First Report of Pitch Canker Disease Caused by Rhizosphaera kalkhoffii on Pinus sylvestris in China.
In November 2010, pitch canker disease was first discovered on Pinus sylvestris var. mongolica Litv. from Daxinganling region in Inner Mongolia Province, China, resulting in severe dieback and bark cracking on the host, accompanied by resin flowing profusely from cankers on the infected branches, cones, and trunks (2). The early stage symptoms consisted of sunken cankers, reddish-brown needles on infected twigs followed by heavy resin soaking of the wood as the disease progressed. Pieces of pitch-soaked wood (3 × 3 mm2) cut from cankerous tissue on branches were surface-sterilized with 0.4% NaOCl for 2 min and then rinsed twice in sterile distilled water. The fragments were placed on potato dextrose agar and incubated at 28°C in the dark. After 7 to 8 days, this process consistently yielded cultures with whitish, dense, aerial mycelium that later darkened to gray. Microconidia were single, oblong to cylindrical, aseptate, and 4 to 10 × 2 to 4 μm. Macroconidia were hyaline, 1- to 2-septate, oblong to cylindrical, with tiny papillae at both ends, and 10 to 13 × 2 to 5 μm, fitting the description of Rhizosphaera kalkhoffii (1). To verify the identification based on morphological features, the internal transcribed spacer (ITS) region of the ribosomal RNA genes was amplified using primers ITS1 (TCCGTAGGTGAACCTGCGG) and ITS4 (TCCTCCGCTTATTGATATGC) according to the published protocol (3), and then sequenced and compared to the GenBank database through BLAST search. Comparison of the sequences revealed 98% homology to R. kalkhoffii (EU700375.1 and EU700376.1). Representative sequences of R. kalkhoffii (JQ353721 and JQ353722) were deposited in GenBank. The pathogenicity of two representative isolates of R. kalkhoffii was also confirmed by spraying 40 μl of conidial suspension (4.6 × 106 conidia/ml) on the bark surface of 20 2-year-old healthy pine seedlings, wounded by scratching with a sterilized knife. Sterile distilled water sprays were used for the controls. Within 4 to 8 weeks after inoculation, 90% of inoculated P. sylvestris exhibited symptoms of pitch cankers around the inoculation site similar to those on the original infection. R. kalkhoffii was consistently reisolated from all inoculated plants but not from water-treated controls, fulfilling Koch's postulates. R. kalkhoffii have previously been documented as pathogens of needle blight of Picea pungens (1). To our knowledge, this is the first report of R. kalkhoffii as a pathogen on Pinus sylvestris in China, and furthermore, pitch canker disease is currently listed as a quarantine disease in China, increasing the significance of this report. References: (1) J. Kumi et al. Eur. J. Forest Pathol. 9:35, 1979. (2) J. K. Lee et al. Plant Pathol. 16:52, 2000. (3) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, CA, 1990.


Strategic aspects of cyberattack, attribution, and blame.
Cyber conflict is now a common and potentially dangerous occurrence. The target typically faces a strategic choice based on its ability to attribute the attack to a specific perpetrator and whether it has a viable punishment at its disposal. We present a game-theoretic model, in which the best strategic choice for the victim depends on the vulnerability of the attacker, the knowledge level of the victim, payoffs for different outcomes, and the beliefs of each player about their opponent. The resulting blame game allows analysis of four policy-relevant questions: the conditions under which peace (i.e., no attacks) is stable, when attacks should be tolerated, the consequences of asymmetric technical attribution capabilities, and when a mischievous third party or an accident can undermine peace. Numerous historical examples illustrate how the theory applies to cases of cyber or kinetic conflict involving the United States, Russia, China, Japan, North Korea, Estonia, Israel, Iran, and Syria.


ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats.
Expansion of CAG trinucleotide repeats that encode polyglutamine is the underlying cause of at least nine inherited human neurodegenerative disorders, including Huntington's disease and spinocerebellar ataxias. PolyQ fragments accumulate as aggregates in the cytoplasm and/or in the nucleus, and induce neuronal cell death. However, the molecular mechanism of polyQ-induced cell death is controversial. Here, we show the following: (1) polyQ with pathogenic repeat length triggers ER stress through proteasomal dysfunction; (2) ER stress activates ASK 1 through formation of an IRE1-TRAF2-ASK1 complex; and (3) ASK1(-/-) primary neurons are defective in polyQ-, proteasome inhibitor-, and ER stress-induced JNK activation and cell death. These findings suggest that ASK1 is a key element in ER stress-induced cell death that plays an important role in the neuropathological alterations in polyQ diseases.


Radiation Exposure in the Medical ICU: Predictors and Characteristics.
Patients admitted to the medical ICU (MICU) are often subjected to multiple radiologic studies. We hypothesized that some endure radiation dose exposure (cumulative effective dose [CED]) in excess of annual US federal occupational health standard limits (CED ≥ 50 mSv) and 5-year cumulative limit (CED ≥ 100 mSv). We also evaluated the correlation of CED with Acute Physiology and Chronic Health Evaluation (APACHE) III score and other clinical variables. Retrospective observational study conducted in an academic medical center involving all adult admissions (N = 4,155) to the MICU between January 2013 and December 2013. Radiation doses from ionizing radiologic studies were calculated from reference values to determine the CED. Three percent of admissions (n = 131) accrued CED ≥ 50 mSv (1% [n = 47] accrued CED ≥ 100 mSv). The median CED was 0.72 mSv (interquartile range, 0.02-5.23 mSv), with a range of 0.00 to 323 mSv. Higher APACHE III scores (P = .003), longer length of MICU stay (P < .0001), sepsis (P = .03), and gastrointestinal disorders and bleeding (P < .0001) predicted higher CED in a multivariable linear regression model. Patients with gastrointestinal bleeding and disorders had an odds ratio of 21.05 (95% CI, 13.54-32.72; P < .0001) and 6.94 (95% CI, 3.88-12.38; P < .0001), respectively, of accruing CED ≥ 50 mSv in a multivariable logistic regression model. CT scan and interventional radiology accounted for 49% and 38% of the total CED, respectively. Patients in the MICU are exposed to radiation doses that can be substantial, exceeding federal annual occupational limits, and in a select subset, are > 100 mSv. Efforts to justify, restrict, and optimize the use of radiologic resources when feasible are warranted.


Genetics of dark skin in mice.
Chemical mutagenesis in the mouse is a powerful approach for phenotype-driven genetics, but questions remain about the efficiency with which new mutations ascertained by their phenotype can be localized and identified, and that knowledge applied to a specific biological problem. During a global screen for dominant phenotypes in about 30,000 animals, a novel class of pigmentation mutants were identified by dark skin (Dsk). We determined the genetic map location, homozygous phenotype, and histology of 10 new Dsk and 2 new dark coat (Dcc) mutations, and identified mutations in Agouti (Met1Leu, Dcc4), Sox18 (Leu220ter, Dcc1), Keratin 2e (Thr500Pro, Dsk2), and Egfr (Leu863Gln, Dsk5). Cutaneous effects of most Dsk mutations are limited to melanocytes, except for the Keratin 2e and Egfr mutations, in which hyperkeratosis and epidermal thickening precede epidermal melanocytosis by 3-6 wk. The Dsk2 mutation is likely to impair intermediate filament assembly, leading to cytolysis of suprabasal keratinocytes and secondary hyperkeratosis and melanocytosis. The Dsk5 mutation causes increased tyrosine kinase activity and a decrease in steady-state receptor levels in vivo. The Dsk mutations represent genes or map locations not implicated previously in pigmentation, and delineate a developmental pathway in which mutations can be classified on the basis of body region, microscopic site, and timing of pigment accumulation.


Attenuation of lipopolysaccharide-induced acute lung injury after (pro)renin receptor blockade.
We performed a randomized, prospective animal study to investigate whether inhibiting the renin-angiotensin system with a (pro)renin receptor blocker (PRRB) prevents acute lung injury (ALI) in a rodent model. We used Thirty-six male Sprague-Dawley rats. We administered lipopolysaccharide (LPS; 2 mg/kg) intratracheally with or without PRRB pretreatment (1 mg/kg/d). We performed bronchoalveolar lavage (BAL) and lung removal at 4 h after LPS administration and measured levels of inflammatory cytokines, high mobility group box 1 (HMGB-1) protein, and total protein in bronchoalveolar lavage fluid (BALF). Myeloperoxidase (MPO) activity was detected in lung tissue homogenates using a sensitive ELISA. We performed hematoxylin and eosin staining and immunohistochemical staining for nonproteolytically activated prorenin in the left lung. The PRRB decreased leukocyte counts and total protein, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-2, IL-6, and IL-10 levels in the BALF and MPO activity in lung tissue. The PRRB reduced interstitial edema, hemorrhage, and the neutrophil count in the lung tissues. Consistent with the reduction in lung tissue damage, immunohistochemical staining showed that the PRRB decreased the amount of nonproteolytically activated prorenin. The PRRB blocked LPS-induced inflammatory response in the lung and protected against ALI. Therefore, it is a potential therapeutic agent for preventing ALI.


A WAGR region gene between PAX-6 and FSHB expressed in fetal brain.
Developmental delay or mental retardation is a frequent component of multi-system anomaly syndromes associated with chromosomal deletions. Isolation of genes involved in the mental dysfunction in these disorders should define loci important in brain formation or function. We have identified a highly conserved locus in the distal part of 11p13 that is prominently expressed in fetal brain. Minimal expression is observed in a number of other fetal tissues. The gene maps distal to PAX-6 but proximal to the loci for brain-derived neurotrophic factor (BDNF) and the beta subunit of follicle stimulating hormone (FSHB), within a region previously implicated in the mental retardation component of some WAGR syndrome patients. Within fetal brain, the corresponding transcript is prominent in frontal, motor and primary visual cortex as well as in the caudate-putamen. The characteristics of this gene, including the striking evolutionary conservation at the locus, suggest that the encoded protein may function in brain development.


