Miracle-dz/UniFAR-FTUs huggingface dataset:
Guidelines for case classification for the National Birth Defects Prevention Study.

BACKGROUND Previous studies have suggested that etiologic heterogeneity may complicate epidemiologic analyses designed to identify risk factors for birth defects. Case classification uses knowledge of embryologic and pathogenetic mechanisms to make case groups more homogeneous and is important to the success of birth defects studies. METHODS The goal of the National Birth Defects Prevention Study (NBDPS), an ongoing multi-site case-control study, is to identify environmental and genetic risk factors for birth defects. Information on environmental risk factors is collected through an hour-long maternal interview, and DNA is collected from the infant and both parents for evaluation of genetic risk factors. Clinical data on infants are reviewed by clinical geneticists to ensure they meet the detailed case definitions developed specifically for the study. To standardize the methods of case classification for the study, an algorithm has been developed to guide NBDPS clinical geneticists in this process. RESULTS Methods for case classification into isolated, multiple, and syndrome categories are described. Defects considered minor for the purposes of case classification are defined. Differences in the approach to case classification for studies of specific defects and of specific exposures are noted. CONCLUSIONS The case classification schema developed for the NBDPS may be of value to other clinicians working on epidemiologic studies of birth defects etiology. Consideration of these guidelines will lead to more comparable case groups, an important element of careful studies aimed at identifying risk factors for birth defects.
Network Based Approach for Discovering Academic Researchers with Shared Interests

Interest or expertise of researchers is a kind of knowledge in organization, like university, research institute and research community. Effectively management of this kind of knowledge can facilitate communication of members in organization and improve their performance. Researchers’ cognitive limit and large amount of relevant information available present great challenge to discover researchers with similar interests. Previous research addresses this problem by investigating their research related relationships. The social network based approached do not satisfy researchers’ needs due to their failure to take into consideration the semantic information related to research interests. To solve this problem, in this research, we propose an integrated model based on ontology and social network analysis to mine researchers with similar interests.
Real-Time PCR Assay for Detection and Enumeration of Dekkera bruxellensis in Wine

ABSTRACT Traditional methods to detect the spoilage yeast Dekkera bruxellensis from wine involve lengthy enrichments. To overcome this difficulty, we developed a quantitative real-time PCR method to directly detect and enumerate D. bruxellensis in wine. Specific PCR primers to D. bruxellensis were designed to the 26S rRNA gene, and nontarget yeast and bacteria common to the winery environment were not amplified. The assay was linear over a range of cell concentrations (6 log units) and could detect as little as 1 cell per ml in wine. The addition of large amounts of nontarget yeasts did not impact the efficiency of the assay. This method will be helpful to identify possible routes of D. bruxellensis infection in winery environments. Moreover, the time involved in performing the assay (3 h) should enable winemakers to more quickly make wine processing decisions in order to reduce the threat of spoilage by D. bruxellensis.
Handgrip-Related Activation in the Primary Motor Cortex Relates to Underlying Neuronal Metabolism After Stroke

Background. Abnormal task-related activation in primary motor cortices (M1) has been consistently found in functional imaging studies of subcortical stroke. Whether the abnormal activations are associated with neuronal alterations in the same or homologous area is not known. Objective. Our goal was to establish the relationships between M1 measures of motor-task-related activation and a neuronal marker, N-acetylaspartate (NAA), in patients with severe to mild hemiparesis. Methods. A total of 18 survivors of an ischemic subcortical stroke (confirmed on T2-weighted images) at more than six months post-onset and 16 age- and sex-matched right-handed healthy controls underwent functional MRI during a handgrip task (impaired hand in patients, dominant hand in controls) and proton magnetic resonance spectroscopy (1H-MRS) imaging. Spatial extent and magnitude of blood oxygen level–dependent response (or activation) and NAA levels were measured in each M1. Relationships between activation and NAA were determined. Results. Compared with controls, patients had a greater extent of contralesional (ipsilateral to impaired hand, P < .001) activation and a higher magnitude of activation and lower NAA in both ipsilesional (P = .008 and P < .001, respectively) and contralesional (P < .0001, P < .05) M1. There were significant negative correlations between extent of activation and NAA in each M1 (P = .02) and a trend between contralesional activation and ipsilesional NAA (P = .08) in patients but not in controls. Conclusions. Our results suggest that after stroke greater neuronal recruitment could be a compensatory response to lower neuronal metabolism. Thus, dual-modality imaging may be a powerful tool for providing complementary probes of post-stroke brain reorganization.
Cidades Artificiais: Um Estudo Exploratório do Projeto Urbano Porto Alegre 4D.

