Miracle-dz/UniFAR-FTUs huggingface dataset:
Adeno‐associated virus‐mediated gene transfer of human aromatic l‐amino acid decarboxylase protects mixed striatal primary cultures from l‐DOPA toxicity

Although l‐DOPA is the drug of choice for Parkinson's disease, prolonged l‐DOPA therapy results in decreased drug effectiveness and the appearance of motor complications. This may be due in part to the progressive loss of the enzyme, aromatic l‐amino acid decarboxylase (AADC). We have developed an adeno‐associated virus vector (AAV–hAADC) that contains human AADC cDNA under the control of the cytomegalovirus promoter. Infusion of this vector into the striatum of parkinsonian rats and monkeys improves l‐DOPA responsiveness by improving AADC‐mediated conversion of l‐DOPA to dopamine. This is now the basis of a proposed therapy for advanced Parkinson's disease. A key concern has been that over‐production of dopamine in striatal neurons could cause dopamine toxicity. To investigate this possibility in a controlled system, mixed striatal primary rat neuronal cultures were prepared. Exposure of cultures to high concentrations of l‐DOPA induced the following changes: cell death in nigral and striatal neurons, aggregation of neurofilaments and focal axonal swellings, abnormal expression of DARPP‐32, and activation of astroglia and microglial cells. Transduction of cultures with AAV–hAADC resulted in efficient and sustained neuronal expression of the AADC protein and prevented all the l‐DOPA‐induced toxicities. The protective effects were due primarily to AADC‐dependent conversion of l‐DOPA to dopamine and an increase in induction of vesicular monoamine transporter resulting in dopamine storage in cultured cells. These results suggest a neuroprotective role for AADC gene transfer against l‐DOPA toxicity.
Speech assessment of Chinese–English bilingual children: Accent versus developmental level

Abstract The study aimed to evaluate the phonological profiles of Chinese–English bilingual children in primary grades relative to those of English monolinguals, and to compare these profiles with speech-language pathologists’ (SLPs’) ratings of children's speech in terms of accent or developmental level. Participants were 29 Chinese–English bilinguals and 25 English-monolingual children. Speech samples were collected using the Goldman-Fristoe Test of Articulation–2, either a Cantonese or Mandarin phonology test, and three sentences in a delayed repetition task. In addition, 10 SLPs rated each of the randomized sentences on either an accent or developmental level scale. Bilingual children with identified accents had significantly lower standard scores than monolingual children on the GFTA-2, but on the Chinese phonological assessments the same children showed age-expected speech. The differences in the bilingual children's scores on phonology tests in English vs Chinese highlight the need for phonological assessment in both languages. The SLP listener results further suggest that perceptual judgement may be a useful complement in phonological assessment of bilingual children but not a replacement for more formal testing.
Relative importance of pollen and seed dispersal across a Neotropical mountain landscape for an epiphytic orchid

Populations of many species are isolated within narrow elevation bands of Neotropical mountain habitat, and how well dispersal maintains genetic connectivity is unknown. We asked whether genetic structure of an epiphytic orchid, Epidendrum firmum, corresponds to gaps between Costa Rican mountain ranges, and how these gaps influence pollen and seed flow. We predicted that significant genetic structure exists among mountain ranges due to different colonization histories and limited gene flow. Furthermore, we predicted that pollen movement contributes more to gene flow than seeds because seeds are released into strong winds perpendicular to the narrow northwest–southeast species distribution, while the likely pollinators are strong fliers. Individuals from 12 populations and three mountain ranges were genotyped with nuclear microsatellites (nDNA) and chloroplast sequences (cpDNA). Genetic diversity was high for both markers, while nDNA genetic structure was low (FSTn = 0.020) and cpDNA structure was moderate (FSTc = 0.443). Significant cpDNA barriers occurred within and among mountain ranges, but nDNA barriers were not significant after accounting for geographic distance. Consistent with these contrasting patterns of genetic structure, pollen contributes substantially more to gene flow among populations than seed (mp/ms = 46). Pollinators mediated extensive gene flow, eroding nDNA colonization footprints, while seed flow was comparatively limited, possibly due to directional prevailing winds across linearly distributed populations. Dispersal traits alone may not accurately inform predictions about gene flow or genetic structure, supporting the need for research into the potentially crucial role of pollinators and landscape context in gene flow among isolated populations.
Effects of therapy with recombinant human growth hormone on insulin-like growth factor system components and serum levels of biochemical markers of bone formation in children after severe burn injury.