Making the case for strong health information systems during a pandemic and beyond.
The Sars-CoV-2 pandemic exacerbates existing inequalities across health care systems globally, both within countries and between countries. It also highlights, like no other crisis before, existing weaknesses in health information systems (HIS). This article summarizes these key challenges for HIS in times of a pandemic and beyond, with a focus on European countries. It builds on the experiences of a large consortium representing HIS experts in key positions in national public health or similar institutes across Europe. Data were collected in bi-weekly conference calls organized by the InfAct project between February and June 2020. Emerging themes were clustered and analysed around a WHO framework for health information systems (HIS). We analyse strengths of HIS at two levels: (i) dealing with health information directly, and (ii) dealing with other parts of information systems that allow for a holistic assessment of the pandemic (including health-related aspects). The analysis highlights the need for capacity-building in HIS before a pandemic hits, the relevance of going beyond health information only related to health care but taking a broader perspective (e.g. on vulnerable groups), the need for strong reporting systems on staffing numbers and in primary care. Further, data linkage emerges as a crucial precondition to identify unmet needs for essential health care services in a timely manner. Finally, room for innovation and digitalisation is key to be able to react flexibly in times of crisis. Trust for health information stakeholders is another important factor to create strong HIS. The strengths and shortcomings of European HIS that have been observed during the COVID-19 crisis highlight the need for strong HIS beyond the crisis. The experiences reported leave as a central message that successful reactions to the pandemic are (also) grounded in strong HIS that ultimately not only benefit the health of the population but also create a number of economic and psycho-social benefits. Strong data reporting schemes may also support fine-tuning of containment measures during a pandemic as well as transition phases.


Immunogenicity and safety of Intanza(®)/IDflu(®) intradermal influenza vaccine in South Korean adults: a multicenter, randomized trial.
Intanza(®)/IDflu(®) (Sanofi Pasteur, Lyon, France) is an intradermal inactivated trivalent influenza vaccine developed as an alternative to intramuscular influenza vaccine. The objective of this study was to confirm the immunogenicity and safety of Intanza/IDflu in South Korean adults. In a phase IV multicenter trial, South Korean adults 18-59 y old (n = 120) and ≥ 60 y old (n = 120) were randomized 1:1 to receive a single dose of Intanza/IDflu (9 µg for 18-59 y, 15 µg for ≥ 60 y) or trivalent intramuscular vaccine (Vaxigrip(®) 15 µg, Sanofi Pasteur, Lyon, France). Blood was collected on pre-vaccination (day 0) and on day 21. Hemagglutination inhibition titers, seroprotection rates and seroconversion rates were determined on day 21. Geometric mean titers, seroprotection and seroconversion rates were similar between the intradermal and intramuscular vaccines in both age groups for all three vaccine strains (A/H1N1, A/H3N2 and B). Both vaccines met Committee for Medicinal Products for Human Use criteria for all three strains. Solicited systemic reactions of the intradermal groups were generally mild, transient, and similar to those of the intramuscular groups. Solicited injection site reactions were more frequent in the intradermal groups but were mostly mild, transient, and consisted mainly of pain, erythema, and pruritus. No treatment-related serious adverse events or other safety concerns were reported. These results confirm that Intanza/IDflu is an effective and well-tolerated alternative to IM influenza vaccination. (Clinicaltrials.gov NCT ID: NCT01215669).


Self-harm in people with epilepsy: a retrospective cohort study.
Little is known about self-harm in people with epilepsy, despite suicide being recognized as a leading cause of mortality in this population. This study aimed to investigate the characteristics of self-harm in people with epilepsy, and associated demographic and psychosocial factors. Patients presenting to hospital following self-harm between 1994 and 2008 were identified from the Oxford Monitoring System for Self-Harm. Epilepsy diagnosis was confirmed through review of medical records. Demographic features, patient, and self-harm characteristics of 132 people with epilepsy and 9,778 self-harm patients without epilepsy were compared using a regression model, adjusting for age, sex, and repetition. Patients presenting between 1998 and 2008 were followed up for all-cause mortality to the end of 2011. The rate of self-harm per individual with epilepsy was 2.04 (95% confidence interval [CI] 1.85-2.25) times that of the comparison group, and time between first and second self-harm events was shorter (hazard ratio 1.86; 1.46-2.38). People with epilepsy were significantly more likely to use antiepileptic medication in overdose, although overall methods of self-harm were similar in the two groups. No significant differences in suicide intent scores or the proportion of patients who died by suicide were found. Previous outpatient psychiatric treatment, longer duration of unemployment, experience of violence, and housing problems were associated with self-harm in people with epilepsy. People with epilepsy who self-harm do so more frequently than other self-harm patients. Clinicians should be aware of this and pay attention to contributory factors as these may enhance risk in this population. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.


Fecundity of the crustacean Mysidopsis californica (Mysida, Mysidae) under semi-controlled conditions.
Mysid crustaceans are frequently used in the laboratory to feed cephalopods and fish, but not along the Pacific coast, where they are scarce. There is no commercial aquaculture of mysids in the Pacific Ocean. To change this situation, we calculate fecundity, survival, and sex ratio of Mysidopsis californica under semi-controlled conditions. Mysids were collected manually using a 500 microm-mesh net along the rocky coast of Mazatlin, Sinaloa, Mexico. They were transferred to three 30 L seawater aquaria in the laboratory, and fed (ad libitum) Artemia nauplii and rotifers. Two generations were obtained. The relationship between the number of juveniles born and parent female lengths showed a rate of 1.56 juveniles released per each unit of increasing parent female length. An average parent female length of 6.92 mm (SD=0.82) gave 9.96 (SD=4.29) released juveniles. The frequency of female length showed a mean of 7.3 mm (SD=0.54), whereas that of juveniles showed a mean of 1.7 mm (SD=0.16). Survival and sex ratios (females-males) varied from 77.7% to 88.6% and 2.5:1 to 3.0:1, respectively.


Fertility Preservation for a Transgender Teenager.
In this article, we discuss a case in which a 16-year-old birth-assigned male came out to her parents as transgender. She is referred to the gender management program at a large pediatric academic center to discuss hormone therapy. She was initially evaluated by a psychiatrist, diagnosed with gender dysphoria and anxiety, and treated with medication and psychotherapy. When her anxiety was well controlled and she met eligibility and readiness criteria, she was referred to 1 of 2 pediatric endocrinologists in the gender management program to discuss hormone therapy. As part of the discussion about the risks/benefits of estrogen therapy, the pediatric endocrinologist discussed options for fertility preservation (FP) before potentially gonadotoxic therapy. The patient stated that she was not interested in FP. Her mother requested procedures to preserve the possibility that the daughter could have biological children someday. We asked experts in the care of transgender youth to discuss ways in which the doctor could respond to this disagreement between parents and a teenager about FP.


The diagnostic efficacy of urinary fractionated metanephrines measured by tandem mass spectrometry in detection of pheochromocytoma.
There are limitations to currently available biochemical tests for pheochromocytoma. Our objective was to evaluate the diagnostic efficacy of a novel tandem mass spectrometry assay for the measurement of fractionated urinary metanephrines in patients suspected to have a pheochromocytoma. We also developed clinically based cut-offs for positivity of this measurement. We examined the medical records of 506 patients (including 102 patients with a catecholamine-producing tumour) who underwent measurement of 24-h urinary fractionated metanephrines using tandem mass spectrometry as well as adrenal imaging at Mayo Clinic, Rochester. The cut-offs for positivity were defined as follows: total metanephrines (sum of the metanephrine fractions) 5163 nmol/day, normetanephrine fraction 4001 nmol/day, metanephrine fraction 1531 nmol/day. Receiver operating characteristic (ROC) curves were constructed. The diagnostic efficacy was as follows: normetanephrine fraction sensitivity 87.3% [(95% confidence interval (CI) 79.4-92.4%], specificity 95.0% (92.5-96.8); metanephrine fraction sensitivity 56.9% (47.2-66.1), specificity 95.0% (92.5-96.8); elevation of either normetanephrine or metanephrine fraction sensitivity 97.1% (91.7-99.0) and specificity 91.1% (87.9-93.5). Areas under the ROC curves (AUCs) were 0.972 (95% CI 0.955-0.990) for the normetanephrine fraction, 0.800 (0.741-0.858) for the metanephrine fraction, 0.991 (0.985-0.996) for total metanephrines, and 0.991 (0.985-0.996) for a regression-derived ROC curve incorporating both the metanephrine and normetanephrine fractions. Measurement of 24-h urinary fractionated metanephrines by a tandem mass spectrometry assay appears to be an effective biochemical technique in the investigation of pheochromocytoma.


Developmental programming and transgenerational transmission of obesity.
The global obesity pandemic is often causally linked to marked changes in diet and lifestyle, namely marked increases in dietary intakes of high-energy diets and concomitant reductions in physical activity levels. However, far less attention has been paid to the role of developmental plasticity and alterations in phenotypic outcomes resulting from environmental perturbations during the early-life period. Human and animal studies have highlighted the link between alterations in the early-life environment and increased susceptibility to obesity and related metabolic disorders in later life. In particular, altered maternal nutrition, including both undernutrition and maternal obesity, has been shown to lead to transgenerational transmission of metabolic disorders. This association has been conceptualised as the developmental programming hypothesis whereby the impact of environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the physiology of the offspring. Further, evidence to date suggests that this developmental programming is a transgenerational phenomenon, with a number of studies showing transmission of programming effects to subsequent generations, even in the absence of continued environmental stressors, thus perpetuating a cycle of obesity and metabolic disorders. The mechanisms responsible for these transgenerational effects remain poorly understood; evidence to date suggests a number of potential mechanisms underpinning the transgenerational transmission of the developmentally programmed phenotype through both the maternal and paternal lineage. Transgenerational phenotype transmission is often seen as a form of epigenetic inheritance with evidence showing both germline and somatic inheritance of epigenetic modifications leading to phenotype changes across generations. However, there is also evidence for non-genomic components as well as an interaction between the developing fetus with the in utero environment in the perpetuation of programmed phenotypes. A better understanding of how developmental programming effects are transmitted is essential for the implementation of initiatives aimed at curbing the current obesity crisis.


