First Report of Leaf Blight Caused by Septoria allii on Garlic Chives in Korea.
Garlic chives, Allium tuberosum Roth., are widely cultivated in Asia and are the fourth most important Allium crop in Korea. In June 2011, a leaf blight of garlic chives associated with a Septoria spp. was observed on an organic farm in Hongcheon County, Korea. Similar symptoms were also found in fields within Samcheok City and Yangku County of Korea during the 2011 and 2012 seasons. Disease incidence (percentage of plants affected) was 5 to 10% in organic farms surveyed. Diseased voucher specimens (n = 5) were deposited at the Korea University Herbarium (KUS). The disease first appeared as yellowish specks on leaves, expanding to cause a leaf tip dieback. Half of the leaves may be diseased within a week, especially during wet weather. Pycnidia were directly observed in leaf lesions. Pycnidia were amphigenous, but mostly epigenous, scattered, dark brown to rusty brown, globose, embedded in host tissue or partly erumpent, separate, unilocular, 50 to 150 μm in diameter, with ostioles of 20 to 40 μm in diameter. Conidia were acicular, straight to sub-straight, truncate at the base, obtuse at the apex, hyaline, aguttulate, 22 to 44 × 1.8 to 3 μm, mostly 3-septate, occasionally 1- or 2-septate. These morphological characteristics matched those of Septoria allii Moesz, which is differentiated from S. alliacea on conidial dimensions (50 to 60 μm long) (1,2). A monoconidial isolate was cultured on potato dextrose agar (PDA). Two isolates have been deposited in the Korean Agricultural Culture Collection (Accession Nos. KACC46119 and 46688). Genomic DNA was extracted using the DNeasy Plant Mini DNA Extraction Kit (Qiagen Inc., Valencia, CA). The internal transcribed spacer (ITS) region of rDNA was amplified using the ITS1/ITS4 primers and sequenced. The resulting sequence of 482-bp was deposited in GenBank (JX531648 and JX531649). ITS sequence information was at least 99% similar to those of many Septoria species, however no information was available for S. allii. Pathogenicity was tested by spraying leaves of three potted young plants with a conidial suspension (2 × 105 conidia/ml), which was harvested from a 4-week-old culture on PDA. Control leaves were sprayed with sterile water. The plants were placed in humid chambers (relative humidity 100%) for the first 48 h. After 7 days, typical leaf blight symptoms started to develop on the leaves of inoculated plants. S. allii was reisolated from the lesions of inoculated plants, confirming Koch's postulates. No symptoms were observed on control plants. The host-parasite association of A. tuberosum and S. allii has been known only from China (1). S. alliacea has been recorded on several species of Allium, e.g. A. cepa, A. chinense, A. fistulosum, and A. tuberosum from Japan (4) and A. cepa from Korea (3). To the best of our knowledge, this is the first report of S. allii on garlic chives. No diseased plants were observed in commercial fields of garlic chives which involved regular application of fungicides. The disease therefore seems to be limited to organic garlic chive production. References: (1) P. K. Chi et al. Fungous Diseases on Cultivated Plants of Jilin Province, Science Press, Beijing, China, 1966. (2) P. A. Saccardo. Sylloge Fungorum Omnium Hucusque Congnitorum. XXV. Berlin, 1931. (3) The Korean Society of Plant Pathology. List of Plant Diseases in Korea, Suwon, Korea, 2009. (4) The Phytopathological Society of Japan. Common Names of Plant Diseases in Japan, Tokyo, Japan, 2000.


Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells.
Tumor-infiltrating myeloid cells convey proangiogenic programs that counteract the efficacy of antiangiogenic therapy. Here, we show that blocking angiopoietin-2 (ANG2), a TIE2 ligand and angiogenic factor expressed by activated endothelial cells (ECs), regresses the tumor vasculature and inhibits progression of late-stage, metastatic MMTV-PyMT mammary carcinomas and RIP1-Tag2 pancreatic insulinomas. ANG2 blockade did not inhibit recruitment of MRC1(+) TIE2-expressing macrophages (TEMs) but impeded their upregulation of Tie2, association with blood vessels, and ability to restore angiogenesis in tumors. Conditional Tie2 gene knockdown in TEMs was sufficient to decrease tumor angiogenesis. Our findings support a model wherein the ANG2-TIE2 axis mediates cell-to-cell interactions between TEMs and ECs that are important for tumor angiogenesis and can be targeted to induce effective antitumor responses.


