Miracle-dz/UniFAR-FTUs huggingface dataset:
Concurrent signaling from Gαq‐ and Gαi‐coupled pathways is essential for agonist‐induced αvβ3 activation on human platelets

Summary. The integrin αvβ3 mediates platelet adhesion to the matrix protein osteopontin and likely is the predominant integrin mediating platelet adhesion to the matrix protein vitronectin. To address the mechanism that regulates αvβ3 activity in platelets, we measured the effect of the P2Y1 antagonist adenosine 3′‐phosphate‐5′‐phosphate (A3P5P) and the P2Y12 antagonist AR‐C66096 on ADP‐stimulated platelet adhesion to osteopontin and vitronectin. Each antagonist completely inhibited platelet adhesion, implying that concurrent stimulation of P2Y1 and P2Y12 was required to activate αvβ3. The reducing agent dithiothreitol and Mn2+ also induced platelet adhesion to osteopontin, but did so without stimulating platelet activation. Thus, these data suggest that ADP stimulation regulates αvβ3 activity by perturbing the conformation of its extracellular domain. The actin polymerization inhibitors cytochalasin D and latrunculin A also induced platelet adhesion to osteopontin and vitronectin. Thus, αvβ3 activity in resting platelets appears to be constrained by the platelet cytoskeleton. Moreover, the effect of these agents was inhibited by A3P5P and AR‐C66096 at micromolar and subnanomolar concentrations, respectively, suggesting that subthreshold platelet stimulation by ADP was required. Our data suggest that signals from both Gαq‐ and Gαi‐coupled receptors converge to release cytoskeletal constraints on αvβ3. We propose that the release of cytoskeletal constraints and a concurrent increase in affinity for ligands is responsible for αvβ3‐mediated platelet adhesion.
Effects of TFGs on cultured interstitial fibroblasts of rats' myocardium

To observe effects of trigonella foenum greacum. L Saponin (TFGs) on the proliferation of the interstitial fibroblast of rats' myocardium (CFs), and the expression of U II-induced TGF-β1 and CTGF mRNA. The interstitial fibroblasts of rats' myocardium were cultivated in vitro and identified,and were treated with TFGs whose concentrations is 0,25,50,100 and 200 mg.L−1 separately. The untreated cells were taken as the control group and U II is used as the stimulating factor. Effects of TFGs on the cell proliferation were examined by MTT assay,and effects of TFGs on mRNA levels of TGF-β1 and CTGF were measured by RT-PCR. Compared with that of the control group, the proliferation of CFs stimulated by U II increased significantly (P&#60;0.05) and it could be inhibitted by TFGs, which showed concentration-dependent and time-dependent; Results measured by RT-PCR showed that U II can increased the expressions of TGF-β1 and CTGF mRNA significantly compared with the control group (P&#60;0.01), and TFGs can attenuated overexpressions of TGF-β1 and CTGF mRNA induced by U II (P&#60;0.01, P&#60;0.05). TFGs can depress CFs proliferation and down-regulate U II-induced TGF-β1 and CTGF mRNA overexpressions, which suggests that it may be one of mechanisms through which TFGs can be used for the prevention and treatment of myocardial interstitial fibrosis.
Traumatic Brain Injury‐Induced Excitotoxicity Assessed in a Controlled Cortical Impact Model