The utility of cyclodextrins in lipase-catalyzed transesterification in organic solvents: enhanced reaction rate and enantioselectivity.
The use of enzymes as valuable catalysts in organic solvents has been well documented. However, some of their features limit their application in organic synthesis, especially the frequently lower enzyme activity under nonaqueous conditions, which constitutes a major drawback in the application of enzymes in organic solvents. In addition, many enzymatic reactions are subject to substrate or product inhibition, leading to a decrease in the reaction rate and enantioselectivity. To overcome these drawbacks and to make enzymes more appealing to organic chemists, we demonstrate the use of cyclodextrins as regulators for the Pseudomonas cepacia lipase (PSL) and macrocyclic additives to enhance the reaction rate and enantioselectivity E in lipase-catalyzed enantioselective transesterification of 1-(2-furyl)ethanol in organic solvents. Both reaction rate and enantioselectivity were significantly enhanced by several orders of magnitude when using co-lyophilized lipase in the presence of cyclodextrins. The effect of cyclodextrin derivatives as well as solvents on the improvement of the reaction parameters has been studied. The observed enhancement was tentatively interpreted in terms of their ability to give a certain flexibility to the enzyme and to form a host-guest complex, thus avoiding product inhibition and leading to enhancement of the reaction rate and enantioselectivity. The effect of cyclodextrin additives on the enzyme morphology has been studied using scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) of the co-lyophilized lipase with cyclodextrins. The ability of cyclodextrins to form a host-guest complex to avoid product inhibition, which leads to the observed enhancement, has been proved by NOESY, COSY, 13C and 1H NMR.


Impact of a New Adaptive Statistical Iterative Reconstruction (ASIR)-V Algorithm on Image Quality in Coronary Computed Tomography Angiography.
A new postprocessing algorithm named adaptive statistical iterative reconstruction (ASIR)-V has been recently introduced. The aim of this article was to analyze the impact of ASIR-V algorithm on signal, noise, and image quality of coronary computed tomography angiography. Fifty consecutive patients underwent clinically indicated coronary computed tomography angiography (Revolution CT; GE Healthcare, Milwaukee, WI). Images were reconstructed using filtered back projection and ASIR-V 0%, and a combination of filtered back projection and ASIR-V 20%-80% and ASIR-V 100%. Image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were calculated for left main coronary artery (LM), left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA) and were compared between the different postprocessing algorithms used. Similarly a four-point Likert image quality score of coronary segments was graded for each dataset and compared. A cutoff value of P < .05 was considered statistically significant. Compared to ASIR-V 0%, ASIR-V 100% demonstrated a significant reduction of image noise in all coronaries (P < .01). Compared to ASIR-V 0%, SNR was significantly higher with ASIR-V 60% in LM (P < .01), LAD (P < .05), LCX (P < .05), and RCA (P < .01). Compared to ASIR-V 0%, CNR for ASIR-V ≥60% was significantly improved in LM (P < .01), LAD (P < .05), and RCA (P < .01), whereas LCX demonstrated a significant improvement with ASIR-V ≥80%. ASIR-V 60% had significantly better Likert image quality scores compared to ASIR-V 0% in segment-, vessel-, and patient-based analyses (P < .01). Reconstruction with ASIR-V 60% provides the optimal balance between image noise, SNR, CNR, and image quality.


Antioxidant potential of Coriandrum sativum L. seed extract.
The seeds of C. sativum are used as a traditional drug for the treatment of diabetes. The antioxidant and free-radical-scavenging property of seeds in vitro was studied and also investigated whether the administration of seeds curtails oxidative stress in the kidney of streptozotocin-induced diabetic rats. Incorporation of seed powder in the diet led to marked lowering of blood glucose and a rise in the levels of insulin in diabetic rats. A parallel beneficial effect was observed on oxidant -antioxidant balance in the kidney. Addition of coriander seed powder not only inhibited the process of peroxidative damage but also significantly reactivated the antioxidant enzymes and antioxidant levels in diabetic rats. The total polyphenolic content of the seeds was found to be 12.2 gallic acid equivalents (GAE)/g while total flavanoid content was found to be 12.6 quercetin equivalents/g. The seeds also showed scavenging activity against superoxides and hydroxyl radicals in a concentration-dependent manner. Maximum free radical-scavenging action and free radical reducing power of coriander seed extract was observed at a concentration of 50 microg GAE. Islet histology structures showed degeneration of pancreatic islets in diabetic rats which was also reduced in diabetic rats treated with seed powder. These results show that C. sativum seeds not only possess antihyperglycemic properties but antioxidative properties also. Increased dietary intake of coriander seeds decrease the oxidative burden in diabetes mellitus.


Satellite cell number and cell cycle kinetics in response to acute myotrauma in humans: immunohistochemistry versus flow cytometry.
In humans, muscle satellite cell (SC) enumeration is an important measurement used to determine the myogenic response to various stimuli. To date, the standard practice for enumeration is immunohistochemistry (IHC) using antibodies against common SC markers (Pax7, NCAM). Flow cytometry (FC) analysis may provide a more rapid and quantitative determination of changes in the SC pool with potential for additional analysis not easily achievable with standard IHC. In this study, FC analysis revealed that the number of Pax7(+) cells per milligram isolated from 50 mg of fresh tissue increased 36% 24 h after exercise-induced muscle injury (300 unilateral maximal eccentric contractions). IHC analysis of Pax7 and neural cell adhesion molecule (NCAM) appeared to sufficiently and similarly represent the expansion of SCs after injury (28-36% increase). IHC and FC data illustrated that Pax7 was the most widely expressed SC marker in muscle cross-sections and represented the majority of positive cells, while NCAM was expressed to a lesser degree. Moreover, FC and IHC demonstrated a similar percentage change 24 h after injury (36% increase, Pax7; 28% increase, NCAM). FC analysis of isolated SCs revealed that the number of Pax7(+) cells per milligram in G(2)/M phase of the cell cycle increased 202% 24 h after injury. Number of cells per milligram in G(0)/G(1) and cells in S-phase increased 32% and 59% respectively. Here we illustrate the use of FC as a method for enumerating SC number on a per milligram tissue basis, providing a more easily understandable relation to muscle mass (vs. percentage of myonuclei or per myofibre). Although IHC is a powerful tool for SC analysis, FC is a fast, reliable and effective method for SC quantification as well as a more informative method for cell cycle kinetics of the SC population in humans.


Making a molecular wire: charge and spin transport through para-phenylene oligomers.
Functional molecular wires are essential for the development of molecular electronics. Charge transport through molecules occurs primarily by means of two mechanisms, coherent superexchange and incoherent charge hopping. Rates of charge transport through molecules in which superexchange dominates decrease approximately exponentially with distance, which precludes using these molecules as effective molecular wires. In contrast, charge transport rates through molecules in which incoherent charge hopping prevails should display nearly distance independent, wirelike behavior. We are now able to determine how each mechanism contributes to the overall charge transport characteristics of a donor-bridge-acceptor (D-B-A) system, where D = phenothiazine (PTZ), B = p-oligophenylene, and A = perylene-3,4:9,10-bis(dicarboximide) (PDI), by measuring the interaction between two unpaired spins within the system's charge separated state via magnetic field effects on the yield of radical pair and triplet recombination product.


Efficacy and harms of convalescent plasma for treatment of hospitalized COVID-19 patients: a systematic review and meta-analysis.
We systematically reviewed benefits and harms of convalescent plasma (CP) in hospitalized COVID-19 patients. Randomized controlled trials (RCTs) and observational studies assessing CP effects on hospitalized, adult COVID-19 patients were searched until November 24, 2020. We assessed risk of bias (RoB) using Cochrane RoB 2.0 and ROBINS-I tools. Inverse variance random effect meta-analyses were performed. Quality of evidence was evaluated using GRADE methodology. Primary outcomes were all-cause mortality, clinical improvement, and adverse events. Five RCTs (n = 1067) and 6 cohorts (n = 881) were included. Three and 1 RCTs had some concerns and high RoB, respectively; and there was serious RoB in all cohorts. Convalescent plasma did not reduce all-cause mortality in RCTs of severe (RR = 0.60, 95% CI: 0.33-1.10) or moderate (RR = 0.60, 95% CI: 0.09-3.86) COVID-19 vs. standard of care (SOC); CP reduced all-cause mortality vs. SOC in cohorts (RR = 0.66, 95% CI: 0.49-0.91). Convalescent plasma did not reduce invasive ventilation vs. SOC in moderate disease (RR = 0.85, 95% CI: 0.47-1.55). In comparison to placebo + SOC, CP did not affect all-cause mortality (RR = 0.75, 95% CI: 0.48-1.16) or clinical improvement (HR = 1.07, 95% CI: 0.82-1.40) in severe patients. Adverse and serious adverse events were scarce, similar between CP and controls. Quality of evidence was low or very low for most outcomes. In comparison to SOC or placebo + SOC, CP did not reduce all-cause mortality in RCTs of hospitalized COVID-19 patients. Convalescent plasma did not have an effect on other clinical or safety outcomes. Until now there is no good quality evidence to recommend CP for hospitalized COVID-19 patients.


Overt and covert competition in a promiscuous mammal: the importance of weaponry and testes size to male reproductive success.
Male contests for access to receptive females are thought to have selected for the larger male body size and conspicuous weaponry frequently observed in mammalian species. However, when females copulate with multiple males within an oestrus, male reproductive success is a function of both pre- and postcopulatory strategies. The relative importance of these overt and covert forms of sexual competition has rarely been assessed in wild populations. The Soay sheep mating system is characterized by male contests for mating opportunities and high female promiscuity. We find that greater horn length, body size and good condition each independently influence a male's ability to monopolize receptive females. For males with large horns at least, this behavioural success translates into greater siring success. Consistent with sperm-competition theory, we also find that larger testes are independently associated with both higher copulation rates and increased siring success. This advantage of larger testes emerges, and strengthens, as the number of oestrous females increases, as dominant males can no longer control access to them all. Our results thus provide direct quantitative evidence that male reproductive success in wild populations of mammals is dependent upon the relative magnitude of both overt contest competition and covert sperm competition.


