Life stress and first onset of psychiatric disorders in daughters of depressed mothers.
This study used a comprehensive, interview-based measure of life stress to assess the role of different types of stress in predicting first onset of psychiatric disorders among daughters of depressed (n = 22) mothers and healthy (n = 22) mothers. Several types of stress were assessed: Chronic interpersonal stress, chronic non-interpersonal stress, episodic dependent (i.e., self-generated) interpersonal stress, episodic dependent non-interpersonal stress, episodic independent interpersonal stress, and episodic independent non-interpersonal stress. Daughters (ages 9-14) were recruited to have no clinically significant symptoms upon entry (T1). By a 30-month follow-up assessment (T2), 45% of the daughters of depressed mothers, but none of the daughters of healthy mothers, had developed a psychiatric disorder. Overall, daughters of depressed mothers were exposed to more severe chronic interpersonal and non-interpersonal stress than were daughters of healthy mothers. Further, daughters of depressed mothers who developed a psychiatric disorder by T2 were exposed to more severe chronic non-interpersonal stress and episodic dependent stress than were daughters of depressed mothers who remained healthy. We discuss the implications of these findings in the context of a stress-generation model for the intergenerational transmission of psychiatric risk among children of depressed mothers.


A Biomechanical Study of Two Distinct Methods of Anterior Cruciate Ligament Rupture, and a Novel Surgical Reconstruction Technique, in a Small Animal Model of Posttraumatic Osteoarthritis.
Small animal models are critical for studies of sports-related knee injury and disease such as posttraumatic osteoarthritis (PTOA) following anterior cruciate ligament (ACL) rupture. In such models, ACL damage can be achieved by surgical transection or, using a more recent innovation, by noninvasive biomechanical means. Whether these approaches differentially alter normal mechanics is unknown. Furthermore, while surgical reconstruction of ruptured ACL can greatly improve joint stability, its effect on PTOA development is also unclear. Our primary purpose was to characterize rodent knee joint mechanics in two models of ACL rupture using a novel quantitative laxity mechanical test. Our secondary aim was to characterize a new reconstruction technique using autograft tail tendon, and to assess its effect on joint mechanics. Our hypothesis was that surgical ACL transection would have a greater effect on joint mechanics. A total of 24 rat knee specimens underwent surgical or biomechanical ACL rupture and were stabilized using a new reconstruction technique using autograft tail tendon. Joint mechanics were assessed three times; preinjury, postinjury, and again after reconstruction, using quantitative joint laxity testing. Primary test readouts were maximum anteroposterior (AP) laxity, loading curve slope, and energy absorption. Student's t-tests were performed to identify intragroup differences. All surgical transections were completed successfully; maximum load in the biomechanical model was 67 ± 7.7 N, with a coefficient of variation of 11.43%. Surgical transection caused increased AP laxity, while biomechanical injury nonsignificantly increased this parameter. In both cases, these changes recovered to baseline by reconstruction. Loading curve slope was reduced in both models and was also returned to baseline by repair. Energy absorption followed the same pattern except it remained significantly different from baseline postreconstruction in the surgical group. This study supports our hypothesis knee joint mechanics is differentially affected by injury mechanism in a small animal model. We also report a novel reconstruction technique in this model, using autograft tail tendon.


NtSWEET1 promotes tobacco resistance to Fusarium oxysporum-induced root rot disease.
Sugars Will Eventually be Exported Transporter (SWEET) is a newly characterized family of sugar transporters, which plays critical roles in plant-pathogen interactions. However, the function of SWEET in tobacco and its interaction with Fusarium oxysporum, a causal agent of root rot, remain unclear. This study aimed to dissect the function of NtSWEETs in tobacco root rot using stem bases from tobacco plants inoculated with F. oxysporum. RNA-sequencing (RNA-Seq) analysis was performed, and the results indicated that Sucrose Transporter 4 (NtSUC4), Sugar Transporter 12 (NtSTP12), Hexose Transporter 6 (NtHEX6), NtSWEET1, NtSWEET3b, and NtSWEET12 were downregulated by infection with F. oxysporum. The expression of NtSWEET1, but not of NtSUC4, NtSTP12, NtHEX6, NtSWEET3b, or NtSWEET12, was suppressed at all the time points tested after inoculation with F. oxysporum. The NtSWEET1-green fluorescent protein was localized on the plasma membrane and possessed the ability to transport glucose, fructose and galactose. Compared with the wild-type plants, NtSWEET1 RNAi plants were more susceptible to root rot, indicating that NtSWEET1 positively regulated the defense of tobacco against root rot. This study identified the role of SWEETs in tobacco and their interaction with F. oxysporum. The results might be useful in protecting tobacco plants from root rot.


Homonuclear zero-quantum recoupling in fast magic-angle spinning nuclear magnetic resonance.
Solid-state magic-angle-spinning NMR pulse sequences which implement zero-quantum homonuclear dipolar recoupling are designed with the assistance of symmetry theory. The pulse sequences are compensated on a short time scale by the use of composite pulses and on a longer time scale by the use of supercycles. (13)C dipolar recoupling is demonstrated in powdered organic solids at high spinning frequencies. The new sequences are compared to existing pulse sequences by means of numerical simulations. Experimental two-dimensional magnetization exchange spectra are shown for [U-(13)C]-L-tyrosine.


Predictors of cigarette and alcohol susceptibility and use among Hispanic migrant adolescents.
Little is known about interpersonal and broader sociocultural factors related to protection from or use of tobacco and alcohol among immigrant adolescents. This study presents the baseline predictors of tobacco and alcohol use and susceptibility to tobacco and alcohol among Hispanic migrant adolescents. The sample consisted of 660 Hispanic adolescents (51% male) between the ages of 11 and 16 years enrolled in the Migrant Education Program through the County Office of Education. Slightly more than 75% of the study sample was first generation Hispanics and 79% preferred to speak Spanish. An interviewer-administered survey assessed the following information: standard demographic characteristics, modeling of cigarette smoking (including parental and peer smoking), attitudes (including self-standards and anticipated outcomes), acculturation, communication with parents, amount of social support, and satisfaction with social support. Significant predictors of susceptibility to tobacco and smoking status included age, gender, attitudes toward cigarettes (e.g., anticipated outcomes, self-standards), satisfaction with social support, and parent-child communication. Factors that were also significant predictors of susceptibility to alcohol and drinking status were age, attitudes toward drinking, satisfaction with social support, and level of parent-child communication. In addition, peer and household use of alcohol predicted adolescent outcomes. Based on these results it is suggested that tobacco and alcohol prevention efforts for first-generation Hispanic adolescents should target not only usual concerns (e.g., availability, peer pressure, modeling, expectancies), but also parent-child communication.


Effect of high-dose oral cholecalciferol on cardiac mechanics in children with chronic kidney disease.
Cardiovascular factors are an important cause of mortality in chronic kidney disease, and vitamin-D deficiency is common in this patient population. Therefore, we aimed to investigate the effect of oral cholecalciferol on cardiac mechanics in children with chronic kidney disease. A total of 41 children with chronic kidney disease - the patient group - and 24 healthy subjects - the control group - free of any underlying cardiac or renal disease with low 25-hydroxyvitamin-D3 levels were evaluated by conventional tissue Doppler imaging and two-dimensional speckle-tracking echocardiography, both at baseline and following Stoss vitamin-D supplementation. Left ventricular strain and strain rate values were compared between the study groups. Initial longitudinal and radial strain as well as strain rate values of the left ventricle were significantly lower in patients. After vitamin-D supplementation, these improved significantly in patients, whereas no significant change was observed in the control group. Our study showed that, although conventional and tissue Doppler imaging methods could not determine any effect, two-dimensional speckle-tracking echocardiography revealed the favourable effects of high-dose cholecalciferol on cardiac mechanics, implying the importance of vitamin-D supplementation in children with chronic kidney disease.


Cytopathic effects and focus formation by reticuloendotheliosis viruses in a quail fibroblast cell line.
The T and CS (chick syncytial) strains of reticuloendotheliosis virus (REV) induced focus formation and cytonecrotic changes in a Japanese quail fibroblast cell line designated QT35. The focus was distinctive and readily discernible, consisting of rounded refractile and larger dark-appearing (syncytia) cells usually aggregated along the periphery of a hole within a focus. The foci and cytopathic effects induced by the two strains of REV were morphologically indistinguishable. The focus formation in QT35 cultures was inhibited by chicken antiserum against the homologous or heterologous strain of REV; the homologous antiserum induced a greater inhibition. The altered cells composed of focus exhibited cytoplasmic fluorescence when stained by an indirect fluorescent-antibody technique with either the homologous or heterologous anti-REV serum. When foci that developed in QT35 cultures maintained under fluid medium were enumerated 3 days postinoculation, there were a highly significant correlation (P less than 0.001) and a linear relationship between the number of foci developed and relative virus concentration inoculated, thus justifying the validity of focus assay of REV by this system. The QT35 cell line may provide a useful in vitro system for virological and serological studies of REV.


The association between depressive symptoms and cigarette smoking in an urban primary care sample.
To examine the relationship between cigarette smoking and depressive symptoms in an urban primary care sample. Eligible participants were 526 patients aged eighteen to sixty-four presenting in the waiting rooms of two university affiliated internal medicine clinics. Participants were asked to complete a brief interview which ascertained current depressive symptoms using the Center for Epidemiologic Studies Depression Scale (CES-D), demographic information, and smoking status using a modified version of the Fagerstrom Test for Nicotine Dependence (FTND). Smoking status differed significantly by age, gender, education, and employment status. Mean level of depressive severity also differed by smoking status. Current smokers with nicotine dependence symptoms had significantly higher CES-D scores than those who had never smoked, ex-smokers, and non-dependent smokers. Logistic regression analyses indicated that gender, employment status, age, and smoking status were significantly associated with CES-D scores > or = 16. Exploratory analyses suggested that among smokers with a symptom of nicotine dependence, significantly more women than men had clinically significant levels of depressive symptoms. The association between smoking behavior and depressive symptoms in the present study is consistent with that reported in population-based and psychiatric samples. Symptoms of nicotine dependence were significantly associated with clinical levels of depressive symptoms. Primary care physicians may wish to inquire about depressive symptoms among smokers, because these symptoms may interfere with patients' efforts to quit.