Clinically diagnosed insomnia and risk of all-cause and diagnosis-specific sickness absence: a nationwide Swedish prospective cohort study.
Insomnia is a large health problem. In some prior studies, positive associations between insomnia symptoms and sickness absence have been observed. There is, however, no previous nationwide cohort study of clinically diagnosed insomnia and risk of incident sickness absence. Prospective nationwide cohort study based on Swedish population-based registers including all 4,956,358 individuals registered as living in Sweden on 31 December 2004/2005, aged 17-64 years, not on disability pension, old-age pension or on-going sickness absence. Those having insomnia inpatient or outpatient care, defined as having at least one admission/specialist visit with a main or secondary diagnosis of disorders of initiating and maintaining sleep [insomnias] (ICD-10: G47.0) during 2000/2001-2005, were compared to those with no such care. All-cause and diagnosis-specific incident sickness absence were followed during 2006-2010. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression. In models adjusted for prior sickness absence, socio-demographic factors and inpatient and specialized outpatient care, associations between insomnia and increased risks of all-cause sickness absence (IRR 1.18, 95% CI 1.04-1.35) and sickness absence due to mental diagnoses (IRR 1.75, 95% CI 1.36-2.25) were observed. After further adjustment for insomnia medications these associations disappeared. No associations between insomnia and risk of sickness absence due to cancer, circulatory or musculoskeletal diagnoses, or injuries, were observed. In this nationwide cohort study, we observed increased risks of all-cause sickness absence and sickness absence due to mental diagnoses after adjustment for several potential confounders that disappeared after further adjustment for insomnia medications.


Cortical and behavioral sensitivity to eccentric polar form.
Patterns composed of local features aligned relative to polar angle, yielding starbursts, concentric circles, and spirals, can inform the understanding of spatial form perception. Previous studies have shown that starburst and concentric form instantiated in Glass patterns are, relative to spirals, both more readily detected in noise and evoke higher levels of blood-oxygen level-dependent (BOLD) signal, as measured with functional magnetic resonance imaging (fMRI), in the retinotopic cortex. However, such studies have typically presented the polar form at the center of gaze, which confounds the distribution of local orientations relative to fixation with variations in polar form. Here, we measure psychophysical detection thresholds and evoked BOLD signal to Glass patterns of varying polar orientation centered at eccentricity. We find an enhanced behavioral sensitivity to starburst and concentric form, consistent with previous studies. While visual areas V1, V2, V3, V3A/B, and hV4 showed elevated levels of BOLD activity to concentric patterns, V1 and V2 showed little to none of the increased activity to starburst patterns evident in areas V3, V3A/B, and hV4. Such findings demonstrate the anisotropic response of the human visual system to variations in polar form independent of variations in local orientation distributions.


Online prediction of fatty acid profiles in crossbred Limousin and Aberdeen Angus beef cattle using near infrared reflectance spectroscopy.
The objective of this study was to examine the online use of near infrared reflectance (NIR) spectroscopy to estimate the concentration of individual and groups of fatty acids (FA) as well as intramuscular fat (IMF) in crossbred Aberdeen Angus (AA×) and Limousin (LIM×) cattle. This was achieved by direct application of a fibre-optic probe to the muscle immediately after exposing the meat surface in the abattoir at 48 h post mortem. Samples of M. longissimus thoracis from 88 AA× and 106 LIM× were scanned over the NIR spectral range from 350 to 1800 nm and samples of the M. longissimus lumborum were analysed for IMF content and FA composition. Statistically significant differences (P < 0.001) were observed in most FA between the two breeds studied, with FA concentration being higher in AA× meat mainly. NIR calibrations, tested by cross-validation, showed moderate to high predictability in LIM× meat samples for C16:0, C16:1, C18:0, trans11 C18:1, C18:1, C18:2 n-6, C20:1, cis9, trans11 C18:2, SFA (saturated FA), MUFA (monounsaturated FA), PUFA (polyunsaturated FA) and IMF content with R(2) (SE(CV), mg/100 g muscle) of 0.69 (146), 0.69 (28), 0.71 (62), 0.70 (8.1), 0.76 (192), 0.65 (13), 0.71 (0.9), 0.71 (2.9), 0.68 (235), 0.75 (240), 0.64 (17) and 0.75 (477), respectively. FA such as C14:0, C18:3 n-3, C20:4 n-6, C20:5 n-3, C22:6 n-3, n-6 and n-3 were more difficult to predict by NIR in these LIM× samples (R(2) = 0.12 to 0.62; SECV = 0.5 to 26 mg/100 g muscle). In contrast, NIR showed low predictability for FA in AA× beef samples. In particular for LIM×, the correlations of NIR measurements and several FA in the range from 0.81 to 0.87 indicated that the NIR spectroscopy is a useful online technique for the early, fast and relatively inexpensive estimation of FA composition in the abattoir.


