Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of Infectious Clones for Virulent and Avirulent Pichinde Viruses: a Model Virus To Study Arenavirus-Induced Hemorrhagic Fevers

ABSTRACT Several arenaviruses can cause hemorrhagic fever diseases (VHFs) in humans, the pathogenic mechanism of which is poorly understood due to their virulent nature and the lack of molecular clones. A safe, convenient, and economical small animal model of arenavirus hemorrhagic fever is based on guinea pigs infected by the arenavirus Pichinde (PICV). PICV does not cause disease in humans, but an adapted strain of PICV (P18) causes a disease in guinea pigs that mimics arenavirus hemorrhagic fever in humans in many aspects, while a low-passaged strain (P2) remains avirulent in infected animals. In order to identify the virulence determinants within the PICV genome, we developed the molecular clones for both the avirulent P2 and virulent P18 viruses. Recombinant viruses were generated by transfecting plasmids that contain the antigenomic L and S RNA segments of PICV under the control of the T7 promoter into BSRT7-5 cells, which constitutively express T7 RNA polymerase. By analyzing viral growth kinetics in vitro and virulence in vivo, we show that the recombinant viruses accurately recapitulate the replication and virulence natures of their respective parental viruses. Both parental and recombinant virulent viruses led to high levels of viremia and titers in different organs of the infected animals, whereas the avirulent viruses were effectively controlled and cleared by the hosts. These novel infectious clones for the PICV provide essential tools to identify the virulence factors that are responsible for the severe VHF-like disease in infected animals.
Fab fragments from a monoclonal antibody against a germ tube mannoprotein block the yeast-to-mycelium transition in Candida albicans

Fab fragments prepared from the immunoglobulin G monoclonal antibody (MAb) 4C12, which reacts with a determinant expressed on the hyphal extension of germ tubes of Candida albicans, inhibited germ tube formation, but intact MAb 4C12 did not. Indirect immunofluorescence showed a punctate binding pattern on cells incubated with Fab fragments but a confluent binding on cells incubated with intact MAb 4C12.
Elimination of Organic Anions in Response to an Early Stage of Renal Ischemia-Reperfusion in the Rat: Role of Basolateral Plasma Membrane Transporters and Cortical Renal Blood Flow

Background/Aims:The knowledge of molecular mechanisms determining drug pharmacokinetics in pathological states is relevant for the development of new therapeutic approaches. This study was undertaken to evaluate the cortical renal blood flow (cRBF) and the renal protein expression of the organic anion transporters (OAT1 and OAT3) in association with the elimination of organic anions in an early stage of renal ischemia-reperfusion. Methods:Ischemic acute renal failure (ARF) was induced in adult male Wistar rats by occlusion of both renal pedicles during 60 min, followed by 60 min of reperfusion (ARF group). Pair-fed sham-operated rats served as controls. The renal protein expression of OAT1 and OAT3 was evaluated by immunohistochemistry techniques and by Western blotting in renal cortex homogenates and in basolateral plasma membranes. A pharmacokinetic study of p-aminohippurate (PAH, a prototypical organic anion) was performed. cRBF was determined using fluorescent microspheres. Results: ARF rats displayed a significant decrease in systemic clearance and in renal excretion of PAH. OAT1 and OAT3 protein abundance showed a statistically significant reduction both in homogenates and in basolateral plasma membranes from ARF rats. Immunohistochemical studies confirmed the changes in the cortical renal expression of these transporters. ARF animals also showed a decrease in cRBF. Conclusions: The decrease in PAH elimination observed in an early stage of renal ischemia-reperfusion in male Wistar rats might be explained by the sum of the lower OAT1 and OAT3 expression in renal basolateral plasma membranes plus the decrease in cRBF. These findings might have significant implications in the development of novel pharmacological strategies to be applied in the initial stages of ischemic ARF.
Tonic vibration reflex and muscle afferent block in writer's cramp

