Miracle-dz/UniFAR-FTUs huggingface dataset:
TESTS OF PLEISTOCENE SPECIATION IN MONTANE GRASSHOPPERS (GENUS MELANOPLUS) FROM THE SKY ISLANDS OF WESTERN NORTH AMERICA

Abstract There has a been a resurgence of debate on whether the Pleistocene glaciations inhibited speciation. This study tests a model of Pleistocene speciation, estimating the phylogenetic relationships and divergence times of 10 species of montane grasshoppers, genus Melanoplus, using 1300 bp of the mitochondrial gene cytochrome oxidase I (COI). Based on average pairwise distances (corrected for multiple substitutions using Kimura's two-parameter model), all species appear to have originated within the Pleistocene. Sequence divergences between species are less than 4%, corresponding to divergence times less than 1.7 million years ago. Branching patterns among the species suggest that speciation was associated with more than one glacial-interglacial cycle. A likelihood-ratio test rejected a model of simultaneous species origins, the predicted branching pattern if species arose from the fragmentation of a widespread ancestor. These grasshoppers live in an area that was previously glaciated and, as inhabitants of the northern Rocky Mountain sky islands, underwent latitudinal and probably altitudinal shifts in distribution in response to climatic fluctuations. Given the repeated distributional shifts and range overlap of the taxa, there most likely has been ample opportunity for population mixing. However, despite periodic glacial cycles, with more than 10 major glaciations over the past million years and climatic fluctuations over as short a time scale as 103 to 104 years, the dynamic history of the Pleistocene did not preclude speciation. Although relationships among some taxa remain unresolved, these grasshopper species, even with their recent origins, exhibit genetic coherence and monophyletic or paraphyletic gene trees. The frequency of glacial cycles suggests that the speciation process must have been extremely rapid. These species of grasshoppers are morphologically very similar, differing primarily in the shape of the male genitalia. These characters are posited to be under sexual selection, may play an important role in reproductive isolation, and are known to diverge rapidly. This suggests the rapidity of evolution of reproductive isolation may determine whether species divergences occurred during the Pleistocene glaciations. Corresponding Editor: H. A. Orr
LEADING THE TECHNOLOGY DEVELOPMENT PROCESS

OVERVIEW:Long-term or exploratory research aimed at the development of new technology has remained largely outside the scope of management strategies for enhancing productivity in R&D. Increasing the effectiveness of these efforts, however, can have a major impact on the corporate well-being. The concepts of cycle time management can provide a framework and protocol for managing technology development. Effective oversight requires a strategy for assessing progress in such learning-intensive, discovery-oriented research, and ensures from the very outset an alignment with ultimate value to the business. Leaders must cultivate clear and disciplined thinking without curtailing the creativity that is so essential to success in exploratory research.
Does Homocysteine Cause Hypertension?

Abstract Several studies, some population-based, have plasma homocysteine levels linked to blood pressure, especially systolic pressure. In one large and carefully conducted epidemiological study, each 5 μmol/l increase in plasma homocysteine was associated with an increase in systolic and diastolic blood pressure of 0.7/0.5 mmHg in men and 1.2/0.7 mmHg in women, which was independent of renal function and B vitamin status. In addition, observations that homocysteine-lowering therapies with folic acid-based treatments have been followed by decreases in blood pressure raise the possibility that the link between homocysteine and blood pressure is causal, which is important since homocysteine levels can easily be lowered by folic acid-based regimens. Mechanisms that could explain the relationship between homocysteine and blood pressure include homocysteine-induced arteriolar constriction, renal dysfunction and increased sodium reabsorption, and increased arterial stiffness. However, there is only circumstantial evidence that these mechanisms are operative in humans. In addition, confounding by subtle renal dysfunction or by unmeasured dietary and lifestyle factors cannot be excluded as an explanation for the association between homocysteine and blood pressure. At present, therefore, the hypothesis that homocysteine increases blood pressure must be considered unproven. Ongoing large intervention studies with homocysteine-lowering vitamins may show whether blood pressure is indeed lowered by these vitamins, whether the blood pressure decrease, if any, is explained by the decrease in homocysteine levels, and whether a vitamin treatment-associated decrease in cardiovascular morbidity, if any, is explained by the decrease in blood pressure.
Fournier’s Gangrene: A Review of 43 Reconstructive Cases