Effectiveness of a multimodal hand hygiene campaign and obstacles to success in Addis Ababa, Ethiopia.
Hand hygiene is the cornerstone of infection control and reduces rates of healthcare associated infection. There are limited data evaluating hand hygiene adherence and hand hygiene campaign effect in resource-limited settings, especially in Sub-Saharan Africa. This study assessed the impact of implementing a World Health Organization (WHO)-recommended multimodal hand hygiene campaign at a hospital in Ethiopia. This study included a before-and-after assessment of health care worker (HCW) adherence with WHO hand hygiene guidelines. It was implemented in three phases: 1) baseline evaluation of hand hygiene adherence and hospital infrastructure; 2) intervention (distribution of commercial hand sanitizer and implementation of an abbreviated WHO-recommended multimodal hand hygiene campaign); and 3) post-intervention evaluation of HCW hand hygiene adherence. HCWs' perceptions of the campaign and hand sanitizer tolerability were assessed through a survey performed in the post-intervention period. At baseline, hand washing materials were infrequently available, with only 20% of sinks having hand-washing materials. There was a significant increase in hand hygiene adherence among HCWs following implementation of a WHO multimodal hand hygiene program. Adherence increased from 2.1% at baseline (21 hand hygiene actions/1000 opportunities for hand hygiene) to 12.7% (127 hand hygiene actions /1000 opportunities for hand hygiene) after the implementation of the hand hygiene campaign (OR = 6.8, 95% CI 4.2-10.9). Hand hygiene rates significantly increased among all HCW types except attending physicians. Independent predictors of HCW hand hygiene compliance included performing hand hygiene in the post-intervention period (aOR = 5.7, 95% CI 3.5-9.3), in the emergency department (aOR = 4.9, 95% CI 2.8-8.6), during patient care that did not involve Attending Physician Rounds (aOR = 2.4, 95% CI 1.2-4.5), and after patient contact (aOR = 2.1, 95% CI 1.4-3.3). In the perceptions survey, 64.0% of HCWs indicated preference for commercially manufactured hand sanitizer and 71.4% indicated their hand hygiene adherence would improve with commercial hand sanitizer. There was a significant increase in hand hygiene adherence among Ethiopian HCWs following the implementation of a WHO-recommended multimodal hand hygiene campaign. Dissatisfaction with the current WHO-formulation for hand sanitizer was identified as a barrier to hand hygiene adherence in our setting.


Anti-Inflammatory Drugs and Herbs with Special Emphasis on Herbal Medicines for Countering Inflammatory Diseases and Disorders - A Review.
Diseases with inflammatory etiopathology have increased in incidence in recent times. Drugs used for therapeutic management of such inflammatory diseases are relieving the ailment but at the same time also countering serious life threatening consequences. Moreover, they are costly and rarely available at all places. In this context, research and development on medicinal herbs have opened a new era in the prophylactic and therapeutic management of inflammatory diseases. To highlight the importance of anti-inflammatory medicine-synthetic drugs and natural herbs, their constituents, mechanism of action, benefits, side effects and future prospects. The overall aim is to provide better health services to patients regardless of their background on equality basis. Anti-inflammatory herbs have proven beneficial by combating inflammatory responses that lead to severe abnormality in body systems. Inflammation though a protective response to infection or injury and may result in pathological outcome when aggravated or of severe degree thus needs an early intervention for proper resolution. Medicinal plants or their constituents are considered beneficial due to the properties i.e., satisfactory potency, ease of availability, cheapness, less or no side effects, safer and efficient as compared to the synthetic counterparts. These medicinal herbs contain phytoconstituents that can prevent undesirable inflammatory processes and also posses anti-inflammatory activity. Steroids, glycosides, phenolics, flavonoids, alkaloids, polysaccharides, terpenoids, cannabinoids, fatty acids are common phytoconstituents present in these plants. Different mechanisms have been explored for the anti-inflammatory action of these active ingredients. They may synergize the anti-inflammatory pathway enzymes, factors, proteins or interfere with these in the inflammatory pathway like lipooxygenases, cyclooxygenases, tumor necrosis factors, interleukins, prostaglandin, nitric oxide, mitogenactivated protein, nuclear factor, etc. Considering all the above-mentioned factors, further research from molecular to cellular level will enable a better understanding of the mechanisms. Common antiinflammatory herbal plants are Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, Urtica dioica, Uncaria tomentosa, Vaccinium myrtillus, Olea europaea and much more. They are believed to be without side effects unlike the chemical counterparts or synthetic anti-inflammatory agents e.g. steroids, nonsteroid anti-inflammatory drugs, and immunosuppresants used for controlling and suppressing inflammatory crisis. A proper phytochemical, pharmacological and physiological evaluation will enable their safe and effective use in inflammatory conditions. Many of these anti-inflammatory drugs and herbal preparations have been patented with some under consideration. Natural herbs are safe, effective and better options as anti-inflammatory agents than synthetic ones. The phytoconstituents are as effective with the comparable mechanism of action as synthetic molecules. Future research should focus on molecular mechanisms of different beneficial applications of these herbal plants in various diseases. Recent patents on anti-inflammatory drugs and herbal plants have been covered which provide insight into the current status and future prospects in this field.


Sculpting narrowband Fano resonances inherent in the large-area mid-infrared photonic crystal microresonators for spectroscopic imaging.
Fourier transform infrared (FT-IR) imaging spectrometers are almost universally used to record microspectroscopic imaging data in the mid-infrared (mid-IR) spectral region. While the commercial standard, interferometry necessitates collection of large spectral regions, requires a large data handling overhead for microscopic imaging and is slow. Here we demonstrate an approach for mid-IR spectroscopic imaging at selected discrete wavelengths using narrowband resonant filtering of a broadband thermal source, enabled by high-performance guided-mode Fano resonances in one-layer, large-area mid-IR photonic crystals on a glass substrate. The microresonant devices enable discrete frequency IR (DF-IR), in which a limited number of wavelengths that are of interest are recorded using a mechanically robust instrument. This considerably simplifies instrumentation as well as overhead of data acquisition, storage and analysis for large format imaging with array detectors. To demonstrate the approach, we perform DF-IR spectral imaging of a polymer USAF resolution target and human tissue in the C-H stretching region (2600-3300 cm(-1)). DF-IR spectroscopy and imaging can be generalized to other IR spectral regions and can serve as an analytical tool for environmental and biomedical applications.


Assessing measures of comorbidity and functional status for risk adjustment to compare hospital performance for colorectal cancer surgery: a retrospective data-linkage study.
Comparing outcomes between hospitals requires consideration of patient factors that could account for any observed differences. Adjusting for comorbid conditions is common when studying outcomes following cancer surgery, and a commonly used measure is the Charlson comorbidity index. Other measures of patient health include the ECOG performance status and the ASA physical status score. This study aimed to ascertain how frequently ECOG and ASA scores are recorded in population-based administrative data collections in New South Wales, Australia and to assess the contribution each makes in addition to the Charlson comorbidity index in risk adjustment models for comparative assessment of colorectal cancer surgery outcomes between hospitals. We used linked administrative data to identify 6964 patients receiving surgery for colorectal cancer in 2007 and 2008. We summarised the frequency of missing data for Charlson comorbidity index, ECOG and ASA scores, and compared patient characteristics between those with and without these measures. The performance of ASA and ECOG in risk adjustment models that also included Charlson index was assessed for three binary outcomes: 12-month mortality, extended length of stay and 28-day readmission. Patient outcomes were compared between hospital peer groups using multilevel logistic regression analysis. The Charlson comorbidity index could be derived for all patients, ASA score was recorded for 78 % of patients and ECOG performance status recorded for only 24 % of eligible patients. Including ASA or ECOG improved the predictive ability of models, but there was no consistently best combination. The addition of ASA or ECOG did not substantially change parameter estimates for hospital peer group after adjusting for Charlson comorbidity index. While predictive ability of regression models is maximised by inclusion of one or both of ASA score and ECOG performance status, there is little to be gained by adding ASA or ECOG to models containing the Charlson comorbidity index to address confounding. The Charlson comorbidity index has good performance and is an appropriate measure to use in risk adjustment to compare outcomes between hospitals.


Biologically Active Extracts from Different Medicinal Plants Tested as Potential Additives against Bee Pathogens.
Honey bees (Apis mellifera) perform pollination service for many agricultural crops and contribute to the global economy in agriculture and bee products. However, honey bee health is an ongoing concern, as illustrated by persistent local population decline, caused by some severe bee diseases (e.g., nosemosis, AFB, EFB, chalkbrood). Three natural recipes are in development based on the bioactive compounds of different plants extract (Agastache foeniculum, Artemisia absinthium, Evernia prunastri, Humulus lupulus, Laurus nobilis, Origanum vulgare and Vaccinium myrtillus), characterised by HPLC-PDA. The antimicrobial activity of these recipes was tested in vitro against Paenibacillus larvae, Paenibacillus alvei, Brevibacillus laterosporus, Enterococcus faecalis, Ascosphaera apis and in vivo against Nosema ceranae. A mix of 20% blueberry, 40% absinthium, 10% oakmoss, 10% oregano, 10% Brewers Gold hops, 5% bay laurel and 5% anise hyssop extract showed the strongest antibacterial and antifungal activity. Combing several highly active plant extracts might be an alternative treatment against bee-disease-associated parasites and pathogens, in particular to replace synthetic antibiotics.


Hybrid lithography: combining UV-exposure and two photon direct laser writing.
We demonstrate a method for the combination of UV-lithography and direct laser writing using two-photon polymerization (2PP-DLW). First a dye doped photoresist is used for UV-lithography. Adding an undoped photoresist on top of the developed structures enables three-dimensional alignment of the 2PP-DLW structures by detecting the spatially varying fluorescence of the two photoresists. Using this approach we show three dimensional alignment by adding 3D structures made by 2PP-DLW to a previously UV-exposed structure. Furthermore, a fluidic system with an integrated total internal reflection mirror to observe particles in a microfluidic channel is demonstrated.


First report of Bitylenchus ventrosignatus () associated with wild grass in Botswana.
During a survey on the biodiversity of plant-parasitic nematodes of natural areas in Botswana, Bitylenchus ventrosignatus was discovered around the rhizosphere of wild grass. The nematodes were extracted using the tray method and then fixed according to the available protocols. The morphological characters fit well with the description of B. ventrosignatus. In addition, molecular analysis using 18 S and 28 S rDNA indicated 98% (KJ461617) and 95% (KJ461567) similarity with the Spanish population of B. ventrosignatus. The phylogenetic analysis of 18 S and 28 S rDNA placed the examined population with other populations of B. ventrosignatus in a group with a posterior probability support value of 100. According to published literature, this is the first report of B. ventrosignatus from Botswana.


Directionally controlled fluorescence emission in butterflies.
Recently developed, high-efficiency, light-emitting diodes use two-dimensional photonic crystals to enhance the extraction of otherwise internally trapped light and multilayer reflectors to control the direction of light emission. This work describes the characterization of a naturally evolved light-extraction system on the wing scales of a small group of Papilio butterflies. The efficient extraction of fluorescence from these scales is facilitated by a two-dimensional photonic crystal slab that uses a multilayer to help control emission direction. Its light-extraction function is analogous to that of the light-emitting diode.


