Miracle-dz/UniFAR-FTUs huggingface dataset:
Cdc42p-Interacting Protein Bem4p Regulates the Filamentous-Growth Mitogen-Activated Protein Kinase Pathway

ABSTRACT The ubiquitous Rho (Ras homology) GTPase Cdc42p can function in different settings to regulate cell polarity and cellular signaling. How Cdc42p and other proteins are directed to function in a particular context remains unclear. We show that the Cdc42p-interacting protein Bem4p regulates the mitogen-activated protein kinase (MAPK) pathway that controls filamentous growth in Saccharomyces cerevisiae. Bem4p controlled the filamentous-growth pathway but not other MAPK pathways (mating or high-osmolarity glycerol response [HOG]) that also require Cdc42p and other shared components. Bem4p associated with the plasma membrane (PM) protein, Sho1p, to regulate MAPK activity and cell polarization under nutrient-limiting conditions that favor filamentous growth. Bem4p also interacted with the major activator of Cdc42p, the guanine nucleotide exchange factor (GEF) Cdc24p, which we show also regulates the filamentous-growth pathway. Bem4p interacted with the pleckstrin homology (PH) domain of Cdc24p, which functions in an autoinhibitory capacity, and was required, along with other pathway regulators, to maintain Cdc24p at polarized sites during filamentous growth. Bem4p also interacted with the MAPK kinase kinase (MAPKKK) Ste11p. Thus, Bem4p is a new regulator of the filamentous-growth MAPK pathway and binds to general proteins, like Cdc42p and Ste11p, to promote a pathway-specific response.
Botox A injection for pain after laparoscopic ventral hernia: a case report.

INTRODUCTION Laparoscopic ventral hernia repair has many advantages over open techniques: adequate visualization of the entire abdominal wall, ease of placement of preperitoneal mesh with adequate overlap, and cosmesis. Intense and activity limiting pain is often one inferior aspect of this repair. We report the case of a patient who was intolerant of narcotic pain medicine with activity limiting pain. A novel technique for postoperative pain control was instituted utilizing Botox A (Allergan Inc., Irvine, CA, USA). METHODS Botox A was diluted to 2 units per mL and three injection sites were chosen on each side of the abdominal wall. All three muscle bellies (external oblique, internal oblique, and transversus) were identified by ultrasound and 8 mL was injected in each. This resulted in three muscle layers at six sites for a total of 18 injections. A total of 300 units of Botox A were utilized. RESULTS Pain scores improved from 10/10 to 2/10 and were durable at 3-month follow up. CONCLUSION Botox A provided significant pain control for this patient after laparoscopic ventral hernia repair. Continued prospective study to define long-term outcomes, cost savings, and appropriate timing of injections is underway.
Elevated White Blood Cell Count at the Time of Recurrence Diagnosis Is an Indicator of Short Survival in Patients With Recurrent Cervical Cancer

Objectives The aim of this study was to investigate the prognostic significance of elevated white blood cell (WBC) count at the time of the diagnosis of cervical cancer recurrence. Methods The baseline characteristics and outcome data of 219 patients who had a diagnosis of recurrent cervical cancer between April 1996 and September 2010 were collected and reviewed. Survival after recurrence was compared between the leukocytosis group (WBC ≥9000/&mgr;L) and the nonleukocytosis group (WBC <9000/&mgr;L). A Cox proportional hazards regression model was used to investigate the prognostic significance of elevated WBC count in patients with recurrent cervical cancer. Results The patients in the leukocytosis group showed significantly shorter disease-free interval (P = 0.0005) and more frequently had multiple recurrences (P = 0.0101) than those in the nonleukocytosis group. The median survival after recurrence of the patients with elevated WBC count was 9 months, which was significantly shorter than the 21 months observed in the patients without normal WBC count (log rank; P < 0.0001). Multivariate analyses revealed that clinical stage, tumor diameter, histology, an elevated WBC count (≥9000/&mgr;L), and an elevated neutrophil count (≥6500/&mgr;L) were significant prognostic factors in survival after recurrence. Conclusion The elevated WBC count at the time of the diagnosis of recurrence is an independent prognostic factor in patients with recurrent cervical cancer.
The relationship between multiple mating by queens, within‐colony genetic variability and fitness in the ant Lasius niger