Surface Binding of TOTAPOL Assists Structural Investigations of Amyloid Fibrils by Dynamic Nuclear Polarization NMR Spectroscopy.
Dynamic nuclear polarization (DNP) NMR can enhance sensitivity but often comes at the price of a substantial loss of resolution. Two major factors affect spectral quality: low-temperature heterogeneous line broadening and paramagnetic relaxation enhancement (PRE) effects. Investigations by NMR spectroscopy, isothermal titration calorimetry (ITC), and EPR revealed a new substantial affinity of TOTAPOL to amyloid surfaces, very similar to that shown by the fluorescent dye thioflavin-T (ThT). As a consequence, DNP spectra with remarkably good resolution and still reasonable enhancement could be obtained at very low TOTAPOL concentrations, typically 400 times lower than commonly employed. These spectra yielded several long-range constraints that were difficult to obtain without DNP. Our findings open up new strategies for structural studies with DNP NMR spectroscopy on amyloids that can bind the biradical with affinity similar to that shown towards ThT.


Immunosuppressive therapy with horse anti-thymocyte globulin and cyclosporine as treatment for fulminant aplastic anemia in children.
Patients with severe aplastic anemia (SAA) and an absolute neutrophil count (ANC) of 0 typically have fatal outcomes. We defined fulminant AA (FAA) as ANC = 0 for at least 2 weeks prior to and after immunosuppressive therapy (IST). We analyzed the outcomes of 35 children with FAA among 288 children who enrolled in a prospective study for AA (AA-97 study). AA was classified as FAA (n = 35), very SAA (vSAA; n = 129), or SAA (n = 124). All of the children received the IST with horse anti-thymocyte globulin (ATG) and cyclosporine (CsA). A significantly lower response rate at 6 months was seen in children with FAA when compared to those with vSAA or SAA (40.0, 63.6, and 63.7 %, respectively; p = 0.027). Of 20 nonresponder patients in the FAA group, 11 were rescued by alternative donor transplantation, and 5 patients showed a late response after 6 months. Consequently, no significant difference was noted in overall survival when comparing the FAA, vSAA, and SAA groups (88.5, 95.8, and 96.8 %). These findings indicate that IST with ATG and CsA is justified as a first-line treatment for children with FAA who lack a human leukocyte antigen-matched sibling donor.


The Expression of TaRca2-α Gene Associated with Net Photosynthesis Rate, Biomass and Grain Yield in Bread Wheat (Triticum aestivum L.) under Field Conditions.
Improvement in activation of Rubisco by Rubisco activase can potentially enhance CO2 assimilation and photosynthetic efficiency in plants. The three homoeologous copies of TaRca2-α were identified on chromosomes 4AL, 4BS and 4DS (TaRca2-α-4AL, TaRca2-α-4BS, and TaRca2-α-4DS) in bread wheat. Expression patterns of the three copies at heading (Z55), anthesis (Z67) and grain-filling (Z73) stages were investigated through qRT-PCR analyses in a panel of 59 bread wheat genotypes and their effects on net photosynthesis rate (Pn), biomass plant-1 (BMPP) and grain yield plant-1 (GYPP) were further explored. Different but similar expression patterns were observed for the three copies of TaRca2-α at the three growth stages with highest expression at grain-filling stage. TaRca2-α-4BS expressed higher at the three stages than TaRca2-α-4AL and TaRca2-α-4DS. The 59 genotypes could be clustered into three groups as high (7 genotypes), intermediate (41 genotypes) and low (11 genotypes) expression based on the expression of the three copies of TaRca2-α at three growth stages. Significant variations (P<0.01) were observed among the three groups of bread wheat genotypes for Pn, BMPP and GYPP. Generally, the genotypes with higher TaRca2-α expression also showed higher values for Pn, BMPP and GYPP. The expressions of the three copies of TaRca2-α at heading, anthesis and grain-filling stages were positively correlated with Pn, BMPP and GYPP (P<0.01) with stronger association for TaRca2-α-4BS at grain-filling stage. These results revealed that the expression of TaRca2-α contribute substantially to Pn, BMPP and GYPP, and suggested that manipulating TaRca-α expression may efficiently improve Pn, BMPP and GYPP in bread wheat and detecting TaRca-α expression levels with emphasis on TaRca2-α-4BS may be a positive strategy for selection in improving photosynthetic efficiency and grain yield of bread wheat.