Machine Learning in Invasive and Noninvasive Coronary Angiography.
The objective of this review is to shed light on the transformative potential of machine learning (ML) in coronary angiography. We aim to understand existing developments in using ML for coronary angiography and discuss broader implications for the future of coronary angiography and cardiovascular medicine. The developments in invasive and noninvasive imaging have revolutionized diagnosis and treatment of coronary artery disease (CAD). However, CAD remains underdiagnosed and undertreated. ML has emerged as a powerful tool to further improve image analysis, hemodynamic assessment, lesion detection, and predictive modeling. These advancements have enabled more accurate identification of CAD, streamlined workflows, reduced the need for invasive diagnostic procedures, and improved the diagnostic value of invasive procedures when they are needed. Further integration of ML with coronary angiography will advance the prevention, diagnosis, and treatment of CAD. The integration of ML with coronary angiography is ushering in a new era in cardiovascular medicine. We highlight five use cases to leverage ML in coronary angiography: (1) improvement of quality and efficacy, (2) characterization of plaque, (3) hemodynamic assessment, (4) prediction of future outcomes, and (5) diagnosis of non-atherosclerotic coronary disease.


A multidimensional social risk atlas of depression and anxiety: An observational and genome-wide environmental interaction study.
Mental disorders are largely socially determined, yet the combined impact of multidimensional social factors on the two most common mental disorders, depression and anxiety, remains unclear. We constructed a polysocial risk score (PsRS), a multidimensional social risk indicator including components from three domains: socioeconomic status, neighborhood and living environment and psychosocial factors. Supported by the UK Biobank cohort, we randomly divided 110 332 participants into the discovery cohort (60%; n = 66 200) and the replication cohort (40%; n = 44 134). We tested the associations between 13 single social factors with Patient Health Questionnaire (PHQ) score, Generalized Anxiety Disorder Scale (GAD) score and self-reported depression and anxiety. The significant social factors were used to calculate PsRS for each mental disorder by considering weights from the multivariable linear model. Generalized linear models were applied to explore the association between PsRS and depression and anxiety. Genome-wide environmental interaction study (GWEIS) was further performed to test the effect of interactions between PsRS and SNPs on the risk of mental phenotypes. In the discovery cohort, PsRS was positively associated with PHQ score (β = 0.37; 95% CI = 0.35-0.38), GAD score (β = 0.27; 95% CI = 0.25-0.28), risk of self-reported depression (OR = 1.29; 95% CI = 1.28-1.31) and anxiety (OR = 1.19; 95% CI = 1.19-1.23). Similar results were observed in the replication cohort. Emotional stress, lack of social support and low household income were significantly associated with the development of depression and anxiety. GWEIS identified multiple candidate loci for PHQ score, such as rs149137169 (ST18) (Pdiscovery = 1.08 × 10-8, Preplication = 3.25 × 10-6) and rs3759812 (MYO9A) (Pdiscovery = 3.87 × 10-9, Preplication = 6.21 × 10-5). Additionally, seven loci were detected for GAD score, such as rs114006170 (TMPRSS11D) (Pdiscovery = 1.14 × 10-9, Preplication = 7.36 × 10-5) and rs77927903 (PIP4K2A) (Pdiscovery = 2.40 × 10-9, Preplication = 0.002). Our findings reveal the positive effects of multidimensional social factors on the risk of depression and anxiety. It is important to address key social disadvantage in mental health promotion and treatment.


Preparation of Furfural From Xylose Catalyzed by Diimidazole Hexafluorophosphate in Microwave.
In this work, functionalized alkyl imidazolium hexafluorophosphate ILs were synthesized and characterized; then, they were applied in the conversion of xylose to furfural under the microwave method. The results showed that when CnMF was used as a catalyst, an acidic environment was provided to promote the formation of furfural. In addition, the heating method, the solvent, and the different structures of cations in the ionic liquid influenced their catalytic activity. In an aqueous solution, the yield of furfural obtained using the microwave method was better than that of the conventional heating method, and the catalytic activity of diimidazole hexafluorophosphate was better than that of monoimidazole. Meanwhile, for the diimidazole hexafluorophosphate, the change of the carbon chain length between the imidazole rings also slightly influenced the yield. Finally, the optimal yield of 49.76% was obtained at 205°C for 8 min using 3,3'-methylenebis(1-methyl-1H-imidazol-3-ium), C1MF, as a catalyst. Mechanistic studies suggested that the catalytic activity of C1MF was mainly due to the combined effect of POFn (OH)3-n and imidazole ring. Without a doubt, the catalytic activity of C1MF was still available after five cycles, which not only showed its excellent catalytic activity in catalyzing the xylose to prepare the biomass platform compound furfural but also could promote the application of functionalized ionic liquids.


Functional adaptation to reduced renal mass in early development.
To determine whether reduced renal mass in the newborn results in acceleration of normal renal development, the response to unilateral nephrectomy (N) before 36 h of age was compared with sham-operated (S) guinea pigs during the period of most rapid nephron maturation. Studies were performed at 7-13 days (group I) and 19-25 days (group II). Mean arterial blood pressure (AP), left kidney glomerular filtration rate (LKGFR), and urine sodium excretion (UNaV) were measured. Superficial single nephron GFR (sSNGFR) and proximal fractional water reabsorption (FRH2O) were measured by micropuncture, and the number of glomeruli (NG) was determined by India ink perfusion. In view of the susceptibility of the neonate to extracellular fluid loss, groups I and II were plasma infused to maintain euvolemia and group II was compared with 19- to 25-day-old hydropenic animals (group III). Increase in body weight with age was unaffected by neonatal N. In group IN, the compensatory increase in sSNGFR was greater than SNGFR for deeper nephrons, which normally contribute most to GFR at this age. In group IIN there was an 80% adaptive increase in LKGFR that could not be entirely explained by the rise in SNGFR. Since NG in group IIN was greater than in group IIS and similar to that in adulthood, the enhanced adaptation in LKGFR in group IIN may be due in part to earlier recruitment of a population of underperfused glomeruli. FRH2O did not change significantly with age and did not differ in N and S groups. Animals in group III developed a rise in hematocrit during the experiment, and AP, LKGFR, and UNaV were lower in group IIIN than in group IIN. It is concluded that following N at birth, the sequence of renal functional maturation is accelerated while glomerulotubular balance is preserved. As a result of these adaptative changes, homeostasis is maintained and body growth proceeds without impairment.


Idiopathic lymphoplasmacytic rhinitis in 33 dogs.
Idiopathic lymphoplasmacytic rhinitis (LPR) is recognised frequently in dogs with clinical signs typical of other chronic nasal diseases. The purpose of this study was to determine clinical signs, survey radiographic, rhinoscopic and histologic abnormalities and the response to therapy in dogs with LPR. It was a retrospective study of 33 client-owned animals of various breeds and ages that had been diagnosed with LPR. During the study period, a total of 110 dogs were diagnosed with nasal disease, of which 33 (30%) were diagnosed with idiopathic LPR. The median age was 9 years (range 2.3-17 years) and there were 15 female and 18 male dogs. The majority of dogs showed a mucoid nasal discharge, bilateral stertor and no overt radiographic changes. The most common finding on rhinos copy was hyperaemic nasal mucous membranes with mucoid material accumulation within the nasal cavity. In all 33 dogs bacterial culture yielded no pathogenic bacteria and fungal culture was negative. Histologically, all 33 dogs showed lymphoplasmacytic infiltration within the nasal mucosa. All 33 dogs were treated with systemic and topical corticosteroids for varying lengths of time and dosing intervals. Eleven dogs were treated with concurrent cyclosporine and three dogs underwent allergy testing followed by desensitisation therapy. The best response was seen in the dogs that underwent desensitisation therapy, followed by those treated with corticosteroids and cyclosporine.


Novosphingobium olei sp. nov., with the ability to degrade diesel oil, isolated from oil-contaminated soil and proposal to reclassify Novosphingobium stygium as a later heterotypic synonym of Novosphingobium aromaticivorans.
Two yellow-pigmented, non-motile, Gram-stain-negative, and rod-shaped bacteria, designated TW-4T and TNP-2 were obtained from oil-contaminated soil. Both strains degrade diesel oil, hydrolyse aesculin, DNA, Tween 40 and Tween 60. A phylogenetic analysis based on its 16S rRNA gene sequence revealed that strain TW-4T formed a lineage within the family Erythrobacteraceae and clustered as members of the genus Novosphingobium. The closest members of strain TW-4T were Novosphingobium subterraneum DSM 12447T (97.9 %, sequence similarity), Novosphingobium lubricantis KSS165-70T (97.8 %), Novosphingobium taihuense T3-B9T (97.8 %), Novosphingobium aromaticivorans DSM 12444T (97.7 %), Novosphingobium flavum UCT-28T (97.7 %), and Novosphingobium bradum STM-24T (97.6 %). The sequence similarity for other members was ≤97.6 %. The genome of strain TW-4T was 4 683 467 bp long with 44 scaffolds and 4280 protein-coding genes. The sole respiratory quinone was Q-10. The major cellular fatty acids were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), C16 : 0 and C14 : 0 2-OH. The major polar lipids were phosphatidylethanolamine (PE), phosphatidylglycerol (PG), diphosphatidylglycerol (DPG), phosphatidylcholine (PC), phosphatidyl-n-methylethanolamine (PME) and sphingoglycolipid (SGL). The DNA G+C content of the type strain was 65.0 %. The average nucleotide identity (ANIu) and in silico DNA-DNA hybridization (dDDH) relatedness values between strain TW-4T and closest members were below the threshold value for species delineation. Based on polyphasic taxonomic analyses, strain TW-4T represents novel species in the genus Novosphingobium, for which the name Novosphingobium olei sp. nov. is proposed. The type strain is TW-4T (=KACC 21628T=NBRC 114364T) and strain TNP-2 (=KACC 21629=NBRC 114365) represents an additional strain. Based on new data obtained in this study, it is also proposed to reclassify Novosphingobium stygium as a later heterotypic synonym of Novosphingobium aromaticivorans.


Propensity-based standardization to enhance the validation and interpretation of prediction model discrimination for a target population.
External validation of the discriminative ability of prediction models is of key importance. However, the interpretation of such evaluations is challenging, as the ability to discriminate depends on both the sample characteristics (ie, case-mix) and the generalizability of predictor coefficients, but most discrimination indices do not provide any insight into their respective contributions. To disentangle differences in discriminative ability across external validation samples due to a lack of model generalizability from differences in sample characteristics, we propose propensity-weighted measures of discrimination. These weighted metrics, which are derived from propensity scores for sample membership, are standardized for case-mix differences between the model development and validation samples, allowing for a fair comparison of discriminative ability in terms of model characteristics in a target population of interest. We illustrate our methods with the validation of eight prediction models for deep vein thrombosis in 12 external validation data sets and assess our methods in a simulation study. In the illustrative example, propensity score standardization reduced between-study heterogeneity of discrimination, indicating that between-study variability was partially attributable to case-mix. The simulation study showed that only flexible propensity-score methods (allowing for non-linear effects) produced unbiased estimates of model discrimination in the target population, and only when the positivity assumption was met. Propensity score-based standardization may facilitate the interpretation of (heterogeneity in) discriminative ability of a prediction model as observed across multiple studies, and may guide model updating strategies for a particular target population. Careful propensity score modeling with attention for non-linear relations is recommended.