Background: Fournier’s gangrene is a rare and potentially fatal infectious disease characterized by necrotic fasciitis of the perineum and abdominal wall, along with the scrotum and penis in men and the vulva in women. Fournier’s gangrene is a true surgical emergency. Skin loss can be very incapacitating and difficult to repair. Methods: The authors reviewed retrospectively the clinical records of a series of 43 patients with Fournier’s gangrene between the years 1985 and 2003 who, after initial treatment by the Departments of Urology and Surgery, were referred to the Department of Plastic Surgery for reconstruction. The following parameters were evaluated: age, gender, interval between onset of symptoms and diagnosis, clinical symptoms, lesion site, results of bacteriologic cultures, cause and predisposing factors, treatment and reconstructive procedures, length of hospital stay, and outcome. Results: The mean patient age was 56.6 years. Fifteen patients (34.9 percent) had diabetes mellitus. The cause of Fournier’s gangrene was found in 32 patients (74.4 percent). The most common presentation was scrotal swelling, and scrotal involvement was found in 40 cases (93.0 percent). All of the patients underwent surgical debridement, and several reconstruction techniques were used. The mean length of hospital stay was 73.6 days. Two patients died. Conclusions: Management of this infectious entity should be aggressive. Several techniques that are used to reconstruct the lost tissue have shown good results. The superomedial thigh skin flap has proven to be a reliable method of resurfacing large scrotal defects. Reconstructive surgery makes the return to a normal social life possible in many cases.
Improving tuberculosis control through the partnership between university and the health system.

INTRODUCTION Tuberculosis (TB) control is linked to the availability of qualified methods for microbiological diagnostics; however, microscopy with limited sensitivity is the only method available in many locations. The objective of this study was to evaluate the introduction of culture, drug susceptibility testing (DST), and genotyping in the routine of a Municipal Program of Tuberculosis Control. METHODS Direct microscopy of sputum and culture in Ogawa-Kudoh were performed on 1,636 samples from 787 patients. DST of positive cultures was performed by resazurin microtiter assay and genotyping by mycobacterial interspersed repetitive units-variable number tandem repeat. RESULTS A total 91 patients with TB were identified. The culture increased case detection by 32% compared with the microscopy; acquired resistance was 3.3% and the genotyping showed high genetic diversity. CONCLUSIONS Ogawa-Kudoh contributed significantly to the increase in case detection and is suitable for implementation in poor-resource locations. The acquired resistance rate was lower than that reported in a recent Brazilian survey. The high genetic diversity is possibly related to the high TB prevalence in the population, as well as to early detection and suitable treatment of patients. The interaction between research and health care is important for reorienting the practice, transferring technology, and improving TB control.
A Longitudinal Study of Immigrants’ Peer Acceptance and Rejection: Immigrant Status, Immigrant Composition of the Classroom, and Acculturation

Objective: In multiethnic classrooms, acceptance and rejection by classmates of one’s own versus other ethnicity is influenced by in-group preference, the societal status of the ethnicities, and composition of classrooms. We aimed at (a) confirming these effects for immigrant versus nonimmigrant adolescents in newly formed classrooms, (b) longitudinally studying the change of these effects over the next 2 years, and (c) studying the longitudinal links between immigrants’ acculturation and acceptance/rejection by (non)immigrants. Method: This was a multilevel, longitudinal study of 1,057 13-year-old students nested in 49 classrooms over the first 3 years of middle school in Greece. Immigrant composition of classrooms varied strongly (average 44%), and immigrants in a classroom were ethnically homogeneous (78% same-ethnic). Students’ acceptance and rejection by Greek and immigrant students were sociometrically assessed every year. Multilevel analyses were conducted for questions a and b and cross-lagged analyses for question c. Results: Initially, immigrants were less accepted and more rejected by their classmates than Greeks. However, in classrooms with more than 66% immigrants, they were more accepted and less rejected. Over time, (a) immigrants and Greeks did not differ in being rejected and (b) immigrants in classrooms with few immigrants became increasingly more accepted. Finally, immigrants with higher involvement with the Greek culture were more accepted by their Greek classmates. Conclusion: Immigrants’ peer relations with Greeks were positively affected by increasing opportunity for intergroup contact and involvement with the Greek culture. Interventions supporting acculturation and intergroup contact may prove beneficial for immigrant students.
Increased endothelial cell permeability in endoglin‐deficient cells