3D steady-state diffusion-weighted imaging with trajectory using radially batched internal navigator echoes (TURBINE).
While most diffusion-weighted imaging (DWI) is acquired using single-shot diffusion-weighted spin-echo echo-planar imaging, steady-state DWI is an alternative method with the potential to achieve higher-resolution images with less distortion. Steady-state DWI is, however, best suited to a segmented three-dimensional acquisition and thus requires three-dimensional navigation to fully correct for motion artifacts. In this paper, a method for three-dimensional motion-corrected steady-state DWI is presented. The method uses a unique acquisition and reconstruction scheme named trajectory using radially batched internal navigator echoes (TURBINE). Steady-state DWI with TURBINE uses slab-selection and a short echo-planar imaging (EPI) readout each pulse repetition time. Successive EPI readouts are rotated about the phase-encode axis. For image reconstruction, batches of cardiac-synchronized readouts are used to form three-dimensional navigators from a fully sampled central k-space cylinder. In vivo steady-state DWI with TURBINE is demonstrated in human brain. Motion artifacts are corrected using refocusing reconstruction and TURBINE images prove less distorted compared to two-dimensional single-shot diffusion-weighted-spin-EPI.


Improving diagnostic capability for HPV disease internationally within the NIH-NIAID Division of AIDS Clinical Trial Networks.
To evaluate an external quality assurance (EQA) program for the laboratory diagnosis of human papillomavirus (HPV) disease that was established to improve international research capability within the Division of AIDS at the National Institute of Allergy and Infectious Disease-supported Adult AIDS Clinical Trials Group network. A three-component EQA scheme was devised comprising assessments of diagnostic accuracy of cytotechnologists and pathologists using available EQA panels, review of quality and accuracy of clinical slides from local sites by an outside expert, and HPV DNA detection using a commercially available HPV test kit. Seven laboratories and 17 pathologists in Africa, India, and South America participated. EQA scores were suboptimal for EQA proficiency testing panels in three of seven laboratories. There was good agreement between the local laboratory and the central reader 70% of the time (90% confidence interval, 42%-98%). Performance on the College of American Pathologists' HPV DNA testing panel was successful in all laboratories tested. The prequalifying EQA round identified correctable issues that will improve the laboratory diagnosis of HPV-related cervical disease at the participating international study sites and will provide a mechanism for ongoing education and continuous quality improvement.


Adaptations for vision in dim light: impulse responses and bumps in nocturnal spider photoreceptor cells (Cupiennius salei Keys).
The photoreceptor cells of the nocturnal spider Cupiennius salei were investigated by intracellular electrophysiology. (1) The responses of photoreceptor cells of posterior median (PM) and anterior median (AM) eyes to short (2 ms) light pulses showed long integration times in the dark-adapted and shorter integration times in the light-adapted state. (2) At very low light intensities, the photoreceptors responded to single photons with discrete potentials, called bumps, of high amplitude (2-20 mV). When measured in profoundly dark-adapted photoreceptor cells of the PM eyes these bumps showed an integration time of 128 +/- 35 ms (n = 7) whereas in dark-adapted photoreceptor cells of AM eyes the integration time was 84 +/- 13 ms (n = 8), indicating that the AM eyes are intrinsically faster than the PM eyes. (3) Long integration times, which improve visual reliability in dim light, and large responses to single photons in the dark-adapted state, contribute to a high visual sensitivity in Cupiennius at night. This conclusion is underlined by a calculation of sensitivity that accounts for both anatomical and physiological characteristics of the eye.


Fast and robust extraction of hippocampus from MR images for diagnostics of Alzheimer's disease.
Assessment of temporal lobe atrophy from magnetic resonance images is a part of clinical guidelines for the diagnosis of prodromal Alzheimer's disease. As hippocampus is known to be among the first areas affected by the disease, fast and robust definition of hippocampus volume would be of great importance in the clinical decision making. We propose a method for computing automatically the volume of hippocampus using a modified multi-atlas segmentation framework, including an improved initialization of the framework and the correction of partial volume effect. The method produced a high similarity index, 0.87, and correlation coefficient, 0.94, with semi-automatically generated segmentations. When comparing hippocampus volumes extracted from 1.5T and 3T images, the absolute value of the difference was low: 3.2% of the volume. The correct classification rate for Alzheimer's disease and cognitively normal cases was about 80% while the accuracy 65% was obtained for classifying stable and progressive mild cognitive impairment cases. The method was evaluated in three cohorts consisting altogether about 1000 cases, the main emphasis being in the analysis of the ADNI cohort. The computation time of the method is about 2 minutes on a standard laptop computer. The results show a clear potential for applying the method in clinical practice.


Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates.
Epithelial metaplasia occurs when one predominant cell type in a tissue is replaced by another, and is frequently associated with an increased risk of subsequent neoplasia. In both mouse and human pancreas, acinar-to-ductal metaplasia has been implicated in the generation of cancer precursors. We show that pancreatic epithelial explants undergo spontaneous acinar-to-ductal metaplasia in response to EGFR signaling, and that this change in epithelial character is associated with the appearance of nestin-positive transitional cells. Lineage tracing involving Cre/lox-mediated genetic cell labeling reveals that acinar-to-ductal metaplasia represents a true transdifferentiation event, mediated by initial dedifferentiation of mature exocrine cells to generate a population of nestin-positive precursors, similar to those observed during early pancreatic development. These results demonstrate that a latent precursor potential resides within mature exocrine cells, and that this potential is regulated by EGF receptor signaling. In addition, these observations provide a novel example of rigorously documented transdifferentiation within mature mammalian epithelium, and suggest that plasticity of mature cell types may play a role in the generation of neoplastic precursors.


A Novel Non-invasive Method to Detect RELM Beta Transcript in Gut Barrier Related Changes During a Gastrointestinal Nematode Infection.
Currently, methods for monitoring changes of gut barrier integrity and the associated immune response via non-invasive means are limited. Therefore, we aimed to develop a novel non-invasive technique to investigate immunological host responses representing gut barrier changes in response to infection. We identified the mucous layer on feces from mice to be mainly composed of exfoliated intestinal epithelial cells. Expression of RELM-β, a gene prominently expressed in intestinal nematode infections, was used as an indicator of intestinal cellular barrier changes to infection. RELM-β was detected as early as 6 days post-infection (dpi) in exfoliated epithelial cells. Interestingly, RELM-β expression also mirrored the quality of the immune response, with higher amounts being detectable in a secondary infection and in high dose nematode infection in laboratory mice. This technique was also applicable to captured worm-infected wild house mice. We have therefore developed a novel non-invasive method reflecting gut barrier changes associated with alterations in cellular responses to a gastrointestinal nematode infection.


Prognostic and predictive molecular markers in colorectal carcinoma.
Tumour markers are molecules occurring in blood or tissue that are associated with cancer and whose measurement or identification is useful in patient diagnosis or clinical management. The ideal marker would occur only in patients with malignancy, and would correlate with stage and response to treatment, however, to date there are few reliable prognostic markers in colorectal cancer (CRC), consequently much research is focused on identifying such markers. This review aims to summarise the most important currently available markers in CRC that provide prognostic or predictive information. Amongst others, it covers serum markers such as CEA and CA19-9, markers expressed in tumour tissue such as thymidylate synthase and also the expression/loss of expression of certain oncogenes and tumour suppressor genes such as K-ras and p53. The prognostic value of genomic instability, angiogenesis and proliferative indices such as apoptotic index is discussed.


Sodium channel kinetic changes that produce Brugada syndrome or progressive cardiac conduction system disease.
Some mutations of the sodium channel gene Na(V1.5) are multifunctional, causing combinations of LQTS, Brugada syndrome and progressive cardiac conduction system disease (PCCD). The combination of Brugada syndrome and PCCD is uncommon, although they both result from a reduction in the sodium current. We hypothesize that slow conduction is sufficient to cause S-T segment elevation and undertook a combined experimental and theoretical study to determine whether conduction slowing alone can produce the Brugada phenotype. Deletion of lysine 1479 in one of two positively charged clusters in the III/IV inter-domain linker causes both syndromes. We have examined the functional effects of this mutation using heterologous expression of the wild-type and mutant sodium channel in HEK-293-EBNA cells. We show that DeltaK1479 shifts the potential of half-activation, V(1/2m), to more positive potentials (V(1/2m) = -36.8 +/- 0.8 and -24.5 +/- 1.3 mV for the wild-type and DeltaK1479 mutant respectively, n = 11, 10). The depolarizing shift increases the extent of depolarization required for activation. The potential of half-inactivation, V(1/2h), is also shifted to more positive potentials (V(1/2h) = -85 +/- 1.1 and -79.4 +/- 1.2 mV for wild-type and DeltaK1479 mutant respectively), increasing the fraction of channels available for activation. These shifts are quantitatively the same as a mutation that produces PCCD only, G514C. We incorporated experimentally derived parameters into a model of the cardiac action potential and its propagation in a one dimensional cable (simulating endo-, mid-myocardial and epicardial regions). The simulations show that action potential and ECG changes consistent with Brugada syndrome may result from conduction slowing alone; marked repolarization heterogeneity is not required. The findings also suggest how Brugada syndrome and PCCD which both result from loss of sodium channel function are sometimes present alone and at other times in combination.