C9orf72 promoter hypermethylation is neuroprotective: Neuroimaging and neuropathologic evidence.
To use in vivo neuroimaging and postmortem neuropathologic analysis in C9orf72 repeat expansion patients to investigate the hypothesis that C9orf72 promoter hypermethylation is neuroprotective and regionally selective. Twenty patients with a C9orf72 repeat expansion participating in a high-resolution MRI scan and a clinical examination and a subset of patients (n = 11) were followed longitudinally with these measures. Gray matter (GM) density was related to C9orf72 promoter hypermethylation using permutation-based testing. Regional neuronal loss was measured in an independent autopsy series (n = 35) of C9orf72 repeat expansion patients. GM analysis revealed that hippocampus, frontal cortex, and thalamus are associated with hypermethylation and thus appear to be relatively protected from mutant C9orf72. Neuropathologic analysis demonstrated an association between reduced neuronal loss and hypermethylation in hippocampus and frontal cortex. Longitudinal neuroimaging revealed that hypermethylation is associated with reduced longitudinal decline in GM regions protected by hypermethylation and longitudinal neuropsychological assessment demonstrated that longitudinal decline in verbal recall is protected by hypermethylation. These cross-sectional and longitudinal neuroimaging studies, along with neuropathologic validation studies, provide converging evidence for neuroprotective properties of C9orf72 promoter hypermethylation. These findings converge with prior postmortem studies suggesting that C9orf72 promoter hypermethylation may be a neuroprotective target for drug discovery.


Are fast food restaurants an environmental risk factor for obesity?
Eating at "fast food" restaurants has increased and is linked to obesity. This study examined whether living or working near "fast food" restaurants is associated with body weight. A telephone survey of 1033 Minnesota residents assessed body height and weight, frequency of eating at restaurants, and work and home addresses. Proximity of home and work to restaurants was assessed by Global Index System (GIS) methodology. Eating at "fast food" restaurants was positively associated with having children, a high fat diet and Body Mass Index (BMI). It was negatively associated with vegetable consumption and physical activity. Proximity of "fast food" restaurants to home or work was not associated with eating at "fast food" restaurants or with BMI. Proximity of "non-fast food" restaurants was not associated with BMI, but was associated with frequency of eating at those restaurants. Failure to find relationships between proximity to "fast food" restaurants and obesity may be due to methodological weaknesses, e.g. the operational definition of "fast food" or "proximity", or homogeneity of restaurant proximity. Alternatively, the proliferation of "fast food" restaurants may not be a strong unique cause of obesity.


A quick guide for building a successful bioinformatics community.
"Scientific community" refers to a group of people collaborating together on scientific-research-related activities who also share common goals, interests, and values. Such communities play a key role in many bioinformatics activities. Communities may be linked to a specific location or institute, or involve people working at many different institutions and locations. Education and training is typically an important component of these communities, providing a valuable context in which to develop skills and expertise, while also strengthening links and relationships within the community. Scientific communities facilitate: (i) the exchange and development of ideas and expertise; (ii) career development; (iii) coordinated funding activities; (iv) interactions and engagement with professionals from other fields; and (v) other activities beneficial to individual participants, communities, and the scientific field as a whole. It is thus beneficial at many different levels to understand the general features of successful, high-impact bioinformatics communities; how individual participants can contribute to the success of these communities; and the role of education and training within these communities. We present here a quick guide to building and maintaining a successful, high-impact bioinformatics community, along with an overview of the general benefits of participating in such communities. This article grew out of contributions made by organizers, presenters, panelists, and other participants of the ISMB/ECCB 2013 workshop "The 'How To Guide' for Establishing a Successful Bioinformatics Network" at the 21st Annual International Conference on Intelligent Systems for Molecular Biology (ISMB) and the 12th European Conference on Computational Biology (ECCB).


Prox1 regulates Olig2 expression to modulate binary fate decisions in spinal cord neurons.
Specification of spinal cord neurons depends on gene regulation networks that impose distinct fates in neural progenitor cells (NPCs). Olig2 is a key transcription factor in these networks by inducing motor neuron (MN) specification and inhibiting interneuron identity. Despite the critical role of Olig2 in nervous system development and cancer progression, the upstream molecular mechanisms that control Olig2 gene transcription are not well understood. Here we demonstrate that Prox1, a transcription repressor and downstream target of proneural genes, suppresses Olig2 expression and therefore controls ventral spinal cord patterning. In particular, Prox1 is strongly expressed in V2 interneuron progenitors and largely excluded from Olig2+ MN progenitors (pMN). Gain- and loss-of-function studies in mouse NPCs and chick neural tube show that Prox1 is sufficient and necessary for the suppression of Olig2 expression and proper control of MN versus V2 interneuron identity. Mechanistically, Prox1 interacts with the regulatory elements of Olig2 gene locus in vivo and it is critical for proper Olig2 transcription regulation. Specifically, chromatin immunoprecipitation analysis in the mouse neural tube showed that endogenous Prox1 directly binds to the proximal promoter of the Olig2 gene locus, as well as to the K23 enhancer, which drives Olig2 expression in the pMN domain. Moreover, plasmid-based transcriptional assays in mouse NPCs suggest that Prox1 suppresses the activity of Olig2 gene promoter and K23 enhancer. These observations indicate that Prox1 controls binary fate decisions between MNs and V2 interneurons in NPCs via direct repression of Olig2 gene regulatory elements.


Results from a pilot promotora program to reduce depression and stress among immigrant Latinas.
The stressful experiences that Latino immigrants face throughout the migration process to the United States put them at increased risk for poor mental health. Latinas are at heightened risk due to stigma, limited access to mental health resources, domestic violence, and gender role expectations. In addition, for those who live in new immigrant settlement areas, such as the Southeast, these disparities are magnified by even fewer culturally appropriate services and limited social support. This study evaluates the impact of ALMA (Amigas Latinas Motivando el Alma/Latina Friends Motivating the Soul), a pilot promotora intervention offered in three North Carolina counties to improve mental health among Latinas by offering coping skills training. The intervention trained community-based promotoras to conduct outreach to Latina women in their social network (compañeras). Using a pre-post test design, we assessed the mental health outcomes of compañeras. Compañeras improved on the following outcomes: depressive symptoms, attitudes of depression treatment, perceived and acculturative stress, perceived social support, and positive coping responses. Our findings suggest that promotora interventions, such as ALMA, that focus on building self-care strategies can be valuable to reducing preclinical symptoms and addressing health care disparities that are exacerbated by unavailable or underused mental health services.


The flowering locus Hr colocalizes with a major QTL affecting winter frost tolerance in Pisum sativum L.
An understanding of the genetic determinism of frost tolerance is a prerequisite for the development of frost tolerant cultivars for cold northern areas. In legumes, it is not known to which extent vernalization requirement or photoperiod responsiveness are necessary for the development of frost tolerance. In pea (Pisum sativum L.) however, the flowering locus Hr is suspected to influence winter frost tolerance by delaying floral initiation until after the main winter freezing periods have passed. The objective of this study was to dissect the genetic determinism of frost tolerance in pea by QTL analysis and to assess the genetic linkage between winter frost tolerance and the Hr locus. A population of 164 recombinant inbred lines (RILs), derived from the cross Champagne x Terese was evaluated both in the greenhouse and in field conditions to characterize the photoperiod response from which the allele at the Hr locus was inferred. In addition, the population was also assessed for winter frost tolerance in 11 field conditions. Six QTL were detected, among which three were consistent among the different experimental conditions, confirming an oligogenic determinism of frost tolerance in pea. The Hr locus was found to be the peak marker for the highest explanatory QTL of this study. This result supports the hypothesis of the prominent part played by the photoperiod responsiveness in the determinism of frost tolerance for this species. The consistency of three QTL makes these positions interesting targets for marker-assisted selection.


Planar versus puckered nets in the polar intermetallic series EuGaTt (Tt = Si, Ge, Sn).
The ternary polar intermetallic compounds EuGaTt (Tt = Si, Ge, Sn) have been synthesized and characterized experimentally, as well as theoretically. EuGaSi crystallizes in the hexagonal AlB(2)-type structure (space group P6/mmm, Z = 1, Pearson symbol hP3) with randomly distributed Ga and Si atoms on the graphite-type planes: a = 4.1687(6) A, c = 4.5543(9) A. On the other hand, EuGaGe and EuGaSn adopt the hexagonal YPtAs-type structure (space group P6(3)/mmc, Z = 4, Pearson symbol hP12): a = 4.2646(6) A and c = 18.041(5) A for EuGaGe; a = 4.5243(5) A and c = 18.067(3) A for EuGaSn. The three crystal structures contain formally [GaTt](2-) polyanionic 3-bonded, hexagonal networks, which change from planar to puckered and exhibit a significant decrease in interlayer Ga-Ga distances as the size of Tt increases. Magnetic susceptibility measurements of this series of compounds show Curie-Weiss behavior above 86(5), 95(5), and 116(5) K with magnetic moments of 7.93, 7.97, and 7.99 mu(B) for EuGaSi, EuGaGe, and EuGaSn, respectively, indicating a 4f(7) electronic configuration (Eu(2+)) for Eu atoms. X-ray absorption spectra (XAS) are also consistent with these magnetic properties. Electronic structure calculations supplemented by a crystal orbital Hamilton population (COHP) analysis identifies the synergy between atomic sizes, from both Eu and Tt atoms, and the orbital contributions from Eu toward influencing the structural features of EuGaTt. A multicentered interaction between planes of Eu atoms and the [GaTt](2-) layers rather than through-space Ga-Ga bonding is seen in ELF distributions.


Dose dependent sun protective effect of topical melatonin: A randomized, placebo-controlled, double-blind study.
Ultraviolet radiation (UVR) by sunlight results in an increasing number of skin conditions. Earlier studies have suggested a protective effect of topical treatment with the pineal hormone melatonin. However, this protective effect has never been evaluated in natural sunlight, and the optimal dosing has not been clarified. The aim of this study was to investigate the sun protective effect of topical treatment with three different doses of melatonin (0.5%, 2.5%, 12.5%) against erythema induced by natural sunlight. The study was a randomized, placebo-controlled, double-blind study in healthy volunteers. Twenty-three healthy volunteers, 8 male and 15 female, were enrolled. The protective effect of three different doses of melatonin cream (0.5%, 2.5%, 12.5%) against erythema induced by natural sunlight was tested. All participants had their backs exposed to sun from 1:22 PM to 2:02 PM local time and UV-index was 9. Primary outcome was reduction in erythema evaluated by chromatography after sun exposure, when treated with topical melatonin cream (0.5%, 2.5%, 12.5%) versus placebo and no treatment. The erythema reaction was evaluated with chromatography and visual scoring at baseline, one, four, eight and 24h after exposure. Significant difference in erythema formation was found between areas treated with melatonin cream 12.5% and areas receiving placebo or no treatment (repeated measures ANOVA p=0.001). No differences were found between placebo and the 0.5% and 2.5% concentrations. Application of melatonin cream 12.5% protects against natural sunlight induced erythema.


