Quantitative trait loci analysis of hormone levels in Arabidopsis roots.
Quantitative trait loci (QTL) analyses for five groups of hormones, including cytokinins in Arabidopsis roots were performed using recombinant inbred lines (Ler×Cvi). Significant QTLs were detected for cytokinins, jasmonic acid and salicylic acid. Separate analysis of two sub-populations, viz., vegetative and flowering plants revealed that many of the QTLs were development-specific. Using near-isogenic lines, several significant QTLs were confirmed; three co-localized QTL regions were responsible for determining several cytokinin metabolites. Using a knock-out plant, a functional role of zeatin N-glucosyltransferase gene (UGT76C2) underlying a large-effect QTL for levels of tZ-N-glucosides and tZRMP was evaluated in the metabolism of cytokinins. Pleotropic effects of this gene were found for cytokinin levels in both roots and leaves, but significant changes of morphological traits were observed only in roots. Hormone QTL analysis reveals development-specific and organ-dependent aspects of the regulation of plant hormone content and metabolism.


Myosin I can act as a molecular force sensor.
The ability to sense molecular tension is crucial for a wide array of cellular processes, including the detection of auditory stimuli, control of cell shape, and internalization and transport of membranes. We show that myosin I, a motor protein that has been implicated in powering key steps in these processes, dramatically alters its motile properties in response to tension. We measured the displacement generated by single myosin I molecules, and we determined the actin-attachment kinetics with varying tensions using an optical trap. The rate of myosin I detachment from actin decreases >75-fold under tension of 2 piconewtons or less, resulting in myosin I transitioning from a low (<0.2) to a high (>0.9) duty-ratio motor. This impressive tension sensitivity supports a role for myosin I as a molecular force sensor.


Prevalence of Mycoplasma genitalium infection with antimicrobial resistance mutations among gay sex workers in China.
Gay sex workers (GSWs) within the population of men who have sex with men in China are known as money boys (MBs). Limited research has been conducted to investigate the infection rate and antimicrobial resistance of Mycoplasma genitalium (M. genitalium) among GSWs in China. This study aimed to evaluate the status of M. genitalium infection among in GSWs. This study was performed among 349 GSWs who were followed up for four years by internet-based sampling collection. The participants were asked to complete an online questionnaire using a mobile app, and trained interviewers took urethral, anorectal, and saliva swab specimens. STIs, including HIV and M. genitalium, were detected. Detection of resistance-associated mutations (RAMs) to macrolides and fluoroquinolones was performed via Sanger sequencing of the 23S rRNA, parC and gyrA genes. GSWs were enrolled by identifying 10 initial "seeds" from the Blued and WeChat apps. Face-to-face interviews were conducted with 349 GSWs from June 2017 to July 2021. The prevalence of M. genitalium and HIV positivity was 92/349 (26.4%, 95% confidence interval [CI] 21.7-31.0) and 71/349 (20.3%, 95% CI 16.3-24.4), respectively. The proportion of GSWs with M. genitalium infection alone in urethral swabs was 16, and the proportion with symptoms was 2/16 (12.5%). The proportion of GSWs with M. genitalium infection alone in anorectal swabs was 36, and the proportion with symptoms was 3/36 (8.3%). Multivariate regression analysis showed that using new types of drugs in the past 3 months and inconsistent condom usage with clients in the past 30 days were associated with M. genitalium infection. Macrolide resistance within the 23S rRNA gene was detected in 73/88 (83.0%) of the M. genitalium-positive GSWs. Moreover, 79.8% (71/89) of parC and 21.1% (19/90) of gyrA genes had mutations responsible for fluoroquinolone resistance. Three cases had no mutations in any of the three genes, 11 cases had mutations in all three genes, five cases had gyrA and parC gene mutations with no mutation in the 23S rRNA gene, and 42 cases had 23S rRNA and parC gene mutations with no mutation in the gyrA gene. M. genitalium infections in our study displayed a high prevalence and very high levels of macrolide and fluoroquinolone resistance among GSWs in China. Asymptomatic M. genitalium infections are quite common among GSWs. Routine resistance testing of M. genitalium-positive specimens and antimicrobial resistance surveillance are crucial.


Copper-Catalyzed Synthesis of Substituted 2,4-Diamino-1,3,5-triazines from 1,1-Dibromoalkenes and Biguanides.
An efficient copper-catalyzed synthesis of substituted 2,4-diamino-1,3,5-triazines from 1,1-dibromoalkenes and biguanides under mild conditions has been developed. The reaction occurred in moderate to good yields and tolerated alkyl-, heterocyclic-, or aryl-substituted 1,1-dibromoalkenes containing functionalities such as nitriles, ethers, and halogens. Monosubstituted to tetrasubstituted biguanidines also afforded the desired products.


Case of Lemierre's syndrome presenting with thyroid abscess.
Lemierre's syndrome is an uncommon condition characterized by post-anginal septicemia due to anaerobes. Reported here is a case of Lemierre's syndrome presenting with thyroid and liver abscesses. At presentation, the 70-year-old female patient complained of fever, jaundice and neck pain. Computed tomography (CT) and ultrasound confirmed the presence of a left-sided internal jugular vein thrombosis as well as abscesses in the left thyroid lobe and the right lobe of the liver with pleural effusion. The thyroid abscess was treated with a left lobectomy.


Adolescent coping with grief after the death of a loved one.
The purpose of this article was to describe adolescent coping after the death of a loved one. Data were obtained by two self-report questionnaires filled in by 14-16-year-old pupils in two secondary schools in Finland. The sample consisted of 89 adolescents (70% girls) who had each experienced the death of a loved one. The instrument used in the study was developed by Hogan and DeSantis. The article reports the responses to two open-ended questions. The data were analyzed using content analysis. The most important factors that helped adolescents cope with grief were self-help and support from parents, relatives and friends. However, the official social support system was not experienced as very helpful. No one reported help, for example, from school health services. According to the adolescents, fear of death, a sense of loneliness and intrusive thoughts were factors that hindered coping with grief. Some respondents felt that parents or friends were an additional burden on them. The results are discussed in terms of identifying the different impact of social support, the importance of self-help and professional help. Knowledge of factors that have an effect on adolescent coping with bereavement is important for families, effective nursing practice, school health services and parents.


Support of an anephric dog for 54 days with ambulatory peritoneal dialysis and a newly designed peritoneal catheter.
A bilaterally nephrectomized dog was successfully supported with peritoneal dialysis for 54 days, using a radically new design of access catheter and a human dialysis schedule designated as continuous ambulatory peritoneal dialysis. The dog remained active and alert with a stabilized blood urea nitrogen of 30 to 40 mg/dl and a serum creatinine concentration of 4 to 6.5 mg/dl. Problems encountered with the peritoneal dialysis included the propensity for developing peritonitis, anorexia, and a significant plasma protein loss in the dialysate fluid as result of leakage across the peritoneum. Protein loss coupled with anorexia produced a catabolic state, and the animal was euthanatized because of this, at postnephrectomy day 54. The development of a new catheter design alleviated the drainage problems of the straight tube Tenckhoff catheter. Its use coupled with the continuous ambulatory peritoneal dialysis schedule and detailed management techniques allowed using the anephric dog as a model of uremia. In addition, peritoneal dialysis could be a viable treatment for animals presenting with acute reversible anuric or oliguric renal failure where conservative medical management with fluids and diuretics has failed to give clinical improvement.


E-cadherin expression in invasive breast cancer.
There were investigated 22 cases with invasive breast carcinoma from the archive material, and the immunohistochemical expression of E-cadherin was correlated with clinical stage, pathological type, grade of the tumor, and lymph nodes status. The expression of E-cadherin was assessed by the pattern of the final product of reaction and number of positive cells. The reaction was appreciated as normal if over 70% of tumor cells showed membrane of membrane and cytoplasmic pattern, and aberrant, if less than 70% of tumor cells were positive. There were found 45.5% cases with normal expression and 54.5% with aberrant expression. Strong positive reaction was found mainly in tumor cells invading the adipose tissue, but the reaction was weak or negative in tumor cells within the vessels. Both normal and aberrant expression of E-cadherin correlates with grade and with clinical stage. In our study was found that the increase of the tumor grade is associated with decrease in the expression of E-cadherin. Tumors over 2 cm in their larger diameter showed a decreased expression of E-cadherin. Seventeen from 22 cases with lymph node metastasis had positive reaction in the primary, but there were not found significant differences between the normal and aberrant expression.


Antibiotic administration reduces the rate of intraamniotic inflammation in preterm prelabor rupture of the membranes.
Preterm prelabor rupture of the membranes (PPROM) is frequently complicated by intraamniotic inflammatory processes such as intraamniotic infection and sterile intraamniotic inflammation. Antibiotic therapy is recommended to patients with PPROM to prolong the interval between this complication and delivery (latency period), reduce the risk of clinical chorioamnionitis, and improve neonatal outcome. However, there is a lack of information regarding whether the administration of antibiotics can reduce the intensity of the intraamniotic inflammatory response or eradicate microorganisms in patients with PPROM. The first aim of the study was to determine whether antimicrobial agents can reduce the magnitude of the intraamniotic inflammatory response in patients with PPROM by assessing the concentrations of interleukin-6 in amniotic fluid before and after antibiotic treatment. The second aim was to determine whether treatment with intravenous clarithromycin changes the microbial load of Ureaplasma spp DNA in amniotic fluid. A retrospective cohort study included patients who had (1) a singleton gestation, (2) PPROM between 24+0 and 33+6 weeks, (3) a transabdominal amniocentesis at the time of admission, and (4) intravenous antibiotic treatment (clarithromycin for patients with intraamniotic inflammation and benzylpenicillin/clindamycin in the cases of allergy in patients without intraamniotic inflammation) for 7 days. Follow-up amniocenteses (7th day after admission) were performed in the subset of patients with a latency period lasting longer than 7 days. Concentrations of interleukin-6 were measured in the samples of amniotic fluid with a bedside test, and the presence of microbial invasion of the amniotic cavity was assessed with culture and molecular microbiological methods. Intraamniotic inflammation was defined as a bedside interleukin-6 concentration ≥745 pg/mL in the samples of amniotic fluid. Intraamniotic infection was defined as the presence of both microbial invasion of the amniotic cavity and intraamniotic inflammation; sterile intraamniotic inflammation was defined as the presence of intraamniotic inflammation without microbial invasion of the amniotic cavity. A total of 270 patients with PPROM were included in this study: 207 patients delivered within 7 days and 63 patients delivered after 7 days of admission. Of the 63 patients who delivered after 7 days following the initial amniocentesis, 40 underwent a follow-up amniocentesis. Patients with intraamniotic infection (n = 7) and sterile intraamniotic inflammation (n = 7) were treated with intravenous clarithromycin. Patients without either microbial invasion of the amniotic cavity or intraamniotic inflammation (n = 26) were treated with benzylpenicillin or clindamycin. Treatment with clarithromycin decreased the interleukin-6 concentration in amniotic fluid at the follow-up amniocentesis compared to the initial amniocentesis in patients with intraamniotic infection (follow-up: median, 295 pg/mL, interquartile range [IQR], 72-673 vs initial: median, 2973 pg/mL, IQR, 1750-6296; P = .02) and in those with sterile intraamniotic inflammation (follow-up: median, 221 pg/mL, IQR 118-366 pg/mL vs initial: median, 1446 pg/mL, IQR, 1300-2941; P = .02). Samples of amniotic fluid with Ureaplasma spp DNA had a lower microbial load at the time of follow-up amniocentesis compared to the initial amniocentesis (follow-up: median, 1.8 × 104 copies DNA/mL, 2.9 × 104 to 6.7 × 108 vs initial: median, 4.7 × 107 copies DNA/mL, interquartile range, 2.9 × 103 to 3.6 × 107; P = .03). Intravenous therapy with clarithromycin was associated with a reduction in the intensity of the intraamniotic inflammatory response in patients with PPROM with either intraamniotic infection or sterile intraamniotic inflammation. Moreover, treatment with clarithromycin was related to a reduction in the load of Ureaplasma spp DNA in the amniotic fluid of patients with PPROM <34 weeks of gestation.