Persistent Ductus Arteriosus in Critically Ill Preterm Infants.
Persistent ductus arteriosus (PDA) is found with increased incidence in preterm infants, significantly affecting neonatal morbidity and mortality rates. To evaluate the association between the presence of PDA and the severity of clinical condition at birth in critically ill preterm infants, with gestational ages (GA) ≤ 32 weeks and severe respiratory distress. All preterm infants with GA ≤ 32 weeks admitted to the neonatal intensive care unit (NICU) of the Clinical County Emergency Hospital, Sibiu between 1 January 2010 and 31 December 2015 were included in the study. These were categorized as Group 1 [Preterm infants with PDA; n=154] and Group 2 [Preterm infants without PDA; n=186]. Epidemiological and clinical data were collected in the National Registry for Respiratory Distress Syndrome for all children, and data related to prenatal period, clinical characteristics at birth i.e GA, weight, gender, Apgar scores, and clinical features such as resuscitation at birth, surfactant administration, need and duration of respiratory support, neonatal sepsis, complications associated with prematurity, and death, were analyzed. Group 1 infants had significantly lower GA and birth weights, were more often out born (p=0.049, HR 1.69), and had significantly lower Apgar scores at 1 and 10 minutes (p=0.022, p=0.000). They presented a significantly higher need for surfactant administration (42.9% vs 24.7%, p<0.0001) and respiratory support (96.8% vs 90.3%, HR 3.19, p=0.019 for need of CPAP and 22.1% vs 10.8%, HR 2.35, p=0.004 for mechanical ventilation). Duration of respiratory support was also significantly higher in the Group 1 (7.6%±7.5 vs. 5.1±3.8 days, p<0.0001 for CPAP and 20.1±22.5 vs. 12.0±15.7 days, p<0.0001 for mechanical ventilation). In very preterm infants, PDA may be associated with a critical clinical condition leading to serious complications. The presence of PDA after the seventh day of life was associated with an increased need for respiratory support, both CPAP and mechanical ventilation, increased severity of the respiratory distress syndrome, requiring a longer duration of respiratory support, and increased the hospitalization length. In very preterm infants, PDA presence was also associated with a higher rate of severe complications and death, indicating the need for a careful and proper management of these critical cases in neonatal intensive care units.


Inner strength and its relationship to health threats in ageing-A cross-sectional study among community-dwelling older women.
To explore the relationship between inner strength and health threats among community-dwelling older women. Inner strength is described as a resource that promotes experiences of health, despite adversities. Inner strength and its dimensions (i.e. connectedness, creativity, firmness and flexibility) can be assessed using the Inner Strength Scale (ISS). Exploring attributes of weaker inner strength may yield valuable information about areas to focus on in enhancing a person's inner strength and may ultimately lead to the perception of better health. Cross-sectional questionnaire survey. The study is based on responses from 1270 community-dwelling older women aged 65 years and older; these were collected in the year 2010 and describe the situation that still exists today for older women. The questionnaire included the ISS, background characteristics and explanatory variables known to be health threats in ageing. Data were analysed using descriptive and inferential statistics. Poorer mental health was related to weaker inner strength in total and in all the dimensions. Symptoms of depressive disorders and feeling lonely were related to three of the dimensions, except firmness and creativity respectively. Furthermore, poor physical health was associated with the dimensions firmness and flexibility. Other health threats were significantly related to only one of the dimensions, or not associated at all. Mental ill health has overall the strongest association with weaker inner strength. Longitudinal studies are recommended to confirm the results. However, the ISS does not only estimate inner strength but can also be a tool for discovering where (i.e. dimension) interventions may be most profitable.