[Hospital Panorama in Zamora at the middle of the XVIIIth Century].
The XVIIIth century was an era of reforms in multiple fields, including healthcare. To advance in its study, the present article delves into the knowledge about the hospital network in the middle of said century within the territories which integrate the current province of Zamora. Accordingly, the type of establishment, its funding, organisation and operation are analysed. As a result, a panorama dotted with numerous rural refuges and some hospitals in the centre of certain built-up areas is drawn, dedicated, basically, to the reception and religious assistance of poor vagrants. Such establishments were funded, above all, by agricultural income and by census rents. They counted , moreover, on a notable, ecclesiastic presence.


Best practice guidelines for the management of adverse events associated with amphotericin B lipid complex.
Amphotericin B lipid complex is a widely used lipid-based formulation of amphotericin B, which has a broad spectrum of activity against a variety of fungal pathogens. It has also been shown to be significantly less nephrotoxic than conventional amphotericin B. However, infusional drug reactions, similar to those seen when using conventional amphotericin B, have been reported in a significant number of patients, so it is important that these are prevented or managed effectively, particularly in light of the changing epidemiology of systemic fungal infections. This article reviews effective strategies that can be used to reduce the risk of drug delivery reactions associated with amphotericin B lipid complex. Preserving renal function and managing spikes in serum creatinine levels are also discussed. The aim of this paper is to provide healthcare professionals with clear guidance on the management of adverse events associated with amphotericin B lipid complex. Recommendations are based upon the published evidence and clinical experience from a number of different centres. Amphotericin B lipid complex represents a valuable therapeutic option in the treatment of fungal infections but improved strategies for the management of infusion-related adverse events are required.


Comparison of gastrointestinal adverse effects of ketoprofen between adult and young cats.
This study elucidated differences in predisposition to the gastrointestinal adverse effects of ketoprofen between young and adult cats. Ketoprofen was administered subcutaneously (2.0 mg/kg, s.c.) once a day for 3 days. The animals were sacrificed 24 hr after final injection to allow examination of gastrointestinal mucosal lesions. Ketoprofen caused gastric lesions in adult cats (>6 months) but not in young cats (<3 months). Ketoprofen caused more severe small intestinal lesions in adult cats than in young cats. In the study of prevention of lipopolysaccharide (LPS)-induced hyperthermia using ketoprofen, young and adult cats of both sexes were administered LPS (0.3 μg/kg, intravenously), and body temperature was measured 24 hr later. Ketoprofen was administered subcutaneously 30 min before LPS injection. LPS-induced hyperthermia was almost completely inhibited by pretreatment with ketoprofen in both adult and young cats. In the pharmacokinetics of ketoprofen, plasma concentrations were analyzed by high-performance liquid chromatography. No significant differences were observed in plasma concentrations of two mirror-image R(-) and S(+) ketoprofen between young and adult cats from 0.5-4 hr after injection. As observed in a previous study using flunixin, the degree of gastrointestinal damage was unrelated to plasma concentrations of ketoprofen. The results of this study demonstrated that ketoprofen is safer for use in young cats than in adult cats from the viewpoint of gastrointestinal adverse effects.


High-global warming potential F-gas emissions in California: comparison of ambient-based versus inventory-based emission estimates, and implications of refined estimates.
To provide information for greenhouse gas reduction policies, the California Air Resources Board (CARB) inventories annual emissions of high-global-warming potential (GWP) fluorinated gases, the fastest growing sector of greenhouse gas (GHG) emissions globally. Baseline 2008 F-gas emissions estimates for selected chlorofluorocarbons (CFC-12), hydrochlorofluorocarbons (HCFC-22), and hydrofluorocarbons (HFC-134a) made with an inventory-based methodology were compared to emissions estimates made by ambient-based measurements. Significant discrepancies were found, with the inventory-based emissions methodology resulting in a systematic 42% under-estimation of CFC-12 emissions from older refrigeration equipment and older vehicles, and a systematic 114% overestimation of emissions for HFC-134a, a refrigerant substitute for phased-out CFCs. Initial, inventory-based estimates for all F-gas emissions had assumed that equipment is no longer in service once it reaches its average lifetime of use. Revised emission estimates using improved models for equipment age at end-of-life, inventories, and leak rates specific to California resulted in F-gas emissions estimates in closer agreement to ambient-based measurements. The discrepancies between inventory-based estimates and ambient-based measurements were reduced from -42% to -6% for CFC-12, and from +114% to +9% for HFC-134a.


Effects of adolescent online gaming time and motives on depressive, musculoskeletal, and psychosomatic symptoms.
To investigate whether adolescent online gaming time and the additive effect of gaming motives were associated with depressive, musculoskeletal, and psychosomatic symptoms. The hypothesis was that adolescents who engage in online gaming with escape motives and increased online gaming time have higher probability for depressive, musculoskeletal, and psychosomatic symptoms compared to adolescents with other online gaming motives and/or less online gaming time. An anonymous and voluntary questionnaire was completed during class hours by 7,757 Swedish adolescents aged 13-18 years. The questionnaire included demographic background, gaming habits, and depressive, musculoskeletal, and psychosomatic symptoms. It was found that increased online gaming time during weekdays increased the probability of having depressive, musculoskeletal, and psychosomatic symptoms. However, these relations with time spent gaming were further explained by online gaming motives. Weekday online gaming for more than five hours a day, in combination with escape motives, was associated with an increased probability of depressive symptoms (odds ratio (OR) 4.614, 95% CI 3.230-6.590), musculoskeletal symptoms (OR 2.494, 95% CI 1.598-3.892), and psychosomatic symptoms (OR 4.437, 95% CI 2.966-6.637). The probability of ill health decreased when gaming was for fun or had social motives. Excessive gaming time and escape motives were found to be associated with increased probability of ill health among adolescents. Gaming motives may identify gamers in need of support to reduce unhealthy gaming behaviour as well as identify individuals at risk for ill health.


Incidence of anemia in older Koreans: community-based cohort study.
Most epidemiologic data are related to the prevalence of anemia, and there is little information regarding the incidence or etiology of newly diagnosed anemia in older people. The purpose of this study was to define the incidence and characteristics of anemia in the elderly population of Korea. Three hundred thirty-two independent, community-living, elderly persons aged 60 years and older were enrolled, and laboratory tests including iron profiles were performed. The mean age was 72+/-4.8 years and the mean hemoglobin was 13.4+/-1.1g/dl. During the follow-up period of 3 years, 24 subjects (3 males and 21 females) were newly diagnosed with anemia, which led to a 3-year incidence of 7.2% (24/332). Among the 24 subjects with new-onset anemia, iron deficiency anemia (IDA) was diagnosed in 5 subjects, while anemia of chronic disease (ACD) was detected in 8 subjects. Underlying illnesses were diabetes mellitus, osteoarthritis, renal insufficiency, hypothyroidism and malignancy. In those subjects with new-onset anemia, the serum iron, ferritin, transferrin saturation and albumin were lower than in the normal group. In conclusion, the 3-year incidence of anemia among Korean elderly people was determined to be 7.2%, and ACD was the most commonly defined cause of anemia.


Utility of ultrasound-guided fine needle aspiration cytology in assessing malignancy in head and neck pathology.
Fine needle aspiration cytology (FNAC) is a well-established diagnostic procedure for head and neck masses not clearly originating from mucosal or cutaneous surfaces. We analysed head and neck masses evaluated over a 2-year period, to assess the reliability of FNAC for the evaluation of malignancy. We enrolled all patients undergoing FNAC, from April 2013 to July 2015, in a single service of a large Italian university hospital. Relevant clinical data and ultrasonographic parameters of the lesions were recorded. We performed both conventional and thin-prep smears. Clinical presentation, ultrasonographic features and final cytology diagnoses were analysed and correlated with histology. The series included 301 lesions in 285 patients, with a single (94.4%) or two (5.6%) lesions. Only eight samples were considered non-diagnostic/inadequate (2.6%). Among the cases, 139 FNAC (46.1%) underwent surgery. Cytological-histological correspondence was found in 89% of the cases. Concerning malignancy, we documented less than 4% false positives and less than 2.5% false negatives, with 92.7% sensitivity and 94.6% specificity. FNAC diagnosis can be highly specific. Most importantly, it is highly reliable in assessing malignancy, thus defining the priority and guiding the management procedures.


Brachybacterium phenoliresistens sp. nov., isolated from oil-contaminated coastal sand.
A coccoid- to ovoid-shaped, Gram-positive, non-motile bacterial strain, designated phenol-AT, was isolated from an oil-contaminated coastal sand sample collected from Pingtung County, southern Taiwan, and characterized by use of a polyphasic approach. Phylogenetic analyses based on 16S rRNA gene sequences showed that the novel strain formed a monophyletic branch at the periphery of the evolutionary radiation occupied by the genus Brachybacterium in the family Dermabacteraceae, class Actinobacteria. The closest neighbours were Brachybacterium rhamnosum LMG 19848T (96.9% 16S rRNA gene sequence similarity), Brachybacterium nesterenkovii DSM 9573T (97.0%) and Brachybacterium muris C3H-21T (96.3%). The peptidoglycan type of strain phenol-AT was variation A4gamma with meso-diaminopimelic acid as the diagnostic cell-wall diamino acid. The isolate contained MK-7 as the major component of the quinone system. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, and unidentified phospholipids and glycolipids. The predominant fatty acid was anteiso-C15:0 (59.5%); significant amounts of iso-C16:0 (9.4%), iso-C14:0 (9.5%) and anteiso-C17:0 (10.8%) were also present. The isolate was also distinguished from recognized members of the genus Brachybacterium on the basis of several phenotypic and biochemical characteristics. It is evident from the genotypic, chemotaxonomic and phenotypic data that isolate phenol-AT represents a novel species of the genus Brachybacterium, for which the name Brachybacterium phenoliresistens sp. nov. is proposed. The type strain is phenol-AT (=LMG 23707T=BCRC 17589T).