Single-molecule tracking in live Yersinia enterocolitica reveals distinct cytosolic complexes of injectisome subunits.
In bacterial type 3 secretion, substrate proteins are actively transported from the bacterial cytoplasm into the host cell cytoplasm by a large membrane-embedded machinery called the injectisome. Injectisomes transport secretion substrates in response to specific environmental signals, but the molecular details by which the cytosolic secretion substrates are selected and transported through the type 3 secretion pathway remain unclear. Secretion activity and substrate selectivity are thought to be controlled by a sorting platform consisting of the proteins SctK, SctQ, SctL, and SctN, which together localize to the cytoplasmic side of membrane-embedded injectisomes. However, recent work revealed that sorting platform proteins additionally exhibit substantial cytosolic populations and that SctQ reversibly binds to and dissociates from the cytoplasmic side of membrane-embedded injectisomes. Based on these observations, we hypothesized that dynamic molecular turnover at the injectisome and cytosolic assembly among sorting platform proteins is a critical regulatory component of type 3 secretion. To determine whether sorting platform complexes exist in the cytosol, we measured the diffusive properties of the two central sorting platform proteins, SctQ and SctL, using live cell high-throughput 3D single-molecule tracking microscopy. Single-molecule trajectories, measured in wild-type and mutant Yersinia enterocolitica cells, reveal that both SctQ and SctL exist in several distinct diffusive states in the cytosol, indicating that these proteins form stable homo- and hetero-oligomeric complexes in their native environment. Our findings provide the first diffusive state-resolved insights into the dynamic regulatory network that interfaces stationary membrane-embedded injectisomes with the soluble cytosolic components of the type 3 secretion system.


Combined transcranial direct current stimulation and robotic upper limb therapy improves upper limb function in an adult with cerebral palsy.
Robotic therapy can improve upper limb function in hemiparesis. Excitatory transcranial direct current stimulation (tDCS) can prime brain motor circuits before therapy. We tested safety and efficacy of tDCS plus robotic therapy in an adult with unilateral spastic cerebral palsy (USCP). In each of 36 sessions, anodal tDCS (2 mA, 20 min) was applied over the motor map of the affected hand. Immediately after tDCS, the participant completed robotic therapy, using the shoulder, elbow, and wrist (MIT Manus). The participant sat in a padded chair with affected arm abducted, forearm supported, and hand grasping the robot handle. The participant controlled the robot arm with his affected arm to move a cursor from the center of a circle to each of eight targets (960 movements). Motor function was tested before, after, and six months after therapy with the Wolf Motor Function Test (WMFT) and Fugl-Meyer (FM). Reaching accuracy on the robot task improved significantly after therapy. The WMFT and FM improved clinically meaningful amounts after therapy. The motor map of the affected hand expanded after therapy. Improvements were maintained six months after therapy. Combined tDCS and robotics safely improved upper limb function in an adult with USCP.


MR characteristics of histopathologic subtypes of spinal ependymoma.
To examine MR characteristics and enhancement patterns of spinal ependymomas and compare these data with histopathologic subtypes. The MR images from 26 cases of pathologically proved spinal ependymomas were evaluated with respect to seven criteria: signal characteristics, enhancement pattern, length of involvement, cysts or syrinxes, hemorrhage, bony changes, and type of cord expansion. Signal characteristics were then correlated with histologic subtype. In the category of enhancement pattern, our results differed markedly from published data, with only 38% of cases demonstrating classic homogeneous enhancement. The remainder of our cases (62%) demonstrated other enhancement patterns, including heterogeneous (31%), rim (19%), minimal (6%), and no enhancement (6%). Pathologic comparison revealed that one histologic subtype, the myxopapillary ependymoma, demonstrated unique imaging characteristics on T1-weighted images. A highly statistically significant percentage of this variant was hyperintense on T1, whereas most nonmyxopapillary ependymomas were hypointense. The radiologist should be aware of alternative patterns of enhancement of spinal ependymomas and not be dissuaded from the diagnosis in appropriate clinical settings. In addition, one histologic subtype, myxopapillary, often exhibits signal characteristics different from nonmyxopapillary types, appearing hyperintense on T1 probably because of their intracellular and perivascular accumulation of mucin.


One-year mortality among elderly people after hospitalization due to fall-related fractures: comparison with a control group of matched elderly.
Fall-related fractures among the elderly represent an important public health problem. Severe fractures have been related to increased risk of death. In order to investigate the mortality profile of elderly individuals with severe fractures, 250 patients aged 60 years and over, hospitalized due to fall-related fractures and 250 elderly without fractures living in the local community were followed-up for one year. They were matched according to sex, age, time of hospitalization and neighborhood. Deaths were identified using probabilistic linkage of the research dataset and the local mortality registry. The one-year cumulative mortality was 25.2% in the case of individuals with severe fractures and 4% for those individuals without. The mortality distribution was not homogeneous across the follow-up period. Two-thirds of deaths among the elderly individuals hospitalized due to fracture occurred within the first 3 months, whereas mortality among those individuals without fractures took place later. Heart disease, pneumonia, GI bleeding, sepsis, and pulmonary embolism, diabetes and stroke were important causes of one-year mortality.


Change in proportional protein intake in a 10-week energy-restricted low- or high-fat diet, in relation to changes in body size and metabolic factors.
To investigate in a secondary analysis of a randomised trial the effects of a low-/high-fat diet and reported change from baseline in energy% from protein (prot%), in relation to changes in body size and metabolic factors. Obese adults (n = 771) were randomised to a 600 kcal energy-deficient low-fat (20-25 fat%) or high-fat (40-45 fat%) diet over 10 weeks. Dietary intake data at baseline and during the intervention were available in 585 completers. We used linear regression to calculate the combined effects of randomised group and groups of prot% change (<-2 /-2 to 2/>2) on outcomes. The low-fat group with >2 prot% increase lost 1.1 kg more weight (p = 0.03) and reduced cholesterol by 0.25 mmol/l more (p = 0.003) than the high-fat group with >2 prot% decrease. These differences were 2.5-fold and 1.8-fold greater than the differences between the low-fat and high-fat groups while not considering prot% change. The high-fat group reduced plasma triglycerides more than the low-fat group, but not compared to those in the low-fat group with >2 units prot% increase (p fat-protein interaction = 0.01). Under energy restriction, participants on a low-fat diet who had increased the percentage energy intake from protein showed the greatest reduction in weight and cholesterol, and a triglyceride reduction equally large to that of participants on a high-fat diet.


Lossless equalization of frequency combs.
Frequency combs obtained by sinusoidal phase modulation of narrowband cw lasers are widely used in the field of optical communications. However, the resulting spectral envelope of the comb is not flat. We propose a general and efficient approach to achieve flat frequency combs with tunable bandwidth. The idea is based on a two-step process. First, efficient generation of a train with a temporal flat-top-pulse profile is required. Second, we use large parabolic phase modulation in every train period to map the temporal intensity shape into the spectral domain. In this way the resulting spectral envelope is flat, and the size is tunable with the chirping rate. Two different schemes are proposed and verified through numerical simulations.


Computationally analyzing the possible biological function of YJL103C--an ORF potentially involved in the regulation of energy process in yeast.
Although the complete genomes of a number of organisms have been sequenced, the biological functions of many genes are still not known. Because experimentally studying the functions of those genes one by one requires tremendous time, it is vital to use published resources like microarray gene expression data for computational analysis of gene functions. One example is YJL103C, a yeast gene of unknown function in the Saccharomyces Genome Database (SGD). It is possible to quickly infer its biological function by computational analysis. In this study, we present an efficient model to explore the biological function of a novel gene using microarray data. We showed that the expression pattern of YJL103C is most similar to the genes in the energy group and respiratory chain subgroup. We further found that YJL103C contains a HAP2,3,4 box in its promoter region and a cytochrome C heme-binding signature in its protein sequence. Our findings define a potential role for YJL103C in the regulation of energy metabolism, specifically in the process of oxidative phosphorylation. Similar bioinformatics methods can be applied to infer the biological functions of other novel genes in organisms for which microarray data are available. In this work, we selected a single gene of unknown function as a case study. By focusing on the power of computer analysis and bioinformatics on the available microarray data, we have determined the likely biological function of YJL103C. Our study provides a method by which to explore the potential function of other genes currently annotated as having an unknown function in any organism for which global gene expression data are available.


Histopathological and Immunohistochemical Findings in Congenital Pouch Colon: A Prospective Study.
There is a paucity of literature on the histopathological aspects of congenital pouch colon (CPC) and immunohistochemical (IHC) assessment has not been reported. So we planned to study the histopathological and IHC findings within the spectrum of CPC and compare the findings with the normal colon. This is a descriptive prospective study on CPC patients. There were 49 cases of CPC (42 males and 7 females) and 13 controls. Histological examination was done using hematoxylin and eosin and Masson trichrome stain. IHC analysis was done with actin, myosin, and desmin antibodies, and neuron-specific enolase and S100 markers for counting ganglionic cells. Histologically, congestion, edema and hemorrhage were seen in mucosa, submucosa, and serosa. Muscle layers were disrupted and divided into bands. An additional muscle coat inside of the muscularis propria was seen in CPC types 1 and 2. Mature ganglionic cells were reduced and muscle layers showed reduced and patchy positivity for smooth muscle actin, myosin, and desmin compared to a normal colon. Histopathological and IHC findings suggest that CPC has distinct defects in the neuromusculature.


Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways delays axonal degeneration after axotomy.
Axonal degeneration occurs in many neurodegenerative diseases and after traumatic injury and is a self-destructive program independent from programmed cell death. Previous studies demonstrated that overexpression of nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) or exogenous application of nicotinamide adenine dinucleotide (NAD) can protect axons of cultured dorsal root ganglion (DRG) neurons from degeneration caused by mechanical or neurotoxic injury. In mammalian cells, NAD can be synthesized from multiple precursors, including tryptophan, nicotinic acid, nicotinamide, and nicotinamide riboside (NmR), via multiple enzymatic steps. To determine whether other components of these NAD biosynthetic pathways are capable of delaying axonal degeneration, we overexpressed each of the enzymes involved in each pathway and/or exogenously administered their respective substrates in DRG cultures and assessed their capacity to protect axons after axotomy. Among the enzymes tested, Nmnat1 had the strongest protective effects, whereas nicotinamide phosphoribosyl transferase and nicotinic acid phosphoribosyl transferase showed moderate protective activity in the presence of their substrates. Strong axonal protection was also provided by Nmnat3, which is predominantly located in mitochondria, and an Nmnat1 mutant localized to the cytoplasm, indicating that the subcellular location of NAD production is not crucial for protective activity. In addition, we showed that exogenous application of the NAD precursors that are the substrates of these enzymes, including nicotinic acid mononucleotide, nicotinamide mononucleotide, and NmR, can also delay axonal degeneration. These results indicate that stimulation of NAD biosynthetic pathways via a variety of interventions may be useful in preventing or delaying axonal degeneration.


Studying distributed cognition of simulation-based team training with DiCoT.
Health care organizations employ simulation-based team training (SBTT) to improve skill, communication and coordination in a broad range of critical care contexts. Quantitative approaches, such as team performance measurements, are predominantly used to measure SBTTs effectiveness. However, a practical evaluation method that examines how this approach supports cognition and teamwork is missing. We have applied Distributed Cognition for Teamwork (DiCoT), a method for analysing cognition and collaboration aspects of work settings, with the purpose of assessing the methodology's usefulness for evaluating SBTTs. In a case study, we observed and analysed four Emergo Train System® simulation exercises where medical professionals trained emergency response routines. The study suggests that DiCoT is an applicable and learnable tool for determining key distributed cognition attributes of SBTTs that are of importance for the simulation validity of training environments. Moreover, we discuss and exemplify how DiCoT supports design of SBTTs with a focus on transfer and validity characteristics. Practitioner Summary: In this study, we have evaluated a method to assess simulation-based team training environments from a cognitive ergonomics perspective. Using a case study, we analysed Distributed Cognition for Teamwork (DiCoT) by applying it to the Emergo Train System®. We conclude that DiCoT is useful for SBTT evaluation and simulator (re)design.


Characteristics that predict physician participation in a Web-based CME activity: the MI-Plus study.
Physician use of the Internet for practice improvement has increased dramatically over the last decade, but research shows that many physicians choose not to participate. The current study investigated the association of specific physician characteristics with enrollment rates and intensity of participation in a specific Internet-delivered educational intervention to improve care to post-myocardial infarction (MI) patients. Primary-care physicians were recruited for participation in a randomized controlled trial designed to compare effectiveness of an intervention Web site versus a control Web site in the management of adult chronic disease. Physicians were informed that the intervention focused on ambulatory post-myocardial infarction patients. Physician characteristics were obtained from a commercial vendor with data merged from the American Medical Association and Alabama State Licensing Board. Enrollment and Web use were tracked electronically. Out of a sample of 1337 eligible physicians, 177 (13.2%) enrolled in the study. Enrollment was higher for physicians with more post-MI patients (> or = 20 vs < 20 patients, 15.3% vs 9.3%, P = .002) and for those practicing in rural compared to urban areas (16.3% vs 12.1%, P = .046). Intensity of use of the Internet courses after initial enrollment was not predicted by physician characteristics in the current sample. Physicians with more post-MI patients and rural practice location were found to predict enrollment in an Internet-delivered continuing medical education (CME) intervention designed to improve care for post-MI patients. These factors predicted program interest but not program use. More research is needed to replicate these findings to investigate variables that determine physician engagement in Internet CME.


Estimating prevalence of functional iron deficiency anaemia in advanced cancer.
Anaemia is a common complication of cancer causing symptoms including fatigue. It is also associated with shorter survival. Cancer causes systemic inflammation which interrupts iron metabolism leading to a functional iron deficiency (FID). There are few data on prevalence or aetiology of anaemia in those with advanced cancer. We aimed to establish the prevalence of anaemia and estimate extent of FID anaemia in patients with advanced cancer. All patients with advanced cancer referred to two UK specialist palliative care services over 1 year were identified. Demographic and clinical data were linked with routinely collected haematological and biochemical profiles. We assessed the numbers of patients with abnormal values for haemoglobin, % hypochromic red cells (>5% indicates iron-restricted erythropoiesis) and CRP (>10 indicates systemic inflammation). We judged that FID anaemia was likely when patients had all three abnormalities and ferritin 30-800 ng/ml. Out of 2416 patients, 1797 had a cancer diagnosis and laboratory data available. Mean haemoglobin was 116 g/l. Sixty-three percent of patients were anaemic, mild 25%, moderate 35% and severe 3%. Women had significantly higher mean haemoglobin than men, and there was wide variation in anaemia prevalence across tumour sites. Thirty-nine percent of patients who had all four parameters checked met our criteria for FID anaemia. There were significant relationships between haemoglobin, % hypochromic red cells and CRP (p = 0.0001). Anaemia was common in this population, and we estimate this was caused by FID in 66% of anaemic patients. Further research is needed to validate our diagnostic criteria before this approach can be used in clinical practice.


Association of human, rat, and rabbit apolipoprotein E with beta-amyloid.
In humans, apolipoprotein E (apoE) has three major isoforms, E2 (Cys112, Cys158), E3 (Cys112, Arg158), and E4 (Arg112, Arg158). While epsilon4 is a genetic risk factor for Alzheimer's disease (AD), epsilon2 may protect against late-onset AD. Using native preparations of apoE from conditioned tissue culture media or plasma lipoproteins, we have previously shown that when equivalent amounts of apoE3 or E4 were incubated with beta-amyloid (A beta), apoE3 formed 20 times as much SDS-stable complex with the peptide as apoE4. This preferential binding of A beta to apoE3 was abolished when apoE was purified by a process which includes delipidation and denaturation. Here we expand these observations to include A beta binding to lipoprotein-associated and purified apoE2. Lipoproteins isolated from the plasma of individuals homozygous for either epsilon2 or epsilon3 were incubated with A beta(1-40). SDS-stable complex formation was analyzed by a non-reducing gel shift assay, followed by immunoblotting with either A beta or apoE antibodies. ApoE2:A beta complex formation was comparable to apoE3:A beta in both native and purified preparations of apoE. In addition, lipoprotein-associated rat apoE (Arg112, Arg158), like human apoE4, did not form complex with A beta, while lipoprotein-associated rabbit apoE (Cys112, Arg158) did bind the peptide. These binding studies provide one possible explanation for protective effects of both apoE2 and E3 against the development of Alzheimer's disease.


That Escalated Quickly-Planning to Ignore RPE Can Backfire.
Ratings of perceived exertion (RPE) are routinely assessed in exercise science and RPE is substantially associated with physiological criterion measures. According to the psychobiological model of endurance, RPE is a central limiting factor in performance. While RPE is known to be affected by psychological manipulations, it remains to be examined whether RPE can be self-regulated during static muscular endurance exercises to enhance performance. In this experiment, we investigate the effectiveness of the widely used and recommended self-regulation strategy of if-then planning (i.e., implementation intentions) in down-regulating RPE and improving performance in a static muscular endurance task. 62 female students (age: M = 23.7 years, SD = 4.0) were randomly assigned to an implementation intention or a control condition and performed a static muscular endurance task. They held two intertwined rings as long as possible while avoiding contacts between the rings. In the implementation intention condition, participants had an if-then plan: "If the task becomes too strenuous for me, then I ignore the strain and tell myself: Keep going!" Every 25 ± 10 s participants reported their RPE along with their perceived pain. Endurance performance was measured as time to failure, along with contact errors as a measure of performance quality. No differences emerged between implementation intention and control participants regarding time to failure and performance quality. However, mixed-effects model analyses revealed a significant Time-to-Failure × Condition interaction for RPE. Compared to the control condition, participants in the implementation intention condition reported substantially greater increases in RPE during the second half of the task and reached higher total values of RPE before task termination. A similar but weaker pattern evinced for perceived pain. Our results demonstrate that RPE during an endurance task can be self-regulated with if-then plans. This finding is particularly important given how frequently RPE is used in exercise science as a correlate of physiological processes that ultimately limit performance. Unexpectedly, participants with implementation intentions reported higher RPE than control participants. This suggests that strategies to self-regulate RPE might have ironic effects that hamper performance, maybe by increasing attention to RPE. This implication is important for exercise physiologists, athletes and coaches.


Evolution and pleiotropy of TRITHORAX function in Arabidopsis.
The SET domain-containing genes of the TRITHORAX family encode epigenetic factors that maintain the expression of targeted genes. Trithorax homologs have been found in both animals and plants. Since these are thought to have evolved multicellularity independently, common mechanisms of epigenetic regulation must be evolutionarily ancient and derived from a common ancestor. In addition, each lineage has evolved unique mechanisms to expand the original repertoire of epigenetic functions. Phylogenetic analysis of SET domain proteins has outlined some intriguing evolutionary trends. In plants, epigenetic gene silencing mechanisms have been aggressively pursued. In contrast, studies of epigenetic mechanisms maintaining active gene expression have been scarce. The goal of this review is to draw attention to this gap. Trithorax function in plants are analyzed here in an evolutionary context tracing phylogenetic relationships between the histone methyltransferase activities in unicellular and multicellular domains of life. The involvement of two members of the Arabidopsis Trithorax family, ARABIDOPSIS HOMOLOG of TRITHORAX1 (ATX1), and ARABIDOPSIS HOMOLOG of TRITHORAX2 (ATX2), in developmental and adaptation processes of the plant is overviewed.


Sequential loading of Saccharomyces cerevisiae Ku and Cdc13p to telomeres.
Ku is a heterodimeric protein involved in nonhomologous end-joining of the DNA double-stranded break repair pathway. It binds to the double-stranded DNA ends and then activates a series of repair enzymes that join the broken DNA. In addition to its function in DNA repair, the yeast Saccharomyces cerevisiae Ku (Yku) is also a component of telomere protein-DNA complexes that affect telomere function. The yeast telomeres are composed of duplex C(1-3)(A/T)G(1-3) telomeric DNA repeats plus single-stranded TG(1-3) telomeric DNA tails. Here we show that Yku is capable of binding to a tailed-duplex DNA formed by telomeric DNA that mimics the structure of telomeres. Addition of Cdc13p, a single-stranded telomeric DNA-binding protein, to the Yku-DNA complex enables the formation of a ternary complex with Cdc13p binding to the single-stranded tail of the DNA substrate. Because pre-loading of Cdc13p to the single-stranded telomeric tail inhibits the binding of Yku, the results suggested that loading of Yku and Cdc13p to telomeres is sequential. Through generating a double-stranded break near telomeric DNA sequences, we found that Ku protein appears to bind to the de novo synthesized telomeres earlier than that of Cdc13p in vivo. Thus, our results indicated that Yku interacts directly with telomeres and that sequential loading of Yku followed by Cdc13p to telomeres is required for both proteins to form a ternary complex on telomeres. Our results also offer a mechanism that the binding of Cdc13p to telomeres might prevent Yku from initiating DNA double-stranded break repair pathway on telomeres.


