Miracle-dz/UniFAR-FTUs huggingface dataset:
Cyclosporin A inhibits T cell receptor‐induced interleukin‐2 synthesis of human T lymphocytes by selectively preventing a transmembrane signal transduction pathway leading to sustained activation of a protein kinase C isoenzyme, protein kinase C‐β

Stimulation of human peripheral blood lymphocytes via T cell receptor/CD3 complex resulted in a bimodal activation of protein kinase(s) C (PKC). Within 10 min of stimulation PKC‐α was translocated to, and thus activated in, the plasma membranes of human lymphocytes, followed by a fast dissociation of this isotype from the plasma membrane. This short term activation and translocation PKC‐α proved to be cyclosporin A (CsA) insensitive. After 90 min of stimulation PKC‐β was translocated to and remained bound to the plasma membranes for up to 4 h. Preincubation of human lymphocytes with 200 ng/ml CsA specifically and completely abolished the sustained activation of PKC‐β. Neither the phorbol ester‐induced direct activation of PKC nor the specific activity of the plasma membrane‐bound enzyme was influenced by CsA, suggesting that a signal transduction pathway leading to sustained activation of PKC‐β was influenced by the immunosuppressive agent. In fact, CsA inhibited, in a concentration‐dependent manner, the activation of lysophosphatid acyltransferase‐catalyzed elevated incorporation of cis‐polyunsaturated fatty acids into plasma membrane phospholipids. While interleukin‐2 (IL‐2) synthesis and cellular proliferation were completely inhibited by 200 ng/ml CsA in BMA 030‐ or BMA 031‐stimulated cells, expression of high‐affinity IL‐2 receptors was not influenced by the immunosuppressive drug. These results suggest that synthesis and expression of high‐affinity IL‐2 receptors might be regulated by a signal‐transducing pathway involving activation and translocation of PKC‐α. Lysophosphatid acyltransferase‐catalyzed incorporation of cis‐polyunsaturated fatty acids might represent another mechanism of signal transduction implicated in the activation and translocation of PKC‐β, which is specifically inhibited by CsA. Neutralization of PKC‐β by introducing anti‐PKC‐β antibodies prevented IL‐2 synthesis and proliferation in stimulated human lymphocytes. The results suggest a possible link between activation of PKC‐β and regulation of IL‐2 synthesis in activated human lymphocytes. Thus, inhibition of the activation and translocation of PKC‐β by CsA may result in inhibition of IL‐2 gene expression in human lymphocytes.
Phytate: impact on environment and human nutrition. A challenge for molecular breeding

Phytic acid (PA) is the primary storage compound of phosphorus in seeds accounting for up to 80% of the total seed phosphorus and contributing as much as 1.5% to the seed dry weight. The negatively charged phosphate in PA strongly binds to metallic cations of Ca, Fe, K, Mg, Mn and Zn making them insoluble and thus unavailable as nutritional factors. Phytate mainly accumulates in protein storage vacuoles as globoids, predominantly located in the aleurone layer (wheat, barley and rice) or in the embryo (maize). During germination, phytate is hydrolysed by endogenous phytase(s) and other phosphatases to release phosphate, inositol and micronutrients to support the emerging seedling. PA and its derivatives are also implicated in RNA export, DNA repair, signalling, endocytosis and cell vesicular trafficking. Our recent studies on purification of phytate globoids, their mineral composition and dephytinization by wheat phytase will be discussed. Biochemical data for purified and characterized phytases isolated from more than 23 plant species are presented, the dephosphorylation pathways of phytic acid by different classes of phytases are compared, and the application of phytase in food and feed is discussed.
Parallel pathways from whisker and visual sensory cortices to distinct frontal regions of mouse neocortex