Patients with focal dystonia take advantage of certain cutaneous or proprioceptive sensory inputs to alleviate their symptoms (“sensory trick”). We examined the effects of increasing muscle spindle activity by the tonic vibration reflex maneuver and Decemberreasing it by intramuscular injection of lidocaine. The vibration was applied to the palm or the tendon of forearm muscles in 15 patients with writer's cramp and 15 age‐matched normal subjects. In 11 patients, the vibration induced dystonic postures or movements typical of those seen during writing. Normal subjects showed either no response to the vibration or a gradually developing tonic vibration reflex only in the wrist and finger flexors, which produced visible movements with a significantly longer latency (12.5 ± 6.7 seconds [mean ± standard deviation]) than what was observed in the patients (2.7 ± 2.5 seconds, p < 0.0001). Local injection of lidocaine (0.5%, 5–40 ml/muscle) attenuated the tendon reflex with relatively little effect on the M response. Injection into muscles with increased activity produced Marchked reduction of dystonic movements and significant clinical improvement in 13 patients, whereas injection into the other muscles had no effect. The clinical benefit lasted for 1 to 24 hours after injection. In 13 patients who had additional injections of 10% ethanol, which blocks sodium channels for a longer period than does lidocaine, the duration of action was prolonged to 5 to 21 days. These findings suggest that muscles causing dystonic movements have abnormal sensitivities to vibration at rest and that muscle afferents may play a pivotal role in producing dystonic movements. Local injection of lidocaine or ethanol reduces the effectiveness of muscle spindle afferent and may provide a means of treating patients with writer's cramp without causing unwanted weakness.
Vemurafenib Potently Induces Endoplasmic Reticulum Stress–Mediated Apoptosis in BRAFV600E Melanoma Cells

Drug resistance in melanomas may be overcome by therapies that trigger endoplasmic reticulum stress. Stressing Out Resistance Many melanomas harbor a form of the kinase BRAF with an amino acid substitution (V600E) that renders the protein constitutively active. The mutant BRAF drives cancer growth by activating extracellular signal–regulated kinase (ERK), which promotes cell proliferation and survival. The BRAFV600E kinase inhibitor vemurafenib is initially an effective therapy for melanoma but loses its efficacy because the tumor cells become drug-resistant. Beck et al. found that vemurafenib inhibited survival signaling mediated by ERK and induced endoplasmic reticulum (ER) stress, a form of cellular stress that can culminate in apoptosis. Combined application of vemurafenib with the ER stress inducer thapsigargin to BRAFV600E melanoma cell lines that were resistant to vemurafenib resulted in an enhanced ER stress response and apoptosis. Their findings indicate a potential strategy to overcome drug resistance in BRAF-mutated melanoma. The V600E mutation in the kinase BRAF is frequently detected in melanomas and results in constitutive activation of BRAF, which then promotes cell proliferation by the mitogen-activated protein kinase signaling pathway. Although the BRAFV600E kinase inhibitor vemurafenib has remarkable antitumor activity in patients with BRAFV600E-mutated melanoma, its effects are limited by the onset of drug resistance. We found that exposure of melanoma cell lines with the BRAFV600E mutation to vemurafenib decreased the abundance of antiapoptotic proteins and induced intrinsic mitochondrial apoptosis. Vemurafenib-treated melanoma cells showed increased cytosolic concentration of calcium, a potential trigger for endoplasmic reticulum (ER) stress, which can lead to apoptosis. Consistent with an ER stress–induced response, vemurafenib decreased the abundance of the ER chaperone protein glucose-regulated protein 78, increased the abundance of the spliced isoform of the transcription factor X-box binding protein 1 (XBP1) (which transcriptionally activates genes involved in ER stress responses), increased the phosphorylation of the translation initiation factor eIF2α (which would be expected to inhibit protein synthesis), and induced the expression of ER stress–related genes. Knockdown of the ER stress response protein activating transcription factor 4 (ATF4) significantly reduced vemurafenib-induced apoptosis. Moreover, the ER stress inducer thapsigargin prevented invasive growth of tumors formed from vemurafenib-sensitive melanoma cells in vivo. In melanoma cells with low sensitivity or resistance to vemurafenib, combination treatment with thapsigargin augmented or induced apoptosis. Thus, thapsigargin or other inducers of ER stress may be useful in combination therapies to overcome vemurafenib resistance.
High atmospheric demand for water can limit forest carbon uptake and transpiration as severely as dry soil