Uma cidade artificial e uma cidade projetada, criada do zero. Projetos contemporâneos de renovacao urbana podem ser considerados um projeto de cidade artificial pois o foco do projeto nao esta na populacao residente, ao contrario, desencadeiam processos de gentrificacao e de atracao de populacao externa. O objetivo deste artigo e, portanto, mostrar o carater-pratico operacional dos projetos urbanos desta natureza . O estudo se baseia na exploracao da aplicacao da triade da producao do espaco (LEFEBVRE, 1991) para o projeto Porto Alegre 4D . O argumento passa pela compreensao de como as ferramentas de planejamento urbano deixaram de ser garantidoras do bem social comum, do valor de uso, para se tornar um instrumento que reforca o valor de troca. O desafio reside, portanto, na propagacao de espacos heterotopicos capazes de driblar o carater pratico-operacional dos projetos urbanos contemporâneos.
TAK1–JNK Axis Mediates Survival Signal through Mcl1 Stabilization in Activated T Cells

TAK1, a member of MAPK kinase kinase (MAPKK-K) family, can activate JNK, p38 MAPK, and NF-κB signaling pathways. Although targeted gene disruption studies have demonstrated that TAK1 plays a critical role in T cell functions, precise functions of downstream mediators remain elusive. We used the chemical compound LL-Z1640-2, which preferentially suppressed MAPK activation but not NF-κB signal downstream of TAK1. LL-Z1640-2 blocked TCR-induced T cell proliferation and activation, confirming that a TAK1-mediated MAPK signal is essential for T cell activation. LL-Z1640-2 induced apoptosis of activated mouse splenic T cells in a caspase- and caspase-activated DNase–dependent manner. TAK1-JNK pathway, which is activated downstream of IL-2R, induced the phosphorylation of antiapoptotic protein Mcl1 in activated T cells, resulting in the stabilization of Mcl1 protein. Our data uncover that among signal transduction pathways downstream of TAK1, JNK mediates a survival program through Mcl1 stabilization downstream of IL-2R in activated T cells and that blockade of TAK1-JNK pathway can eliminate activated T cells by apoptosis.
PHO2, MicroRNA399, and PHR1 Define a Phosphate-Signaling Pathway in Plants1[W][OA]

Inorganic phosphate (Pi)-signaling pathways in plants are still largely unknown. The Arabidopsis (Arabidopsis thaliana) pho2 mutant overaccumulates Pi in leaves in Pi-replete conditions. Micrografting revealed that a pho2 root genotype is sufficient to yield leaf Pi accumulation. In pho2 mutants, Pi does not repress a set of Pi starvation-induced genes, including AtIPS1, AT4, and Pi transporters Pht1;8 and Pht1;9. Map-based cloning identified PHO2 as At2g33770, an unusual E2 conjugase gene. It was recently shown that Pi deprivation induces mature microRNA (miRNA [miR399]) and that overexpression of miR399 in Pi-replete conditions represses E2 conjugase expression and leads to high leaf Pi concentrations, thus phenocopying pho2. We show here that miR399 primary transcripts are also strongly induced by low Pi and rapidly repressed after addition of Pi. PHO2 transcripts change reciprocally to miR399 transcripts in Pi-deprived plants and in miR399 overexpressers. However, responses after Pi readdition and in β-glucuronidase reporter lines suggest that PHO2 expression is also regulated by Pi in a manner unrelated to miR399-mediated transcript cleavage. Expression of miR399 was strongly reduced in Pi-deprived Arabidopsis phr1 mutants, and a subset of Pi-responsive genes repressed in Pi-deprived phr1 mutants was up-regulated in Pi-replete pho2 mutants. This places miR399 and PHO2 in a branch of the Pi-signaling network downstream of PHR1. Finally, putative PHO2 orthologs containing five miR399-binding sites in their 5′-untranslated regions were identified in other higher plants, and Pi-dependent miR399 expression was demonstrated in rice (Oryza sativa), suggesting a conserved regulatory mechanism.
Osteogenesis in rats induced by a novel recombinant helper‐dependent bone morphogenetic protein‐9 (BMP‐9) adenovirus