Endoglin (ENG) is a TGF‐β superfamily coreceptor essential for vascular endothelium integrity. ENG mutations lead to a vascular dysplasia associated with frequent hemorrhages in multiple organs, whereas ENG null mouse embryos die at midgestation with impaired heart development and leaky vasculature. ENG interacts with several proteins involved in cell adhesion, and we postulated that it regulates vascular permeability. The current study assessed the permeability of ENG homozygous null (Eng‐/‐), heterozygous (Eng+/‐), and normal (Eng+/+) mouse embryonic endothelial cell (EC) lines. Permeability, measured by passage of fluorescent dextran through EC monolayers, was increased 2.9‐ and 1.7‐fold for Eng‐/‐ and Eng+/‐ ECs, respectively, compared to control ECs and was not increased by TGF‐p 1 or VEGF. Prolonged starvation increased Eng‐/‐ EC permeability by 3.7‐fold with no effect on control ECs; neutrophils transmigrated faster through Eng‐/‐ than Eng+/+ monolayers. Using a pull‐down assay, we demonstrate that Ras homolog gene family (Rho) Ais constitutively active in Eng‐/‐ and Eng+/‐ECs. We show that the endothelial barrier destabilizing factor thrombospondin‐1 and its receptor‐like protein tyrosine phosphatase are increased, whereas stabilizing factors VEGF receptor 2, vascular endothelial‐cadherin, p21‐activated kinase, and Ras‐related C3 botulinum toxin substrate 2 are decreased in Eng‐/‐ cells. Our findings indicate that ENG deficiency leads to EC hyper‐permeability through constitutive activation of RhoA and destabilization of endothelial barrier function. —Jerkic, M. , Letarte, M. Increased endothelial cell permeability in endoglin‐deficient cells. FASEB J. 29, 3678‐3688 (2015). www.fasebj. org
Multicenter, randomized phase II trial of oral CI-1033 for previously treated advanced ovarian cancer.

PURPOSE To evaluate the antitumor activity and toxicity of two doses of CI-1033 in patients with platinum-refractory or recurrent ovarian cancer, and to determine baseline expression of epidermal growth factor receptor in tumor cells. PATIENTS AND METHODS This phase II, open-label clinical trial evaluated CI-1033 in patients with ovarian cancer who failed prior platinum-based therapy. Two oral doses of CI-1033 were evaluated--a 50-mg and a 200--mg oral dose administered daily for 21 days in a 28-day cycle. Patients were evaluated for tumor response and toxicity; in addition, archival baseline tumor samples were analyzed by immunohistochemistry for erbB1 to erbB4 status. RESULTS One hundred five eligible patients were treated. Baseline demographic characteristics were balanced in this heavily pretreated patient population. The median number of prior chemotherapy regimens received was four. The most commonly encountered drug-related adverse events for both dose arms were gastrointestinal (diarrhea, nausea, stomatitis) toxicity, asthenia, and rash. No responses were observed. Stable disease was confirmed in 34% and 26% of patients in the 200-mg and 50-mg arms, respectively, and 1-year survival rates were 38.5% and 37.7%, respectively. Baseline erbB3 and erbB4 revealed the highest frequencies of expression, while erbB2 was the lowest. CONCLUSION CI-1033 did not show activity in unscreened patients with advanced ovarian cancer. At 50 mg/d, CI-1033 had a more favorable adverse events profile than at 200 mg/d. erbB3 and erbB4 receptors showed the highest expression in tumor samples while erbB2 revealed the least. There appears to be no association between baseline erbB expression and disease stability.
Detection of monoclonality in intestinal lymphoma with polymerase chain reaction for antigen receptor gene rearrangement analysis to differentiate from enteritis in dogs