When stressed by low soil water content (SWC) or high vapor pressure deficit (VPD), plants close stomata, reducing transpiration and photosynthesis. However, it has historically been difficult to disentangle the magnitudes of VPD compared to SWC limitations on ecosystem‐scale fluxes. We used a 13 year record of eddy covariance measurements from a forest in south central Indiana, USA, to quantify how transpiration and photosynthesis respond to fluctuations in VPD versus SWC. High VPD and low SWC both explained reductions in photosynthesis relative to its long‐term mean, as well as reductions in transpiration relative to potential transpiration estimated with the Penman‐Monteith equation. Flux responses to typical fluctuations in SWC and VPD had similar magnitudes. Integrated over the year, VPD fluctuations accounted for significant reductions of GPP in both nondrought and drought years. Our results suggest that increasing VPD under climatic warming could reduce forest CO2 uptake regardless of changes in SWC.
Recovery from hip and knee arthroplasty: Patients' perspective on pain, function, quality of life, and well-being up to 6 months postoperatively.

OBJECTIVE To provide a more detailed description from patients' perspectives than is yet available of recovery from hip and knee arthroplasty and to use this information to test 2 assumptions about recovery from these procedures: that recovery from knee arthroplasty, as assessed by patients, routinely reaches the level achieved by hip arthroplasty; and that fatigue is prolonged after major orthopedic surgery. DESIGN A cohort study. SETTING University teaching hospitals. PARTICIPANTS Consecutive patients undergoing hip (n = 107) or knee (n = 53) arthroplasty. INTERVENTIONS Unilateral hip or knee arthroplasty. MAIN OUTCOME MEASURES Standardized self-rated measurements of pain, function, quality of life, and well-being from preoperatively to 6 months follow-up. RESULTS Pain and function improved significantly less after knee arthroplasty than after hip arthroplasty, but the 2 procedures led to similar improvements in life evaluation, mood, and subjective health. Fatigue was only transiently increased. CONCLUSION The findings were inconsistent with both assumptions. Nevertheless, despite poorer recovery in pain and function, patients receiving knee arthroplasty felt that life had improved as much as did patients with hip arthroplasty. Detailed information about how major joint arthroplasty in routine practice affects patients' lives can be used to advise patients and clinicians and can invalidate influential, but inaccurate, assumptions.
Knowledge and Practices of safety use of Pesticides among Farm workers

This paper is focused on level of Knowledge and Practice of safety pesticide use among various farmworkers in agricultural field. Certain level of education and experience has contributed significant knowledge on safety use of pesticides which further has to make them to practice correct methods while applying pesticides. But no such practice has been identified which tells the need of special training to implement known safety measures rather than knowing further. Age and gender have not influenced their knowledge and practice on safety use of pesticides. Interestingly, farm workers who are working in closed farms had more knowledge than those of in open farms but both group of workers are practicing only half of the safety measures which are known to them. Hence, they extremely need a motivational programme rather than awareness programme.
Role of vascular endothelial cells in bone biology

Bone development and remodeling depend on complex interactions between bone‐forming osteoblasts, bone‐degrading osteoclasts, and other cells present within the bone microenvironment. Balanced control of bone formative and degradative processes is normally carefully maintained in the adult skeleton but becomes uncoupled in the course of aging or in various pathological disease states. Systemic regulators of bone metabolism and local mediators, including matrix molecules, cytokines, prostaglandins, leukotrienes, and other autocrine or paracrine factors, regulate the recruitment, differentiation, and function of cells participating in bone formation and turnover. Although some of these interactions are now understood, many yet remain to be elucidated. Recent studies have begun exploring in detail how vascular endothelial cells and their products function in bone physiology. The findings are revealing that bone vascular endothelial cells may be members of a complex communication network in bone which operates between endothelial cells, osteoblasts, osteoclasts, macrophages, stromal cells, and perhaps other cell types found in bone as well. Therefore, multiple systemic and locally produced signals may be received, transduced, and integrated by individual cells and then propagated by the release from these cells of further signals targeted to other members of the bone cell network. In this manner, bone cell activities may be continuously coordinated to afford concerted actions and rapid responses to physiological changes. The bone microvasculature may play a pivotal role in these processes, both in linking circulatory and local signals with cells of the bone microenvironment and in actively contributing itself to the regulation of bone cell physiology. Thus, skeletal homeostasis and the coupling observed between bone resorption and bone formation during normal bone remodeling may be manifestations of this dynamic interactive communication network, operating via diverse signals not only between osteoblasts and osteoclasts but between many cell types residing within bone. © 1994 Wiley‐Liss, Inc.
SOCIAL DETERMINANTS AND UPTAKE OF SOLAR COOKING PROJECTS- KAKUMA REFUGEE CAMP IN KENYA