Encephalomalacia associated with hypovitaminosis E in turkey poults.
Four-to-five-week-old turkey poults fed a diet markedly deficient in vitamin E (alpha-tocopherol) abruptly developed neurologic signs such as tremor, incoordination, and recumbency shortly after being moved to new quarters. Serum concentrations of alpha-tocopherol in birds on this diet were significantly lower than control values. Associated lesions included recent ischemic necrosis of the cerebellum and spinal cord. The condition closely resembled nutritional encephalomalacia of chicks. This report represents the initial published description of that entity in turkeys.


T-cell receptor sequences correlate with and predict gene expression levels in T cells.
T cells exhibit high heterogeneity in both their gene expression profiles and antigen specificities. We analyzed fifteen single-cell immune profiling datasets to systematically investigate the association between T-cell receptor (TCR) sequences and the gene expression profiles of T cells. Our findings reveal that T cells sharing identical or similar TCR sequences tend to have highly similar gene expression profiles. Additionally, we developed a foundational model that leverages TCR information to predict gene expression levels in T cells.


Impaired erythrocyte deformability precedes vascular changes in experimental diabetes mellitus.
The effect of diabetes on the red blood cell (RBC) deformability and its association with histological vascular changes was investigated in 35 streptozotocin-induced diabetic Wistar rats in a 30-day experiment and compared to 10 controls. RBC deformability was significantly impaired in the diabetic rats on day 5 (p < 0.001) and continued to deteriorate until day 20. On the 20 (th) day, the diabetic rats were randomly divided into two groups (group A: insulin-treated; group B: non-insulin-treated). A slight, non-significant (p = 0.20) improvement in RBC deformability was noticed in the insulin-treated group. In vitro incubation of RBCs with insulin did not improve the acquired RBC rigidity in either diabetic group. In contrast, it caused a significant reduction in RBC-deformability in the controls. On day 30, histological examination of arterial specimens from various sites revealed moderate to significant thickening in medium- and small-size artery and arteriole walls in both diabetic groups, with no evidence of diabetes-related changes in large, elastic-type arteries. No vascular changes were noticed in nine diabetic rats that succumbed between days 10 and 15. The results of this study indicate that reduced RBC deformability is an early manifestation of abnormal blood rheology in experimental diabetes, and precedes the evolution of vascular changes.


Primary Intracranial Germinomas: Retrospective Analysis of Five Cases.
Primary intracranial germinomas (PIGs) are rare malignant brain tumors that represent approximately 0.2% to 1.7% of all primary intracranial tumors. PIGs have infrequent, but there is a possibility of spinal cord metastases. In this study, clinical outcomes of five consecutive PIGs have been presented. Medical records were retrospectively reviewed in 1,849 cases of intracranial tumors who underwent surgery between the years 2005 and 2015 and cases confirmed as germinoma histopathologically were included in this study. Five cases of PIGs were detected in two female (40%) and 3 male (60%) patients. The mean age was 15.2±5.6 (8-23) years. The mean follow-up period was 52.3±56.4 (9-135) months. The most common complaint was headache (60%), followed by nausea±vomiting (40%). Four cases (80%) affected the suprasellar region while the fifth patient"s tumor was localized in the pineal region. The duration between the initial symptom and time of surgical intervention ranged between 15 days and 2 months. Twelve months after the first operation, one patient presented with drop seeding metastasis. Four-year survival (with exception of the case that died as a early surgical complication) was 100%. Gross total resection (GTR) was achieved in one patient. Surgical mortality rate was 20%. PIGs" morbidity rate was 60%. PIG is a mostly malignant tumor that generally affects the pediatric age group. They are radiosensitive tumors. Subtotal or near-total resection using stereotactic guide or direct surgery to confirm the histopathological diagnosis followed by chemotherapy and whole brain or in some cases craniospinal radiotherapy rather than GTR is therefore the treatment of choice.


The utility of injury narratives for prioritising future prevention activities in small and medium enterprises in rural Vietnam.
Injuries are a leading cause of work-related disability and death in rapidly developing countries such as Vietnam. The authors' objective was to demonstrate the utility of detailed injury narratives, derived from a household survey, in providing information on the determinants of work-related injuries to inform potential intervention targets. In a cross-sectional survey administered to 2615 households of a rapidly developing community of Vietnam where many workers engage in both agriculture and industrial work, the authors collected information about self-reported work-related injuries, annual hours worked in each industry and narrative text describing the circumstances of each injury. The authors used a customised coding taxonomy to describe injury scenarios. Several intervention themes emerged, including the implementation of machine guarding, the use of cut resistant gloves and safety glasses which would benefit the small- and medium-sized enterprises. Calculation of incidence rates using full-time equivalents, stratified by work group, provided some unexpected observations of the risks of working in agriculture; workers who work in agriculture in addition to another industry are at an increased risk of fatigue or overexertion and other consequences of working too hard in their agricultural activities. A lack of aggregate injury statistics makes it difficult for the owners of small- and medium-sized enterprises to recognise a priori the most effective safety interventions. This analysis of detailed injury narratives with an appropriate taxonomic basis offers the ability to focus on the level of cause, activity and source and may inform the choice of various potential interventions at the workplace or enterprise level.


How Nurse Work Environments Relate to the Presence of Parents in Neonatal Intensive Care.
Parental presence in the neonatal intensive care unit (NICU) is essential for families to participate in infant care and prepare them to transition from hospital to home. Nurses are the principal caregivers in the NICU. The nurse work environment may influence whether parents spend time with their hospitalized infants. To examine the relationship between the NICU work environment and parental presence in the NICU using a national data set. We conducted a cross-sectional, observational study of a national sample of 104 NICUs, where 6060 nurses reported on 15,233 infants cared for. Secondary analysis was used to examine associations between the Practice Environment Scale of the Nursing Work Index (PES-NWI) (subscale items and with a composite measure) and the proportion of parents who were present during the nurses' shift. Parents of 60% (SD = 9.7%) of infants were present during the nurses' shift. The PES-NWI composite score and 2 domains-Nurse Participation in Hospital Affairs and Manager Leadership and Support-were significant predictors of parental presence. A 1 SD higher score in the composite or either subscale was associated with 2.5% more parents being present. Parental presence in the NICU is significantly associated with better nurse work environments. NICU practices may be enhanced through enhanced leadership and professional opportunities for nurse managers and staff. Future work may benefit from qualitative work with parents to illuminate their experiences with nursing leaders and nurse-led interventions in the NICU and design and testing of interventions to improve the NICU work environment.


Calcium increases Xylella fastidiosa surface attachment, biofilm formation, and twitching motility.
Xylella fastidiosa is a plant-pathogenic bacterium that forms biofilms inside xylem vessels, a process thought to be influenced by the chemical composition of xylem sap. In this work, the effect of calcium on the production of X. fastidiosa biofilm and movement was analyzed under in vitro conditions. After a dose-response study with 96-well plates using eight metals, the strongest increase of biofilm formation was observed when medium was supplemented with at least 1.0 mM CaCl(2). The removal of Ca by extracellular (EGTA, 1.5 mM) and intracellular [1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA/AM), 75 μM] chelators reduced biofilm formation without compromising planktonic growth. The concentration of Ca influenced the force of adhesion to the substrate, biofilm thickness, cell-to-cell aggregation, and twitching motility, as shown by assays with microfluidic chambers and other assays. The effect of Ca on attachment was lost when cells were treated with tetracycline, suggesting that Ca has a metabolic or regulatory role in cell adhesion. A double mutant (fimA pilO) lacking type I and type IV pili did not improve biofilm formation or attachment when Ca was added to the medium, while single mutants of type I (fimA) or type IV (pilB) pili formed more biofilm under conditions of higher Ca concentrations. The concentration of Ca in the medium did not significantly influence the levels of exopolysaccharide produced. Our findings indicate that the role of Ca in biofilm formation may be related to the initial surface and cell-to-cell attachment and colonization stages of biofilm establishment, which rely on critical functions by fimbrial structures.


Endoplasmic reticulum stress and renal disease.
The accumulation of unfolded proteins in the endoplasmic reticulum (ER), leading to ER stress, is caused by a wide range of physiologic and pathologic conditions. Cells respond to ER stress by activating a series of integrative stress pathways termed the unfolded protein response (UPR). This either may be adaptive and promote cell survival, or if the ER stress is chronic or excessive, may lead to cell death. The role of ER stress in the pathophysiology of both acute and chronic kidney diseases has been gaining increasing interest. This review highlights the current knowledge of ER stress in renal disease, with emphasis on more recent advances. Potential therapeutic options targeting ER stress are discussed.


Development of an integrated model for analysis of the kinetics of apolipoprotein B in plasma very low density lipoproteins, intermediate density lipoproteins, and low density lipoproteins.
To quantify more precisely the metabolism of apolipoprotein B (apo B) in human beings, an integrated model was developed for the analysis of the isotope kinetics of apo B in very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and low density lipoproteins (LDL). The experimental basis for model development was a series of 30 triple-isotope studies in which patients received autologous 131I-VLDL, 125I-IDL, and [3H]glycerol as a precursor of VLDL triglycerides. The currently proposed model contains the following components: (a) a VLDL delipidation cascade that has a variable number of subcompartments, (b) a slowly catabolized pool of VLDL, (c) an IDL compartment consisting of two closely connected subcompartments, one of which is outside the immediate circulation, and (d) a two-compartment subsystem for LDL. Because mass data indicate that not all VLDL were converted to LDL, the model allows for irreversible removal of apo B from VLDL (or IDL) subsystems. It accounts for apparent "direct" input of LDL by postulating an early, rapidly metabolized compartment of VLDL that is converted directly to IDL. The model appears to be consistent with specific activity curves from the current triple-isotope studies and with present concepts of lipoprotein physiology; it also can be used to quantify pathways of lipoprotein apo B transport in normal and abnormal states.