Burn injury in children is associated with low bone formation and long-term bone loss. Because recombinant human GH (rHGH) may accelerate burn wound healing, and because rHGH increases bone formation and density in GH-deficient patients, we studied the short-term effects of rHGH on bone fomation, reflected by osteocalcin and type I procollagen propeptide levels in a randomized, double-blind, placebo-controlled study. Nineteen patients were enrolled and received either rHGH (0.2 mg/kg.day) or an equal volume of saline. Mean burn size and age were not different between the groups, and test substances were given from admission to time of wound healing (mean: 43 +/- 22 days). At wound healing, serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 in the rHGH group rose to mean values of 229% and 187% of the respective means of the placebo group (P < 0.025). Serum osteocalcin concentrations remained below normal in both groups, and type I procollagen propeptide levels achieved a low normal level IGFBR-4 levels were twice that of normal on admission and doubled further at wound healing; IGFBP-5 levels were low on admission but rose to normal at wound healing. We conclude that large doses of rHGH were ineffective in improving disordered bone formation despite increasing serum IGF-1 and IGFBP-3. The rHGH-independent rise in serum levels of the inhibitory binding protein IGFBP-4 suggests a mechanism by which improved bone formation is prevented despite successful elevation of IGF-1 and IGFBP-3 in the burned child.
A 4′‐Phosphopantetheinyl Transferase Mediates Non‐Ribosomal Peptide Synthetase Activation in Aspergillus fumigatus

Aspergillus fumigatus is a significant human pathogen. Non‐ribosomal peptide (NRP) synthesis is thought to be responsible for a significant proportion of toxin and siderophore production in the organism. Furthermore, it has been shown that 4′‐phosphopantetheinylation is required for the activation of key enzymes involved in non‐ribosomal peptide synthesis in other species. Here we report the cloning, recombinant expression and functional characterisation of a 4′‐phosphopantetheinyl transferase from A. fumigatus and the identification of an atypical NRP synthetase (Afpes1), spanning 14.3 kb. Phylogenetic analysis has shown that the NRP synthetase exhibits greatest identity to NRP synthetases from Metarhizium anisolpiae (PesA) and Alternaria brassicae (AbrePsy1). Northern hybridisation and RT‐PCR analysis have confirmed that both genes are expressed in A. fumigatus. A 120 kDa fragment of the A. fumigatus NRP synthetase, containing a putative thiolation domain, was cloned and expressed in the baculovirus expression system. Detection of a 4′‐phosphopantetheinylated peptide (SFSAMK) from this protein, by MALDI‐TOF mass spectrometric analysis after coincubation of the 4′‐phosphopantetheinyl transferase with the recombinant NRP synthetase fragment and acetyl CoA, confirms that it is competent to play a role in NRP synthetase activation in A. fumigatus. The 4′‐phosphopantetheinyl transferase also activates, by 4′‐phosphopantetheinylation, recombinant α‐aminoadipate reductase (Lys2p) from Candida albicans, a key enzyme involved in lysine biosynthesis.
SARM inhibits both TRIF‐ and MyD88‐mediated AP‐1 activation