Using a controlled cortical impact model of traumatic brain injury (TBI) coupled with tissue microdialysis, interstitial concentrations of aspartate and glutamate (together with serine and glutamine) were assessed in rat frontal cortex. Histological analysis indicated that the severity of injury following severe TBI (depth of deformation = 3.5 mm) was approximately twice that occurring following moderate TBI (depth of deformation = 1.5 mm). Both groups demonstrated significant postinjury maximal increases in excitatory amino acid (EAA) concentration, which were proportional to the severity of injury. The mean ± SEM fold increase in dialysate concentrations of aspartate was 38 ± 13 (n = 5) for moderate TBI and 74 ± 12 (n = 5) for severe TBI. Fold increases in glutamate concentrations were 81 ± 26 and 144 ± 23 for moderate and severe TBI, respectively. Although these increases normalized within 20–30 min following moderate TBI, concentrations of aspartate and glutamate took >60 min to normalize after severe TBI. Changes in levels of nontransmitter amino acids were much smaller. Fold increases for serine concentrations were 4.6 ± 0.6 and 7.6 ± 1.7 in moderate and severe TBI, respectively; glutamine concentrations had similar small fold increases (2.6 ± 0.2 and 4.1 ± 0.6, respectively). Calculation of interstitial concentrations following severe TBI indicated that aspartate and glutamate maximally increased to 123 ± 20 and 414 ± 66 μM, respectively. To determine the extent to which such tissue concentrations of EAAs could contribute to the injury seen in TBI, the EAA receptor agonists N‐methyl‐d‐ aspartate and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid were slowly injected into rat cortex. Remarkably similar histological injuries were produced by this procedure, supporting the notion that TBI is an excitotoxic injury.
Global stabilization for constrained robot motions with constraint uncertainties

In this paper, the global stability problem for constrained robot motions in the presence of constraint uncertainties is investigated. We focus on the uncertainties in the constraint functions and their effects on the global stability. PD type controllers are used and conditions for global stability are developed using Lyapunov's direct approach. In the presence of the constraint uncertainties under investigation, the desired position and constraint force can be guaranteed with global asymptotic convergence. The developed conditions for feedback gain selections clearly show the effects of the constraint uncertainties. For the case when the velocity measurements are not available, conditions for global stability regulation are also established and the robot controller uses only the measurements of the position angles. Finally, we consider the case where the robot joints are flexible and global stability conditions are given.
The cytoplasmic linker protein CLIP‐170 is a human autoantigen

The purpose of this study was to identify autoantigens that are recognized by human sera and are associated with a speckled cytoplasmic fluorescent staining pattern on tissue culture cells, and to determine clinical features associated with specific autoantibodies. A serum from a patient with systemic lupus erythematosus was used to identify a 3·7‐kb cDNA insert from a HeLa cell expression library. The purified cDNA (VLK2·1) encoded a peptide of 1051 amino acids that shared 98·4% similarity with the carboxyl terminal portion of a previously reported 170 kD protein named cytoplasmic linker protein‐170 (CLIP‐170). Antibodies affinity purified with the recombinant CLIP‐170 protein, the prototype human serum and a monoclonal antibody raised against CLIP‐170 exhibited identical speckled staining of the cytoplasm in HEp‐2 cells. The human autoantibodies reacted with the purified recombinant protein in a Western immunoblot and immunoprecipitated the in vitro translated recombinant protein. Three additional human sera also immunoprecipitated the recombinant CLIP‐170 protein. The clinical diagnoses in these patients were limited scleroderma, glioblastoma and idiopathic pleural effusion. This is the first report that identifies CLIP‐170 as a human autoantigen.
A protocol for in vitro production of microtubers in Chinese yam (Dioscorea opposita)

Chinese yam (Dioscorea opposita) is an important tuberous crop owing to its dual use as a food as well as a medicine. Tissue culture techniques allow the rapid multiplication of virus-free plant materials. The use of microtubers offers an attractive alternative to in vitro-grown plantlets for the micropropagation and exchange of healthy Chinese yam materials. A protocol for the in vitro production of Chinese yam microtubers was developed in this study. Though we tested both one-step and two-step procedures, only the two-step procedure showed favorable results for tuberization. Media with 60 g L−1 sucrose yielded the highest microtuber index. We demonstrate that table sugar was an efficient and economical alternative to analytical grade sucrose for microtuber production. Using an orthogonal experimental design, we determined the optimal growth regulator combination for microtuber induction and development. The microtubers obtained from our protocol sprouted readily both in vitro and in soil. Graphical Abstract In Vitro Production of Microtubers in Chinese yam and Sprouting Test. A Protocol for Efficient Microtuber Production was Developed in This Study.
Aberrant activation of Wnt/β-catenin signaling drives proliferation of bone sarcoma cells

