation of Placental Mesenchymal Stromal Cells Enhances Single and Double Cord Blood Engraftment in Nonobese Diabetic/Severe Combined Immune Deficient Mice

Limited cell numbers in a unit restricts cord blood transplantation (CBT) in adults. We evaluated whether cotransplantation of placental mesenchymal stromal cells (MSCs) would enhance engraftment. Plastic adherent cells from placenta demonstrated typical characteristics of MSCs. In six individual experiments, 4 cohorts of 24 nonobese diabetic/severe combined immune deficient (NOD/SCID) mice were evaluated. Cohort 1 received 5 × 104 CD34+ cells from unit (U) one (SCBT); cohort 2 received 5 × 104 CD34+ cells from U1 + 4 × 104 MSCs (SCBT+MSCs); cohort 3 received 2.5 × 104 CD34+ cells from U1 + 2.5 × 104 CD34+ cells from U2 (double cord blood transplant [DCBT]); cohort 4 received 2.5 × 104 CD34+ cells from U1 + 2.5 × 104 CD34+ cells from U2 + 4 × 104 MSCs (DCBT+MSCs). Hematopoietic engraftment evaluated after 6 to 8 weeks, was similar in recipients of SCBT and DCBT. MSC cotransplantation demonstrated enhanced engraftment in DCBT (51.8 ± 6.8% versus 14.9 ± 6.5%; p = .04) with an increased trend in SCBT (48.7 ± 7.7% versus 17.5 ± 6.1%; p = .07). In DCBT, cotransplantation of placental MSCs reduced single cord dominance. Self‐renewal capacity was assessed by serial transplantation in secondary recipients infused with engrafted human cells from primary mice transplanted with or without MSCs. In secondary transplant experiments, 13 of 17 evaluable mice engrafted at levels of 1% to 6.5%. Despite enhanced engraftment in primary mice, long‐term engraftment capacity was unaltered with MSC cotransplantation. Imaging studies showed MSCs migrated to pelvic region and improved cord blood (CB) CD34+ homing. Cotransplantation of placental MSCs enhanced cord blood engraftment and may act by improving homing of CD34+ cells. STEM CELLS 2009;27:2293–2300
Caracterização do Perfil Antropométrico, Lipídico e Dietético de Mulheres no Climatério Associados com o Risco de Doenças Cardiovasculares

O climaterio e definido como uma fase biologica da vida e nao um processo patologico, que compreende a transicao entre o periodo reprodutivo e o nao reprodutivo na vida da mulher. O objetivo deste estudo foi caracterizar o perfil antropometrico, lipidico e dietetico associado com o risco de doencas cardiovasculares das mulheres no climaterio. Estudo de corte transversal realizado em Pinheiral, RJ. Foi aplicado questionario de insercao socio-economica das voluntarias, realizado avaliacao antropometrica e composicao corporal (peso, altura, bioimpedância e circunferencia da cintura). Os exames bioquimicos utilizados foram Colesterol Total, LDL-Colesterol, HDL-Colesterol, Triglicerideos e avaliado a, Relacao LDL/HDL, Relacao Colesterol Total/HDL. Para avaliacao do consumo alimentar foi utilizado o recordatorio de 24 horas. Os resultados mostraram que 50% das mulheres encontravam-se obesas, 30% apresentaram obesidade de grau I e 20% obesidade de grau II. Em relacao a circunferencia da cintura e a gordura corporal, 70% das voluntarias encontraram-se com risco de doencas cardiometabolicas e risco muito elevado de complicacoes metabolicas. A relacao entre LDL/HDL e de igual proporcao (50%), tanto para baixo risco de doencas cardiovasculares quanto para o elevado risco destas. A relacao entre o Colesterol Total/ HDL foi baixo risco de doencas cardiovasculares em 55% das mulheres. Com relacao ao consumo energetico, apenas 5% voluntaria encontrava- -se com consumo alimentar adequado, 55% consumiam abaixo da media recomendada 40% acima do que e recomendado. A ingestao de fibras teve-se que 30% estavam consumindo adequadamente. Pode-se concluir que houve uma elevada prevalencia de inadequacao nutricional, de sobrepeso e obesidade, e um alto risco de desenvolver doencas cardiovasculares, mostrado pelos parâmetros antropometricos e pelo lipidograma.
Regulation of iro3 expression in the zebrafish spinal cord