The Na+ /Ca2+ antiporter Slr0681 affects carotenoid production in Synechocystis sp. PCC 6803 under high-light stress.
Carotenoids play key roles in photosynthesis and are widely used in foods as natural pigments, antioxidants, and health-promoting compounds. Enhancing carotenoid production in microalgae via biotechnology has become an important area of research. We knocked out the Na+ /Ca2+ antiporter gene slr0681 in Synechocystis sp. PCC 6803 via homologous recombination and evaluated the effects on carotenoid production under normal (NL) and high-light (HL) conditions. On day 7 of NL treatment in Ca2+ -free medium, the cell density of Δslr0681 decreased by 29% compared to the wild type (WT). After 8 days of HL treatment, the total carotenoid contents decreased by 35% in Δslr0681, and the contents of individual carotenoids were altered: myxoxanthophyll, echinenone, and β-carotene contents increased by 10%, 50%, and 40%, respectively, while zeaxanthin contents decreased by ~40% in Δslr0681 vs. the WT. The expression patterns of carotenoid metabolic pathway genes also differed: ipi expression increased by 1.2- to 8.5-fold, whereas crtO and crtR expression decreased by ~90% and 60%, respectively, in ∆slr0681 vs. the WT. In addition, in ∆slr0681, the expression level of psaB (encoding a photosystem I structural protein) doubled, whereas the expression levels of the photosystem II genes psbA2 and psbD decreased by ~53% and 84%, respectively, compared to the WT. These findings suggest that Slr0681 plays important roles in regulating carotenoid biosynthesis and structuring of the photosystems in Synechocystis sp.. This study provides a theoretical basis for the genetic engineering of microalgae photosystems to increase their economic benefits and lays the foundation for developing microalgae germplasm resources with high carotenoid contents. This article is protected by copyright. All rights reserved.


Testosterone withdrawal promotes stage-specific detachment of round spermatids from the rat seminiferous epithelium.
Testosterone (T) has been shown to be essential for the completion of spermiogenesis. Our previous studies showed that when intratesticular T was suppressed for 11 wk, the conversion of round spermatids between stages VII and VIII of the spermatogenic cycle was markedly suppressed and that elongated spermatids were undetectable. The fate of the round spermatids that did not proceed through this conversion was unclear. The current study aimed to investigate this T-dependent loss of round spermatids during stages VII and VIII. Adult male Sprague-Dawley rats received 24-cm T implants for 1 wk to suppress LH while maintaining spermatogenesis. The T24 implants were removed and replaced with 3-cm T plus 0.4-cm estradiol (TE treatment) to suppress intratesticular T and spermatogenesis, and animals were killed at 0 and 4 days and 1, 2, 3, 4, and 6 wk later. The number of homogenization-resistant elongated spermatids in the testis was counted, and round spermatid populations in stages VII and VIII were quantified using stereological techniques. The hourly production rates (HPR) were calculated, and a ratio was made between the HPR of round spermatids in stages VII and VIII to assess the efficiency of their conversion through these stages. Testicular T levels were suppressed to 2-4% of control values by TE treatment. After 2 wk of TE treatment, the number of homogenization-resistant elongated spermatids was significantly suppressed, falling to < 0.5% of the control value by 6 wk. The HPR of round spermatids in stages VII and VIII was not affected by up to 2 wk of TE treatment, nor was the conversion between these stages interrupted. After 3 wk of TE treatment, the HPR of round spermatids in stages VII and VIII was significantly suppressed, as was the conversion between these stages, the ratio falling to 27% of the control value by 6 wk. In rats treated with TE, histological examination of the cauda epididymidis showed occasional round spermatids after 3 wk of treatment, and large numbers after 6 wk. We conclude that the failure of round spermatids to complete spermiogenesis following T withdrawal is due to stage-specific detachment of round spermatids between stages VII and VIII.


Intra-arterial and intravenous chemotherapy for the treatment of malignant glioma. Preliminary results.
Twenty-one patients with malignant glioma were treated with cis-diamminedichloroplatinum II (CDDP II) 60-90 mg/m2 intra-arterial (I.A.) bolus on day 1 and Carmustine (BCNU) 100 mg/m2 intravenously (I.V.) on days 1 and 2. Three patients received additional Aziridinylbenzoquinone (AZQ) 7 mg/m2 (I.V.) on days 1 and 2. At the time of this treatment, seven patients had local recurrence after previous surgery and radiotherapy. Nine patients had subtotal tumor resection or biopsy, one patient had macroscopic tumor resection, and four patients had no previous surgery because of medical contraindication. Six patients received five or more courses of I.A. and I.V. chemotherapy. Five of these patients showed complete remission (CR) and one had a partial remission (PR) by brain computerized tomography (CT scan). Another 15 patients treated with two to four courses of I.A., and I.V. chemotherapy showed eight partial responses (PR), and seven showed no changes (NC) by brain CT scan. Five patients died with disease. Patients who achieved CR also received radical radiotherapy for remission consolidation. Sixteen patients are still alive; five patients are off treatment, four of these with no evidence of disease (NED), one alive with disease (AWD); and the remaining 11 patients are still on treatment. Toxicity, symptomatic neurological recovery, disease stabilization, and causes of death will be discussed.


Developing a Neural-Kalman Filtering Approach for Estimating Traffic Stream Density Using Probe Vehicle Data.
This paper presents a novel model for estimating the number of vehicles along signalized approaches. The proposed estimation algorithm utilizes the adaptive Kalman filter (AKF) to produce reliable traffic vehicle count estimates, considering real-time estimates of the system noise characteristics. The AKF utilizes only real-time probe vehicle data. The AKF is demonstrated to outperform the traditional Kalman filter, reducing the prediction error by up to 29%. In addition, the paper introduces a novel approach that combines the AKF with a neural network (AKFNN) to enhance the vehicle count estimates, where the neural network is employed to estimate the probe vehicles' market penetration rate. Results indicate that the accuracy of vehicle count estimates is significantly improved using the AKFNN approach (by up to 26%) over the AKF. Moreover, the paper investigates the sensitivity of the proposed AKF model to the initial conditions, such as the initial estimate of vehicle counts, initial mean estimate of the state system, and the initial covariance of the state estimate. The results demonstrate that the AKF is sensitive to the initial conditions. More accurate estimates could be achieved if the initial conditions are appropriately selected. In conclusion, the proposed AKF is more accurate than the traditional Kalman filter. Finally, the AKFNN approach is more accurate than the AKF and the traditional Kalman filter since the AKFNN uses more accurate values of the probe vehicle market penetration rate.


[Investigation of genetically modified soybean biosafety in the center of the origin and diversity of Russian Far East].
Wild soybean (Glycine soja Sieb. & Zucc.) is the nearest relative of a soybean crop (Glycine max (L.) Merr.). Study of population genetic structure of wild-growing relatives ofgenetically modified (GM) plants in the centers of their origin is one of the main procedures before introduction of GM crops in these areas. We have studied genetic variability of nine wild growing soya populations of Primorye Territory using RAPD analysis. The level of G. soja genetic variability was considerably higher than that of G. max. We have analyzed phylogenetic relationships in the genus Glycine subgenus Soja using RAPD markers. Our data confirm validity of allocation G. gracilis in a rank of a species.


National clinical guidelines for stroke: a concise update.
The National Clinical Guidelines for Stroke (1) cover the management of stroke from the acute illness through to transfer of care from hospital to the community, to longer-term problems including carer support and secondary prevention. They are designed to be read by all health and social service professionals, including those working in primary care. Since the guidelines were first published there have been some major developments in stroke research. These have now been incorporated into an updated supplement to the guidelines (2). The new updates include: The recommendation that specialist stroke services should include a neurovascular clinic to enable patients with transient ischaemic attack (TIA) and minor stroke, (where the patient has not been admitted to hospital), to be investigated and treated within a maximum of two weeks. Changes in the recommendations about the management of blood pressure after stroke following the publication of the HOPE and PROGRESS trials. Although advances in therapy research do not warrant radical alterations to practice, two changes have been made. These recommend the use of resisted exercise to improve motor function in targeted muscles and that patients should be given as much opportunity to practice tasks as possible. More precise recommendations on the management of depression. The withdrawal of some recommendations concerning the management of shoulder pain, deep venous thromboses and biofeedback. With the research evidence evolving at a rapid rate a new version of the complete guidelines will be published in 2003.


Mutations in the draT and draG genes of Rhodospirillum rubrum result in loss of regulation of nitrogenase by reversible ADP-ribosylation.
Reversible ADP-ribosylation of dinitrogenase reductase forms the basis of posttranslational regulation of nitrogenase activity in Rhodospirillum rubrum. This report describes the physiological effects of mutations in the genes encoding the enzymes that add and remove the ADP-ribosyl moiety. Mutants lacking a functional draT gene had no dinitrogenase reductase ADP-ribosyltransferase (DRAT, the draT gene product) activity in vitro and were incapable of modifying dinitrogenase reductase with ADP-ribose in vivo. Mutants lacking a functional draG gene had no dinitrogenase reductase-activating glycohydrolase (DRAG, the draG gene product) activity in vitro and were unable to remove ADP-ribose from the modified dinitrogenase reductase in vivo. Strains containing polar mutations in draT had no detectable DRAG activity in vitro, suggesting likely cotranscription of draT and draG. In strains containing draT and lacking a functional draG, dinitrogenase reductase accumulated in the active form under derepressing conditions but was rapidly ADP-ribosylated in response to conditions that cause inactivation. Detection of DRAT in these cells in vitro demonstrated that DRAT is itself subject to posttranslational regulation in vivo. Mutants affected in an open reading frame immediately downstream of draTG showed regulation of dinitrogenase reductase by ADP-ribosylation, although differences in the rates of ADP-ribosylation were apparent.


The phytoplasma associated with ash yellows and lilac witches'-broom: 'Candidatus phytoplasma fraxini'.
Phytoplasmas associated with the plant diseases ash yellows (AshY, occurring in Fraxinus) and lilac witches'-broom (LWB, occurring in Syringa) represent a putative species-level taxon. Phytoplasmal DNA from 19 ash or lilac sources across the known geographic range of AshY (71-113 degrees W) was examined to determine if AshY and LWB phytoplasmas are a coherent group, if variability exists in both conserved and anonymous DNA, and if variability in 16S rDNA is related to host or geographic origin. The 16S rRNA gene and the 16S-23S spacer were amplified using primer pair P1/P7 and analysed using 15 restriction enzymes. RFLPs were detected in digests obtained with Alul, Hhal or Taql, for a total of four RFLP profile types. Sequencing of the amplimers from strains AshY1T, AshY3, AshY5 and LWB3 (which represent the four 16S rDNA RFLP profile types) revealed only three positions in the 16S rRNA gene and one position in the 16S-23S spacer at which differences occurred; these were single nucleotide substitutions. Sequence homology between any two strains was > 99.8%. A portion of a ribosomal protein operon, amplified with primer pair rpF1/R1 from each of the four strains noted above, was analysed with six restriction enzymes, resulting in the detection of two RFLP profiles with Msel. Southern analysis, utilizing two non-specific probes from other phytoplasma groups, revealed three RFLP profile types in anonymous chromosomal DNA of strains representing the four 16S rDNA genotypes. Two strains, AshY3 and LWB3, had unique combinations of characters in the various assays. On the basis of RFLP profiles, the strains from the other plants sampled comprised two groups. The grouping was not clearly related to host or geographic origin. The genome size of strain AshY3 was estimated from PFGE data to be 645 kbp. Phylogenetic analysis of a 1423 bp 16S rDNA sequence from strains AshY1T, AshY3, AshY5 and LWB3, together with sequences from 14 other mollicutes archived in GenBank, produced a tree on which the AshY and LWB strains clustered as a discrete group, consistent with previous analyses utilizing only type strain AshY1T. Thus, the AshY phytoplasma group is coherent but heterogeneous. The name 'Candidatus Phytoplasma fraxini' is proposed for this group.