Low back pain after a dental procedure: a case of Streptococcus viridans vertebral osteomyelitis.
Vertebral osteomyelitis due to Streptococcus viridans following a dental procedure is a rarely reported phenomenon. We discuss the case of a 67-year-old immunocompetent woman who presented with low back pain of 3 weeks duration associated with subjective fever and chills. On admission, the MRI of the lumbar spine showed L5-S1 vertebral osteomyelitis with associated paravertebral and epidural abscesses. Subsequently, detailed history was retaken and the patient reported having had a maxillary tooth extraction followed by a dental implant 2 months prior to the onset of her symptoms. Blood and abscess fluid cultures grew S. viridans Transthoracic echocardiogram showed no evidence of endocarditis. The patient was started on intravenous ceftriaxone but her treatment course was complicated by agranulocytosis requiring a switch to vancomycin. She required a total of 9 weeks of intravenous antibiotics for complete clinical cure.


[Advances in the genetic diagnosis and treatment of prostate cancer].
As the incidence of prostate cancer (PCa) increases with the aging of men, more and more attention is paid to the prevention and treatment of the pregnancy. In addition to widely used PSA test, MRI and other diagnostic strategies, PCa-related gene screening, with the development of such new technologies as second-generation gene sequencing, is more and more applied in the detection of PCa. Different types of tumor-related genes have different effects on the development and progression of PCa as well as different values in the diagnosis, treatment and prognosis of the malignancy. This review focuses on the advances in the studies of PCa-related critical genes and key gene pathways.


Identification and characterization of a TNF alpha antagonist derived from a monoclonal antibody.
Peptides derived from the CDRs of the anti-TNF alpha monoclonal antibody Di62 were tested for inhibition of binding of Di62 to TNF alpha as well as of TNF alpha to its 55 and 75 kDa receptor. A peptide derived from the CDR1 of the light chain was shown to specifically inhibit Di62 binding to TNF alpha with markedly higher activity (Ki = 4 microM) than all other CDR-derived peptides. This peptide also significantly inhibited binding of TNF alpha to its 55 and 75 kDa receptor and protected L929 cells from the cytotoxic effect of TNF alpha (IC50 = 6 microM). The C-terminal region of this peptide, which is homologous to the 55 and 75 kDa TNF receptor, was found to be essential for activity.


A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA-PBC Study Group.
In primary biliary cirrhosis the hepatic lesions may result, at least in part, from the intracellular accumulation of potentially toxic endogenous bile acids. Preliminary work suggests that the administration of ursodiol (also called ursodeoxycholic acid), a hydrophilic bile acid without hepatotoxicity, leads to improvement in the condition of patients with primary biliary cirrhosis. We conducted a two-year, multicenter, double-blind trial to compare the efficacy of ursodiol with that of placebo. Patients with biopsy-proved primary biliary cirrhosis were randomly assigned to receive either ursodiol (13 to 15 mg per kilogram of body weight per day) (n = 73) or placebo (n = 73). Treatment failure was defined as a doubling of bilirubin levels to more than 70 mumol per liter or the occurrence of a severe complication (ascites or variceal bleeding) or an adverse reaction. Treatment failed in 6 patients in the ursodiol group, as compared with 13 in the placebo group (P less than 0.01 by Cox regression model). A single patient in each group withdrew because of minor adverse effects. After two years of treatment, the proportion of patients with clinically overt disease decreased only in the ursodiol group (P less than 0.02). The patients treated with ursodiol had significant improvements in serum levels of bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, cholesterol, and IgM (all P less than 0.001); the antimitochondrial-antibody titer (P less than 0.01); and the Mayo risk score (P less than 0.001). Follow-up analysis of 95 liver-biopsy specimens showed a significant improvement in the mean histologic score (P less than 0.002) and in all the characteristic histologic features except fibrosis only in the group given ursodiol. Ursodiol is a safe and effective treatment for primary biliary cirrhosis.


Development of anti-HBV agents targeting HBV capsid proteins.
Hepatitis B is a viral hepatitis, which is caused by infection of hepatitis B virus (HBV). This disease progresses to chronic hepatitis, cirrhosis and liver cancer. To treat hepatitis B, exclusion of virus and covalently closed circular DNA (cccDNA) that is formed in hepatocyte nucleus is necessary. A hepatitis B capsid protein (HBc) is an indispensable protein, which forms the capsid that encapsulates viral DNA. Since HBc is correlated to the transcriptional regulation of cccDNA, this protein would be an attractive target for complete cure of hepatitis B. By in silico screening of a library of compounds, a small compound, Cpd4 (1), which binds to a hydrophobic cavity located in the inner pocket on the tetramer interface of HBc proteins, was identified. In anti-HBV assays, this synthetic compound, Cpd4 (1) decreased the amount of HBV core related antigen (HBcrAg), which has been correlated with the proliferation of HBV, and decreased the amount of HBV surface antigen (HBsAg), which is correlated with the amount of cccDNA. Based on Cpd4 (1) as a lead compound, 20 derivatives of 1 were designed and synthesized and their structure-activity relationships were examined. As a result, specific interactions between each compound and amino acid residues of the target protein appeared to be unimportant but the shape/size of compounds which can bind to the hydrophobic cavity might be important in the expression of high anti-HBV activity, and a more potent derivative, TKB-HBV-CA-001 (3b), was discovered. These results will be useful in the development of novel anti-HBV agents for a complete cure of hepatitis B.


Influence of feed efficiency classification and growing and finishing diet type on meat tenderness attributes of beef steers.
Enhancing feed efficiency (FE) in cattle continues to be an important goal in the beef industry. Previous research suggests improving FE may alter calpain system activity, potentially having negative effects on meat tenderness. The objective of this study was to assess the potential influence of beef cattle FE on postmortem meat tenderness. During the growing phase, 181 crossbred steers were fed for 76 d at the University of Missouri on a whole shell corn-based diet (MU-Corn; = 90) or a roughage-based diet (MU-Rough; = 91). Within diet, steers were classified for FE based on residual feed intake (RFI) calculations. Within each growing phase diet, the 12 most feed efficient (HFE; average RFI -3.33 ± 0.77) and 12 least feed efficient (LFE; average RFI 2.90 ± 0.94) steers (48 steers total) were selected and shipped to Iowa State University for the finishing phase. Steers were fed in pens with GrowSafe bunks and equally assigned to a cracked corn-based finishing diet (ISU-Corn) or a byproduct-based finishing diet (ISU-Byp) for the 87-d finishing phase. After a 24-h chill, rib sections were collected from all carcasses and aged for 2 or 14 d prior to analysis of calpastatin activity and calpain 1 autolysis (d 2), troponin-T degradation (d 2 and 14), proximate composition (d 2), and Warner-Bratzler shear force (WBSF; d 14). Data were analyzed as a 2 × 2 × 2 factorial, with steer or steak as the experimental unit ( = 6 per treatment combination). There were no 3- or 2-way interactions ( ≥ 0.12) noted for any data, with the exception of steak lipid content, which tended ( = 0.08) to be affected by FE × Iowa State University diet. Steaks from LFE steers had greater lipid content compared with steaks from HFE steers within ISU-Byp, with no differences due to FE within ISU-Corn. Growing diet did not affect calpastatin activity, calpain 1 autolysis, or troponin T degradation ( ≥ 0.12); however, MU-Rough had greater WBSF than MU-Corn ( = 0.05). Day-2 calpastatin activity tended ( = 0.10) to be greater in steaks from HFE vs. LFE steers, although no differences due to FE classification were observed for calpain 1 protein, troponin-T degradation, or WBSF ( ≥ 0.13). Finishing diet did not affect calpastatin activity, calpain 1 autolysis, d-2 troponin-T degradation, or WBSF ( ≥ 0.24); however, d-14 troponin-T degradation was greater in ISU-Corn than in ISU-Byp ( = 0.005). In this study, using phenotypic extremes for FE revealed a tendency for greater calpastatin activity only in highly feed-efficient steers; however, these data indicate that high-fiber diets may negatively impact meat tenderness, and further work is needed to clarify the influence of diet type on parameters of meat tenderness.


Role of nitric oxide and cyclooxygenase pathways in the coronary vascular effects of halothane, isoflurane and desflurane in red blood cell-perfused isolated rabbit hearts.
The coronary vascular endothelium could mediate some of the coronary effects of halogenated anaesthetic agents. The role of the endothelial vasodilator substances nitric oxide (NO) and prostaglandins (PGs) in the coronary effects of halothane and isoflurane remains to be determined and has not been investigated for desflurane. In this study, the roles of NO and cyclooxygenase pathways in the coronary effects of halothane, isoflurane and desflurane were studied in isolated red blood cell-perfused rabbit hearts. Rabbit hearts were perfused by a Langendorf technique with red blood cells mixed with modified Krebs-Henseleit buffer. Coronary blood flow (CBF), oxygen consumption and myocardial performance were evaluated during exposure to 0.5, 1 and 2 rabbit minimum alveolar concentrations of halothane, desflurane and isoflurane. Thereafter, the same protocol was applied with the addition of N(G)-nitro-L-arginine (L-NNA), indomethacin or a combination of both inhibitors. Similar and significant increases in CBF were observed with increasing concentrations of isoflurane and desflurane. In contrast, CBF did not change with halothane. The combination of the two antagonists abolished desflurane-induced vasodilation, whereas it did not change the isoflurane-mediated increase in CBF. Halothane-induced vasoconstriction was observed in the presence of a combination of indomethacin with L-NNA. Halothane and desflurane induce the release of vasodilating prostaglandins and NO in rabbit coronary arteries. In contrast, these mediators are not involved in the coronary vasodilating properties of isoflurane.