Increased expression of fibronectin-binding proteins by fluoroquinolone-resistant Staphylococcus aureus exposed to subinhibitory levels of ciprofloxacin.
Bacterial adhesion, which plays an important role in Staphylococcus aureus colonization and infection, may be altered by the presence of antibiotics or/and antibiotic resistance determinants. This study evaluated the effect of fluoroquinolone resistance determinants on S. aureus adhesion to solid-phase fibronectin, which is specifically mediated by two surface-located fibronectin-binding proteins. Five isogenic mutants, derived from strain NCTC 8325 and expressing various levels of quinolone resistance, were tested in an in vitro bacterial adhesion assay with polymethylmethacrylate coverslips coated with increasing amounts of fibronectin. These strains contained single or combined mutations in the three major loci contributing to fluoroquinolone resistance, namely, grlA, gyrA, and flqB, which code for altered topoisomerase IV, DNA gyrase, and increased norA-mediated efflux of fluoroquinolones, respectively. Adhesion characteristics of the different quinolone-resistant mutants grown in the absence of fluoroquinolone showed only minor differences from those of parental strains. However, more important changes in adhesion were exhibited by mutants highly resistant to quinolones following their exponential growth in the presence of one-quarter MIC of ciprofloxacin. Increased bacterial adhesion of the highly quinolone-resistant mutants, which contained combined mutations in grlA and gyrA, was associated with and explained by the overexpression of their fibronectin-binding proteins as assessed by Western ligand affinity blotting. These findings contradict the notion that subinhibitory concentrations of antibiotics generally decrease the expression of virulence factors by S. aureus. Perhaps the increased adhesion of S. aureus strains highly resistant to fluoroquinolones contributes in part to that emergence in clinical settings.


Clinical Profile and Predictors of Outcome in Spontaneous Intracerebral Hemorrhage from a Tertiary Care Centre in South India.
Background. This article attempts to evaluate the clinical profile and outcome determinants following hypertensive SICH in a South Indian population. The study represents the largest series of SICH reported from a single centre in India. Materials and Methods. Prospective data collection and analysis of patients with SICH admitted to our centre between 1st January 2015 and 31st December 2018. The variables analysed include: age, sex, comorbidities, Glasgow coma score (GCS) on admission, radiological features, treatment modality, and outcome at three months. Modified Rankin score (mRS) was used to assess the outcome at discharge and three months. Results. Our study group of 905 patients included 638 males and 267 females and the mean age at presentation was 58.10 ± 12.76 years. The study group included 523 patients (57.8%) previously diagnosed hypertensive, of whom 36.3% (n = 190) were on irregular medication. The most frequent locations of hematoma were basal ganglia (478), thalamus (202), lobar (106), cerebellar (61), brainstem (31), and primary intraventricular haemorrhage (27). Secondary intraventricular extension was seen in 425 (47%) patients on admission. The mean volume of the clot on admission was 23.45 ± 19.79 ml, and clot progression was seen in only 46 (5.08%) cases. Surgical evacuation through craniotomy was done in 147 (16.8%) patients, and external ventricular drainage (EVD) was placed in 56 (6.2%) patients. Overall 3-month mortality was 30.1% (266 patients). On the last follow up a favorable outcome (mRS 0-3) was observed in 412 (45.53%) patients and a poor outcome (mRS 4-5) in 207 patients (22.87%). Independent predictors of mortality are Age >70 (p = <0.001, OR 4.806, 95% CI 3.064-7.54), admission GCS <8 (p = <0.001, OR7.684, 95% CI 5.055#x2013;11.68), and Hematoma volume >30 ml (p = <0.001, OR 2.45, 95% CI 1.626-3.691). Intraventricular haemorrhage was an additional poor outcome predictor (p < 0.015, CI 1.105-2.585). Surgical evacuation reduced mortality in the group, but morbidity rates remained the same. Conclusions. SICH predominantly affects a younger population in India in comparison to the Western society. Elderly age, poor GCS on admission, clot volume above 30 ml and intraventricular extension remain the most consistent predictors of death and poor outcome. Further studies are needed to assess the risk of SICH among hypertensive patients and to prognosticate the outcome after SICH using novel predictors, including biomarkers.