Tales of the unexpected: phylogeography of the arctic-alpine model plant Saxifraga oppositifolia (Saxifragaceae) revisited.
Arctic-alpine biota occupy enormous areas in the Arctic and the northern hemisphere mountain ranges and have undergone major range shifts during their comparatively short history. The origins of individual arctic-alpine species remain largely unknown. In the case of the Purple saxifrage, Saxifraga oppositifolia, an important model for arctic-alpine plants, phylogeographic studies have remained inconclusive about early stages of the species' spatiotemporal diversification but have provided evidence for long-range colonization out of a presumed Beringian origin to cover today's circumpolar range. We re-evaluated the species' large-scale range dynamics based on a geographically extended sampling including crucial areas such as Central Asia and the (south-)eastern European mountain ranges and employing up-to-date phylogeographic analyses of a plastid sequence data set and a more restricted AFLP data set. In accordance with previous studies, we detected two major plastid DNA lineages also reflected in AFLP divergence, suggesting a long and independent vicariant history. Although we were unable to determine the species' area of origin, our results point to Europe (probably the Alps) and Central Asia, respectively, as the likely ancestral areas of the two main lineages. AFLP data suggested that contact areas between the two clades in the Carpathians, Northern Siberia and western Greenland were secondary. In marked contrast to high levels of diversity revealed in previous studies, populations from the major arctic refugium Beringia did not exhibit any plastid sequence polymorphism. Our study shows that adequate sampling of the southern, refugial populations is crucial for understanding the range dynamics of arctic-alpine species.


The Oxford medial unicompartmental arthroplasty: a ten-year survival study.
Retrieval studies have shown that the use of fully congruent meniscal bearings reduces wear in knee replacements. We report the outcome of 143 knees with anteromedial osteoarthritis and normal anterior cruciate ligaments treated by unicompartmental arthroplasty using fully congruous mobile polyethylene bearings. At review, 34 knees were in patients who had died and 109 were in those who were still living. The mean elapsed time since operation was 7.6 years (maximum 13.8). We established the status of all but one knee. There had been five revision operations giving a cumulative prosthetic survival rate at ten years (33 knees at risk) of 98% (95% CI 93% to 100%). Considering the knee lost to follow-up as a failure, the 'worst-case' survival rate was 97%. No failures were due to polyethylene wear or aseptic loosening of the tibial component. One bearing which dislocated at four years was reduced by closed manipulation. The ten-year survival rate is the best of those reported for unicompartmental arthroplasty and not significantly different from the best rates for total knee replacement.


Long-term outcome of RPE allografts in non-immunosuppressed patients with AMD.
To determine the long-term outcome of human retinal pigment epithelium (RPE) transplants in patients with advanced age-related macular degeneration (AMD). Using pars plana microsurgical techniques, RPE allografts were transplanted subretinally to four groups of AMD patients: five patients received organized patch transplants after removal of choroidal neovascular membranes, four got small patch transplants in dry AMD; suspensions of RPE cells were transplanted in five cases with dry AMD, and two patients with RPE tears. None received immunosuppression. Transplants were followed for 24-38 months by biomicroscopy, fundus photography, SLO microperimetry, and fluorescein angiography. Rejection was defined as loss of visual function over the transplant, development of an exudative response (subretinal fluid with or without neovascularization), fluorescein leakage, and disruption, depigmentation, or encapsulation of the transplant. Four of 16 transplants (25%) presented no clinical signs of rejection. Three of the four small patch transplants remained pigmented and essentially unchanged after 30-32 months. Clinical signs of graft rejection appeared within three months in all cases of neovascular AMD (disrupted blood-retinal barrier, BRB), but after 6-20 months in five of nine eyes with non-exudative AMD (intact BRB). Subretinal human RPE allografts present a high rejection rate (75%) without immunosuppression. However, small extrafoveal transplants remained unchanged in shape, size and color for more than two years in non-exudative AMD. A disrupted BRB is likely to enhance graft rejection, which occurs earlier in exudative than in non-exudative AMD.


Phosphoribosyl pyrophosphate and phosphoribosyl pyrophosphate synthetase in rat mammary gland. Changes in the lactation cycle and effects of diabetes, insulin and phenazine methosulphate.
Changes in the tissue content of phosphoribosyl pyrophosphate (PPRibP), glucose 6-phosphate, ribose 5-phosphate (Rib5P), RNA and DNA, of the activity of PPRibP synthetase (EC 184.108.40.206) and the conversion of [1-14C]- and [6-14C]-glucose into 14CO2 were measured at mid-lactation in the normal and diabetic rat and in pregnancy, lactation and mammary involution in the normal rat. The PPRibP, glucose 6-phosphate and Rib5P contents increase during pregnancy and early lactation to reach a plateau value at mid-lactation, before falling sharply during weaning. The PPRibP content, PPRibP synthetase activity and flux of glucose through the oxidative pentose phosphate pathway (PPP) all change in parallel during the lactation cycle. Similarly, after 3 and 5 days duration of streptozotocin-induced diabetes, ending on day 10 of lactation, there were parallel declines in PPRibP content, PPRibP synthetase and PPP activity. The effect of streptozotocin was prevented by pretreatment with nicotinamide and partially reversed by insulin administration. Addition of insulin to lactating rat mammary-gland slices incubated in vitro significantly raised the PPRibP content (+47%) and the activity of the PPP (+40%); phenazine methosulphate, which gives a 2-fold increase in PPP activity, raised the PPRibP content of lactating mammary gland slices by approx. 3-fold. It is concluded that Rib5P, generated in the oxidative segment of the PPP, is an important determinant of PPRibP synthesis in the lactating rat mammary gland and that insulin plays a central role in the regulation of the bioavailability of this precursor of nucleotide and nucleic acid synthesis.


The Snowmelt Niche Differentiates Three Microbial Life Strategies That Influence Soil Nitrogen Availability During and After Winter.
Soil microbial biomass can reach its annual maximum pool size beneath the winter snowpack and is known to decline abruptly following snowmelt in seasonally snow-covered ecosystems. Observed differences in winter versus summer microbial taxonomic composition also suggests that phylogenetically conserved traits may permit winter- versus summer-adapted microorganisms to occupy distinct niches. In this study, we sought to identify archaea, bacteria, and fungi that are associated with the soil microbial bloom overwinter and the subsequent biomass collapse following snowmelt at a high-altitude watershed in central Colorado, United States. Archaea, bacteria, and fungi were categorized into three life strategies (Winter-Adapted, Snowmelt-Specialist, Spring-Adapted) based upon changes in abundance during winter, the snowmelt period, and after snowmelt in spring. We calculated indices of phylogenetic relatedness (archaea and bacteria) or assigned functional attributes (fungi) to organisms within life strategies to infer whether phylogenetically conserved traits differentiate Winter-Adapted, Snowmelt-Specialist, and Spring-Adapted groups. We observed that the soil microbial bloom was correlated in time with a pulse of snowmelt infiltration, which commenced 65 days prior to soils becoming snow-free. A pulse of nitrogen (N, as nitrate) occurred after snowmelt, along with a collapse in the microbial biomass pool size, and an increased abundance of nitrifying archaea and bacteria (e.g., Thaumarchaeota, Nitrospirae). Winter- and Spring-Adapted archaea and bacteria were phylogenetically clustered, suggesting that phylogenetically conserved traits allow Winter- and Spring-Adapted archaea and bacteria to occupy distinct niches. In contrast, Snowmelt-Specialist archaea and bacteria were phylogenetically overdispersed, suggesting that the key mechanism(s) of the microbial biomass crash are likely to be density-dependent (e.g., trophic interactions, competitive exclusion) and affect organisms across a broad phylogenetic spectrum. Saprotrophic fungi were the dominant functional group across fungal life strategies, however, ectomycorrhizal fungi experienced a large increase in abundance in spring. If well-coupled plant-mycorrhizal phenology currently buffers ecosystem N losses in spring, then changes in snowmelt timing may alter ecosystem N retention potential. Overall, we observed that snowmelt separates three distinct soil niches that are occupied by ecologically distinct groups of microorganisms. This ecological differentiation is of biogeochemical importance, particularly with respect to the mobilization of nitrogen during winter, before and after snowmelt.


Antigenic comparison of envelope protein E between Japanese encephalitis virus and some other flaviviruses using monoclonal antibodies.
The antigenic relationships between Japanese encephalitis (JE) virus and several other flaviviruses have been investigated using anti-JE virus monoclonal antibodies (MAbs). Seventeen MAbs directed against envelope protein E of JE virus were characterized and divided into eight MAb groups based on reactivity patterns in haemagglutination inhibition test, neutralization (N) test, ELISA and competitive binding assay with JE virus. The results suggest the existence of at least eight epitopes on the E protein of JE viruses. Analysis of cross-reactivity of the antibodies with several other flaviviruses indicated these findings JE virus, belonging to West Nile (WN) subgroup, is antigenically closely related to viruses in the same subgroup, i.e. Murray Valley encephalitis (MVE), WN and St. Louis encephalitis (SLE) viruses. Of these three viruses, JE virus has the closest relationship with MVE virus. WN virus is relatively close to JE virus, whereas SLE virus is the least closely related. Dengue viruses types 1 and 2, which belong to another subgroup of flaviviruses, show markedly less antigenic homology to JE virus. One of the critical N sites on the E protein showed JE virus specificity. Some cross-reactive antibodies which did not neutralize JE virus showed low but significant N activity against several other flaviviruses. Mixtures of several MAbs, which showed different reactivity patterns, potentiated the N activity against not only JE virus but also other members of the WN subgroup of flaviviruses, namely MVE, WN and SLE viruses.