Although recombinant first‐generation BMP adenoviruses can induce ectopic bone formation in immune deficient animals, the osteoinductive activity of these BMP vectors is reduced in immune competent animals. Helper‐dependent adenoviral vectors have been developed to decrease the immune response and, therefore, increase gene expression in immune competent animals compared with first‐generation vectors. In the present study, the osteoinductive activity of a helper‐dependent GFP and BMP‐9 adenoviral vector (ADGBMP9) was evaluated in vitro and in vivo.
The focal adhesion targeting domain of p130Cas confers a mechanosensing function

ABSTRACT Members of the Cas family of focal adhesion proteins contain a highly conserved C-terminal focal adhesion targeting (FAT) domain. To determine the role of the FAT domain in these proteins, we compared wild-type exogenous NEDD9 with a hybrid construct in which the NEDD9 FAT domain had been exchanged for the p130Cas (also known as BCAR1) FAT domain. Fluorescence recovery after photobleaching (FRAP) revealed significantly slowed exchange of the fusion protein at focal adhesions and significantly slower two-dimensional migration. No differences were detected in cell stiffness as measured using atomic force microscopy (AFM) and in cell adhesion forces measured with a magnetic tweezer device. Thus, the slowed migration was not due to changes in cell stiffness or adhesion strength. Analysis of cell migration on surfaces of increasing rigidity revealed a striking reduction of cell motility in cells expressing the p130Cas FAT domain. The p130Cas FAT domain induced rigidity-dependent phosphorylation of tyrosine residues within NEDD9. This in turn reduced post-translational cleavage of NEDD9, which we show inhibits NEDD9-induced migration. Collectively, our data therefore suggest that the p130Cas FAT domain uniquely confers a mechanosensing function. Highlighted Article: This study shows that force transduction is mediated by the focal adhesion targeting domain of p130Cas.
Peak torque, reaction time, and rate of torque development of hip abductors and adductors of older women

ABSTRACT Impaired muscle function at the hip has been implicated to be a major factor related to falls in older adults. Therefore, the aim of this study was to analyze the rate of torque development (RTD), reaction time (RT), and peak torque (PT) of hip abductors and hip adductors in young women (YW), older women nonfallers (ONF), and older women fallers (OF). Eighteen YW and 44 older women divided among OF (n = 20) and ONF (n = 24) performed maximum isometric hip abductor and adduction contractions on a dynamometer. YW had 40% greater PT and 61.5% greater RTD for hip abductors than the ONF. Compared with OF, YW had 47.5% greater PT and 68% greater RTD. OF showed less RTD at 150 ms (31%) and 200 ms (34.5%) than ONF for hip abductors. PT of hip adductors was 52% greater in YW than in the two older groups, whereas RTD was 71% greater. OF showed less RTD than ONF for hip abductors according to standardized effect sizes. No RT differences were observed between the three groups. We conclude that older women (OF and ONF) have less strength and ability to develop force rapidly than YW for hip abductors and adductors. Low hip strength and slowed force development in ONF during hip abduction may increase fall risk in older women.
Psychological Distress After Major Burn Injury