Abstract. The spatial organization of mouse frontal cortex is poorly understood. Here, we used voltage-sensitive dye to image electrical activity in the dorsal cortex of awake head-restrained mice. Whisker-deflection evoked the earliest sensory response in a localized region of primary somatosensory cortex and visual stimulation evoked the earliest responses in a localized region of primary visual cortex. Over the next milliseconds, the initial sensory response spread within the respective primary sensory cortex and into the surrounding higher order sensory cortices. In addition, secondary hotspots in the frontal cortex were evoked by whisker and visual stimulation, with the frontal hotspot for whisker deflection being more anterior and lateral compared to the frontal hotspot evoked by visual stimulation. Investigating axonal projections, we found that the somatosensory whisker cortex and the visual cortex directly innervated frontal cortex, with visual cortex axons innervating a region medial and posterior to the innervation from somatosensory cortex, consistent with the location of sensory responses in frontal cortex. In turn, the axonal outputs of these two frontal cortical areas innervate distinct regions of striatum, superior colliculus, and brainstem. Sensory input, therefore, appears to map onto modality-specific regions of frontal cortex, perhaps participating in distinct sensorimotor transformations, and directing distinct motor outputs.
Development of EEG-based stress index

This paper presents a non-parametric method to produce stress index using Electroencephalogram (EEG) signals. 180 EEG datasets from healthy subjects were evaluated at two cognitive states; resting state (Eyes Closed) and working state (Eyes Open). In working cognitive state, subjects were asked to answer the Intelligence Quotient (IQ) test questions. The EEG datasets were categorized into 4 groups. Energy Spectral Density (ESD) ratios and Spectral Centroids (SC) from the two tasks were calculated and selected as input features to k-Nearest Neighbor (k-NN) classifier. Shannon's Entropy (SE) was used to detect and quantify the distribution of ESD due to stressors (stress factors). The stress indexes were assigned based on the results of classification, ESD ratios, SC and SE. There were 3 types of stress indexes can be assigned which represent the stress level (low stress, moderate stress and high stress) at classification accuracy of 88.89%. The regression coefficient of the SC of Beta and Alpha was 77%.
Prefrontal dopamine D4 receptors are involved in encoding fear extinction

The medial prefrontal cortex is known to be crucially involved in the memory for fear extinction. It has been shown that the dopamine D4 receptor is abundantly localized in the medial prefrontal cortex of rodents and that this receptor subtype is involved in the mediation of fear-related behaviour. In the present study, we tested whether dopamine D4 receptors within the medial prefrontal cortex are involved in the learning and encoding of fear extinction. Infusions of the specific dopamine D4 receptor antagonist L-741,741 into the medial prefrontal cortex immediately before fear extinction did not affect fear extinction learning but attenuated the memory on fear extinction on the following day. These results suggest that medial prefrontal cortex dopamine D4 receptors are involved in the consolidation of fear extinction memory.
Localization and early time course of TGF‐β1 mRNA expression in dystrophic muscle

Fibrosis is a common pathological feature observed in muscle from patients with Duchenne muscular dystrophy (DMD). In the dystrophic (mdx) mouse model of DMD, the diaphragm is more severely affected than other skeletal muscles. The level of transforming growth factor‐beta1 (TGF‐β1), an inflammatory cytokine, is significantly elevated in mdx diaphragm. However, little is known about the onset of TGF‐β1 messenger ribonucleic acid (mRNA) expression, or which cells express the mRNA. In this study, we characterized the location and time course of expression of TGF‐β1 mRNA in diaphragm from mdx mice. TGF‐β1 mRNA was significantly elevated in mdx diaphragm at 6 and 9 but not 12 weeks of age, and these changes corresponded with changes in type I collagen mRNA and hydroxyproline concentration. Mononucleated cells localized to areas of fiber necrosis highly expressed the TGF‐β1 transcript in mdx diaphragm. Neutralization of TGF‐β1 by decorin administration resulted in a 40% reduction in the level of diaphragm muscle type I collagen mRNA. These findings support a role for TGF‐β1 during the early stages of fibrogenesis in dystrophic diaphragm muscle. Therapeutic interventions aimed at neutralizing this cytokine may be beneficial in slowing the development of fibrosis in DMD. Muscle Nerve, 2004
On the Capacity-Performance Trade-Off of Online Policy in Delayed Mobile Offloading