Purpose: To investigate the influence of social determinants on uptake of solar cooking projects in Kakuma Refugee Camp in Kenya. Methodology: A cross-sectional study of 122 systematically sampled households in Kakuma Refugee Camp was done. Questionnaires were completed to collect information about social norms, family size, security and safety, education level and beneficiary participation. Descriptive statistics were used to summarize the findings. Findings: All the 122 questionnaires completed by respondents had a mean age (SD) 37.8 (8.6); 85% female. Households in Kakuma mainly acquire their domestic fuel via different means within the camp such as firewood collection, purchases from local vendors or donations from aid agencies. Firewood on open fires was the modal cooking practice at 83.6%, followed by charcoal at 15.6% and solar cooking at 0.8%, while use of alternative fuels like gas, ethanol or kerosene was found to be insignificant. Adoption of solar cooking was observed to be under influence of social norms, family size and education. A greater uptake of solar cooking was noted among respondents with higher education levels and lower uptake among large families. Unique Contribution to Theory, Practice and Policy: Firewood is given to refugees for domestic fuel in Kakuma Refugee Camp; however, getting adequate supplies for the sprawling camp population is getting increasingly difficult, and environmentally damaging. Solar cooking projects have been implemented as possible solutions albeit with little success. There is a need for humanitarian agencies to make refugees aware and conversant with use of the free, sustainable solar fuel to cook and cognizant of benefits of shifting from wood-based cooking to the cleaner solar cooking option. Household cooking is such a socio-culturally embedded practice in Kakuma that context-specific solar cookers that can fry, boil, and bake using ordinally cooking styles of refugees would be key to a wider-spread solar cooking uptake. In addition, there is a gap between the refugees’ preferred fuel option and their ability to pay. To get solar cooking to scale, more investment is needed and agencies should explore working with local businesses to subsidize cost of solar cookers in camps. Finally, the Kenya and the ISO standards for clean cookstoves need developing since there is a gap and the existing standards mainly focus on solid fuel, biomass or ethanol cookstoves.
Pleistocene radiation of the serpentine-adapted genus Hesperolinon and other divergence times in Linaceae (Malpighiales).

PREMISE OF THE STUDY Hesperolinon (western flax; Linaceae) is endemic to the western United States, where it is notable for its high and geographically concentrated species diversity on serpentine-derived soils and for its use as a model system in disease ecology. We used a phylogenetic framework to test a long-standing hypothesis that Hesperolinon is a neoendemic radiation. METHODS Five plastid and two ribosomal nuclear DNA gene regions were sampled from 105 populations of Hesperolinon, including all 13 recently recognized species across their known ranges. We used these data to generate population-level phylogenies of Hesperolinon. We also generated a robustly sampled chronogram of Linaceae using an eight-gene, 100-taxon supermatrix calibrated using fossil Linum pollen and a published chronogram of Malpighiales. KEY RESULTS Most diversification in Hesperolinon has taken place in the past 1-2 million yr, much more recently than previous estimates. Only the earliest-diverging species, H. drymarioides, was resolved as a clade. Denser taxon and gene sampling generally support previously proposed relationships within Linaceae, but with more recent diversification of key clades. CONCLUSIONS Hesperolinon is an excellent example of edaphic neoendemism, in support of Raven and Axelrod's hypothesis for the genus. Dense population-level sampling reveals a complex of incipient species, with clades poorly aligned with traditional morphological circumscriptions, likely due in part to continued gene flow. The diversification of Linaceae is more recent than previously estimated, and other recent radiations (e.g., Hugonia) warrant further study.
The Costs and Benefits of Reducing Complex Disclosures