Multiple mating has been suggested to benefit social insect queens because high genetic variation within colonies might decrease the load imposed by sterile diploid males, enhance resistance to parasites and pathogens, and lead to a more effective division of labour and/or a wider range of tolerable environmental conditions. We tested these hypotheses in the ant Lasius niger with three population samples from Switzerland and Sweden. We found no diploid males in young or mature colonies suggesting a lack of diploid male load. Colonies with multiply‐mated queens were not larger nor did they produce more sexuals than colonies with singly‐mated queens. We did find a significantly lower frequency of multiple mating among newly mated queens than among the queens heading mature colonies in one population sample (Switzerland 1997). However, this result was not repeated in the other study population, or in the following year in the Swiss population.
Sociodemographic and psychosocial factors in childhood as predictors of adult mortality.

OBJECTIVES Childhood sociodemographic, psychosocial, and environmental factors are often assumed to affect adult health and longevity. These relationships were prospectively tested by using the 7-decade Terman Life Cycle Study of Children With High Ability (n = 1285). METHODS Parental socioeconomic status, childhood health, objective childhood stressors (e.g., death or divorce of parents), and childhood personality were considered as potential predictors in hazard regression analyses of longevity through 1991. RESULTS Parental divorce during childhood predicted decreased longevity, with sex controlled. Other potential social predictors failed to show significant associations with longevity. Three dimensions of childhood personality--conscientiousness, lack of cheerfulness, and permanency of mood (males only)--predicted increased longevity. The effects of parental divorce and childhood personality were largely independent and did not account for any of the gender difference in mortality. CONCLUSIONS A small number of childhood factors significantly predicted mortality across the life span in this sample. Further research should focus on how these psychosocial factors influence longevity.
Involvement of interleukin‐1, prostaglandins and mast cells in rectal distension‐induced colonic water secretion in rats

1 In vivo rectal distension (RD) induces a neurally mediated colonic net water hypersecretion in rats. Interleukin‐1β (IL‐1β) also induces neural colonic water hypersecretion involving the release of prostaglandins (PGs) and a mast cell degranulation in rats. This study investigated in vivo the role of IL‐1, PGs and mast cells in RD‐induced colonic hypersecretion. 2 Proximal colonic net water flux was determined using [14C]polyethylene glycol (PEG) 4000 (mol. wt, 4000) in anaesthetized rats. On strips taken from the distal colon: (i) a histological analysis was performed to determine the number of mucosal mast cells (MMC); and (ii) histamine levels were measured by radioimmunoassay after stimulation with compound 48/80. 3 RD induced a net colonic water secretion that was blocked by i.c. v. administration of IL‐1ra (an IL‐1 receptor antagonist) and indomethacin, and by systemic treatment with doxantrazole and indomethacin. RD decreased the number of resident mast cells and the release of histamine from the distal colonic strips. Moreover, using SDS‐PAGE immunoblotting the expression of IL‐1β was detected in the brain. 4 These results suggest that, in rats, RD induces colonic net water hypersecretion by the activation of a neuro‐immunological reflex pathway, involving brain IL‐1β, PG release and peripheral mast cell degranulation.
Seasonal changes in the production of two novel and abundant ovarian steroids in the channel catfish (Ictalurus punctatus).