[Quo vadis, children's shoe industry and children's shoe specialty retailers? In memory of Karl Benscheidt].
The German children's shoe industry is shrinking. Some manufacturers are trying to hold their own, concentrating on medically recommended children's shoes in standard sizes and in the three widths W, M, and S. The shoe retailers who stock these shoes and offer satisfactory services for children's shoes are listed in a register kept by the German Shoe Institute in Frankfurt.


Mothers' stress and expectations as a function of time since child's cochlear implantation.
This study examined stress, attitudes, and expectations among mothers of deaf children who underwent cochlear implantation (CI), as related to time elapsed since surgery. Participants were 64 mothers of such children at different points in the implantation process: candidates, 0-3 years postimplantation, and more than 3 years later. Expectations in communication and academic domains decreased as time since implantation passed. No differences emerged in stress levels between the 3 groups. Higher levels of mothers' and fathers' education correlated with lower stress levels. Older mothers expressed lower levels on the cohesion dimension of family functioning. Findings suggested the need to consider mothers' expectations in the rehabilitation process and to encourage mothers' realistic expectations with regard to the effects of CI.


[Plasmodium yoeli 265 BY--new possibilities in the study of the resting stages of the malarial parasites].
When Swiss mice were experimentally infected with P. yoelii yoelii 264 BY sporozoites through bites of the mosquito Anopheles stephensi, there were no blood parasites in most (85%) animals after a short (on day 4-5) incubation period. The hepatic parenchymal cells from the animals without primary infection manifestation (following 2 months of the infection) or with the disease self-arrested (on day 26 of postinfection) were the first to display 5-11-microunits mononuclear parasites that are likely to be similar to the hypnozoites of some malaria parasite strains in man and primates. This suggests that rodent malaria parasites, as P. vivax, might cause infection with prolonged incubation and true relapses previously unknown for these parasites. Therefore, P. yoelii is a promising accessible model for studying the persistence phenomenon of malarial parasites at the tissue level.


Effects of season and sex on the distribution of cytosolic estrogen receptors within the brain and the anterior pituitary gland of sheep.
This study was undertaken to evaluate the effects of season and sex on the distribution of cytosolic estradiol-17 beta receptors (E2-receptors) within multiple regions of the ovine brain and the anterior pituitary gland. Our data confirm the existence of a saturable, high-affinity receptor specific for estradiol-17 beta (E2) in the hypothalamus and anterior pituitary gland. The concentrations of E2-receptors in tissues from castrated ewes and rams killed in December (breeding season) and May ( nonbreeding season) were determined by incubating cytosols with a saturating concentration of [3H] E2. For both sexes, the anterior pituitary gland contained the highest concentration of E2-receptor. Within the brain, the highest concentrations of E2-receptor were in the hypothalamus and preoptic area (POA), and within the hypothalamus, the median eminence-infundibular stalk (ME) contained a higher concentration of E2-receptor than the anterior and posterior hypothalamus. The numbers of E2-receptors in the anterior hypothalamus and ME of ewes were 2- 3X those for rams. In ewes, there was little seasonal difference in the numbers of E2-receptors in the POA, anterior hypothalamus and ME. In rams, there was little seasonal difference in the numbers of E2-receptors in the POA and anterior hypothalamus. For both sexes, there were fewer E2-receptors in the anterior pituitary gland and posterior hypothalamus in May than in December. Thus, during the nonbreeding season, the major neuroendocrine site of action of E2 probably is within the brain, specifically in the POA, anterior hypothalamus and ME of the ewe, and in the POA and the anterior hypothalamus of the ram. These data do not support a mechanism whereby the increased sensitivity to sex steroids during the nonbreeding season is due to enhanced numbers of E2-receptors.


Effects of N-acetylcysteine and imipramine in a model of acute rhythm disruption in BALB/c mice.
Circadian rhythm disturbances are among the risk factors for depression, but specific animal models are lacking. This study aimed to characterize the effects of acute rhythm disruption in mice and investigate the effects of imipramine and N-acetylcysteine (NAC) on rhythm disruption-induced changes. Mice were exposed to 12:12-hour followed by 10:10-hour light:dark cycles (LD); under the latter, mice were treated with saline, imipramine or NAC. Rhythms of rest/activity and temperature were assessed with actigraphs and iButtons, respectively. Hole-board and social preference tests were performed at the beginning of the experiment and again at the 8th 10:10 LD, when plasma corticosterone and IL-6 levels were also assessed. Actograms showed that the 10:10 LD schedule prevents the entrainment of temperature and activity rhythms for at least 13 cycles. Subsequent light regimen change activity and temperature amplitudes showed similar patterns of decline followed by recovery attempts. During the 10:10 LD schedule, activity and temperature amplitudes were significantly decreased (paired t test), an effect exacerbated by imipramine (ANOVA/SNK). The 10:10 LD schedule increased anxiety (paired t test), an effect prevented by NAC (30 mg/kg). This study identified mild but significant behavioral changes at specific time points after light regimen change. We suggest that if repeated overtime, these subtle changes may contribute to lasting behavioral disturbancess relevant to anxiety and mood disorders. Data suggest that imipramine may contribute to sustained rhythm disturbances, while NAC appears to prevent rhythm disruption-induced anxiety. Associations between sleep/circadian disturbances and the recurrence of depressive episodes underscore the relevance of potential drug-induced maintenance of disturbed rhythms.


Excessive ventilatory response during exercise in patients with non-hypoxic pulmonary hypertension.
The slope of the regression line between carbon dioxide output (VCO2) and minute ventilation (VE) (SLOPE) is useful for evaluating ventilation-perfusion inequality during exercise. A cardiopulmonary exercise test was carried out in 8 pulmonary hypertension (PH) patients without hypoxemia (group PH), 38 male patients with old myocardial infarction (group OMI), and 20 healthy men (group Ctrl). The average SLOPE for each group was 36.3+/-3.3, 28.7+/-0.9 and 25.6+/-0.5, respectively. There were significant differences among them. Group OMI was divided into 3 groups: OMI class 0: peak oxygen consumption (VO2) > or =21 ml x kg(-1) min(-1); OMI class I: 14 ml x kg(-1) x min(-1) < or =peak VO2<21 ml x kg(-1) min(-1); OMI class II: peak VO2< 14ml x kg(-1) x min(-1). There were no significant differences in peak VO2 between the groups PH and OMI class I, but the SLOPE in the group PH was greater than the SLOPE in OMI class I (p=0.0019). Compared with OMI class II, group PH had a greater peak VO2 (p=0.0215), although their SLOPE was equivalent to that of OMI class II. These results suggest that PH patients have severe ventilation-perfusion inequality despite good exercise capacity. When performing a cardiopulmonary exercise test on PH patients, it is necessary to observe not only VO2 or VCO2, but also VCO2/VE, in order to prevent aggravation of the ventilation-perfusion inequality, which leads to exercise-induced hypoxemia.


Biotopes of the intertidal zone in Clarence Island (south of the Strait of Magellan).
The characteristics of the Strait of Magellan promote the formation of unique environments, with diverse habitats and marine organisms. This fragmentation of the landscape generates diverse little-explored ecological associations, especially in the zone of sub-Antarctic islands of the Tierra del Fuego archipelago. One way to address this lack of knowledge is through the biotope characterization methodology, with ecological units composed of the habitat and the communities associated with these environments, obtaining data and information on the dominant and incidental taxonomic groups. This is a good research model to conduct baseline studies in coastal benthic marine environments. A data set in Darwin Core standard is presented of the species that make up the intertidal biotopes of Clarence Island (Tierra del Fuego Archipelago, south of the Strait of Magellan). This includes 50 identified species and the specific coordinates for each sampled location, with a total of 1400 georeferenced records. Mollusks were the most diverse taxon with 21 species, followed by algae (14 species). Sessile organisms such as the barnacles Elminiuskingii and Austromegabalanuspsittacus predominate in these ecosystems, followed by bivalve mollusks such as Choromytiluschorus and Mytiluschilensis, which together with Nacellamagellanica and the alga Hildenbrandia sp. make up more than 50% of the total records. The inclusion of biotope patterns in this study complements the information on benthic marine flora and fauna in the intertidal zone, including new records for the coast in the Clarence Island area, which is within the boundary of the Kawésqar National Park.


Manganese carbonyl nitrosyls: comparison with isoelectronic iron carbonyl derivatives.
The manganese carbonyl nitrosyls Mn(NO)(CO)4, Mn2(NO)2(CO)n (n = 7, 6, 5, 4), and Mn3(NO)3(CO)9 have been studied by density functional theory (DFT) using the B3LYP and BP86 methods for comparison of their predicted structures with those of isoelectronic iron carbonyl derivatives. DFT predicts a trigonal bipyramidal structure for Mn(NO)(CO)4 with an equatorial NO group very close to the experimental structure. The predicted lowest energy structure for Mn2(NO)2(CO)7 has two bridging NO groups in contrast to the known structure of the isoelectronic Fe2(CO)9, which has three bridging CO groups. The structures for the unsaturated binuclear Mn2(NO)2(CO)n (n = 6, 5, 4) derivatives are similar to those of the corresponding binuclear iron carbonyls Fe2(CO)n+2 derivatives but always with a preference of bridging NO groups over bridging CO groups. The trinuclear Mn3(NO)3(CO)9 is predicted to have a structure analogous to the known structure for Fe3(CO)12 but with two bridging NO groups rather than two bridging CO groups across one of the metal-metal edges of the M3 triangle. The dark red solid photolysis product of Mn(NO)(CO)4 characterized by its nu(CO) and nu(NO) frequencies approximately 45 years ago is suggested by these DFT studies not to be the originally assumed Mn2(NO)2(CO)7 analogous to Fe2(CO)9. Instead, this photolysis product appears to be Mn2(NO)2(CO)5 with a Mn(triple bond)Mn formal triple bond analogous to (eta5-C5H5)2V2(CO)5 obtained from the photolysis of (eta5-C5H5)V(CO)4.