Photophysics of Coumarin and Carbostyril-Sensitized Luminescent Lanthanide Complexes: Implications for Complex Design in Multiplex Detection.
Luminescent lanthanide (Ln(III)) complexes with coumarin or carbostyril antennae were synthesized and their photophysical properties evaluated using steady-state and time-resolved UV-vis spectroscopy. Ligands bearing distant hydroxycoumarin-derived antennae attached through triazole linkers were modest sensitizers for Eu(III) and Tb(III), whereas ligands with 7-amidocarbostyrils directly linked to the coordination site could reach good quantum yields for multiple Ln(III), including the visible emitters Sm(III) and Dy(III), and the near-infrared emitters Nd(III) and Yb(III). The highest lanthanide-centered luminescence quantum yields were 35% (Tb), 7.9% (Eu), 0.67% (Dy), and 0.18% (Sm). Antennae providing similar luminescence intensities with 2-4 Ln-emitters were identified. Photoredox quenching of the carbostyril antenna excited states was observed for all Eu(III)-complexes and should be sensitizing in the case of Yb(III); the scope of the process extends to Ln(III) for which it has not been seen previously, specifically Dy(III) and Sm(III). The proposed process is supported by photophysical and electrochemical data. A FRET-type mechanism was identified in architectures with both distant and close antennae for all of the Lns. This mechanism seems to be the only sensitizing one at long distance and probably contributes to the sensitization at shorter distances along with the triplet pathway. The complexes were nontoxic to either bacterial or mammalian cells. Complexes of an ester-functionalized ligand were taken up by bacteria in a concentration-dependent manner. Our results suggest that the effects of FRET and photoredox quenching should be taken into consideration when designing luminescent Ln complexes. These results also establish these Ln(III)-complexes for multiplex detection beyond the available two-color systems.


Ixekizumab improves patient-reported outcomes in patients with active psoriatic arthritis and inadequate response to tumour necrosis factor inhibitors: SPIRIT-P2 results to 52 weeks.
To report patient-reported outcomes (PROs) of ixekizumab-treated patients with psoriatic arthritis (PsA) and an inadequate response (IR) or intolerance to tumour necrosis factor inhibitors (TNFi) to 52 weeks. In SPIRIT-P2, patients with active PsA and an IR or intolerance to TNFi were randomised to ixekizumab 80 mg every 4 weeks (IXEQ4W; N=122) or every 2 weeks (IXEQ2W; N=123), or placebo (PBO; N=118) during the initial 24-week double-blind treatment period. At Week 16, background therapy was modified for IRs; additionally, IRs in the placebo group were re-randomised (1:1) to IXEQ2W or IXEQ4W. Patients receiving ixekizumab at Week 24 received the same dose during the study remainder. Patients completed several PROs for PsA disease activity, skin, health-related quality of life (HRQOL, and work through Week 52. Ixekizumab-treated patients reported significant improvements versus PBO in 36-Item Short Form Health Survey version 2, European Quality of Life 5 Dimensions visual analogue scale, Bath Ankylosing Spondylitis Disease Activity Index (total score and question 2), and Work Productivity and Activity Impairment Questionnaire-Specific Health Problem (3 of 4 domains) through Week 24. At Week 24, 9% (PBO), 52% (IXEQ4W), and 50% (IXEQ2W) of patients reported Dermatology Life Quality Index scores of 0 or 1; 0% (PBO) and 24% (IXEQ4W and IXEQ2W) reported Itch Numeric Rating Scale score of 0. Where data were collected, improvements persisted through Week 52. In patients with PsA and an IR or intolerance to TNFi, ixekizumab significantly improved disease activity, skin symptoms, HRQOL, and work productivity to 52 weeks.


Nucleotide sequence of wild-type hepatitis A virus GBM in comparison with two cell culture-adapted variants.
In order to study cell tropism and attenuation of hepatitis A virus (HAV), the genome of HAV wild-type GBM and two cell culture-adapted variants, GBM/FRhK and GBM/HFS, were cloned and sequenced after amplification by reverse transcriptase-PCR. During virus cultivation, the HAV variant GBM/FRhK had a strict host range for FRhK-4 cells, in contrast to GBM/HFS, which can be grown in HFS and FRhK-4 cells. The HAV variant GBM/HFS was shown to be attenuated when inoculated into chimpanzees (B. Flehmig, R. F. Mauler, G. Noll, E. Weinmann, and J. P. Gregerson, p. 87-90, in A. Zuckerman, ed., Viral Hepatitis and Liver Disease, 1988). On the basis of this biological background, the comparison of the nucleotide sequences of these three HAV GBM variants should elucidate differences which may be of importance for cell tropism and attenuation. The comparison of the genome between the GBM wild type and HAV wild types HM175 (J. I. Cohen, J. R. Ticehurst, R. H. Purcell, A. Buckler-White, and B. M. Baroudy, J. Virol. 61:50-59, 1987) and HAV-LA (R. Najarian, O. Caput, W. Gee, S. J. Potter, A. Renard, J. Merryweather, G. Van Nest, and D. Dina, Proc. Natl. Acad. Sci. USA 82:2627-2631, 1985) showed a 92 to 96.3% identity, whereas the identity was 99.3 to 99.6% between the GBM variants. Nucleotide differences between the wild-type and the cell culture-adapted variants, which were identical in both cell culture-adapted GBM variants, were localized in the 5' noncoding region; in 2B, 3B, and 3D; and in the 3' noncoding region. Our result concerning the 2B/2C region confirms a mutation at position 3889 (C-->T, alanine to valine), which had been shown to be of importance for cell culture adaptation (S. U. Emerson, C. McRill, B. Rosenblum, S. M. Feinstone, and R. H. Purcell, J. Virol. 65:4882-4886, 1991; S. U. Emerson, Y. K. Huang, C. McRill, M. Lewis, and R. H. Purcell, J. Virol. 66:650-654, 1992), whereas other mutations differ from published HAV sequence data and may be cell specific. Further comparison of the two cell culture-adapted GBM variants showed cell-specific mutations resulting in deletions of six amino acids in the VP1 region and three amino acids in the 3A region of the GBM variant GBM/FRhK.


New developments in transplant-acquired allergies.
Transplant-acquired allergy (TAA) was firstly described as transplant-acquired food allergy (TAFA) after bone marrow transplantations and mostly observed in a transient form. The picture is complicated by numerous case reports of TAFA after the receipt of liver grafts from donors with no documented history of food allergy. The estimated prevalence of TAFA among young children in the literature has been documented in various studies ranging from 6% to 57%. Although TAA is mostly found to be associated with liver transplantation; it has been recently reported to be related with heart, intestinal, lung and even renal transplantations in adults. Previous reviews of published cases of liver TAA misleadingly emphasized the predominance of children and the absence of TAA in cardiac, pulmonary, and renal transplant recipients. In different studies, the male/female ratio is equal. Literature data suggest that children with TAFA typically present within the first year after surgery and are typically allergic to multiple foods. The pathogenesis of TAA is not still completely understood. Most of the studies support the concept that the functioning liver itself, and not only tacrolimus immunosuppression, is one of the main contributors to TAA in these patients. In the light of recent findings, other possible mechanisms can be summarized as following: (1) the recovery of delayed type hypersensitivity; (2) late manifestation of food allergy; (3) intestinal injury as well as inhibition of cellular energy production by tacrolimus; and (4) transfer of food-specific IgE or lymphocytes. Thus, interplay between hematopoietic cells from the transplanted organ and recipient specific factors (e.g., younger age and atopic background) seem to underlie the development of TAA. Most patients will have symptomatic improvement following reduced immunosuppression and an appropriately restricted diet. Nevertheless, some studies suggest that atopic diseases occur in some of pediatric liver transplant recipients, with manifestations including food allergy, eczema, allergic rhinitis, and asthma. More studies would be needed including greater number of patients to determine whether TAA is transient or not in pediatric/adult solid organ recipients.


Lumbar Intervertebral Kinematics During an Unstable Sitting Task and Its Association With Standing-Induced Low Back Pain.
People developing transient low back pain during standing have altered control of their spine and hips during standing tasks, but the transfer of these responses to other tasks has not been assessed. This study used video fluoroscopy to assess lumbar spine intervertebral kinematics of people who do and do not develop standing-induced low back pain during a seated chair-tilting task. A total of 9 females and 8 males were categorized as pain developers (5 females and 3 males) or nonpain developers (4 females and 5 males) using a 2-hour standing exposure; pain developers reported transient low back pain and nonpain developers did not. Participants were imaged with sagittal plane fluoroscopy at 25 Hz while cyclically tilting their pelvises anteriorly and posteriorly on an unstable chair. Intervertebral angles, relative contributions, and anterior-posterior translations were measured for the L3/L4, L4/L5, and L5/S1 joints and compared between sexes, pain groups, joints, and tilting directions. Female pain developers experienced more extension in their L5/S1 joints in both tilting directions compared with female nonpain developers, a finding not present in males. The specificity in intervertebral kinematics to sex-pain group combinations suggests that these subgroups of pain developers and nonpain developers may implement different control strategies.


Identification of U251 glioma stem cells and their heterogeneous stem-like phenotypes.
Glioblastoma, the most common and lethal type of intracranial tumor, is characterized by extensive heterogeneity at the cellular and molecular levels. The discovery of glioma stem cells (GSCs) lends support to a new paradigm in tumor biology. In the present study, we aimed to clarify the validity of using U251 glioma cells as a source of GSC culture and critically evaluate the heterogeneous stem-like phenotypes of these cells when grown under various culture conditions. The findings suggested that U251 cells (U251-Adh, U251-SC-Sph and U251-SC-Adh) showed distinctive growth patterns and self-renewal capacity. The U251 glioma cell line is endowed with certain GSC phenotypes that may be moderately enriched in vitro when transferred into stem cell culture conditions, although this is not sustainable and reproducible in vivo. Notably, glioma cells are plastic in response to their environment. The reversible adaptive plasticity contributes to the GSC heterogeneity, which may lead to the heterogeneity of glioblastoma and the differing responses to current therapies. Therefore, an improved understanding of GSC heterogeneity is urgently required for designing more effective therapies against this highly malignant brain tumor.


Interplay between cartilage and subchondral bone contributing to pathogenesis of osteoarthritis.
Osteoarthritis (OA) is a common debilitating joint disorder, affecting large sections of the population with significant disability and impaired quality of life. During OA, functional units of joints comprising cartilage and subchondral bone undergo uncontrolled catabolic and anabolic remodeling processes to adapt to local biochemical and biological signals. Changes in cartilage and subchondral bone are not merely secondary manifestations of OA but are active components of the disease, contributing to its severity. Increased vascularization and formation of microcracks in joints during OA have suggested the facilitation of molecules from cartilage to bone and vice versa. Observations from recent studies support the view that both cartilage and subchondral bone can communicate with each other through regulation of signaling pathways for joint homeostasis under pathological conditions. In this review we have tried to summarize the current knowledge on the major signaling pathways that could control the cartilage-bone biochemical unit in joints and participate in intercellular communication between cartilage and subchondral bone during the process of OA. An understanding of molecular communication that regulates the functional behavior of chondrocytes and osteoblasts in both physiological and pathological conditions may lead to development of more effective strategies for treating OA patients.