Objective: To track the prevalence and stability of clinically significant psychological distress and to identify potentially modifiable inhospital symptoms predictive of long-term distress (physical, psychological, and social impairment). Method: We obtained data from the Burn Model Systems project, a prospective, multisite, cohort study of major burn injury survivors. The Brief Symptom Inventory (BSI) was used to assess symptoms in-hospital (n = 1232) and at 6 (n = 790), 12 (n = 645), and 24 (n = 433) months post burn. Distress was examined dimensionally (BSI’s Global Severity Index (GSI)) and categorically (groups formed by dichotomizing GSI: T score ≥63). Attrition was unrelated to in-hospital GSI score. Results: Significant in-hospital psychological distress occurred in 34% of the patients, and clinically significant and reliable change in symptom severity by follow-up visits occurred infrequently. Principal components analysis of in-hospital distress symptoms demonstrated “alienation” and “anxiety” factors that robustly predicted distress at 6, 12, and 24 months, controlling for correlates of baseline distress. Conclusions: This is the largest prospective, multisite, cohort study of patients with major burn injury. We found that clinically significant in-hospital psychological distress was common and tends to persist. Two structural components of in-hospital distress seemed particularly predictive of long-term distress. Research is needed to determine if early recognition and treatment of patients with in-hospital psychological distress can improve long-term outcomes. TBSA = total body surface area; BMS = burn model systems; PTSD = posttraumatic stress disorder; ASD = acute stress disorder; BSI = Brief Symptom Inventory; ROM = range of motion; GSI = Global Severity Index (of the BSI); OR = odds ratio; RCI = Reliable Change Index; SD = standard deviation; CI = confidence interval.
Molecular-based isothermal tests for field diagnosis of malaria and their potential contribution to malaria elimination

In countries where malaria transmission has decreased substantially, thanks to the scale-up of control interventions, malaria elimination may be feasible. Nevertheless, this goal requires new strategies such as the active detection and treatment of infected individuals. As the detection threshold for the currently used diagnostic methods is 100 parasites/μL, most low-density, asymptomatic infections able to maintain transmission cannot be detected. Identifying them by molecular methods such as PCR is a possible option but the field deployment of these tests is problematic. Isothermal amplification of nucleic acids (at a constant temperature) offers the opportunity of addressing some of the challenges related to the field deployment of molecular diagnostic methods. One of the novel isothermal amplification methods for which a substantial amount of work has been done is the loop-mediated isothermal amplification (LAMP) assay. The present review describes LAMP and several other isothermal nucleic acid amplification methods, such as thermophilic helicase-dependent amplification, strand displacement amplification, recombinase polymerase amplification and nucleic acid sequence-based amplification, and explores their potential use as high-throughput, field-based molecular tests for malaria diagnosis.
Plant Water Stress Affects Interactions Between an Invasive and a Naturalized Aphid Species on Cereal Crops

Abstract In cereal cropping systems of the Pacific Northwestern United States (PNW), climate change is projected to increase the frequency of drought during summer months, which could increase water stress for crop plants. Yet, it remains uncertain how interactions between herbivore species are affected by drought stress. Here, interactions between two cereal aphids present in PNW cereal systems, Metopolophium festucae (Theobald) subsp. cerealium (a newly invasive species) and Rhopalosiphum padi L. (a naturalized species), were tested relative to wheat water stress. When aphids were confined in leaf cages on wheat, asymmetrical facilitation occurred; per capita fecundity of R. padi was increased by 46% when M. festucae cerealium was also present, compared to when only R. padi was present. Imposed water stress did not influence this interaction. When aphids were confined on whole wheat plants, asymmetrical competition occurred; cocolonization inhibited M. festucae cerealium population growth but did not affect R. padi population growth. Under conditions of plant water stress, however, the inhibitory effect of R. padi on M. festucae cerealium was not observed. We conclude that beneficial effects of cocolonization on R. padi are due to a localized plant response to M. festucae cerealium feeding, and that cocolonization of plants is likely to suppress M. festucae cerealium populations under ample water conditions, but not when plants are water stressed. This suggests that plant responses to water stress alter the outcome of competition between herbivore species, with implications for the structure of pest communities on wheat during periods of drought.
Location of antigenic determinants on primary sequences of subunits of nicotinic acetylcholine receptor by peptide mapping.