The diagnosis of canine intestinal lymphoma by morphological examination is challenging, especially when endoscopic tissue specimens are used. The utility of detection of antigen receptor gene rearrangement by polymerase chain reaction (PARR) in canine lymphoma has been well established, but its usefulness to distinguish enteritis and intestinal lymphoma remains unclear. In this retrospective study we assessed clonality of 29 primary canine intestinal lymphoma, 14 enteritis and 15 healthy control cases by PARR analysis, using formalin-fixed, paraffin-embedded full-thickness tissue specimens. We could detect monoclonal rearrangements in 22 of 29 canine intestinal lymphomas [76%; 95% confidence interval (CI) 56-90%] and polyclonal rearrangements in all of the enteritis and healthy control cases (100%; CI 88-100%). We revealed a predominance of T-cell phenotype compared to B-cell phenotype (85%; CI 65-96% and 15%; CI 4-35%, respectively). We showed that PARR analysis contributes to differentiation of canine intestinal lymphoma from enteritis and to phenotyping of lymphomas.
Distinct Steps in Dislocation of Luminal Endoplasmic Reticulum-associated Degradation Substrates

Dislocation of endoplasmic reticulum-associated degradation (ERAD) substrates from the endoplasmic reticulum (ER) lumen to cytosol is considered to occur in a single step that is tightly coupled to proteasomal degradation. Here we show that dislocation of luminal ERAD substrates occurs in two distinct consecutive steps. The first is passage across ER membrane to the ER cytosolic face, where substrates can accumulate as ubiquitin conjugates. In vivo, this step occurs despite proteasome inhibition but requires p97/Cdc48p because substrates remain entrapped in ER lumen and are prevented from ubiquitination in cdc48 yeast strain. The second dislocation step is the release of accumulated substrates to the cytosol. In vitro, this release requires active proteasome, consumes ATP, and relies on salt-removable ER-bound components, among them the ER-bound p97 and ER-bound proteasome, which specifically interact with the cytosol-facing substrates. An additional role for Cdc48p subsequent to ubiquitination is revealed in the cdc48 strain at permissive temperature, consistent with our finding that p97 recognizes luminal ERAD substrates through multiubiquitin. BiP interacts exclusively with ERAD substrates, suggesting a role for this chaperone in ERAD. We propose a model that assigns the cytosolic face of the ER as a midpoint to which luminal ERAD substrates emerge and p97/Cdc48p and the proteasome are recruited. Although p97/Cdc48p plays a dual role in dislocation and is involved both in passage of the substrate across ER membrane and subsequent to its ubiquitination, the proteasome takes part in the release of the substrate from the ER face to the cytosol en route to degradation.
Binding of polymyxin B nonapeptide to gram-negative bacteria

The binding of the outer membrane-disorganizing peptide polymyxin B nonapeptide (PMBN) to gram-negative bacteria was studied by using tritium-labeled PMBN. Smooth Salmonella typhimurium had a binding capacity of ca. 6 nmol of PMBN per mg (dry weight) of bacteria, which corresponds to ca. 1 X 10(6) to 2 X 10(6) molecules of PMBN per single cell. The binding was of relatively high affinity (Kd, 1.3 microM). The isolated outer membrane of S. typhimurium bound ca. 100 nmol of PMBN per mg of outer membrane protein (Kd, 1.1 microM), whereas the cytoplasmic membrane bound 9 to 10 times less. Other bacteria which are susceptible to the action of PMBN (Escherichia coli strains, Pseudomonas aeruginosa, Haemophilus influenzae) also bound large amounts of PMBN. The S. typhimurium pmrA mutant, Neisseria gonorrhoeae, and Proteus mirabilis (all known as resistant to polymyxin and PMBN) bound 3.3, 4, and 12 times less than S. typhimurium, respectively. The binding of PMBN to S. typhimurium was effectively inhibited by low concentrations of polymyxin B, compound EM49 (octapeptin), polylysine, and protamine. Spermine, Ca2+, and Mg2+ also inhibited the PMBN binding although they were ca. 160, 700, and 2,400 times less active (based on molarity) than polymyxin B, respectively. No binding inhibition was found at the tested concentrations of streptomycin, tetralysine, spermidine, or cadaverine.
Determination of the feasibility of using a portable X-ray fluorescence (XRF) analyzer in the field for measurement of lead content of sieved soil.