SARM (sterile α‐ and armadillo‐motif‐containing protein), the fifth identified TIR (Toll–interleukin 1 receptor (IL‐1R)) domain‐containing adaptors in humans, downregulates NF‐κB and IRF3 (interferon‐regulatory factor 3)‐mediated TLR3 and TLR4 signaling. SARM was characterized as a negative regulator of the TRIF (TIR‐domain‐containing adaptor protein inducing IFN‐β)‐dependent pathway via its interaction with TRIF. However, the precise mechanism of action of SARM remains unclear. Here, we demonstrate that SARM inhibits MAPK activation in human embryonic kidney 293 cells, and U937 cells. Both the TRIF‐ and MyD88‐mediated, as well as basal MAPK activity, were repressed, indicating that SARM‐mediated inhibition may not be exclusively directed at TRIF or MyD88, but that SARM may also directly inhibit MAPK phosphorylation. The MAPK inhibition effect was verified by RNAi, which increased the basal level of AP‐1. Furthermore, LPS challenge upregulated SARM at both the mRNA and protein levels. Finally, we provide evidence to show that truncated SARM changes its subcellular localization, suggesting the importance of the N‐terminal and sterile alpha motif domains in the autoregulation of SARM activity.
The design of the community tracking study: a longitudinal study of health system change and its effects on people.

Editor's Note: "The Design of the Community Tracking Study: A Longitudinal Study of Health System Change and Its Effects on People" is the first in what I hope will be a series of occasional articles describing large-scale data collection efforts and plans for analyzing such data. The series will be known as "Data Reports " New surveys or changes in existing, ongoing surveys ought to be known widely if the research to be done with the collected data can have a meaningful impact on policy making. I hope articles about various surveys' sample designs and topics to be covered in the questionnaires will shorten the time between public release and analyses of the data. Because of the costs of large-scale data collection, most of the projects likely to be described in this series will be government-funded efforts. It is, perhaps, all the more interesting then that the subject of the first <(Data Reports," the Community Tracking Study, is funded by the Robert Wood Johnson Foundation. K. Swartz
HMGB factors are required for posterior digit development through integrating signaling pathway activities

The chromatin factors Hmgb1 and Hmgb2 have critical roles in cellular processes, including transcription and DNA modification. To identify the function of Hmgb genes in embryonic development, we generated double mutants of Hmgb1;Hmgb2 in mice. While double null embryos arrest at E9.5, Hmgb1−/−; Hmgb2+/− embryos exhibit a loss of digit5, the most posterior digit, in the forelimb. We show that Hmgb1−/−; Hmgb2+/− forelimbs have a reduced level of Shh signaling, as well as a clear downregulation of Wnt and BMP target genes in the posterior region. Moreover, we demonstrate that hmgb1 and hmgb2 in zebrafish embryos enhance Wnt signaling in a variety of tissues, and that double knockdown embryos have reduced Wnt signaling and shh expression in pectoral fin buds. Our data show that Hmgb1 and Hmgb2 function redundantly to enhance Wnt signaling in embryos, and further suggest that integrating Wnt, Shh, and BMP signaling regulates the development of digit5 in forelimbs. Developmental Dynamics 240:1151–1162, 2011. © 2011 Wiley‐Liss, Inc.
Hypnotizability and traumatic experience: a diathesis-stress model of dissociative symptomatology.

OBJECTIVE The authors propose a diathesis-stress model to describe how pathological dissociation may arise from an interaction between innate hypnotizability and traumatic experience. METHOD To support the proposition that pathological dissociation may reflect autohypnotic process, the authors highlight clinical and research data indicating parallels between controlled hypnotic dissociative states and uncontrolled pathological dissociative symptoms and summarize evidence of hypnotizability in persons with psychiatric disorders that manifest these symptoms. The authors present this evidence by examining dissociative symptomatology in four psychological domains: perception, behavior and will, affect, and memory and identity. In addition, modern cognitive and neuropsychological models of dissociation are briefly reviewed. RESULTS Several lines of evidence converge in support of the role of autohypnosis in pathological dissociation. There is considerable evidence that controlled formal hypnosis can produce a variety of dissociations of awareness and control that resemble many of the symptoms in uncontrolled pathological dissociative conditions; and it is possible to discern in dissociative pathology the features of absorption, dissociation, and suggestibility/automaticity that characterize formal hypnotic states. There is also accumulating evidence of high levels of hypnotic capacity in all groups with dissociative symptomatology that have been systematically assessed. In addition, the widespread and successful therapeutic use of hypnosis in the treatment of many dissociative symptoms and conditions (and the potential for hypnosis to induce dissociative symptomatology) also supports the assumption that hypnosis and pathological dissociation share an underlying process. CONCLUSIONS High hypnotizability may be a diathesis for pathological dissociative states, particularly under conditions of acute traumatic stress.
Influence of demographics on clinical outcome of dengue: a cross-sectional study of 6703 confirmed cases in Vitória, Espírito Santo State, Brazil