The binding domains of 28 monoclonal antibodies (mAbs) against the alpha, beta, and delta subunits of the Torpedo acetylcholine receptor were mapped on the primary sequences of these subunits. Small peptide fragments (2000-20,000 daltons) of the purified subunits were obtained by digestion with staphylococcal V8 protease and papain, separated on a discontinuous polyacrylamide gel electrophoretic system, and electroblotted onto diaminophenyl thioether paper. The blots were probed with the various monoclonal antibodies and also with antibodies against carboxy-terminal decapeptides of the alpha, beta, and delta subunits to identify the carboxy-terminal fragments. From inspection of the binding patterns of the various antibodies to the subunits fragments and the molecular weights of these fragments, and by using the carboxy termini of the subunits as reference points, it was possible to deduce the regions on the primary sequence of each subunit in which the antibodies bound and in some cases to order the binding sites within these sequences. mAb 148, which inhibits receptor function by cross-linking receptor molecules on the cytoplasmic side, was mapped to the sequence beta 368-406. The main immunogenic region of the native receptor, which is of pathological importance in the autoimmune disease myasthenia gravis, was mapped by using mAb 210 to within 80 amino acid residues (alpha 46-127). The overall antigenic structure of alpha subunits was examined. Synthetic peptides have been used to locate determinants responsible for 83% of the antibodies in antisera to denatured alpha subunits and 46% of the antibodies to denatured alpha subunits in antisera to intact receptor. Theoretical models of the transmembrane orientation of the subunit polypeptide chains were tested by determining whether mapped monoclonal antibodies bound to the extracellular or intracellular surface of receptor-rich membranes. Our results confirm previous reports that the carboxy termini of the subunits are exposed on the intracellular surface, as is part of the region between a putative channel-forming domain (M5) and a putative membrane-spanning region (M3). However, contrary to current theoretical models, the region between M5 and the putative membrane-spanning sequence M4 also appears to be on the intracellular surface, implying that M4 and M5 are not membrane-spanning domains. (ABSTRACT TRUNCATED AT 400 WORDS)
The in vivo role of p38 MAP kinases in cardiac remodeling and restrictive cardiomyopathy

Stress-induced mitogen-activated protein kinase (MAP) p38 is activated in various forms of heart failure, yet its effects on the intact heart remain to be established. Targeted activation of p38 MAP kinase in ventricular myocytes was achieved in vivo by using a gene-switch transgenic strategy with activated mutants of upstream kinases MKK3bE and MKK6bE. Transgene expression resulted in significant induction of p38 kinase activity and premature death at 7–9 weeks. Both groups of transgenic hearts exhibited marked interstitial fibrosis and expression of fetal marker genes characteristic of cardiac failure, but no significant hypertrophy at the organ level. Echocardiographic and pressure-volume analyses revealed a similar extent of systolic contractile depression and restrictive diastolic abnormalities related to markedly increased passive chamber stiffness. However, MKK3bE-expressing hearts had increased end-systolic chamber volumes and a thinned ventricular wall, associated with heterogeneous myocyte atrophy, whereas MKK6bE hearts had reduced end-diastolic ventricular cavity size, a modest increase in myocyte size, and no significant myocyte atrophy. These data provide in vivo evidence for a negative inotropic and restrictive diastolic effect from p38 MAP kinase activation in ventricular myocytes and reveal specific roles of p38 pathway in the development of ventricular end-systolic remodeling.
Pattern‐mapped multiple detection of 11 pathogenic bacteria using a 16s rDNA‐based oligonucleotide microarray

Pathogen detection is an important issue in human health due to the threats posed by severe communicable diseases. In the present study, to achieve efficient and accurate multiple detection of 11 selected pathogenic bacteria, we constructed a 16S rDNA oligonucleotide microarray containing doubly specific capture probes. Many target pathogens were specifically detected by the microarray with the aid of traditional perfect match‐based analysis using our previously proposed two‐dimensional visualization plot tool. However, some target species or subtypes were difficult to discriminate by perfect match analysis due to nonspecific binding of conserved 16S rDNA‐derived capture probes with high sequence similarity. We noticed that the patterns of specific spots for each strain were somewhat different in the two‐dimensional gradation plot. Therefore, to discriminate subtle differences between phylogenetically related pathogens, a pattern‐mapping statistical model was established using an artificial neural network algorithm trained by experimental repeats. The oligonucleotide microarray system harboring doubly specific capture probes combined with the pattern‐mapping analysis tool resulted in successful detection of all target pathogens including even subtypes of two closely related species showing strong nonspecific binding. Collectively, the results indicate that our novel combined system of a 16S rDNA‐based DNA microarray and a pattern‐mapping statistical analysis tool is a simple and effective method for detecting multiple pathogens. Biotechnol. Bioeng. 2010;106: 183–192. © 2010 Wiley Periodicals, Inc.