WiFi offloading, where mobile users opportunistically obtain data through WiFi rather than cellular networks, is a promising technique for greatly improving spectrum efficiency and reduce cellular network congestion. We consider a system where the service provider deploys multiple WiFi hotspots to offload mobile traffic, and study the scheduling policy to maximize the amount of offloaded data. Since users’ movements are unpredictable, we focus on online scheduling policy, where APs have no knowledge of users’ mobility patterns. We study the performance of online policies by comparing them against the optimal offline policy. We prove that any work-conserving policy is able to offload at least half as much data as the offline policy, and then propose an online policy such that when the requested data by each user is very large, the policy can offload <inline-formula> <tex-math notation="LaTeX">$(e-1)/e$ </tex-math></inline-formula> as much data as the offline policy, where <inline-formula> <tex-math notation="LaTeX">$e$ </tex-math></inline-formula> is Euler’s constant. We further study the case where the service provider can increase the capacity of WiFi so as to provide some guarantees on the amount of offloaded data. We derive a lower-bound on the trade-off between capacity and the amount of offloaded data, and propose a simple online policy that achieves this lower bound. In addition, we show that our policy only needs half as much capacity as current mechanisms to provide the same performance guarantee.
BNIP3 Heterodimerizes with Bcl-2/Bcl-XL and Induces Cell Death Independent of a Bcl-2 Homology 3 (BH3) Domain at Both Mitochondrial and Nonmitochondrial Sites*

BNIP3 (formerly NIP3) is a pro-apoptotic, mitochondrial protein classified in the Bcl-2 family based on limited sequence homology to the Bcl-2 homology 3 (BH3) domain and COOH-terminal transmembrane (TM) domain. BNIP3 expressed in yeast and mammalian cells interacts with survival promoting proteins Bcl-2, Bcl-XL, and CED-9. Typically, the BH3 domain of pro-apoptotic Bcl-2 homologues mediates Bcl-2/Bcl-XLheterodimerization and confers pro-apoptotic activity. Deletion mapping of BNIP3 excluded its BH3-like domain and identified the NH2 terminus (residues 1–49) and TM domain as critical for Bcl-2 heterodimerization, and either region was sufficient for Bcl-XL interaction. Additionally, the removal of the BH3-like domain in BNIP3 did not diminish its killing activity. The TM domain of BNIP3 is critical for homodimerization, pro-apoptotic function, and mitochondrial targeting. Several TM domain mutants were found to disrupt SDS-resistant BNIP3 homodimerization but did not interfere with its killing activity or mitochondrial localization. Substitution of the BNIP3 TM domain with that of cytochromeb 5 directed protein expression to nonmitochondrial sites and still promoted apoptosis and heterodimerization with Bcl-2 and Bcl-XL. We propose that BNIP3 represents a subfamily of Bcl-2-related proteins that functions without a typical BH3 domain to regulate apoptosis from both mitochondrial and nonmitochondrial sites by selective Bcl-2/Bcl-XL interactions.
CD6 Regulates T-Cell Responses through Activation-Dependent Recruitment of the Positive Regulator SLP-76

ABSTRACT Deciphering the role of lymphocyte membrane proteins depends on dissecting the role of a protein in the steady state and on engagement with its ligand. We show that expression of CD6 in T cells limits their responsiveness but that engagement by the physiological ligand CD166 gives costimulation. This costimulatory effect of CD6 is mediated through phosphorylation-dependent binding of a specific tyrosine residue, 662Y, in its cytoplasmic region to the adaptor SLP-76. A direct interaction between SLP-76 and CD6 was shown by binding both to a phosphorylated peptide (equilibrium dissociation constant [KD] = 0.5 μM at 37°C) and, using a novel approach, to native phosphorylated CD6. Evidence that CD6 and SLP-76 interact in cells was obtained in coprecipitation experiments with normal human T cells. Analysis of human CD6 mutants in a murine T-cell hybridoma model showed that both costimulation by CD6 and the interaction between CD6 and SLP-76 were dependent on 662Y. The results have implications for regulation by CD6 and the related T-cell surface protein, CD5.
Molecular identification number for substructure searches

A method for producing molecular identification numbers for hydrogen-depleted organic structures from the eigenvalues of a connectivity matrix is presented. Over 20000 structures have been successfully tested, and the method can also be used produce a unique numbering for the atoms in a structure and to identify which atoms belong to each of the substructures of a disconnected main structure
A virtual reality test battery for assessment and screening of spatial neglect

Fordell H, Bodin K, Bucht G, Malm J. A virtual reality test battery for assessment and screening of spatial neglect. Acta Neurol Scand: 2011: 123: 167–174. © 2010 John Wiley & Sons A/S.
Diastemas in primary dentition and their relationships to sex, age and dental occlusion.