SUMMARY Dengue presents a wide clinical spectrum of signs and symptoms, with characteristics of the host potentially influencing the disease evolution. Therefore, the purpose of this study was to evaluate the influence of gender and age on dengue clinical outcomes in a recent outbreak situation in Brazil, applying a cross-sectional design and including 6703 dengue cases with laboratory confirmation, occurring in Vitória, Espírito Santo State, Brazil, between 2007 and 2013. Data were obtained from the Information System for Notifiable Diseases. Overall, 11·3% of the sample presented with severe dengue, which affected 13·0% of males, 10·0% of females, 8·8% of children, 12·5% of adolescents, 10·5% of adults and 15·5% of the elderly. Age was higher in the severe dengue group (P = 0·03). Severe dengue was associated with males and the elderly (P < 0·01); however, considering only severe cases, children presented haemorrhage and plasma leakage more frequently than older age groups. The results emphasize the importance of a differentiated protocol for management of dengue cases, taking into consideration host factors like age. These findings also suggest the elderly and children as priority groups for immunization in a future implementation of a vaccine.
Ergonomic design and evaluation of a diagnostic ultrasound transducer holder

Background. Work-related musculoskeletal disorders (WMSDs) are injuries and disorders that affect the body’s movement and musculoskeletal system. Awkward postures represent one of the major ergonomic risk factors that cause WMSDs among sonographers while working with an ultrasound transducer. This study aimed to design and evaluate a new holder for the ultrasound transducer. Materials and methods. In the first phase a new holder was designed for the transducer, considering design principles. Evaluation of the new holder was then carried out by electrogoniometry and a locally perceived discomfort (LPD) scale. Results. The application of design principles to the new holder resulted in an improvement of wrist posture and comfort. Wrist angles in extension, flexion, radial deviation and ulnar deviation were lower with utilization of the new holder. The severity of discomfort based on the LPD method in the two modes of work with and without the new holder was reported with values of 1.3 and 1.8, respectively (p < 0.05). Conclusion. Overall, this study indicated that applying ergonomics design principles was effective in minimizing wrist deviation and increasing comfort while working with the new holder.
Studies on desi and kabuli chickpea (Cicer arietinum l.) cultivars. 3. Mineral and trace element composition.

Eight desi and 7 kabuli type chickpea cultivars grown at the ICRISAT Center (17’ N) and at Hissar (29’ N) were analyzed for phosphorus, potassium, calcium, magnesium, zinc, copper, iron, and manganese. Whole seed, dhal (decorticated split cotyledons), and seed coat were analyzed. Except for calcium, zinc, and manganese, the mean values of other mineral elements of desi and kabuli whole seed and dhal samples from both the locations showed no significant differences. Seed coats of kabuli cultivars contained significantly more calcium, zinc, copper, iron, and manganese when grown at both locations and significantly more potassium and phosphorus only when grown at Hissar.
Gender Differences in Age at Onset of Schizophrenia

Numerous studies have found that male schizophrenic patients have earlier ages at onset than females. However, none of these studies have corrected the observed ages for known gender differences in the age distribution of the population. Using a pre-existing data set, we applied a non-parametric method to correct the male and female distributions of observed age at onset for sex-specific age distributions. The distributions of observed age at onset indicated earlier onset among males. After correction, the age-at-onset distributions shifted toward older ages, but the difference between males and females remained statistically significant. Thus, gender differences in the age at onset of schizophrenia are not artefactual.
RNAi-mediated gene silencing in Rhynchophorus ferrugineus (Oliver) (Coleoptera: Curculionidae)