Bone sarcomas such as osteosarcoma and chondrosarcoma are frequently refractory to conventional chemotherapy and radiotherapy that exhibit poor prognosis. The Wnt signaling are evolutionarily conserved and implicated in cell proliferation and sarcomagenesis. However, the potential role of the Wnt signaling in bone sarcomas is still unclear. Here we demonstrate aberrant activation of Wnt/β-catenin signaling in bone sarcoma cells, involving an autocrine Wnt signaling loop with upregulation of specific Wnt ligands and receptors. Activation of Wnt/β-catenin signaling with Wnt3a or GSK-3β inhibitor drives the proliferation of bone sarcoma cells, whereas downregulation of activated Wnt signaling with dnTCF4 or siLEF1 suppresses bone sarcoma proliferation and induces cell cycle arrest. Taken together, our findings establish the evidence that aberrant activation of Wnt/β-catenin pathway involving an autocrine Wnt singaling drives the proliferation of bone sarcoma cells, and identify the autocrine activation of the Wnt/β-catenin signaling as a potential novel therapeutic target for bone sarcomas.
Chlamydia trachomatis infection and non-gonococcal urethritis in homosexual and heterosexual men in Edinburgh

In 1998, when ligase chain reaction testing for chlamydial infection was introduced in our clinic in Edinburgh, routine clinic protocol included the testing of all heterosexual, but not homosexual, men for urethral chlamydial infection. We audited all new homosexual and bisexual male attendees with a diagnosis of chlamydial infection or non-gonococcal urethritis (NGU) in 1999, together with heterosexual men with the same diagnoses attending in alternate months of the same year. Urethral Chlamydia trachomatis infection was detected in 14.6% (350/2402) of heterosexual men and 2.4% (11/465) of homosexual men tested. Fifty percent of chlamydial infections were asymptomatic. In this population 44% (84/190) of NGU in heterosexual men is attributable to C. trachomatis as opposed to only 10% (6/59) of that in homosexual men. These rates of chlamydial infection differ from previous reports in Scotland and recent studies from the USA. Our clinic protocol has been revised to include routine testing for chlamydial infection in all men.
The contrasting influence of chronic nicotine intake on gastrin and gastric acid secretion

The effects of chronic nicotine treatment on gastric acid secretion stimulated by subcutaneous injection of pentagastrin, as well as on serum gastrin levels and the stomach parietal cell population, were examined. Rats drank a solution of nicotine 25 μg/mL tap water for periods of 10, 30 or 45 days. Pentagastrin increased the gastric secretory volume and acid output in pylorus‐ligated control animals that drank tap water. Animals given nicotine in their drinking water for 10, 30 or 45 days showed increased basal gastric secretion and acid output. Pentagastrin produced maximum stimulatory effects at lower dose levels of 50 μg/kg in the 10‐day treatment group and 25 μg/kg in the 30‐ or 45‐day treatment groups; however, the maximum responses to pentagastrin in all nicotine‐treated batches were comparable to those of their corresponding controls. Serum gastrin levels remained unchanged from the 10th day of nicotine treatment, whereas the levels in the control animals continued to rise with age. Nicotine 25 μg/mL drinking water given for 10, 30 or 45 days caused no significant changes in the parietal cell population, mucosal surface area or mucosal thickness. These findings are consistent with the idea that chronic nicotine administration, for at least 10 days, will lead to increased muscarinic receptor sensitivity; basal acid secretion is consequently elevated, and this in turn may depress gastrin secretion.
Weather, habitat composition, and female behavior interact to modify offspring survival in Greater Sage-Grouse.