AIM The prevalence of interincisive and primate spaces in the primary dentition, relating them to age and sex, was studied. An analysis was made as to what extent various occlusal aspects of the arches affect the existence of spacing. MATERIALS AND METHODS A population of 267 children, 153 males and 114 females, aged 2.2-8.2 years, was evaluated. All were white Caucasian, apparently healthy and lacking any congenital malformations; they had complete primary dentition and no erupted permanent teeth, without existing dental malformation and not having undergone any type of orthodontic treatment. Cast models were fabricated from impressions taken of all the children. Tooth sizes and interdental spaces were measured on these models and the various occlusal aspects were noted. RESULTS The prevalence of spacing was high in the primary dentition, being independent of the chronological age of each child. Spacing was more frequent in males than in females. The presence or absence of spacing was not directly related to occlusion except in cases of posterior cross-bite, where it was less frequently, and open-bites, in which spaces appeared more often than usual. CONCLUSION Spaces in the primary dentition were very common among the population studied and more frequent in male children than in females. Primate spaces were more frequent at the earliest ages, but chronological age had no influence on the presence of interincisive spacing. The lack of the spaces in the maxillary arches, typical of the primary dentition, prevailed among individuals with posterior cross-bite, contrary to what normally happens in the rest of the population.
Ribosomal DNA and phylogeny of the Ascaridoidea (Nemata: Secernentea): implications for morphological evolution and classification.

Nematodes of the superfamily Ascaridoidea are parasites of the alimentary tract of vertebrates and include species that are of medical and economic importance. Existing evolutionary hypotheses for these organisms have frequently been based on interpretation of one or few "key" structural or life history features. We used nuclear-encoded small (1764 characters) and large subunit (757 characters) ribosomal DNA sequences to estimate the phylogeny of representative taxa from this superfamily. Trees inferred by maximum parsimony and maximum likelihood methods strongly support clades that are primarily consistent with one recent classification of the group. In contrast, most previously proposed phylogenetic hypotheses were significantly worse when compared to the maximum likelihood tree by a statistical method. Hypotheses for the evolution of morphological and life history characters were explored by parsimony mapping these features on several tree topologies, including optimal molecular trees and alternative topologies reflecting traditional expectations deemed not worse in statistical tests. The results identify some consistent putative shared-derived morphological features, but also strongly suggest that some key features emphasized by previous workers represent ancestral states or highly homoplastic characters.
Adenovirus Detection by the cGAS/STING/TBK1 DNA Sensing Cascade

ABSTRACT Adenovirus (Ad) infection triggers a cell-specific antiviral response following exposure of viral DNA to the intracellular compartment. A variety of DNA sensors (DAI, AIM2, DDx41, RNA polymerase [Pol] III, and IFI16 [p204]) have been identified in recent years; however, the DNA sensor involved in detection of adenovirus has not been established. Cyclic GMP-AMP synthase (cGAS), a DNA sensor that produces a cyclic guanine-adenine dinucleotide (cGAMP) inducer of STING, has been examined to determine its role in generating an antiadenoviral response. Short hairpin RNA (shRNA) lentiviral vectors targeting TBK1, STING, and cGAS were established in murine MS1 endothelial and RAW 264.7 macrophage cell lines. Knockdown of TBK1, STING, and cGAS results in a dramatic reduction in the activation of the primary antiviral response marker phosphorylated interferon (IFN) response factor 3 (IRF3) following exposure to adenovirus. Furthermore, activation of secondary type I IFN signaling targets (ptyrSTAT1 and ptyrSTAT2 [ptyrSTAT1/2]) was also compromised. Consistent with compromised activation of primary and secondary response markers, transcriptional activation of IRF3-responsive genes (beta IFN [IFN-β], ISG15, ISG54) and secondary response transcripts were diminished in cells knocked down in cGAS, STING, or TBK1. These data establish cGAS as the dominant cytosolic DNA sensor responsible for detection of internalized adenovirus leading to induction of the type I interferon antiviral cascade.
A biodegradable tri‐component graft for anterior cruciate ligament reconstruction