Specification of spinal cord neurons is regulated by several different transcription factors. In this study, we analyze expression and regulation of the transcription factor iro3 in zebrafish spinal cord. In addition to its broad expression in the progenitor domain of intermediate spinal cord, iro3 is also expressed in postmitotic ventral neurons, starting at early somitogenesis stages. Initially, this expression is only in two primary motoneurons, CaP and VaP, but by 24 hr postfertilization, iro3 is expressed by all classes of zebrafish spinal motoneurons as well as by a ventral interneuron called VeLD. iro3 expression in the progenitor domain of intermediate spinal cord is regulated independently from its expression in ventral neurons. Hedgehog (Hh) signaling is unnecessary for iro3 expression in intermediate spinal cord, but it is required to repress iro3 expression in the progenitor domain of ventral spinal cord. We also show that the basic helix‐loop‐helix transcription factor Olig2 is required for repression of iro3 expression in the progenitor domain of ventral spinal cord. We discuss our findings in the context of previous studies, suggesting that iro3 represses formation of motoneurons and promotes formation of interneurons. Developmental Dynamics 232:140–148, 2005. © 2004 Wiley‐Liss, Inc.
Efficacy and Safety of an Aclidinium Bromide Treatment for 12 Weeks or Longer in Patients with Moderate-To-Severe COPD: A Meta-Analysis

Abstract Background: Bronchodilators are commonly used to manage patients with stable chronic obstructive pulmonary disease (COPD). This meta-analysis assessed the efficacy of aclidinium bromide with respect to clinical events, health-related quality of life and symptom scales, pulmonary function, and safety among patients with stable COPD. Methods: A comprehensive search of MEDLINE, EMBASE, CINAHL and the Cochrane Library databases was undertaken to identify randomized controlled trials (RCTs) that compared aclidinium with placebo, treatment over at least 12 weeks. Trials were measured using either odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CI). Results: Seven studies, containing 7001 patients, were included in this meta-analysis. Compared with placebo, aclidinium bromide reduced the incidence of exacerbation-related hospitalizations (OR 0.64; 95% CI 0.47 to 0.89) and improved quality of life as measured by a lower total George's Respiratory Questionnaire [SGRQ] score (MD −2.34; 95% CI −3.18 to −1.51) and attenuated dyspnea symptom as assessed by changes in the Transitional Dyspnea Index [TDI] (MD 0.76; 95% CI 0.43 to 1.10). Similar changes were observed with regard to trough FEV1 and FVC and peak FEV1 and FVC. No significant differences were observed with regard to all-cause mortality, COPD exacerbations, non-fatal serious adverse events or cardiac adverse events. Conclusions: Aclidinium reduced the incidence of exacerbation-related hospitalizations and improved quality of life, COPD symptoms and pulmonary function. In addition, aclidinium did not increase the incidence of non-fatal serious adverse events, cardiac adverse events, or COPD exacerbations and was not associated with increased mortality.
Effects of TNFα inhibitors on adiposity and other cardiovascular risk factors: implications for the cardiovascular prognosis in patients with rheumatoid arthritis

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease that is associated with increased cardiovascular (CV) morbidity and mortality. This increased CV burden is the result of an enhanced prevalence of traditional CV risk factors, the effects of treatments given for RA but also systemic inflammation. In this setting, the control of inflammation by the current therapeutic approach may improve the overall CV prognosis of RA. Areas covered: This paper analyses the impact of TNFα inhibitors on the different CV risk factors with a special emphasis on lipid profile and body composition. The lipid profile under TNFα inhibitors changes, an increase in total and high density lipoprotein (HDL) cholesterol is observed but the atherogenic index and low density lioprotein cholesterol are unaffected. In parallel, TNFα inhibitors induce an accumulation of fat in the abdominal/visceral region. Analysis of cohort and registry studies indicates that CV events are reduced under this treatment. Expert opinion: Overall, the favourable CV effect under TNFα inhibitors does not seem to be explained by the changes in traditional CV risk factors, but rather by the improvement in systemic inflammation. Alternatively, the changes in body composition raise the question of their effect on long-term CV safety.
Vowel Epenthesis in Arabic Loanwords in Hausa

Vowel epenthesis is discussed in this paper as a phonological process utilized to avoid codas in Arabic loanwords in Hausa language in light of Optimality Theory (OT), as an analytical framework, even though this language permits codas in heavy syllables of the form CVC (Caron, 2011). This process results in having disyllabic, trisyllabic, or qadri-syllabic words (words with four syllables) depending on the forms of Arabic loanwords as well as mono-syllabic words with final bi-consonant clusters. This study primarily relies on extant literature including theses, books, articles. Furthermore, the authors’ intuition is crucially deemed the judge on the facts of the data . This paper concludes that codas in Arabic loanwords in Hausa motivate vowel epenthesis either once or twice, depending on the forms of words; i.e. disyllabic or monosyllabic. Also, the number of vowel insertion depends on the number of consonants in the coda postion, i.e. /CVCC/→ vowel epenthesis→ [CVC.C V ] or [CV.C V . C V ].
Head and neck cancer: from anatomy to biology