Timely and appropriate changes in steroid plasma titers are necessary for successful reproduction in all vertebrates. Gonadal steroidogenesis of the most intensively cultured teleost species in North America, the channel catfish (Ictalurus punctatus), is poorly understood so a year-long study was conducted to investigate seasonal changes in ovarian steroidogenesis. Incubations of ovarian tissue were conducted monthly with [3H]pregnenolone and the medium was analyzed by high-performance liquid chromatography (HPLC) with radioactivity detection. The suite of steroids produced by the catfish ovary included the expected sex steroids (estradiol and testosterone) and 18 additional ovarian metabolites, including five steroids that have yet to be identified. Androstenedione, 20beta-dihydroprogesterone, 5|P-dihydrotestosterone, estriol, 11beta-hydroxyandrostenedione, 17-hydroxypregnenolone, 17-hydroxyprogesterone, 11beta-hydroxytestosterone, and progesterone were characterized by a combination of HPLC and thin-layer chromatography. Two of the most abundant steroids were isolated and analyzed by gas chromatography coupled with mass spectrometry (GC-MS). One of the steroids, 7alpha-hydroxypregnenolone (7P5), is a novel steroid in teleosts and was produced late in vitellogenic growth of the oocyte. Evidence suggests that the enzyme responsible for converting pregnenolone to 7P5, 7alpha-hydroxylase, is a cytochrome P450. The second abundant steroid metabolite was partially characterized by GC-MS as an hydroxylated form of 17-hydroxy-pregnenolone (chi,17P5). This steroid was most abundant when the ovary was regressed and during early vitellogenesis and rapidly decreased prior to spawning. In mammals, 7P5 has been identified as an important neurosteroid; however, the reproductive significance of 7P5 and chi,17P5 in catfish is unknown.
An association study between catechol-O-methyl transferase gene polymorphism and methamphetamine psychotic disorder

Objective A series of methamphetamine psychosis reveals two kinds of clinical courses of methamphetamine psychosis: transient type and prolonged type. Furthermore, paranoid psychosis sometimes recurs without methamphetamine reuse, referred to as spontaneous relapse. Dysfunction of central dopaminergic neurotransmission has been implicated in the pathogenesis of these psychiatric states. Catechol-O-methyl transferase appears to play a unique role in regulating synaptic dopaminergic activity. This study aimed to investigate whether a functional polymorphism of the catechol-O-methyl transferase gene would be involved in the development of these psychiatric states. Basic methods We examined the functional polymorphism of val 158 met (catechol-O-methyl transferase) in 143 patients with methamphetamine psychosis and 200 healthy controls in Japan. The patients were divided into subgroups by several characteristic clinical features. Main results We found a significant difference in the catechol-O-methyl transferase allele frequency between patients with spontaneous relapse and the controls (P=0.018, odds ratio=1.67). Odds ratio implied that the patients with spontaneous relapse had a nearly 1.7-fold higher rate of the low activity alleles (met) than the controls. Conclusions Our results indicate that the met allele frequency of the catechol-O-methyl transferase is associated with patients who experienced methamphetamine psychosis and spontaneous relapse, suggesting that patients with a met allele appear to be at increased risk of an adverse response to methamphetamine.
Treatment of severe steroid resistant acute GVHD with mesenchymal stromal cells (MSC).

BACKGROUND Several studies revealed that MSC from human bone marrow can downregulate graft-versus-host disease (GVHD) after allogeneic HSCT. METHODS Herein we present 50 patients with acute GVHD who got 74 (1-4) MSC infusions for 54 separate episodes of aGVHD. RESULTS aGVHD was defined as steroid resistant grade IV aGVHD in 42 cases. The major presentation was gastrointestinal GVHD; two (n=18) or more (n=21) systems were involved in the majority of cases. The 1(st) infusion with MSC was given on day +27 (range, 1 to 136); d+45 (range, +11 to +150) post diagnosis of aGVHD and HSCT, respectively. In 2/3 of the cases treatment was performed with frozen stocked MSCs; in 62 cases early passages (1-3) were used. The median number of infused cells was 1.14±0.47 million per kg in the first injection and up to 4.27 (1.70±1.10) millions in total. The two patients with aggressive liver GVHD received MSCs injections intra hepatic arteries without changes of blood flow or evidence cytolysis, but also without a visible effect. Disease free survival at 3.6 years was 56%. We observed better overall survival in patients with GVHD grade < 4, in responders to the 1(st) treatment with MSC, and in pediatric group. The multivariate analysis demonstrated independent influence on survival of initial response and younger age. There were no immediate or late toxicity or side effects. CONCLUSION Injection of MSCs seems to be a promising and safe treatment of GVHD. The encouraging results obviously should be confirmed in a randomized prospective study.
Protein sequence analysis and mapping of IgE and IgG epitopes of an allergenic 98‐kDa Dermatophagoides farinae paramyosin, Der f 11