Weather is a source of environmental variation that can affect population vital rates. However, the influence of weather on individual fitness is spatially heterogeneous and can be driven by other environmental factors, such as habitat composition. Therefore, individuals can experience reduced fitness (e.g., decreased reproductive success) during poor environmental conditions through poor decisions regarding habitat selection. This requires, however, that habitat selection is adaptive and that the organism can correctly interpret the environmental cues to modify habitat use. Greater Sage-Grouse (Centrocercus urophasianus) are an obligate of the sagebrush ecosystems of western North America, relying on sagebrush for food and cover. Greater Sage-Grouse chicks, however, require foods with high nutrient content (i.e., forbs and insects), the abundance of which is both temporally and spatially dynamic and related primarily to water availability. Our goal was to assess whether nest site selection and movements of broods by females reduced the negative effect of drought on offspring survival. As predicted, chick survival was negatively influenced by drought severity. We found that sage-grouse females generally preferred to nest and raise their young in locations where their chicks would experience higher survival. We also found that use of habitats positively associated with chick survival were also positively associated with drought severity, which suggests that females reduced drought impacts on their dependent young by selecting more favorable environments during drought years. Although our findings suggest that female nest site selection and brood movement rates can reduce the negative effects of drought on early offspring survival, the influence of severe drought conditions was not completely mitigated by female behavior, and that drought conditions should be considered a threat to Greater Sage-Grouse population persistence.
UNDERSTANDING THE IMPERATIVES OF ACCULTURATION AND JOB SATISFACTION AMONG FILIPINO NURSES' IN THE SULTANATE OF OMAN

The Philippines is a country that has gained a global reputation for exporting nurses to other countries to fill in shortage. Deliberately or not deliberately done, the Philippine government does not only support this move, but more so, it strengthened Filipino nurses' deployment outside the country as the remittances of Overseas Filipino Workers (OFW) added a boost to the national economy. Relevant to this, their nursing academic system is highly westernized making Filipino Nurses more adept in the provision of undivided nursing care regardless of race, culture and gender. This has made Filipino nurses one of the most sought-after nurses in the global horizon. A common labor destination for Filipinos is the Middle East which includes the Sultanate of Oman. Oman is a Muslim country whose ways of life, tradition and culture is far different from that of the Philippines. It is imperative to understand acculturation and job satisfaction of Filipino nurses working [and who plan to work] in the Sultanate as these factors largely affect their job performance, physical and psychological health. A highly accultured and satisfied nurse is a happy and a productive nurse. Finally, maintaining and grooming them relieves global nursing shortage.
Anomalous Phase Separation Kinetics Observed in a Micelle Solution.

We report a real-time, two-dimensional light scattering study of the evolution of structure in a two-component nonionic micelle system undergoing phase separation. We find that the structure of the domains is qualitatively similar to that observed in binary fluid systems, with some anomalies observed. However, compared to the Lifshitz-Slyozov prediction for simple binary fluids, the domain growth is unexpectedly slow. In fact, the growth kinetics can be empirically described as a stretched exponential approach to a pinned domain size. This anomalous behavior may be due to the ability of the spherical micelles to reorganize into more complex structures.
Components of the Reelin signaling pathway are expressed in the spinal cord

The Reelin signaling pathway in the brain involves the binding of Reelin to very‐low‐density lipoprotein receptors (VLDLR) and apolipoprotein E receptor 2 (ApoER2). After Reelin binds the lipoprotein receptors on migrating neurons, the intracellular adaptor protein Disabled‐1 (Dab1) becomes phosphorylated, ultimately resulting in the proper positioning of cortical neurons. Previous work showed that Reelin also affects the positioning of sympathetic preganglionic neurons (SPN) in the spinal cord (Yip et al. [ 2000 ] Proc Natl Acad Sci USA 97:8612–8616). We asked in the present study whether components of the Reelin signaling pathway in the brain also function to control SPN migration in developing spinal cord. Results showed that Reelin and reelin mRNA are found adjacent to migrating SPN. In addition, dab1 mRNA and protein are expressed by migrating SPN, and dab1‐null mice show abnormal SPN migration similar to that seen in reeler. Finally, vldlr and apoER2 are also expressed in migrating SPN, and mice lacking both vldlr and apoER2 show aberrant SPN location that is identical to that of reeler and dab1‐null mice. Because molecules known to be involved in Reelin signaling in the brain are present in the developing spinal cord, it is likely that the Reelin signaling pathways in the brain and spinal cord function similarly. The relative simplicity of the organization of the spinal cord makes it a potentially useful model system with which to study the molecular and cellular function of the Reelin signaling pathway in control of neuronal migration. J. Comp. Neurol. 470:210–219, 2004. © 2004 Wiley‐Liss, Inc.
Phenomenology of Childhood Psychosis: Findings From a Large Sample of Psychiatrically Referred Youth