Pterocarpus marsupium extract (Vijayasar) prevented the alteration in metabolic patterns induced in the normal rat by feeding an adequate diet containing fructose as sole carbohydrate.
Insulin resistance (hyperinsulinaemia) is now recognized as a major contributor to the development of glucose intolerance, dyslipidaemia and hypertension in non-insulin-dependent diabetes mellitus (NIDDM) patients. Sedentary lifestyle, consumption of energy-rich diet, obesity, longer lifespan, etc., are important reasons for this rise (J. R. Turtle, Int J Clin Prac 2000; 113: 23). Aqueous extracts of Pterocarpus marsupium Linn bark (PM), Ocimum sanctum Linn leaves (OS) and Trigonella foenumgraecum Linn seeds (FG) have been shown to exert hypoglycaemic/antihyperglycaemic effect in experimental as well as clinical setting. As no work has been carried out so far to assess the effect of PM, OS and FG on fructose-induced hyperglycaemia, hyperinsulinaemia and hypertriglyceridaemia, we undertook this study to assess whether these extracts attenuate the metabolic alteration induced by fructose-rich diet in rats. Five groups of rats (eight each) were fed chow diet, 66% fructose diet, 66% fructose diet + PM leaves extract (1 g/kg/day), 66% fructose diet + OS leaves extract (200 mg/kg/day) and 66% fructose diet + FG seeds extract (2 g/kg/day) for 30 days. Fructose feeding to normal rats for 30 days significantly increased serum glucose, insulin and triglyceride levels in comparison with control. Treatment with all the three plants extract for 30 days significantly lowered the serum glucose levels in comparison with control group. However, only PM extract substantially prevented hypertriglyceridaemia and hyperinsulinaemia, while OS and FG had no significant effect on these parameters. Results of this study, in addition to previous clinical benefits of PM seen in NIDDM subjects, are suggestive of usefulness of PM bark (Vijayasar) in insulin resistance, the associated disorder of type 2 diabetes; however, OS and FG may not be useful. Though several antidiabetic principles (-epicatechin, pterosupin, marsupin and pterostilbene) have been identified in the PM, yet future studies are required to certify their efficacy and safety before clinical scenario.


Overview of the 2016 South African Health Review.
The Global Report on Urban Health: Equitable, Healthier Cities for Sustainable Development, issued in March 2016 by the World Health Organization and the United Nations Human Settlements Programme (UN-Habitat), emphasises the need for enhanced governance and leadership to achieve universal health coverage and the Sustainable Development Goals. Noting that a healthy population forms the foundation for 'sustainable economic growth, social stability, and full realisation of human potential', the report presents 'practical, proven solutions for working across sectors to tackle these … health challenges', and includes examples of such successes in South Africa.


Induction and Regulation of Expression of a Low-CO2-Induced Mitochondrial Carbonic Anhydrase in Chlamydomonas reinhardtii
The time course of and the influence of light intensity and light quality on the induction of a mitochondrial carbonic anhydrase (CA) in the unicellular green alga Chlamydomonas reinhardtii was characterized using western and northern blots. This CA was expressed only under low-CO2 conditions (ambient air). In asynchronously grown cells, the mRNA was detected 15 min after transfer from air containing 5% CO2 to ambient air, and the 21-kD polypeptide was detected on western blots after 1 h. When transferred back to air containing 5% CO2, the mRNA disappeared within 1 h and the polypeptide was degraded within 3 d. Photosynthesis was required for the induction in asynchronous cultures. The induction increased with light up to 500 mumol m-2 s-1, where saturation occurred. In cells grown synchronously, however, expression of the mitochondrial CA was also detected in darkness. Under such conditions the expression followed a circadian rhythm, with mRNA appearing in the dark 30 min before the light was turned on. Algae left in darkness continued this rhythm for several days.


Multiplexed transposon-mediated stable gene transfer in human cells.
Generation of cultured human cells stably expressing one or more recombinant gene sequences is a widely used approach in biomedical research, biotechnology, and drug development. Conventional methods are not efficient and have severe limitations especially when engineering cells to coexpress multiple transgenes or multiprotein complexes. In this report, we harnessed the highly efficient, nonviral, and plasmid-based piggyBac transposon system to enable concurrent genomic integration of multiple independent transposons harboring distinct protein-coding DNA sequences. Flow cytometry of cell clones derived from a single multiplexed transfection demonstrated approximately 60% (three transposons) or approximately 30% (four transposons) stable coexpression of all delivered transgenes with selection for a single marker transposon. We validated multiplexed piggyBac transposon delivery by coexpressing large transgenes encoding a multisubunit neuronal voltage-gated sodium channel (SCN1A) containing a pore-forming subunit and two accessory subunits while using two additional genes for selection. Previously unobtainable robust sodium current was demonstrated through 38 passages, suitable for use on an automated high-throughput electrophysiology platform. Cotransfection of three large (up to 10.8 kb) piggyBac transposons generated a heterozygous SCN1A stable cell line expressing two separate alleles of the pore-forming subunit and two accessory subunits (total of four sodium channel subunits) with robust functional expression. We conclude that the piggyBac transposon system can be used to perform multiplexed stable gene transfer in cultured human cells, and this technology may be valuable for applications requiring concurrent expression of multiprotein complexes.


Imaging ultrafast excited state pathways in transition metal complexes by X-ray transient absorption and scattering using X-ray free electron laser source.
This report will describe our recent studies of transition metal complex structural dynamics on the fs and ps time scales using an X-ray free electron laser source, Linac Coherent Light Source (LCLS). Ultrafast XANES spectra at the Ni K-edge of nickel(ii) tetramesitylporphyrin (NiTMP) were measured for optically excited states at a timescale from 100 fs to 50 ps, providing insight into its sub-ps electronic and structural relaxation processes. Importantly, a transient reduced state Ni(i) (π, 3dx2-y2) electronic state is captured through the interpretation of a short-lived excited state absorption on the low-energy shoulder of the edge, which is aided by the computation of X-ray transitions for postulated excited electronic states. The observed and computed inner shell to valence orbital transition energies demonstrate and quantify the influence of the electronic configuration on specific metal orbital energies. A strong influence of the valence orbital occupation on the inner shell orbital energies indicates that one should not use the transition energy from 1s to other orbitals to draw conclusions about the d-orbital energies. For photocatalysis, a transient electronic configuration could influence d-orbital energies up to a few eV and any attempt to steer the reaction pathway should account for this to ensure that external energies can be used optimally in driving desirable processes. NiTMP structural evolution and the influence of the porphyrin macrocycle conformation on relaxation kinetics can be likewise inferred from this study.


PIPKIγ regulates focal adhesion dynamics and colon cancer cell invasion.
Focal adhesion assembly and disassembly are essential for cell migration and cancer invasion, but the detailed molecular mechanisms regulating these processes remain to be elucidated. Phosphatidylinositol phosphate kinase type Iγ (PIPKIγ) binds talin and is required for focal adhesion formation in EGF-stimulated cells, but its role in regulating focal adhesion dynamics and cancer invasion is poorly understood. We show here that overexpression of PIPKIγ promoted focal adhesion formation, whereas cells expressing either PIPKIγ(K188,200R) or PIPKIγ(D316K), two kinase-dead mutants, had much fewer focal adhesions than those expressing WT PIPKIγ in CHO-K1 cells and HCT116 colon cancer cells. Furthermore, overexpression of PIPKIγ, but not PIPKIγ(K188,200R), resulted in an increase in both focal adhesion assembly and disassembly rates. Depletion of PIPKIγ by using shRNA strongly inhibited formation of focal adhesions in HCT116 cells. Overexpression of PIPKIγ(K188,200R) or depletion of PIPKIγ reduced the strength of HCT116 cell adhesion to fibronection and inhibited the invasive capacities of HCT116 cells. PIPKIγ depletion reduced PIP₂ levels to ∼40% of control and PIP₃ to undetectable levels, and inhibited vinculin localizing to focal adhesions. Taken together, PIPKIγ positively regulates focal adhesion dynamics and cancer invasion, most probably through PIP₂-mediated vinculin activation.


Cell-shape regulation and matrix protein p52 content in phenotypic variants of ras-transformed rat kidney fibroblasts. Functional analysis and biochemical comparison of p52 with proteins implicated in cell-shape determination.
The 52 kDa transformation-sensitive protein p52 was previously identified as a major substrate-associated component of normal rat kidney (NRK) fibroblasts [Higgins & Ryan (1989) Biochem. J. 257, 173-182]. p52 selectively localized to cellular fractions enriched in substrate focal-contact sites and associated ventral undersurface elements. Rapid attachment/spreading of NRK cells on to prepared p52 matrices and inhibition of fibroblast spreading by antibodies to p52 indicated that this protein participates in shape determination or cell-to-substrate adhesion. NRK cells transformed with Kirsten murine sarcoma virus (KiMSV), with a temperature-sensitive mutant (ts-371 KiMSV) and maintained at the permissive temperature, or with the cloned EJrasval.12 oncogene, exhibited down-regulated accumulation of p52 in the ventral undersurface region. Immunochemical, lectin-affinity and electrophoretic analyses indicated that p52 shares considerable sequence similarity with plasminogen-activator inhibitor type-1, which is consistent with its subcellular localization and likely morphoregulatory activity. The marked down-regulation of p52 expression seen in four different ras-mediated transformation systems, its induction prior to butyrate-induced morphological reorganization in KiMSV-transformed cells, and the morphological consequences of exogenously added p52 or p52 antibodies on NRK fibroblasts suggest that this protein probably functions in cell-shape regulation. Abrogation of p52 matrix accumulation typically seen in ras transformants may contribute, therefore, to the aberrant cytoarchitecture characteristic of malignant fibroblasts.