The development of neutrophilic polymorphonuclear leukocytes in human bone marrow.
Neutrophilic leukocytes (PMN) and their precursors from normal human marrow and blood were examined by histochemical staining and by electron microscopy and cytochemistry in order to determine the origin and nature of their cytoplasmic granules. Human neutrophils contain two basic types of granules, azurophils and specifics, which differ in morphology, contents, and time of origin. Azurophils are large and may be spherical or ellipsoid, the latter with a crystalline inclusion. They are produced in the first secretory stage (promyelocyte), contain peroxidase and various lysosomal enzymes, and thus correspond to modified primary lysosomes. Specifics are smaller, may be spherical or elongated, and are formed during a later secretory stage (myelocyte). They lack lysosomal enzymes and contain alkaline phosphatase and basic protein; their contents remain largely undetermined. Specifics outnumber azurophils in the mature PMN because of reduction in numbers of azurophils per cell by cell division in the myelocyte stage. The findings indicate that the situation is basically the same as described previously in the rabbit, insofar as the origin, enzymic activity, and persistence in the mature cell of the two types (azurophil and specific) of granules are concerned. The main difference between PMN of the two species is in the morphology (size, shape, and density) of the granules, especially the azurophils.


Identifying misidentifications: a phenomenological study.
This study assessed how well the current classification system of the delusional misidentification syndromes (DMSs) represents the full range of misidentification phenomena encountered in self-descriptions of psychotic patients. To this end, a sample of 58 self-descriptions of ex-patients who had suffered from an episode of psychosis were reviewed. Misidentifications fitting the definition of one of the DMSs were identified in only 3 cases, whereas those fitting a general and broad definition were identified in 16 cases. It is argued that the restrictive nature of the currently dominant DMSs classification may have led to the neglect of a wide range of misidentification phenomena which do not fit the descriptions of any one of the classic DMSs. Proper identification, description and classification of these non-DMS misidentification phenomena is needed.


Polyelectrolyte Multilayers Enhance the Dry Storage and pH Stability of Physically Entrapped Enzymes.
Polyelectrolyte multilayers (PEMs) are attractive materials for immobilizing enzymes due to their unique ionic environment, which can prevent unfolding. Here, we demonstrated that the stability to dry storage and elevated pH were significantly enhanced when negatively charged nitroreductase (NfsB) was embedded in a PEM by depositing alternating layers of the enzyme and polycation (PC) onto porous silica particles. The PC strength (i.e., pKa) and the surface charge of the film were varied to probe the effects that internal and surface chemistry had on the pH stability of the entrapped NfsB. All films showed enhanced activity retention at elevated pH (>6), and inactivation at reduced pH (<6) similar to NfsB in solution, indicating that the primary stabilizing effect of immobilization was achieved through ionic interactions between NfsB and the PC and not through changes to the surface charge of the NfsB. Additionally, films that were stored dry at 4 °C for 1 month retained full activity, while those stored at room temperature lost 30% activity. Remarkably, at 50 °C, above the NfsB melting temperature, 40% activity was retained after 1 month of dry storage. Our results suggest that internal film properties are significantly more important than surface charge, which had minor effects on activity. Specifically, immobilization with the weak PC, poly(l-lysine), increased the optimal pH and the activity of immobilized NfsB (which we attribute to greater permeability), relative to immobilization with the strong PC, poly(diallyldimethylammonium chloride). However, NfsB was leached from the PLL film to a greater extent. Overall, these observations demonstrate that internal ionic cross-linking is key to the stabilizing effects of PEMs and that the pH response can be tuned by controlling the number of cross-links (e.g., by changing the strength of the PC). However, this may be at the cost of reduced loading, illustrating the necessity of simultaneously optimizing enzyme loading, internal ionic cross-linking, and substrate transport.


Kinetics of enzymatic lysis and disruption of yeast cells: I. Evaluation of two lytic systems with different properties.
Many microorganisms produce enzymes which lyse the walls of yeasts, fungi, and bacteria. The proportions of different enzyme activities present in the lytic system, their action patterns, synergism, and dependence on inhibitors, constitute the activity profile of the lytic system. Taken together, the activity profile and process conditions for lysis determine the reaction rate and the distribution of products from lysis of any given type of cells. Kinetics of glucan hydrolysis, proteolysis, and lysis of brewer's yeast were compared for two extracellular yeast-lytic enzyme systems with different properties. The enzyme sources used were filtered culture broths from Cytophaga sp. NCIB 9497 grown in batch culture and from Oerskovia xanthineolytica LL-G109, grown under carbon limitation in continuous culture. Rate and extent of cell hydrolysis, and the accumulation of soluble proteins, peptides, and carbohydrates from the lysed yeast cells, are discussed in terms of the activity profiles and potential applications of the two enzyme systems.


A HU-like protein is required for full virulence in Xanthomonas campestris pv. campestris.
Bacteria harbour several abundant small DNA-binding proteins known as nucleoid-associated proteins (NAPs) that contribute to the structure of the bacterial nucleoid as well as to gene regulation. Although the function of NAPs as global transcriptional regulators has been comprehensively studied in the model organism Escherichia coli, their regulatory functions in other bacteria remain relatively poorly understood. Xanthomonas campestris pv. campestris (Xcc) is a gram-negative bacterium that causes black rot disease in almost all members of the crucifer family. In previous work, we demonstrated that a Fis homologue protein, which we named Fis-like protein (Flp), contributes to the regulation of virulence, type III secretion, and a series of other phenotypes in Xcc. Here we have examined the role of XC_1355, which is predicted to encode a DNA-binding protein belonging to the HU family herein named HU-like protein (Hlp). We show that mutation of XC_1355 in Xcc reduces the virulence, extracellular polysaccharide production, and cell motility, but has no effect on the production of extracellular enzymes and induction of the hypersensitive response. These data together with transcriptome analysis indicate that hlp is a previously uncharacterized gene involved in virulence that has partially overlapping and complementary functions with flp in Xcc, although the two regulators have opposite effects on the expression of genes involved in type III secretion. The findings add to our understanding of the complex regulatory pathways that act to regulate virulence in Xcc.


Monitoring breath during oral glucose tolerance tests.
The evolution of breath composition during oral glucose tolerance tests (OGTTs) was analysed by thermal desorption/gas chromatography/mass spectrometry in 16 subjects and correlated to blood glucose levels. The glucose tolerance tests classified five of the subjects as diabetics, eight as affected by impaired glucose tolerance and three as normoglycaemic. Acetone levels were generally higher in diabetics (average concentration values: diabetics, 300 ± 40 ppbv; impaired glucose tolerance, 350 ± 30 ppbv; normoglycaemic, 230 ± 20 ppbv) but the large inter-individual variability did not allow us to identify the three groups by this parameter alone. The exhalation of 3-hydroxy-butan-2-one and butane-2,3-dione, likely due to the metabolization of glucose by bacteria in the mouth, was also observed. Future work will involve the extension of the analyses to other volatile compounds by attempting to improve the level of discrimination between the various classes of subjects.


Platelet hyaluronidase-2 regulates the early stages of inflammatory disease in colitis.
Platelets are specialized cells essential for hemostasis that also function as crucial effectors capable of mediating inflammatory and immune responses. These sentinels continually survey their environment and discriminate between homeostatic and danger signals such as modified components of the extracellular matrix. The glycosaminoglycan hyaluronan (HA) is a major extracellular matrix component that coats the vascular lumen and, under normal conditions, restricts access of inflammatory cells. In response to tissue damage, the endothelial HA matrix enhances leukocyte recruitment and regulates the early stages of the inflammatory response. We have shown that platelets can degrade HA from the surface of activated endothelial cells via the enzyme hyaluronidase-2 (HYAL2) and that HYAL2 is deficient in platelets isolated from patients with inflammatory bowel disease (IBD). Platelets are known to be involved in the pathogenesis of several chronic disease states, including IBD, but they have been largely overlooked in the context of intestinal inflammation. We therefore wanted to define the mechanism by which platelet HYAL2 regulates the inflammatory response during colitis. In this study, we provide evidence that HA catabolism is disrupted in human intestinal microvascular endothelial cells isolated from patients with IBD. Furthermore, mice deficient in HYAL2 are more susceptible to an acute model of colitis, and this increased susceptibility is abrogated by transfusion of HYAL2-competent platelets. Finally, we show that platelets, via HYAL2-dependent degradation of endothelial HA, regulate the early stages of inflammation in colitis by limiting leukocyte extravasation.


Pathogenesis of hepatic encephalopathy in acute liver failure.
Hepatic encephalopathy (HE) in acute liver injury signifies a serious prognosis. Brain edema and intracranial hypertension are major causes of death in this syndrome. Comparison of HE in acute liver failure (ALF) with that of cirrhosis allows recognition of important differences and similarities. A key role for ammonia in the pathogenesis of both HE and brain edema is now firmly supported by clinical and experimental data. Additional factors, such as infection, products of the necrotic liver, and synergistic toxins, may contribute to an altered mental state. A low plasma osmolarity, high temperature, and both high and low arterial pressure may affect brain water content. A combined derangement of cellular osmolarity coupled with cerebral hyperemia can explain the development of brain edema in ALF. Increasingly, study of the mechanisms responsible for brain swelling provides critical information for understanding the pathogenesis of HE.


Physiology of the human sphincter of Oddi.
During the last 25 years relevant data which contribute to the clarification of pancreatico-biliary sphincter function, have been derived from physiological and pharmacological studies, and from cinefluorographic and manometric observations in man. The human sphincter of Oddi appears to be a complex device, relatively independent of the duodenum and endowed with a primarily occluding action. Perendoscopic, pre- and post-operative sphincter of Oddi manometry has opened up new prospectives for a better definition of old concepts, such as biliary dyskinesia and post-cholecystectomy syndrome. In addition, manometric measurement may provide a more rational basis for sphincterotomy, and could allow endoscopists and surgeons to objectively evaluate the extent of sphincter splitting.


Psychophysics of emotion: the QUEST for emotional attention.
To investigate the mechanisms involved in automatic processing of facial expressions, we used the QUEST procedure to measure the display durations needed to make a gender decision on emotional faces portraying fearful, happy, or neutral facial expressions. In line with predictions of appraisal theories of emotion, our results showed greater processing priority of emotional stimuli regardless of their valence. Whereas all experimental conditions led to an averaged threshold of about 50 ms, fearful and happy facial expressions led to significantly less variability in the responses than neutral faces. Results suggest that attention may have been automatically drawn by the emotion portrayed by face targets, yielding more informative perceptions and less variable responses. The temporal resolution of the perceptual system (expressed by the thresholds) and the processing priority of the stimuli (expressed by the variability in the responses) may influence subjective and objective measures of awareness, respectively.