The 20th century saw great advances in anatomy‐based (surgery and radiotherapy) and chemotherapy approaches for treating head and neck squamous cell carcinoma (HNSCC) and improving quality of life (QoL). However, despite these advances, the survival rate in HNSCC remains at ∼50%. Front‐line treatments often cause severe toxicity and debilitating long‐term impacts on QoL. In recent decades, dramatic advances have been made in our knowledge of fundamental tumor biology and signaling pathways that contribute to oncogenesis and cancer progression. These insights are presenting unprecedented opportunities to develop more effective and less toxic treatments that are specific to particular molecular targets. This review discusses some of the major, potentially targetable, molecular pathways associated with head and neck carcinogenesis. We present the general mechanism underlying the functional components for each signaling pathway, discuss how these components are aberrantly regulated in HNSCC and describe their potential as therapeutic targets. We have restricted our discussion to “drug‐able targets” such as oncogenes including those associated with HPV, tumor hypoxia and microRNAs and present these changes in the context of HNSCC patient care. The specific targeting of these pathways to achieve cancer control/remission and reduce toxicity is now challenging conventional treatment paradigms in HNSCC. This new “biologic era” is transforming our ability to target causal pathways and improve survival outcomes in HNSCC.
Increased thrombin activity following reperfusion after ischemic stroke alters synaptic transmission in the hippocampus

Thrombin, a key player in thrombogenesis, affects cells in the brain through activation of its receptors. Low levels of thrombin activity are protective while high levels are toxic. We sought to quantify thrombin activity levels and their spatial distribution in brains of mice following reperfusion after ischemic stroke focusing on infarct, peri‐infarct and contralateral areas. In order to find out the contribution of brain‐derived thrombin, mRNA levels of both prothrombin and factor X were determined. Furthermore, we assessed the effect of thrombin levels that were measured in the ischemic brain on synaptic transmission. We found that in the brains of mice following transient middle cerebral artery occlusion, thrombin activity is elevated throughout the ischemic hemisphere, including in peri‐infarct areas (90 ± 33 and 60 ± 18 mU/mL, in the infarct and peri‐infarct areas, respectively, compared to 11 ± 3 and 12 ± 5 mU/mL, in the corresponding contralateral areas; mean ± SE; p < 0.05). Brain mRNA levels of prothrombin and, in particular, factor X are up‐regulated in the ischemic core. Hippocampal slices treated with thrombin concentrations as found in the ischemic hemisphere show altered synaptic responses. We conclude that high thrombin activity following reperfusion after ischemic stroke may cause synaptic dysfunction.
Socially Shared Cognition, Affect, and Behavior: A Review and Integration

In this article, we review 4 classes of models of socially shared cognition and behavior: supraindividual models, information-processing models, communication models, and social interaction models. Our review draws on research and theory in social psychology, sociology, and organization behavior. We conclude that these innovative perspectives on socially shared behavior represent a new approach to the study of groups and are distinct from traditional models of the group mind and crowd behavior. The key processes implicated in these models focus on the potency of immediate interaction, reciprocal influence processes between individuals and groups, goal-directed behavior, negotiated processing of information and ideas, and the maintenance and enhancement of social identity. This approach to socially shared understanding is not antagonistic toward the analysis of individual-level processes but rather maintains that individual-level processes are necessary but not sufficient to build a social psychology of shared understanding.
Probing the folding free energy landscape of the src-SH3 protein domain

The mechanism and thermodynamics of folding of the Src homology 3 (SH3) protein domain are characterized at an atomic level through molecular dynamics with importance sampling. This methodology enables the construction of the folding free energy landscape of the protein as a function of representative reaction coordinates. We observe that folding proceeds in a downhill manner under native conditions, with early compaction and structure formation in the hydrophobic sheet consisting of the three central β strands of the protein. This state bears considerable resemblance to the experimentally determined transition state for folding. Folding proceeds further with the formation of the second hydrophobic sheet consisting of the terminal strands and the RT loop. The final stages of folding appear to involve the formation of the hydrophobic core through the expulsion of water molecules bridging the two hydrophobic sheets. This work sheds new light on the complementary roles of sequence and topology in governing the folding mechanism of small proteins and provides further support for the role of water in facilitating the late stages in folding.
Characterization of the gene for a protein kinase which phosphorylates the sporulation-regulatory proteins Spo0A and Spo0F of Bacillus subtilis

The kinA (spoIIJ) locus contains a single gene which codes for a protein of 69,170 daltons showing strong homology to the transmitter kinases of two component regulatory systems. The purified kinase autophosphorylates in the presence of ATP and mediates the transfer of phosphate to the Spo0A and Spo0F sporulation regulatory proteins. Spo0F protein was a much better phosphoreceptor for this kinase than Spo0A protein in vitro. Mutants with deletion mutations in the kinA gene were delayed in their sporulation. They produced about a third as many spores as the wild type in 24 h, but after 72 h on solid medium, the level of spores approximated that found for the wild-type strain. Such mutations had no effect on the regulation of the abrB gene or on the timing of subtilisin expression and therefore did not impair the repression function of the Spo0A protein. Placement of the kinA locus on a multicopy vector suppressed the sporulation-defective phenotype of spo0B, spo0E, and spo0F mutations but not of spo0A mutations. The results suggest that the spo0B-, spo0E-, and spo0F-dependent pathway of activation (phosphorylation) of the Spo0A regulator may be by-passed through the kinA gene product if it is present at sufficiently high intracellular concentration. The results suggest that multiple kinases exist for the Spo0A protein.