Purpose: Reducing annual report disclosure complexity has been a topic of serious debate for standard setters in recent years. In response to that, this study seeks to explore the effect of reducing such complexity on ERC, agency costs, proprietary costs, as well as interest rates on loans given by banks. Methodology: Based on listed companies in Indonesia for the year 2016, required data is collected through the IDX website. All empirical results in this study are obtained through the IBM SPSS Statistics software version 23 using the linear regression function for each hypothesis. Findings: The overall empirical results show that: 1) ERC and proprietary cost is not significantly affected by fog index, suggesting a less effective capital market in Indonesia, where information is not immediately processed in the market; 2) Agency costs are inversely related to disclosure complexity, suggesting that firms producing simpler reports are either mostly involved in tax planning, or larger Indonesian firms with lower fog usually bear higher monitoring costs; and 3) Interest rates on loans given by banks are greatly affected by disclosure complexity. Firms with more complex reports tend to get lower rates on bank loans as compared to those with much more readable reports, suggesting that providing debtholders with more complex information actually reassure them to offer lower rates. Originality: This paper is the first to explore the costs and benefits of reducing disclosure complexity in Indonesia.
Hypothalamic gonadotropin-releasing hormone secretion and follicle-stimulating hormone dynamics during the luteal-follicular transition.

To define the precise neuroendocrine characteristics of the luteal-follicular transition, 11 normal women underwent 12 frequent sampling studies at 10-min intervals for 48 h at various points during the transition from one cycle to the next. Daily blood samples captured both the preceding and subsequent LH surges, so that studies could be characterized in relation to the preceding LH peak (LH+), the subsequent LH peak (LH-), and menses (M). In the frequent sampling study, LH and FSH were measured in all samples, and estradiol (E2) and progesterone (P) were measured in 2-h pools. The frequency of pulsatile LH secretion increased 4.5-fold over an 8-day period spanning the luteal-follicular transition. This increase in LH pulse frequency was strongly related to the preceding LH peak (r = 0.82; P less than 0.00001), but was not at all related to the onset of menses. When the temporal markers (i.e. LH+, LH-, and M) were removed from the analysis, LH pulse frequency was inversely related to the log of serum P (r = 0.50; P less than 0.005), but not E2. FSH levels increased both within the individual studies (P less than 0.005) and in the group as a whole over the duration of the luteal-follicular transition. Mean FSH rose 3.5-fold compared to less than a 2-fold increase in mean LH. As with LH pulse frequency, the increase in FSH was most strongly related to the preceding LH peak, but was also significantly associated with the subsequent LH peak and the onset of menses. The relationship between FSH and the number of days from the preceding LH peak is even better fit by a second degree polynomial, which revealed an abrupt increase in LH beginning at LH+11. With the temporal markers excluded, the increase in FSH related only to LH pulse frequency (r = 0.62; P less than 0.001). FSH was not statistically related to the decreases in P or E2, which are also key variables at this stage of the menstrual cycle. We reached the following conclusions. 1) A dramatic increase in LH pulse frequency, and by inference GnRH pulse frequency, accompanies the selective rise in FSH levels during the luteal-follicular transition of the normal menstrual cycle. 2) Both the increase in GnRH pulse frequency and the rise in FSH levels during this transition are strongly related to the preceding LH peak, while the clinical marker of menses is a relatively poor indicator of these events. (ABSTRACT TRUNCATED AT 400 WORDS)
The effect of inhibiting brain thromboxane biosynthesis on pentylenetetrazole‐induced seizure threshold

The effect of inhibiting endogenous brain thromboxane (TXB2) on pentylenetetrazole‐induced seizures was studied using the thromboxane synthetase inhibitors OKY‐1581 (20 mg/kg) and UK 38,485 (50 mg/kg). Both compounds selectively decreased (> 90%) TXB2 production in brain measured after 2 min of convulsive activity but had no effect on brain PGE2, PGF2α, or 6‐keto‐PGF1α No effect of these agents on the tonic seizure threshold was observed, whereas 10 mg/kg ip indomethacin, an agent which inhibits both TXB2 and prostaglandin production, reduced the tonic seizure threshold from 78 ± 2.6 mg/kg in controls to 62 ± 3.7 mg/kg. Thus, this study concludes that the availability of TXB2 with convulsant activity is unlikely to be a factor in altering tonic seizure activity observed with indomethacin.