Soil samples collected in housing areas with potential lead contamination generally are analyzed with flame atomic absorption spectrometry (FAAS) or other laboratory methods. Previous work indicates that field-portable X-ray fluorescence (XRF) analysis is capable of detecting soil lead levels comparable to those detected by FAAS in samples sieved to less than 125 microm in a laboratory. A considerable savings, both economical and in laboratory reporting time, would occur if a practical field method could be developed that does not require laboratory digestion and analysis. The XRF method also would provide immediate results that would facilitate the provision of information to residents and other interested parties more quickly than is possible with conventional laboratory methods. The goal of the study reported here was to determine the practicality of using the field-portable XRF analyzer for analysis of lead in soil samples that were sieved in the field. The practicality of using the XRF was determined by the amount of time it took to prepare and analyze the samples in the field and by the ease with which the procedure could be accomplished on site. Another objective of the study was to determine the effects of moisture on the process of sieving the soil. Seventy-eight samples were collected from 30 locations near 10 houses and were prepared and analyzed at the locations where they were collected. Mean soil lead concentrations by XRF were 816 ppm before drying and 817 ppm after drying, and by laboratory FAAS were 1,042 ppm. Correlation of field-portable XRF and FAAS results was excellent for samples sieved to less than 125 microm, with R2 values of . 9902 and . 992 before and after drying, respectively. The saturation ranged from 10 percent to 90 percent. At 65 percent saturation or higher, it was not feasible to sieve the soil in the field without a thorough drying step, since the soil would not pass through the sieve. Therefore the field method with sieving was not practical when the soil was 65 percent or more saturated unless a time-consuming drying process was included.
Influence of hepatic venous pressure gradient on the prediction of survival of patients with cirrhosis in the MELD Era

Measurements of portal pressure, usually obtained via the hepatic venous pressure gradient (HVPG) may be a prognostic marker in cirrhosis. The aim of this study was to evaluate the impact of HVPG on survival in patients with cirrhosis in addition to the Model for End‐Stage Liver Disease (MELD) score. We also examined whether inclusion of HVPG in a model with MELD variables improves its prognostic ability. Retrospective analyses of all patients who had HVPG measurements between January 1998 and December 2002 were considered. Proportional hazards Cox models were developed. Prognostic calibrative and discriminative ability of the model was evaluated. In this period, 693 patients had a hepatic hemodynamic study, and 393 patients were included. Survival was significantly worse in those patients with greater HVPG value (univariate HR, 1.05; 95% CI, 1.02‐1.08; P = .001). HVPG remained as an independent variable in a model adjusted by MELD, ascites, encephalopathy, and age (multivariate HR, 1.03; 95% CI, 1.00‐1.06; P = .05) so that each 1‐mmHg increase in HVPG had a 3% increase in death risk. In addition, HVPG as well as MELD score variables and age, significantly contributes to the calibrative predictive capacity of the prognostic model; however, discriminative ability improved only slightly (overall C statistic [95% CI]; MELD score variables: 0.71 [0.62‐0.80], MELD score variables, age, and HVPG 0.76: [0.69‐0.83]). In conclusion, HVPG has an independent effect on survival in addition to the MELD score. Although inclusion of HVPG and age in a survival predicting model would improve the calibrative ability of MELD, its discriminative ability is not significantly improved. (HEPATOLOGY 2005;42:793–801.)
Identification of a Phage-Encoded Ig-Binding Protein from Invasive Neisseria meningitidis

Ig-binding proteins are employed by a variety of organisms to evade the immune system. To our knowledge, we now report for the first time that meningococcal strains from several capsular groups exhibit Ig-binding activity that is dependent on human serum factors. A protein mediating Ig binding was identified as T and B cell–stimulating protein B (TspB) by immunoprecipitation and by mass spectroscopic analysis of tryptic peptides. Recombinant TspB and derivatives verified Ig binding, with a preference for human IgG2 Fc, and localized the IgG-binding region to a highly conserved subdomain of TspB. Antiserum produced in mice against the conserved subdomain detected the presence of TspB on the cell surface by flow cytometry when bacteria were grown in the presence of human serum. By fluorescence microscopy, we observed formation of an extracellular matrix having characteristics of a biofilm containing TspB, human IgG, DNA, and large aggregates of bacteria. TspB is encoded by gene ORF6 in prophage DNA, which others have shown is associated with invasive meningococcal strains. Knocking out ORF6 genes eliminated IgG binding and formation of large bacterial aggregates in biofilm. Reintroduction of a wild-type ORF6 gene by phage transduction restored the phenotype. The results show that TspB mediated IgG binding and aggregate/biofilm formation triggered by factors in human serum. As has been observed for other Ig-binding proteins, the activities mediated by TspB may provide protection against immune responses, which is in accordance with the association of prophage DNA carrying ORF6 with invasive meningococcal strains.