Background: A 98‐kDa mite paramyosin (Der f 11) from Dermatophagoides farinae (Df) is highly allergenic, and its cDNA (Df642) has been cloned. This paper describes the sequence characteristics and the mapping of the immunodominant human IgE and IgG epitopes of Der f 11.
Manipulation of EphB2 Regulatory Motifs and SH2 Binding Sites Switches MAPK Signaling and Biological Activity*

Signaling by the Eph family of receptor tyrosine kinases (RTKs) is complex, because they can interact with a variety of intracellular targets, and can potentially induce distinct responses in different cell types. In NG108 neuronal cells, activated EphB2 recruits p120RasGAP, in a fashion that is associated with down-regulation of the Ras-Erk mitogen-activated kinase (MAPK) pathway and neurite retraction. To pursue the role of the Ras-MAPK pathway in EphB2-mediated growth cone collapse, and to explore the biochemical and biological functions of Eph receptors, we sought to re-engineer the signaling properties of EphB2 by manipulating its regulatory motifs and SH2 binding sites. An EphB2 mutant that retained juxtamembrane (JM) RasGAP binding sites but incorporated a Grb2 binding motif at an alternate RasGAP binding site within the kinase domain had little effect on basal Erk MAPK activation. In contrast, elimination of all RasGAP binding sites, accompanied by the addition of a Grb2 binding site within the kinase domain, led to an increase in phospho-Erk levels in NG108 cells following ephrin-B1 stimulation. Functional assays indicated a correlation between neurite retraction and the ability of the EphB2 mutants to down-regulate Ras-Erk MAPK signaling. These data suggest that EphB2 can be designed to repress, stabilize, or activate the Ras-Erk MAPK pathway by the manipulation of RasGAP and Grb2 SH2 domain binding sites and support the notion that Erk MAPK regulation plays a significant role in axon guidance. The behavior of EphB2 variants with mutations in the JM region and kinase domains suggests an intricate pattern of regulation and target recognition by Eph receptors.
Step training improves the speed of voluntary step initiation in aging.

BACKGROUND Falls related to balance dysfunction are among the major problems of older individuals. The timing characteristics of protective voluntary stepping are critically related to effective balance recovery and are often delayed and slowed with age. This study investigated the influence of step training on the timing characteristics of voluntary step initiation in younger and older adults. METHODS Voluntary reaction time stepping was evaluated before and after training in 12 younger adults and 8 healthy community-dwelling older adults who performed a 3-week regimen of either twice weekly induced step training (destabilizing large waist pulls) or voluntary step practice to a somatosensory reaction stimulus cue (nondestabilizing small waist pulls). RESULTS Overall, the first step initiation times were slower for the older than for the younger subjects for both the somatosensory reaction stimulus cue task and an auditory transfer cue task. Step completion time was completed earlier for the young posttraining subjects, and older subjects generally had a longer step length. Training resulted in significant reductions in step initiation timing for the old (17%) and young (15%) subjects. Across age groups, the induced training group showed greater reductions in step initiation time than the voluntary practice group for the auditory transfer cue task. CONCLUSIONS A 3-week period of either voluntary or waist-pull-induced step training reduced step initiation time in older and younger adults. Moreover, compared with voluntary step practice, induced step training resulted in a significantly greater improvement in reaction time stepping for an auditory transfer cue task. At least in the short term, such step training has the potential to help older adults perform more like younger adults in their step initiation timing.
Evaluation of iohexol clearance used to estimate glomerular filtration rate in clinically normal foals.