Abstract RNA interference (RNAi) is a powerful strategy for gene function analysis, and it is also widely studied in view of a promising use in pest control. The red palm weevil, Rhynchophorus ferrugineus (Oliver) (Coleoptera: Curculionidae), is one of the most devastating pests of palm in the world. Conventional pest management practices are not adequate to control this insect, thus the development of efficient approaches with minimal environmental impact are needed. In this work, the potential of RNAi in R. ferrugineus has been investigated through the silencing of three different genes (α-amylase, V-ATPase, Ecdysone receptor). For each gene we tested two different doses (1,500 and 5,500 ng) and two delivery techniques (injection and ingestion), evaluating both gene knockdown and mortality on insects. Results show that RNAi mediated gene silencing in R. ferrugineus varies from gene to gene, and that the response is dose-dependent, with stronger effects when dsRNA was administered by injection. In parallel, the same study was carried out with the model organism Tribolium castaneum Herbst (Coleoptera: Tenebrionidae), with results showing a different pattern of response, although the two insects belong to the same order.
Predicting participation in the population-based Swedish cardiopulmonary bio-image study (SCAPIS) using register data

Aims: To illustrate the importance of access to register data on determinants and predictors of study participation to assess validity of population-based studies. In the present investigation, we use data on sociodemographic conditions and disease history among individuals invited to the Swedish cardiopulmonary bio-image study (SCAPIS) in order to establish a model that predicts study participation. Methods: The pilot study of SCAPIS was conducted within the city of Gothenburg, Sweden, in 2012, with 2243 invited individuals (50% participation rate). An anonymous data set for the total target population (n = 24,502) was made available by register authorities (Statistics Sweden and the National Board of Health and Welfare) and included indicators of invitation to and participation in SCAPIS along with register data on residential area, sociodemographic variables, and disease history. Propensity scores for participation were estimated using logistic regression. Results: Residential area, country of birth, civil status, education, occupational status, and disposable income were all associated with participation in multivariable models. Adding data on disease history only increased overall classification ability marginally. The associations with disease history were diverse with some disease groups negatively associated with participation whereas some others tended to increase participation. Conclusions: The present investigation stresses the importance of a careful consideration of selection effects in population-based studies. Access to detailed register data also for non-participants can in the statistical analysis be used to control for selection bias and enhance generalizability, thereby making the results more relevant for policy decisions.
Improved PLS Focused on Key-Performance-Indicator-Related Fault Diagnosis

Standard partial least squares (PLS) serves as a powerful tool for key performance indicator (KPI) monitoring in large-scale process industry for last two decades. However, the standard approach and its recent modifications still encounter some problems for fault diagnosis related to KPI of the underlying process. To cope with these difficulties, an improved PLS (IPLS) approach is presented in this paper. IPLS is able to decompose the measurable process variables into the KPI-related and unrelated parts, respectively. Based on it, the corresponding test statistics are designed to offer meaningful fault diagnosis information and thus, the corresponding maintenance actions can be further taken to ensure the desired performance of the systems. In order to demonstrate the effectiveness of the proposed approach, a numerical example and Tennessee Eastman (TE) benchmark process are respectively utilized. It can be seen that the proposed approach shows satisfactory results not only for diagnosing KPI-related faults but also for its high fault detection rate.
Reversible excitation light‐induced enhancement of fluorescence of live mammalian mitochondria

During continuous irradiation with near‐ultraviolet light (λ, = 36510 nm; 16 µW/mm2) for 2–3 min, live mammalian cells increased reversibly the intensity of one or more peaks of their autofluorescence spectrum from an initial (‘ground’) level to a two‐ to threefold higher (‘active’) level. The effect is characterized by the existence of two states of quantum efficiency and a mechanism of transition that expresses a threshold and a refractory period. It appears that mitochondria are the principal sources of the rising autofluorescence intensity; however, not all mitochondria are capable of expressing it. Studying cells from various organisms that belong to various branches of the phylogenetic tree, we found the rapid increase of autofluorescence only in placental mammalian cells. We speculate that the effect may point to the ability of placental mammalian mitochondria to generate pulsating light signals.