Lah is a transmembrane protein and requires Spa10 for stable positioning of Woronin bodies at the septal pore of Aspergillus fumigatus.
Woronin bodies are specialized, fungal-specific organelles that enable an immediate closure of septal pores after injury to protect hyphae from excessive cytoplasmic bleeding. In most Ascomycetes, Woronin bodies are tethered at the septal pore by so-called Lah proteins. Using the pathogenic mold Aspergillus fumigatus as a model organism, we show that the C-terminal 288 amino acids of Lah (LahC288) bind to the rim of the septal pore. LahC288 essentially consists of a membrane spanning region and a putative extracellular domain, which are both required for the targeting to the septum. In an A. fumigatus rho4 deletion mutant that has a severe defect in septum formation, LahC288 is recruited to spot-like structures in or at the lateral membrane. This suggests that LahC is recruited before Rho4 starts to govern the septation process. Accordingly, we found that in wild type hyphae Lah is bound before a cross-wall emerges and thus enables a tethering of Woronin bodies at the site of the newly formed septum. Finally, we identified Spa10, a member of a recently described family of septal pore-associated proteins, as a first protein that directly or indirectly interacts with LahC to allow a stable positioning of Woronin bodies at the mature septum.


The Correlation of Indices in r-TEG with Intra-operative Blood Loss in Neurosurgical Patients.
Objective Intra-operative coagulopathy has a close relationship with blood loss and the prognosis of patients. Rapid-thrombelastography (r-TEG) is a comprehensive assessment of coagulation abnormalities and also an effective way for constructing blood transfusion. This study attempts to investigate the correlation of r-TEG indices with intra-operative hemorrhage.Methods Patients who underwent transphenoidal hypophysectomy and craniotomy from January 15 to April 30, 2013 in Peking Union Medical College hospital were recruited. All patients had pre- and post-operative r-TEG and conventional coagulation tests (CCTs). Patients' information and intra-operative blood loss as a percentage of estimated blood volume were recorded. Spearman's correlation analyses were used for discovering the relationship between indices in r-TEG or CCTs and the intra-operative blood loss. The significant correlated index of r-TEG was further investigated using linear regression analysis. Results A total of 181 patients participated in this study. Intra-operative change of α-angle, which reflects the fibrinogen level and function, was the only r-TEG index that correlated with blood loss significantly (P=0.013, r= -0.184), thus challenging the current empirical cognition of the effects of intra-operative hemorrhage on coagulation. As intra-operative blood loss increased, α-angle decreased, and every 1% loss of estimated blood volume (EBV) led to 0.60 degree decrease of α-angle. As for CCT results, changes of fibrinogen and platelet count were also significantly correlated with blood loss (P=0.015 and P=0.001, respectively).Conclusions Peri-operative change of α-angle, as an index of r-TEG, exhibited a significant negative correlation with intra-operative blood loss. The impact of hemorrhage on fibrinogen, instead of clotting factors, should be scrutinized.


Differential rearing experience, gender, and radial maze performance.
Since both differential rearing and gender have been known to affect maze abilities, the present study examines the performance of male and female hooded rats raised from weaning in either a complex environment (EC) or isolated environment (IC) on the 17-arm radial maze. In two separate replications, EC rats learned the maze more quickly and accurately than IC rats, as assessed by total errors, the number of correct choices to the first error, and the number correct in the first 17 choices. However, EC rats were more likely than IC rats to employ an adjacent-arm strategy which may have contributed to their superior performance. There were no gender differences or environment by gender interaction effects on any measure of accuracy or adjacent arm strategy in either replication. It appears that the performance of both male and female rats on the 17-arm radial maze is similarly influenced by the rearing environment.


Hyperuricemia, urate deposition and the association with hypertension.
Hyperuricemia is associated with hypertension, kidney disease, vascular and cardiovascular (CV) events. In experimental models, the inhibition of hepatic uricase induces hyperuricemia, hypertension and mild renal disease. Notably, the micro- and macrovascular changes observed in the experimental model of hyperuricemia resemble the histological changes of human hypertension. This paper presents and discusses the epidemiological correlation between high serum uric acid levels and hypertension, and reviews current evidence supporting the protective effects of the normalization of uric acid levels. This review is based on a PubMed/Embase database search for articles on hyperuricemia and its impact on cardiovascular and renal function.


Exogenous Insulin Antibody Syndrome in a Pediatric Patient: Successful Treatment with Mycophenolate Mofetil.
Exogenous insulin antibody syndrome (EIAS) rarely occurs in type 1 diabetes and should be considered in those with blood glucose levels outside the target range requiring greater than 2 units/kg/day of insulin without obesity. We describe the novel treatment of this condition using mycophenolate mofetil monotherapy in a pediatric patient in the outpatient setting. A 17-year-old Caucasian male with type 1 diabetes experienced an abrupt increase in insulin requirements from 1.7 to 3.3 units/kg/day. Total insulin level was 7 µIU/mL with free insulin of 4.8 µIU/mL (68% of the total insulin), suggesting the presence of insulin antibodies. Switching from insulin aspart to glulisine was unsuccessful as insulin requirements increased to 4.4 units/kg/day. Treatment with oral mycophenolate mofetil decreased insulin requirements to 1.4 units/kg/day after 7 months. Total and free insulin levels improved to 5.2 and 4.6 µIU/mL, respectively (free insulin was 88% of total insulin). No adverse effects were encountered. Mycophenolate mofetil monotherapy is successful in safely treating EIAS in a pediatric patient.


Pulmonary deposits of titanium dioxide in cytologic and lung biopsy specimens. Light and electron microscopic x-ray analysis.
Although titanium dioxide (TiO2) is widely used in industry, its biologic effects have not been determined. In the present investigation, open lung biopsy samples and sputum specimens from three former TiO2 factory workers and bronchial aspirations from seven TiO2 factory workers were analyzed by conventional and x-ray microanalytic light and electron microscopic methods. These studies showed that in the alveolar macrophages, lysosomes contained a significant amount of titanium as well as smaller amounts of silicon, aluminum, iron, and potassium. It appeared that titanium dioxide was situated in round or oval-shaped particles whereas silica or silicon compounds were localized in separate, more rectangular structures. There fore, the adverse effects may be induced by such quartz or silicon compounds. The latter are utilized as covering substances in the manufacture of TiO2 pigment.


Cardiovascular disease in patients with chronic kidney disease. A clinical review.
Cardiovascular disease (CVD) remains the most common cause of premature death in the chronic kidney disease (CKD) population. Individuals with CKD are at 10-20 times greater risk of cardiac death than controls without CKD, despite stratification for age, race, sex and diabetes. Heightened CVD mortality begins with mild kidney disease and rises further with more advanced kidney disease. Traditional risk factors account for up to 50% of cardiovascular disease in CKD, whilst renal specific markers, including anemia, disordered bone mineral metabolism and oxidative stress, also likely contribute to the total cardiovascular burden in CKD. Despite the increased mortality, there has been a dearth of interventional cardiovascular randomized controlled trials (RCTs) in the CKD population. Furthermore, many patients with kidney disease have been excluded from the majority of mainstream cardiovascular interventional trials. While recently published RCTs on traditional and non-traditional risk factors including dyslipidemia (PPP, 4D and ALERT, VA-HIT), cardiomyopathy (FOSIDIAL, telmisartan, carvedilol), anemia (US Normal Hematocrit, CHOIR and CREATE trials), hyperhomocystenemia (ASFAST, US folic acid trial, HOST), disordered bone mineral metabolism (Cunningham meta-analysis, DCOR), oxidative stress therapy (SPACE, HOPE and ATIC, N-acetylcysteine) and multidisciplinary multiple cardiovascular risk factor intervention clinics (LANDMARK) have added to the available pool of clinical data, level 1 clinical evidence remains significantly lacking. The negative findings in many of these trials highlight the potential dangers of extrapolating findings from non kidney disease patients to those with CKD. Further large, well-designed trials are urgently required to address this issue.


Hepatic MDR3 expression impacts lipid homeostasis and susceptibility to inflammatory bile duct obstruction in neonates.
BackgroundHeterozygous mutations in the gene ABCB4, encoding the phospholipid floppase MDR3 (Mdr2 in mice), are associated with various chronic liver diseases. Here we hypothesize that reduced ABCB4 expression predisposes to extrahepatic biliary atresia (EHBA).MethodsLivers from neonatal wild-type (wt) and heterozygous Mdr2-deficient mice were subjected to mass spectrometry-based lipidomics and RNA sequencing studies. Following postnatal infection with rhesus rotavirus (RRV), liver immune responses and EHBA phenotype were assessed. Hepatic microarray data from 40 infants with EHBA were mined for expression levels of ABCB4.ResultsPhosphatidylcholine (PC) and phosphatidylethanolamine (PE) were increased, whereas the PC/PE ratio was decreased in neonatal Mdr2+/- mice compared with wt mice. Following RRV challenge, hepatic expression of IFNγ and infiltration with CD8+ and NK+ lymphocytes were increased in Mdr2+/- mice. Plasma total bilirubin levels and prevalence of complete ductal obstruction were higher in these mice. In infants with EHBA, hepatic gene expression of ABCB4 was downregulated in those with an inflammatory compared with a fibrosing molecular phenotype.ConclusionDecreased expression of ABCB4 causes dysregulation in (phospho)lipid homeostasis, and predisposes to aberrant pro-inflammatory lymphocyte responses and an aggravated phenotype of EHBA in neonatal mice. Downregulated ABCB4 is associated with an inflammatory transcriptome signature in infants with EHBA.


p21(Waf1/Cip1) deficiency stimulates centriole overduplication.
Inactivation of the cyclin-dependent kinase (CDK) inhibitor p21(Waf1/Cip1) (CDKN1; hereafter p21) has previously been implicated in the induction of numerical centrosome alterations. It is unclear, however, whether p21 deficiency deregulates the centrosome duplication cycle itself or causes an accumulation of centrosomes due to cell division failure and/or polyploidization. Using a novel marker for maternal centrioles, Cep170, we show here that knock-down of p21 protein expression in murine myeloblasts can stimulate excessive centriole numbers in the presence of only one mature centriole. These results indicate that p21 deficiency can trigger a bona fide overduplication of centrioles and that aberrant centrosome numbers cannot solely be explained by polyploidization as suggested by previous studies. Our findings underscore that impaired p21 expression may function as a driving force for chromosomal instability and highlight the importance of markers for maternal centrioles such as Cep170 to elucidate the pathogenesis of numerical centriole aberrations in tumor cells.