Bone–patellar tendon–bone (BPTB) autografts are the gold standard for anterior cruciate ligament (ACL) reconstruction because the bony ends allow for superior healing and anchoring through bone‐to‐bone regeneration. However, the disadvantages of BPTB grafts include donor site morbidity and patellar rupture. In order to incorporate bone‐to‐bone healing without the risks associated with harvesting autogenous tissue, a biodegradable and synthetic tri‐component graft was fabricated, consisting of porous poly(1,8‐octanediol‐co‐citric acid)–hydroxyapatite nanocomposites (POC–HA) and poly(l‐lactide) (PLL) braids. All regions of the tri‐component graft were porous and the tensile properties were in the range of the native ACL. When these novel grafts were used to reconstruct the ACL of rabbits, all animals after 6 weeks were weight‐bearing and showed good functionality. Histological assessment confirmed tissue infiltration throughout the entire scaffold and tissue ingrowth and interlocking within the bone tunnels, which is favourable for graft fixation. In conclusion, this pilot study suggests that a tri‐component, biodegradable graft is a promising strategy to regenerate tissue types necessary for ACL tissue engineering, and provides a basis for developing an off‐the‐shelf graft for ACL repair. Copyright © 2014 John Wiley & Sons, Ltd.
Syphilis screening and intervention in 500 000 pregnant women in Shenzhen, the People’s Republic of China

Objectives: To understand the disease epidemiology of syphilis in pregnant women, and to evaluate the effectiveness of the screening and intervention programme, for the purpose of controlling mother-to-child syphilis transmission in Shenzhen, in the People’s Republic of China (PRC). Methods: At the Shenzhen Center for Disease Control and Prevention (SZCDC), we used the toluidine red unheated serum test (TRUST) for the primary screening of pregnant women, and confirmed positive results with the Treponema pallidum particle agglutination (TPPA) test. We informed and treated those with positive results. For the women who chose to proceed with the pregnancy, we clinically screened their babies for congenital syphilis using the 19S-IgM FTA-Abs test. Results: Between 1 July 2002 and 31 December 2005, we screened 477 656 pregnant women for syphilis, of whom 2208 (0.5%) tested positive. From 2003 to 2005, we collected epidemiological and treatment data from 2019 positive syphilis cases. Of these, 1855 (91.9%) of the pregnant women received treatment. Among the 1020 infants born to these women, 92 (9.0%) were confirmed to have congenital syphilis. If we exclude the mothers who had syphilis positive babies without undergoing prenatal screening, the project’s success rate for mother-to-child transmission intervention was 99.1%. Conclusions: After four years of implementation, we proved the programme to be successful in preventing mother-to-child syphilis transmission. Further work should be done to ensure the earlier screening and treatment of pregnant women.
MALAYSIA AND THE CONSOCIATIONAL OPTION: IS THERE A PATH DEPENDENT LOGIC?

This paper attempts to explain Malaysia’s consociational character. By giving centrality to the historical process and concept of path dependence, the paper explains that Malaysia’s political and economic development necessitated a particular institutional logic, the consociational logic. The paper will describe how, in the post war period, Malaya’s two autonomous communities made various attempts to negotiate the existence of mutuallyexclusive institutions and to find the right institutional permutation that could best distribute political and economic resources. In fact, three institutional arrangements were tried: consociationalism; integration; and partition. Out of the three institutional options, the consociational arrangement stood out as a more durable one.
Artificial hair cell sensors using liquid metal alloy as piezoresistors

In this paper, we present the design, fabrication process, and testing results of an artificial hair cell sensor made by liquid metal encapsulated in a polydimethylsiloxane (PDMS) substrate. Previously, a flexible force sensor was reported from our group, which can detect both normal and shear forces by using liquid metal alloy (Ga-In-Sn) as piezoresistive gauge material encapsulated in a PDMS substrate. Based on this method, we propose an artificial hair cell sensor which can detect two-axis tactile force with a standing artificial hair shaft. Since the liquid-metal piezoresistors deform with the elastomeric substrate, normal and shear force can be detected with resistance changes of the piezoresistors. Each force sensor comprises a pair of symmetric piezoresistors, which is screen-printed on a suspended PDMS membrane with opposite direction to be sensitive to shear forces. The testing results demonstrate the sensitivity of the force sensor in two-axis directions.