Our objective was to evaluate the scope and clinical correlates of psychotic phenomena in psychiatrically referred children and adolescents. Subjects were 1657 psychiatrically referred youth (mean age = 10.9 years) evaluated from 1991 to 2002. DSM-III-R diagnoses were obtained through maternal report by using the Schedule for Affective Disorders and Schizophrenia for School-Age Children—Epidemiologic Version. Childhood-onset psychosis was defined by the presence of delusions or hallucinations. Childhood-onset psychosis was identified in 8% of psychiatrically referred youth. It was associated with a chronic course and high levels of impairment. Comorbidity with disruptive, mood, and anxiety disorders was very severe, with only one of the 132 identified youth with psychosis not having at least one comorbidity. In conclusion, childhood-onset psychosis in referred youth is common and highly morbid. It remains an important topic of research deserving full clinical and scientific attention.
Disrupted Control-Related Functional Brain Networks in Drug-Naive Children with Attention-Deficit/Hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disease featuring executive control deficits as a prominent neuropsychological trait. Executive functions are implicated in multiple sub-networks of the brain; however, few studies examine these sub-networks as a whole in ADHD. By combining resting-state functional MRI and graph-based approaches, we systematically investigated functional connectivity patterns among four control-related networks, including the frontoparietal network (FPN), cingulo-opercular network, cerebellar network, and default mode network (DMN), in 46 drug-naive children with ADHD and 31 age-, gender-, and intelligence quotient-matched healthy controls (HCs). Compared to the HCs, the ADHD children showed significantly decreased functional connectivity that primarily involved the DMN and FPN regions and cross-network long-range connections. Further graph-based network analysis revealed that the ADHD children had fewer connections, lower network efficiency, and more functional modules compared with the HCs. The ADHD-related alterations in functional connectivity but not topological organization were correlated with clinical symptoms of the ADHD children and differentiated the patients from the HCs with a good performance. Taken together, our findings suggest a less-integrated functional brain network in children with ADHD due to selective disruption of key long-range connections, with important implications for understanding the neural substrates of ADHD, particularly executive dysfunction.
Functional Trade-Offs in Promiscuous Enzymes Cannot Be Explained by Intrinsic Mutational Robustness of the Native Activity

The extent to which an emerging new function trades off with the original function is a key characteristic of the dynamics of enzyme evolution. Various cases of laboratory evolution have unveiled a characteristic trend; a large increase in a new, promiscuous activity is often accompanied by only a mild reduction of the native, original activity. A model that associates weak trade-offs with “evolvability” was put forward, which proposed that enzymes possess mutational robustness in the native activity and plasticity in promiscuous activities. This would enable the acquisition of a new function without compromising the original one, reducing the benefit of early gene duplication and therefore the selection pressure thereon. Yet, to date, no experimental study has examined this hypothesis directly. Here, we investigate the causes of weak trade-offs by systematically characterizing adaptive mutations that occurred in two cases of evolutionary transitions in enzyme function: (1) from phosphotriesterase to arylesterase, and (2) from atrazine chlorohydrolase to melamine deaminase. Mutational analyses in various genetic backgrounds revealed that, in contrast to the prevailing model, the native activity is less robust to mutations than the promiscuous activity. For example, in phosphotriesterase, the deleterious effect of individual mutations on the native phosphotriesterase activity is much larger than their positive effect on the promiscuous arylesterase activity. Our observations suggest a revision of the established model: weak trade-offs are not caused by an intrinsic robustness of the native activity and plasticity of the promiscuous activity. We propose that upon strong adaptive pressure for the new activity without selection against the original one, selected mutations will lead to the largest possible increases in the new function, but whether and to what extent they decrease the old function is irrelevant, creating a bias towards initially weak trade-offs and the emergence of generalist enzymes.