Imaging phase separation near the Mott boundary of the correlated organic superconductors kappa-(BEDT-TTF)2X.
Electronic phase separation consisting of the metallic and insulating domains with 50-100 microm in diameter is found in the organic Mott system kappa-[(h8-BEDT-TTF)(1-x)(d8-BEDT-TTF)x]2Cu[N(CN)2]Br by means of scanning microregion infrared spectroscopy using the synchrotron radiation. The phase separation appears below the critical end temperature 35-40 K of the first-order Mott transition. The observation of the macroscopic size of the domains indicates a different class of the intrinsic electronic inhomogeneity from the nanoscale one reported in the inorganic Mott systems such as high-Tc copper and manganese oxides.


The impacts of surface polarity on the solubility of nanoparticle.
In order to study the dependence of water solubility and hydration behavior of nanoparticles on their surface polarity, we designed polar nanoparticles with varying surface polarity by assigning atomic partial charge to the surface of C60. The water solubility of the nanoparticle is enhanced by several orders of magnitude after the introduction of surface polarity. Nevertheless, when the atomic partial charge grows beyond a certain value (qM), the solubility continuously decreases to the level of nonpolar nanoparticle. It should be noted that such qM is comparable with atomic partial charge of a variety of functional groups. The hydration behaviors of nanoparticles were then studied to investigate the non-monotonic dependence of solubility on the surface polarity. The interaction between the polar nanoparticle and the hydration water is stronger than the nonpolar counterpart, which should facilitate the dissolution of the nanoparticles. On the other hand, the surface polarity also reduces the interaction of hydration water with the other water molecules and enhances the interaction between the nanoparticles which may hinder their dispersion. Besides, the introduction of surface polarity disturbs and even rearranges the hydration structure of nonpolar nanoparticle. Interestingly, the polar nanoparticle with less ordered hydration structure tends to have higher water solubility.


Involvement of subcellular organelles in inflammatory pain-induced oxidative stress and apoptosis in the rat hepatocytes.
Subcutaneous injection of formalin in the plantar surface of rat's hind paw is frequently used as an animal model to study pain associated with inflammation. The pain produced by formalin test differs significantly from that of acute nociceptive tests. In this study, we first investigated the cellular and molecular mechanisms responsible for chronic inflammatory pain-induced damage in the rat hepatocytes and finally we tried to figure out whether both selective (celecoxib) and nonselective (acetylsalicylic acid) cyclo-oxygenase inhibitors could protect hepatocytes against pain-induced damage. The male Wistar rats were divided in one-, four-, and seven-day pain groups. Twenty-four hours prior to pain induction with subcutaneous injection of 5% formalin into the hind paw, acetylsalicylic acid or celecoxib was administered to the animals of similar one-, four-, and seven-day pain groups. A no-pain (control) group was also considered for each of the experiments. Our results showed a significant rise in both formation of reactive oxygen species and collapse in the mitochondrial membrane potential (%Delta Psi m) in all pain groups (P<0.05). Significant lysosomal membrane damage and hepatocyte proteolysis were only seen in one-and four-day pain groups (P<0.05). Caspase 3 activity also showed a significant (P<0.05) rise in all three pain groups. Formation of reactive oxygen species and mitochondrial/lysosomal damages were significantly inhibited by both acetylsalicylic acid and celecoxib in hepatocytes of all pain- suffering animals. Nonetheless, celecoxib's tendency to raise caspase 3 activities, suggested that it accelerates the apoptosis in hepatocytes of pain-suffering animals. Our results showed that the pain per se, could initiate some harmful signals that affect other cells other than neurons; these malicious signals could be magnified by use of some analgesics particularly selective cyclo-oxygenase inhibitors.


Simultaneous gas chromatographic analysis of lower fatty acids, phenols and indoles using a glass capillary column.
The simultaneous gas chromatographic separation of a mixture of 14 lower fatty acis, 11 phenols and 7 indoles has been effected by using a glass capillary column. Complete separation of the mixture has been obtained, except for phenol and o-cresol and o-ethylphenol and 3,5-xylenol whose peaks overlapped, and 2- and 3-methylindoles which were poorly separated. The optimum conditions are as follows: stationary phase, FFAP or PEG-20M; column (20 m X 0.28 mm I.D.) temperature, held for 1 min at 145 degrees (FFAP) or 130 degrees (PEG-20M); column oven, heated at 4 degrees/min from 145 or 130 to 180 degrees (FFAP) or 165 degrees (PEG-20M), maintained at 180 or 165 degrees for 30 min; carrier gas (helium) flow-rate, 0.6 ml/min (FFAP), 1.3 ml/min (PEG-20M); flame ionization detector. The method has been applied to the analysis of lower fatty acids, phenols and indoles in Japanese cigarette smoke, where the peaks were identified by the disappearance method using an alkaline pre-column.


Neuronal nitric oxide synthase immunohistochemistry and 4,5-diaminofluorescein diacetate: tools for nitric oxide research.
Nitric oxide plays an important role in many biological processes including the cardiovascular, immune, reproductive and nervous systems. There is much interest surrounding this molecule and the enzyme responsible for its synthesis, nitric oxide synthase. In order to investigate the role of nitric oxide in various biological processes it is necessary to be able to identify the released molecule itself as well as nitric oxide synthase. Detection of nitric oxide synthase was achieved by optimisation of the immunohistochemical localisation of the neuronal isoform of the enzyme in primary cultures of rat ventral mesencephala and in fixed adult rat brain sections. Furthermore, using 4,5-diaminofluorescein diacetate, we have directly visualised endogenously produced nitric oxide in mesencephalic cultures and demonstrated the potential use of this indicator for visualising nitric oxide produced in vivo.


Ever-never heard of 'Malaysian Healthy Plate': How many people know and practice this healthy eating concept?
The current and simpler healthy eating concept 'Malaysian Healthy Plate', was introduced in 2016. This study aims to determine the prevalence of ever-never heard, understanding, and practice of this concept and also the associated factors to never-heard of Malaysian Health Plate after three years of the implementation. This study utilized the data from the National Health and Morbidity Survey (NHMS) 2019, a cross-sectional survey that applied two-stage stratified cluster sampling. Questionnaires pertained to ever heard, knowledge, and practised of Malaysian Healthy Plate were asked along with another questionnaire. Complex sample analysis was applied to fit with the study design. Estimated 16.9 million (79.6%) adults in Malaysia were never heard of the Malaysian Healthy Plate Concept in 2019. Never heard of this concept was significantly associated with sex (men, aOR 0.265), ethnicity (other ethnicities, aOR 1.79), an education level (no education, aOR 9.59; primary, aOR 3.50; secondary, aOR 1.70), occupation (private, aOR 2.16; self-employed, aOR 2.31; retirees, aOR 1.69; student, aOR 2.31; unpaid workers, aOA 2.35; not working, aOR 2.86), non-diabetes aOR 1.43, and low fruit and vegetable intake person aOR 1.86. Meanwhile, another 20.4% or an estimated 4.3 million adults who were ever heard of Malaysian Healthy Plate. Among those who are ever heard, 80.8% (3.5 million) correctly interpreted or understood the concept and among those who ever heard and understood the concept, only 70.5% (2.5 million) have been practising it daily or occasionally. Four-fifth of adults never heard of the 'Malaysian Healthy Plate' and among those who ever heard, the understanding and practising of the concept were probably unsatisfactory. Multisectoral collaboration is an urge to fasten the promotion to spark awareness and educate the public to practice the concept to promote healthy eating and a healthier nation.


Successful treatment of recurrent renovascular hypertension by solitary kidney autotransplantation.
A case of recurrent renovascular hypertension is described in a patient with a solitary kidney successfully treated as an emergency for acute renal failure and unresponsive hypertension, by renal autotransplantation in the right iliac fossa. The results suggests that renal autotransplantation is a safe and reliable procedure in correcting particularly difficult renal vascular diseases where, due to the presence of a solitary kidney, all possible causes of technical failure of revascularization should be avoided.


High prevalence of prion protein genotype associated with resistance to chronic wasting disease in one Alberta woodland caribou population.
Chronic wasting disease (CWD) is a prion disease found in deer, elk and moose in North America and since recently, wild reindeer in Norway. Caribou are at-risk to encounter CWD in areas such as Alberta, Canada, where the disease spreads toward caribou habitats. CWD susceptibility is modulated by species-specific polymorphisms in the prion protein gene (Prnp). We sequenced Prnp of woodland caribou from 9 Albertan populations. In one population (Chinchaga) a significantly higher frequency of the 138N allele linked to reduced CWD susceptibility was observed. These data are relevant for developing CWD management strategies including conservation of threatened caribou populations.


Antero-posterior tissue polarity links mesoderm convergent extension to axial patterning.
Remodelling its shape, or morphogenesis, is a fundamental property of living tissue. It underlies much of embryonic development and numerous pathologies. Convergent extension (CE) of the axial mesoderm of vertebrates is an intensively studied model for morphogenetic processes that rely on cell rearrangement. It involves the intercalation of polarized cells perpendicular to the antero-posterior (AP) axis, which narrows and lengthens the tissue. Several genes have been identified that regulate cell behaviour underlying CE in zebrafish and Xenopus. Many of these are homologues of genes that control epithelial planar cell polarity in Drosophila. However, elongation of axial mesoderm must be also coordinated with the pattern of AP tissue specification to generate a normal larval morphology. At present, the long-range control that orients CE with respect to embryonic axes is not understood. Here we show that the chordamesoderm of Xenopus possesses an intrinsic AP polarity that is necessary for CE, functions in parallel to Wnt/planar cell polarity signalling, and determines the direction of tissue elongation. The mechanism that establishes AP polarity involves graded activin-like signalling and directly links mesoderm AP patterning to CE.


Rebalanced Zero-Shot Learning.
Zero-shot learning (ZSL) aims to identify unseen classes with zero samples during training. Broadly speaking, present ZSL methods usually adopt class-level semantic labels and compare them with instance-level semantic predictions to infer unseen classes. However, we find that such existing models mostly produce imbalanced semantic predictions, i.e. these models could perform precisely for some semantics, but may not for others. To address the drawback, we aim to introduce an imbalanced learning framework into ZSL. However, we find that imbalanced ZSL has two unique challenges: (1) Its imbalanced predictions are highly correlated with the value of semantic labels rather than the number of samples as typically considered in the traditional imbalanced learning; (2) Different semantics follow quite different error distributions between classes. To mitigate these issues, we first formalize ZSL as an imbalanced regression problem which offers empirical evidences to interpret how semantic labels lead to imbalanced semantic predictions. We then propose a re-weighted loss termed Re-balanced Mean-Squared Error (ReMSE), which tracks the mean and variance of error distributions, thus ensuring rebalanced learning across classes. As a major contribution, we conduct a series of analyses showing that ReMSE is theoretically well established. Extensive experiments demonstrate that the proposed method effectively alleviates the imbalance in semantic prediction and outperforms many state-of-the-art ZSL methods.