OBJECTIVE To determine whether pharmacokinetic analysis of data derived from a single i.v. dose of iohexol could be used to predict creatinine clearance and evaluate simplified methods for predicting serum clearance of iohexol with data derived from 2 or 3 blood samples in clinically normal foals. ANIMALS 10 healthy foals. PROCEDURE Serum disposition of iohexol and exogenous creatinine clearance was determined simultaneously in each foal (5 males and 5 females). A 3-compartment model of iohexol serum disposition was selected via standard methods. Iohexol clearance calculated from the model was compared with creatinine clearance. Separate limited-sample models were created with various combinations of sample times from the terminal slope of the plasma versus time profile for iohexol. Correction factors were determined for the limited-sample models, and iohexol clearance calculated via each method was compared with exogenous creatinine clearance by use of method comparison techniques. RESULTS Mean exogenous creatinine clearance was 2.17 mL/min/kg. The disposition of iohexol was best described by a 3-compartment open model. Mean clearance value for iohexol was 2.15 mL/min/kg and was not significantly different from mean creatinine clearance. A method for predicting serum iohexol clearance based on a 2-sample protocol (3- and 4-hour samples) was developed. CONCLUSIONS AND CLINICAL RELEVANCE Iohexol clearance can be used to predict exogenous creatinine clearance and can be determined from 2 blood samples taken after i.v. injection of iohexol. Appropriate correction factors for adult horses and horses with abnormal glomerular filtration rate need to be determined.
Ameliorative effect of naringenin on hyperglycemia-mediated inflammation in hepatic and pancreatic tissues of Wistar rats with streptozotocin- nicotinamide-induced experimental diabetes mellitus

Abstract In diabetes mellitus (DM), sustained hyperglycemia results in the generation of reactive oxygen species, ultimately leading to increased oxidative stress and inflammation in vital tissues. In the present study, possible ameliorative effects of naringenin on hyperglycemia-mediated inflammation in experimental streptozocin (STZ)-nicotinamide-induced DM were sought. DM was induced experimentally in overnight-fasted Wistar rats (150–180 g) by intra-peritoneal injection of STZ (50 mg/kg.b.w) and of nicotinamide (110 mg/kg.b.w); control rats (n = 6) received only vehicle (0.5 ml of 0.1 M of cold citrate buffer; pH 4.5). One group of diabetic rats (n = 6) was left untreated while another group of diabetic rats (n = 6) received naringenin (50 mg/kg b.w./day) orally for 21 days. At this time, hemotological indices (erythrocyte sedimentation rate [ESR], total white blood cell [WBC] count, differential WBC percentage, and platelet count) were measured. Significant alterations in expression of gene and protein biomarkers of inflammation in hepatic and pancreatic tissues were determined by measuring mRNA levels and the level of protein expressed, respectively, as was the total nitric oxide level in these tissues. Diabetic rats showed significantly higher mean ESR values, total WBC counts, differential WBC percentages, and platelet counts than those in control rats; similarly, mean mRNA levels of C-reactive protein, pro-inflammatory cytokine, nuclear factor-κB and inducible nitric oxide synthase genes and mean intensities of expression of the corresponding proteins in the hepatic and pancreatic tissue samples from diabetic rats significantly exceeded those in control rats. However, in diabetic rats treated with naringenin, the values of hematological, mRNA transcript and protein indices of inflammation were all lower than those in diabetic rats. These results suggest that naringenin possibly alleviates hyperglycemia-mediated inflammation in experimental STZ-nicotinamide-induced DM in Wistar rats.
Quality assessments of peptide–spectrum matches in shotgun proteomics

The peptide identification process in shotgun proteomics is most frequently solved with search engines. Such search engines assign scores that reflect similarity between the measured fragmentation spectrum and the theoretical spectra of the peptides of a given database. However, the scores from most search engines do not have a direct statistical interpretation. To understand and make use of the significance of peptide identifications, one must thus be familiar with some statistical concepts. Here, we discuss different statistical scores used to show the confidence of an identification and a set of methods to estimate these scores. We also describe the variance of statistical scores and imperfections of scoring functions of peptide–spectrum matches.