Characteristics and release of isoniazid from inhalable alginate/carrageenan microspheres.
Aim: Inhalable microspheres made of polymers as a targeted drug delivery system have been developed to overcome the limitation of current treatments in Tuberculosis. Materials & methods: Isoniazid inhalable microspheres were created using a gelation ionotropic method with sodium alginate, carrageenan and calcium chloride in four different formulations. Result: The particle morphology has smooth surfaces and round spherical shapes with sizes below 5 μm; good flowability. The drug loading and entrapment efficiency values ranged from 1.69 to 2.75% and 62.44 to 85.30%, respectively. The microspheres drug release followed the Korsmeyer-Peppas model, indicating Fickian diffusion. Conclusion: Isoniazid inhalable microspheres achieved as targeted lung delivery for tuberculosis treatment.


The natural ocean acidification and fertilization event caused by the submarine eruption of El Hierro.
The shallow submarine eruption which took place in October 10(th) 2011, 1.8 km south of the island of El Hierro (Canary Islands) allowed the study of the abrupt changes in the physical-chemical properties of seawater caused by volcanic discharges. In order to monitor the evolution of these changes, seven oceanographic surveys were carried out over six months (November 2011-April 2012) from the beginning of the eruptive stage to the post-eruptive phase. Here, we present dramatic changes in the water column chemistry including large decreases in pH, striking effects on the carbonate system, decreases in the oxygen concentrations and enrichment of Fe(II) and nutrients. Our findings highlight that the same volcano which was responsible for the creation of a highly corrosive environment, affecting marine biota, has also provided the nutrients required for the rapid recuperation of the marine ecosystem.


Lack of c-kit receptor promotes mammary tumors in N-nitrosomethylurea-treated Ws/Ws rats.
c-kit is expressed in various cell types during development and it has been linked to the promotion of cellular migration, proliferation and/or survival of melanoblasts, hematopoietic progenitors and primordial germ cells. Several reports have proposed a role for the c-kit gene on carcinogenesis. Gain-of-function mutations are associated with diseases such as mastocytosis and gastrointestinal stromal tumors among others. However, very little is known about pathologies associated with loss-of-function mutations. Regarding breast cancer, c-kit protein and mRNA are highly expressed in normal breast but their expression decreases or is absent in the presence of breast cancer. We studied the role of c-kit in mammary carcinogenesis in the Ws/Ws rats carrying spontaneous lack-of-function mutation in the c-kit gene. Fifty day-old virgin female Ws/Ws rats and their wild type counterparts were injected with either 50 mg/kg body weight of the chemical carcinogen N-nitrosomethylurea or with vehicle. The animals were followed-up for 6 months. Fisher 344 rats were used as positive controls for tumor development. Eleven weeks after treatment, palpable tumors were detected in the Ws/Ws rats. The tumor incidence was 80% in Ws/Ws rats, while no tumors were observed in the wild type rats (p = 0.006). Our data show that the lack of c-kit is permissive for the development of mammary tumor in Ws/Ws rats treated with carcinogen. We conclude that the lack of c-kit may contribute to an imbalanced homeostatic state in the mammary gland either by affecting signaling between stroma and epithelium, or through the lack of mast cells.


Comparative genomics, proteomics and transcriptomics give new insight into the exoproteome of the basidiomycete Hebeloma cylindrosporum and its involvement in ectomycorrhizal symbiosis.
Extracellular proteins play crucial roles in the interaction between mycorrhizal fungi and their environment. Computational prediction and experimental detection allowed identification of 869 proteins constituting the exoproteome of Hebeloma cylindrosporum. Small secreted proteins (SSPs) and carbohydrate-active enzymes (CAZymes) were the two major classes of extracellular proteins. Twenty-eight per cent of the SSPs were secreted by free-living mycelia and five of the 10 most abundant extracellular proteins were SSPs. By contrast, 63-75% of enzymes involved in nutrient acquisition were secreted. A total of 150 extracellular protein-coding genes were differentially expressed between mycorrhizas and free-living mycelia. SSPs were the most affected. External environmental conditions also affected expression of 199 exoproteome genes in mycorrhizas. SSPs displayed different patterns of regulation in response to presence of a host plant or other environmental signals. Several of the genes most overexpressed in the presence of organic matter encoded oxidoreductases. Hebeloma cylindrosporum has not fully lost its ancestral saprotrophic capacities but rather adapted them not to harm its hosts and to use soil organic nitrogen. The complex and divergent patterns of regulation of SSPs in response to a symbiotic partner and/or organic matter suggest various roles in the biology of mycorrhizal fungi.


Clearing the cervical spine in obtunded patients.
Retrospective cohort study. To determine the frequency of injuries missed by initial computed tomography (CT) of the cervical spine in obtunded blunt trauma victims. Optimal method for excluding cervical spine injury in obtunded trauma patients remains controversial. Trauma centers show marked variation in spine clearance protocols. We reviewed medical records of consecutive obtunded blunt trauma victims admitted over 2 years to a level 1 trauma center and selected patients who had CT imaging of the cervical spine during their initial emergency room evaluation. We excluded patients in whom this study identified an injury and also patients who became examinable before subsequent imaging with upright cervical spine radiographs, as required by institutional protocol. Using composite reference standard of cervical injury diagnosed by subsequent imaging or clinical examinations by the time of discharge from the hospital, we evaluated the frequency and type of injuries missed by the initial CT and the delay in spine clearance due to additional imaging. Of 590 screened patients, 367 met the inclusion and exclusion criteria. The study cohort had mean age 40.2 years (SD 20.8), 75.5% males, mean Glasgow Coma Scale score 5.9 (SD 3.4), and mean Injury Severity Scale score 24.5 (SD 10). Initial CT imaging failed to identify an injury in 1 patient, for a false negative rate of 0.3% (1/367): a cervical cord contusion identified on subsequent physical examination, confirmed by magnetic resonance imaging, and managed nonoperatively. Upright cervical spine radiographs did not identify any injuries missed by CT, but they delayed spine clearance by a mean of 2.6 days and by more than 48 hours in 42% of the patients. Initial CT imaging identified all unstable cervical spine injuries in obtunded trauma patients. Subsequent upright radiographs did not identify any additional injuries but significantly delayed spine clearance.


Fresh Compost Tea Application Does Not Change Rhizosphere Soil Bacterial Community Structure, and Has No Effects on Soybean Growth or Yield.
Soil bacteria drive key ecosystem functions, including nutrient mobilization, soil aggregation and crop bioprotection against pathogens. Bacterial diversity is thus considered a key component of soil health. Conventional agriculture reduces bacterial diversity in many ways. Compost tea has been suggested as a bioinoculant that may restore bacterial community diversity and promote crop performance under conventional agriculture. Here, we conducted a field experiment to test this hypothesis in a soybean-maize rotation. Compost tea application had no influence on bacterial diversity or community structure. Plant growth and yield were also unresponsive to compost tea application. Combined, our results suggest that our compost tea bacteria did not thrive in the soil, and that the positive impacts of compost tea applications reported elsewhere may be caused by different microbial groups (e.g., fungi, protists and nematodes) or by abiotic effects on soil (e.g., contribution of nutrients and dissolved organic matter). Further investigations are needed to elucidate the mechanisms through which compost tea influences crop performance.


[Selection of acupoints in acupuncture-moxibustion for drug abstinence].
Selection (screening) of acupoints, clinical application of acupoints and mechanisms of acupoints in treatment of acupuncture and moxibustion for drug abstinence in recent 10 years are reviewed, considering that the studies of acupuncture and moxibustion for drug abstinence are not enough in the width and depth, especially, lacking deep studies in selection (screening) of acupoints, clinical application of acupoints and the mechanisms. The acupuncture and moxibustion for drug abstinence is a newer field, in future the systematically and scientifically clinical and experimental studies on the acupuncture and moxibustion for drug abstinence should be strengthened, especially, the studies on clinical application of acupoints.


Prevention, by ribosome-bound nascent polyphenylalanine chains, of the functional interaction of t-2 toxin with its receptor site.
1. The inhibitory effects of T-2 toxin and trichodermin on poly(U)-directed polyphenylalanine synthesis were studied by using cell-free systems from reticulocytes. Conditions for amino acid incorporation were carefully chosen in an attempt to ensure that the large majority of poly(U) chains bound only one ribosome engaged in protein synthesis and that all such ribosomes carried nascent polyphenylalanine chains containing approximately the same number of residues. 2. Cell-free systems were allowd to synthesize polyphenylalanine, and T-2 toxin and trichodermin were added to the incorporation mixtures at various times. Irrespective of the time of addition, trichodermin (50 mug/ml) inhibited polyphenylalanine synthesis by approx. 70%. In contrast, although T-2 toxin (40 mug/ml), when added at early incubation times, could inhibit polyphenylalanine synthesis with a maximum of 50%, the drug had no effect on the system when added after a critical time-period. 3. It is concluded that although both T-2 toxin and trichodermin can inhibit peptide-bond formation on ribosomes at the level of the peptidyl transferase catalytic centre the presence, on ribosomes, of nascent polyphenylalanine chains above a certain critical chain length excludes T-2 toxin from functional interaction with its receptor site.


Deregulated intracellular signaling by mutated c-CBL in myeloid neoplasms.
c-CBL encodes a 120-kDa protein involved in intracellular signal transduction in a wide variety of cell types. Recently, frequent mutations of c-CBL have been reported in myeloid neoplasms showing both myelodysplastic and myeloproliferative features, in which most mutations are present in a homozygous state, as a result of allelic conversion in 11q. c-CBL has ubiquitin E3 ligase activity for a wide variety of tyrosine kinases, and thereby, negatively regulates tyrosine kinase signaling. Accordingly, c-CBL seems to have tumor suppressor functions, loss of which promotes tumorigenesis. On the other hand, once mutated, it is converted to an oncogenic protein and commits to myeloid leukemogenesis through a kind of gain of function causing aberrant signal transduction. The inhibition of mutant CBL protein or signaling pathways that it activates would have a role in therapeutics of myeloid neoplasms with CBL mutations.