Circulating microparticles and endogenous estrogen in newly menopausal women.
Estrogen modulates antithrombotic characteristics of the vascular endothelium and the interaction of blood elements with the vascular surface. A marker of these modulatory activities is formation of cell-specific microparticles. This study examined the relationship between blood-borne microparticles and endogenous estrogen at menopause. Platelet activation and plasma microparticles were characterized from women being screened (n = 146) for the Kronos Early Estrogen Prevention Study. Women were grouped according to serum estrogen (< 20 pg/ml; low estrogen, n = 21 or > 40 pg/ml; high estrogen, n = 11). Age, body mass index, blood pressure and blood chemistries were the same in both groups. No woman was hypertensive, diabetic or a current smoker. Platelet counts, basal and activated expression of P-selectin on platelet membranes were the same, but activated expression of glycoprotein IIb/IIIa was greater in the high-estrogen group. Numbers of endothelium-, platelet-, monocyte- and granulocyte-derived microparticles were greater in the low-estrogen group. Of the total numbers of microparticles, those positive for phosphatidylserine and tissue factor were also greater in the low-estrogen group. These results suggest that, with declines in endogenous estrogen at menopause, numbers of procoagulant microparticles increase and thus may provide a means to explore mechanisms for cardiovascular risk development in newly menopausal women.


Predicting Parkinson's disease trajectory using clinical and neuroimaging baseline measures.
Predictive biomarkers of Parkinson's Disease progression are needed to expedite neuroprotective treatment development and facilitate prognoses for patients. This work uses measures derived from resting-state functional magnetic resonance imaging, including regional homogeneity (ReHo) and fractional amplitude of low frequency fluctuations (fALFF), to predict an individual's current and future severity over up to 4 years and to elucidate the most prognostic brain regions. ReHo and fALFF are measured for 82 Parkinson's Disease subjects and used to train machine learning predictors of baseline clinical and future severity at 1 year, 2 years, and 4 years follow-up as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Predictive performance is measured with nested cross-validation, validated on an external dataset, and again validated through leave-one-site-out cross-validation. Important predictive features are identified. The models explain up to 30.4% of the variance in current MDS-UPDRS scores, 55.8% of the variance in year 1 scores, and 47.1% of the variance in year 2 scores (p < 0.0001). For distinguishing high and low-severity individuals at each timepoint (MDS-UPDRS score above or below the median, respectively), the models achieve positive predictive values up to 79% and negative predictive values up to 80%. Higher ReHo and fALFF in several regions, including components of the default motor network, predicted lower severity across current and future timepoints. These results identify an accurate prognostic neuroimaging biomarker which may be used to better inform enrollment in trials of neuroprotective treatments and enable physicians to counsel their patients.


Nucleotide composition of nuclear and mitochondrial deoxyribonucleic acid of fungi.
The buoyant density of nuclear and mitochondrial deoxyribonucleic acid (DNA) from 14 species of fungi was determined by CsCl density gradient equilibrium centrifugation. The buoyant density of both types of DNA was the same for all three Mucorales analyzed. The buoyant density of mitochondrial DNA was significantly lower than that of the nuclear DNA for nine species of Ascomycetes and two species of Basidiomycetes. No simple correlation could be obtained from the comparison of the two types of DNA. Mitochondrial DNA represented a very small proportion of total DNA. Heat-denatured mitochondrial DNA renatured more readily than nuclear DNA.


The prevalence of asthma, allergic rhinitis, and eczema among school-aged children in Qatar: A Global Asthma Network Study.
This cross-sectional study aims to utilize the Global Asthma Network (GAN) questionnaires to estimate the prevalence of asthma, allergic rhinitis, and eczema among children in Qatar. The study population was comprised of children ages 6-7 and 13-14 years, along with their parents or guardians. The English and Arabic versions of the GAN questionnaires were used to collect data for this study. A total of 2646 participants were recruited (1210 in the 6-7 years age group and 1436 in the 13-14 years age group), in addition to a total of 3831 parents or guardians. The overall prevalence of diagnosed asthma, lifetime allergic rhinitis, and diagnosed eczema in our study sample were as follows: 34.6%, 30.9%, and 37.4%, respectively. The current study showed an increased prevalence rate of asthma and eczema comparing to previous local estimates. These rates were higher in some cases or comparable in other cases to those found elsewhere. It is recommended that future research focus on studying the various factors contributing to the cases of asthma, allergic rhinitis, and eczema in Qatar. The reporting of this study conforms with the STROBE statement.


Autoimmune diseases exhibit shared alterations in the gut microbiota.
Accumulating evidence from microbial studies have highlighted the modulatory roles of intestinal microbes in numerous human diseases, however the shared microbial signatures across different diseases remain relatively unclear. To consolidate existing knowledge across multiple studies, we performed meta-analyses of 17 disease types, covering 34 case-control datasets of 16S rRNA sequencing data, to identify shared alterations amongst different diseases. Furthermore, the impact of a microbial species, L. salivarius, was established in a DSS-induced colitis model and a CII-induced arthritis mouse models. Microbial alterations amongst autoimmune diseases were substantially more consistent compared with that of other diseases (cancer, metabolic disease and nervous system disease), with microbial signatures exhibiting notable discriminative power for disease prediction. Autoimmune diseases were characterized by the enrichment of Enterococcus, Veillonella, Streptococcus, Lactobacillus, and the depletion of Ruminococcus, Gemmiger, Oscillibacter, Faecalibacterium, Lachnospiracea incertae sedis, Anaerostipes, Coprococcus, Alistipes, Roseburia, Bilophila, Barnesiella, Dorea, Ruminococcus2, Butyricicoccus, Phascolarctobacterium, Parabacteroides and Odoribacter, amongst others. Functional investigation of L. salivarius, whose genus was commonly enriched in numerous autoimmune diseases, demonstrated protective roles in two separate inflammatory mouse models. Our study highlights a strong link between autoimmune diseases and the gut microbiota, with notably consistent microbial alterations compared with that of other diseases, indicating that therapeutic strategies which target the gut microbiome may be transferable across different autoimmune diseases. Functional validation of L. salivarius highlighted that bacterial genera associated with disease may not always be antagonistic, but may represent protective or adaptive responses to disease.


Factors predicting retention in treatment: 10-year experience of a methadone maintenance treatment (MMT) clinic in Israel.
The aims were to identify predictors of treatment retention in an Israeli methadone maintenance treatment (MMT) clinic, and to compare the findings to other international settings. We prospectively studied 492 patients admitted since 1993 through 10 years to an Israeli MMT clinic associated with a university-affiliated tertiary care medical center. Analyses (Kaplan Meier and Cox regression) included methadone dose and urinalysis results (for methadone, cocaine, opiates, benzodiazepines, THC, amphetamines) of each patient in the first month and after 1 year in treatment (or during the last month if the stay was >3 months and <1 year) and patients' characteristics (modified ASI). The 1-year retention rate was 74.4%; 65.8% stopped opiate abuse after 1 year in treatment. On admission, 13.6% of patients had used cocaine: there was a net decrease of 61.6% after 1 year. Factors predicting prolonged retention in MMT treatment (Cox regression) were daily methadone dose of 100mg or greater, negative urine for opiates after 1 year, and being a parent on admission. We conclude that our good outcome results (high rate of retention after 1 year (74.4%), high proportion of opiate abuse cessation (65.8%), and net reduction in cocaine abuse, similar to normal standards in other MMT clinics elsewhere in the world, justify the expansion of the MMT clinic network in Israel in order to make treatment available to all those who need it. A protocol favoring higher methadone dosage as appropriate is recommended.


The NOAA NCEI marine microplastics database.
Microplastics (<5 mm) pollution is a growing problem affecting coastal communities, marine ecosystems, aquatic life, and human health. The widespread occurrence of marine microplastics, and the need to curb its threats, require expansive, and continuous monitoring. While microplastic research has increased in recent years and generated significant volumes of data, there is a lack of a robust, open access, and long-term aggregation of this data. The National Oceanic and Atmospheric Administration (NOAA) National Centers for Environmental Information (NCEI) now provides a global open access to marine microplastics data on an easily discoverable and accessible GIS web map and data portal ( https://www.ncei.noaa.gov/products/microplastics ). The objective of this data portal is to develop a repository where microplastics data are aggregated, archived, and served in a user friendly, consistent, and reliable manner. This work contributes to NCEI's efforts towards data standardization, integration, harmonization, and interoperability among national and international collaborators for monitoring global marine microplastics. This paper describes the NOAA NCEI global marine microplastics database, its creation, quality control procedures, and future directions.


Polymorphism of C4 and CYP21 genes in various primate species.
To study the genetic heterogeneity of the C4 and CYP21 genes in selected primate species we used the technique of restriction fragment length polymorphism (RFLP). Genomic DNA was digested using several restriction endonucleases and filters were hybridized with a 500 bp BamHI/KpnI fragment derived from the 5' section of a human C4-cDNA and with a 1700 bp BamHI obtained from a human CYP21 gene. Abundant RFLP heterogeneity was observed for the C4 genes within a rhesus monkey population but not for the chimpanzee colony analyzed. Duplicated C4-CYP21 clusters can be traced back in humans, but also in chimpanzees, orang-utans and rhesus monkeys. Thus, duplication of the basic C4-CYP21 cluster in primates may have happened more than 30 million years ago. Non-duplicated C4-CYP21 regions were found for the gorilla and orang-utan. Apart from this, shortened C4A and C4B genes were observed in chimpanzees, orang-utans and rhesus monkeys, whereas the so-called long variety of the C4A gene appears to be present in humans and orang-utans. This ancestral modification, resulting from an insertion of a 6.5 kb intron in the C4A gene, therefore predates at least speciation of human and orang-utan which is estimated to have taken place more than 12 million years ago.


[The Kreutzer Sonata or homicidal jealousy according to Tolstoy].
In the first movement (the presto) of Beethoven's Kreutzer Sonata there are two strongly opposing themes (positive masculine and negative feminine). Inspired by this confrontation, in his novel "The Kreutzer Sonata", Tolstoï describes the marital conflict that drives the jealous husband, Pozdnychev, to kill his wife whom he believes to be unfaithful. The murderer thinks that his wife, a pianist, is betraying him with a violinist when he discovers them in his home at night. The present paper is a criminological study of this murder brought about by passion. In this novel Tolstoï paints a very realistic picture of the criminal workings of Pozdnychev's mind, the tragic tale of this jealousy is perfectly consistent with the judicial understanding of crimes of passion.


Do typically and atypically developing children learn and generalize novel names similarly: The role of conceptual distance during learning and at test.
There is a large body of evidence showing that comparison of multiple stimuli leads to better conceptualization and generalization of novel names than no-comparison settings in typically developing (TD) children. By contrast, the evidence regarding this issue remains scarce in children with intellectual disabilities (ID). Children with intellectual disabilities (ID) and TD children matched on mental age with the Raven's coloured progressive matrices were tested in several novel name learning comparison conditions, with familiar objects. We manipulated the conceptual distance between the learning stimuli in the learning phase and between the learning and generalization phase stimuli for object and relational nouns. Results showed that both populations had rather similar performance profile when matched on their cognitive skills (low- vs. high-functioning). Unexpectedly, ID children's performance was equivalent for relations and better for objects compared to their TD peers' performance. However, when controlling for chronological age, the difference between ID and TD children disappeared in the case of object categories and was better understood by TD children in the case of relations. We discuss the role of conceptual distance on participants' conceptual generalization as a function of their intellectual abilities and cognitive functioning.


Issues facing the dissemination of prevention programs: three decades of research on the adolescent diversion project.
This paper argues that the issues facing effective prevention programs when they embark on dissemination, implementation, and routinization have been largely ignored by the field. Through the example of the Adolescent Diversion Program, these issues are illustrated and discussed. Four sequential longitudinal experimental studies are summarized as a context for the discussion of dissemination issues. In each case, the alternative preventive program is demonstrated to be more effective than traditional approaches. Challenges to widespread implementation of effective prevention programs are then discussed with a call for the field to add such issues to its scientific agenda.


Morphological features of developing synapses as revealed by the E-PTA staining technique.
Synaptogenesis was studied in the optic tectum of chick embryos from the stage 40 to the hatching (last week of incubation). Our object was to characterize the morphological changes occurring in pre- and postsynaptic elements during this period of the development. Specialized interneuronal contact zones have been examined after conventional fixation procedure, or after staining of glutaraldehydefixed blocks with ethanolic phosphotungstic acid (E-PTA). Some mature synapses are seen also at the 14th incubation day (stage 40), and they increase in number to the hatching. In addition, immature synapses are seen in which presynaptic elements seem to be the less differentiated. Also the study of the evolution of the PTA-stainable paramembranous densities at the synaptic sites confirms these observations. These findings suggest a considerable prenatal synaptogenesis, as already demonstrated in various brain areas of the chick embryo, and also that the maturation of the postsynaptic site may precede and determine that of the presynaptic contact and vesicle accumulation.


Spatial and temporal integration of signalling networks regulating pollen tube growth.
The overall function of a cell is determined by its contingent of active signal transduction cascades interacting on multiple levels with metabolic pathways, cytoskeletal organization, and regulation of gene expression. Much work has been devoted to analysis of individual signalling cascades interacting with unique cellular targets. However, little is known about how cells integrate information across hierarchical signalling networks. Recent work on pollen tube growth indicates that several key signalling cascades respond to changes in cell hydrodynamics and apical volume. Combined with known effects on cytoarchitecture and signalling from other cell systems, hydrodynamics has the potential to integrate and synchronize the function of the broader signalling network in pollen tubes. This review will explore recent work on cell hydrodynamics in a variety of systems including pollen, and discuss hydrodynamic regulation of cell signalling and function including exocytosis and endocytosis, actin cytoskeleton reorganization, cell wall deposition and assembly, phospholipid and inositol polyphosphate signalling, ion flux, small G-proteins, fertilization, and self-incompatibility. The combined data support a newly emerging model of pollen tube growth.


Alcelaphine herpesvirus-1 open reading frame 57 encodes an immediate-early protein with regulatory function.
Alcelaphine herpesvirus-1 (AlHV-1) is the causative agent of Malignant Catarrhal fever, a lymphoproliferative and degenerative disease of large ruminants and ungulate species. The Alcelaphine Herpesvirus-1 gene product encoded by open reading frame 57 (ORF 57) is the positional homologue of the ORF 57 of Herpes Virus Saimiri (HVS), Kaposi's Sarcoma associated herpesvirus (KSHV) and Murine Gammaherpesvirus 68 (MHV 68), the Epstein-Barr virus BMLF1 gene, the herpes simplex virus (HSV-1) ICP 27 and the IE 4 gene of Varicella Zoster virus (VZV). In these viruses the ORF 57 gene product is expressed very early and encodes a regulatory protein, which is essential for viral replication acting both at the transcriptional and post-transcriptional levels. The function of ORF 57 gene product in the life cycle of AlHV-1 however remains unknown. Here we examined the expression of this gene and the function of its product. We have demonstrated that it is expressed very early in infection and have shown that the ORF57 gene product activates the promoter of another classical transactivator gene ORF50. It activates ORF50 promoter driving expression of an intron-less reporter gene to 50 fold and does not have any effect on an intron-containing reporter gene driven by the ORF 50 promoter. The 50 fold increase in the luciferase activity was not correlated with a similar fold increase in the luciferase RNA levels indicating that ORF 57 protein acts at a post-transcriptional level to regulate gene expression.


Lecythophora Soft-Tissue Infection: Case Report and Treatment Considerations.
Lecythophora hoffmannii is a saprophytic fungus commonly found in the environment. Able to be isolated from soil, it is frequently associated with the soft rot of wood. Although human infections are not common, they have been reported, and have ranged from keratitis and soft-tissue infection to deep osteomyelitis and endometritis. Here we report a case of soft-tissue infection with this pathogen along with successful treatment with standard-dose terbinafine when other agents were unavailable. The true prevalence of infections with this pathogen is unclear and further data are needed to determine optimal therapy.


Characterization of beta-adrenergic receptors in dispersed rat testicular interstitial cells.
Recent studies have shown that beta-adrenergic agents stimulate steroidogenesis and cyclic AMP formation in mouse Leydig cells in culture. To obtain information about the possible presence and the characteristics of a beta-adrenergic receptor in rat testicular interstitial cells, the potent beta-adrenergic antagonist [125I]cyanopindolol (CYP) was used as ligand. Interstitial cells prepared by collagenase dispersion from rat testis were incubated with the ligand for 2 h at room temperature. [125I]cyanopindolol binds to a single class of high affinity sites at an apparent KD value of 15 pM. A number of sites of 6,600 sites/cell is measured when 0.1 microM (-) propranolol is used to determine non-specific binding. The order of potency of a series of agonists competing for [125I]cyanopindolol binding is consistent with the interaction of a beta 2-subtype receptor: zinterol greater than (-) isoproterenol greater than (-) epinephrine = salbutamol much greater than (-) norepinephrine. In addition, it was observed that the potency of a large series of specific beta 1 and beta 2 synthetic compounds for displacing [125I]cyanopindolol in rat interstitial cells is similar to the potency observed for these compounds in a typical beta 2-adrenergic tissue, the rat lung. For example, the potency of zinterol, a specific beta 2-adrenergic agonist, is 10 times higher in interstitial cells and lung than in rat heart, a typical beta 1-adrenergic tissue. Inversely, practolol, a typical beta 1-antagonist, is about 50 times more potent in rat heart than in interstitial cells and lung.(ABSTRACT TRUNCATED AT 250 WORDS)


Optimal Coatings of Co3 O4 Anodes for Acidic Water Electrooxidation.
Implementation of proton-exchange membrane water electrolyzers for large-scale sustainable hydrogen production requires the replacement of scarce noble-metal anode electrocatalysts with low-cost alternatives. However, such earth-abundant materials often exhibit inadequate stability and/or catalytic activity at low pH, especially at high rates of the anodic oxygen evolution reaction (OER). Here, the authors explore the influence of a dielectric nanoscale-thin oxide layer, namely Al2 O3 , SiO2 , TiO2 , SnO2 , and HfO2 , prepared by atomic layer deposition, on the stability and catalytic activity of low-cost and active but insufficiently stable Co3 O4 anodes. It is demonstrated that the ALD layers improve both the stability and activity of Co3 O4 following the order of HfO2 > SnO2 > TiO2 > Al2 O3 , SiO2 . An optimal HfO2 layer thickness of 12 nm enhances the Co3 O4 anode durability by more than threefold, achieving over 42 h of continuous electrolysis at 10 mA cm-2 in 1 m H2 SO4 electrolyte. Density functional theory is used to investigate the superior performance of HfO2 , revealing a major role of the HfO2 |Co3 O4 interlayer forces in the stabilization mechanism. These insights offer a potential strategy to engineer earth-abundant materials for low-pH OER catalysts with improved performance from earth-abundant materials for efficient hydrogen production.


Peripheral blood and tissue assessment highlights differential tumor-circulatory gradients of IL2 and MIF with prognostic significance in resectable pancreatic ductal adenocarcinoma.
Various reports have pointed out the potential of cytokines as diagnostic and prognostic biomarkers for pancreatic ductal adenocarcinoma (PDA). Nonetheless, the evidence is contradictory and the role of chronic inflammation and relationship between circulatory and corresponding tumoral cytokine levels remain elusive. Utilizing a broad array of cytokines, we identified two opposing parameters: serum levels of interleukin 2 (IL2) and macrophage migration inhibitory factor (MIF) are diagnostic and prognostic factors. While low IL2 levels are associated with PDA, they also relate to a favorable prognosis of patients. In contrast, high MIF levels are associated with PDA and simultaneously related to an unfavorable outcome. MIF levels are associated with the intratumoral density of M2 macrophages (CD163+). Focusing on the tumor-to-serum gradient, we unveiled a different pattern of compartmental cytokine expression between IL2 and MIF. Our findings indicate that an extra-tumoral source of IL2 exists in PDA patients leading to increased detectability in the circulatory system. In case of MIF, the tumor microenvironment is presumably the main site of production and thereby reflected by serum measurements. Taken together, our study describes IL2 and MIF levels as biomarker candidates for diagnosis and prognosis of PDA, highlighting the need for compartmental cytokine analyses. From the perspective of tumor immunobiology, we identify multiple inflammatory states (proposed as types I-III) and see that systemic chronic dysregulation, independent of tumor microenvironment, can be measured and is a possible tool for stratification. Thus, direct correlation of local cytokine levels to peripheral blood levels needs to be regarded with caution.