Fourier transform mass spectrometry: a powerful tool for toxin analysis.
The crude venom of Conus virgo was analyzed by Fourier transform mass spectrometry (FTMS) using both nano-electrospray ionization and MALDI. The analyses were performed directly on the crude venom, without chromatographic separation. The mass fingerprinting of the venom yielded 64 distinct molecular masses in the range 500-4500 Da with two major components at 1328.5142 and 1358.5592 Da. To facilitate the de novo sequencing of these compounds, the disulfide bonds of all components were reduced for the whole venom. The mass accuracy, resolution and sensitivity provided by FTMS were necessary to complete the sequencing of the two new peptides named ViVA and ViVB, that turned out to be conotoxins belonging to the T-superfamily, with the disulfide framework V. The peptides shared 80% similarity and as often observed for this class of compound, they were highly post-translationally modified: amidated C-terminus, pyroglutamic acid residue at the N-terminus and two disulfide bonds. Complementary online nano-LC-nano-ESI-FTMS experiments were undertaken. Among the 130 molecular masses found in the coupling experiments, only 45 were common with those obtained in the direct approach, which means that 21 compounds observed by nano-ESI-FTMS were not detected. This clearly shows that some discriminations against some classes of compounds occur when a chromatographic step is used before mass spectrometry.


Ecological divergence and hybridization of Neotropical Leishmania parasites.
The tropical Andes are an important natural laboratory to understand speciation in many taxa. Here we examined the evolutionary history of parasites of the Leishmania braziliensis species complex based on whole-genome sequencing of 67 isolates from 47 localities in Peru. We first show the origin of Andean Leishmania as a clade of near-clonal lineages that diverged from admixed Amazonian ancestors, accompanied by a significant reduction in genome diversity and large structural variations implicated in host-parasite interactions. Within the Andean species, patterns of population structure were strongly associated with biogeographical origin. Molecular clock and ecological niche modeling suggested that the history of diversification of the Andean lineages is limited to the Late Pleistocene and intimately associated with habitat contractions driven by climate change. These results suggest that changes in forestation over the past 150,000 y have influenced speciation and diversity of these Neotropical parasites. Second, genome-scale analyses provided evidence of meiotic-like recombination between Andean and Amazonian Leishmania species, resulting in full-genome hybrids. The mitochondrial genome of these hybrids consisted of homogeneous uniparental maxicircles, but minicircles originated from both parental species. We further show that mitochondrial minicircles-but not maxicircles-show a similar evolutionary pattern to the nuclear genome, suggesting that compatibility between nuclear-encoded mitochondrial genes and minicircle-encoded guide RNA genes is essential to maintain efficient respiration. By comparing full nuclear and mitochondrial genome ancestries, our data expand our appreciation on the genetic consequences of diversification and hybridization in parasitic protozoa.


The COVID-19 Pandemic: Does Our Early Life Environment, Life Trajectory and Socioeconomic Status Determine Disease Susceptibility and Severity?
A poor socioeconomic environment and social adversity are fundamental determinants of human life span, well-being and health. Previous influenza pandemics showed that socioeconomic factors may determine both disease detection rates and overall outcomes, and preliminary data from the ongoing coronavirus disease (COVID-19) pandemic suggests that this is still true. Over the past years it has become clear that early-life adversity (ELA) plays a critical role biasing the immune system towards a pro-inflammatory and senescent phenotype many years later. Cytotoxic T-lymphocytes (CTL) appear to be particularly sensitive to the early life social environment. As we understand more about the immune response to SARS-CoV-2 it appears that a functional CTL (CD8+) response is required to clear the infection and COVID-19 severity is increased as the CD8+ response becomes somehow diminished or exhausted. This raises the hypothesis that the ELA-induced pro-inflammatory and senescent phenotype may play a role in determining the clinical course of COVID-19, and the convergence of ELA-induced senescence and COVID-19 induced exhaustion represents the worst-case scenario with the least effective T-cell response. If the correct data is collected, it may be possible to separate the early life elements that have made people particularly vulnerable to COVID-19 many years later. This will, naturally, then help us identify those that are most at risk from developing the severest forms of COVID-19. In order to do this, we need to recognize socioeconomic and early-life factors as genuine medically and clinically relevant data that urgently need to be collected. Finally, many biological samples have been collected in the ongoing studies. The mechanisms linking the early life environment with a defined later-life phenotype are starting to be elucidated, and perhaps hold the key to understanding inequalities and differences in the severity of COVID-19.


Application of CRISPR/Cas9 genome editing to the study and treatment of disease.
CRISPR/Cas is a microbial adaptive immune system that uses RNA-guided nucleases to cleave foreign genetic elements. The CRISPR/Cas9 method has been engineered from the type II prokaryotic CRISPR system and uses a single-guide RNA to target the Cas9 nuclease to a specific genomic sequence. Cas9 induces double-stranded DNA breaks which are repaired either by imperfect non-homologous end joining to generate insertions or deletions (indels) or, if a repair template is provided, by homology-directed repair. Due to its specificity, simplicity and versatility, the CRISPR/Cas9 system has recently emerged as a powerful tool for genome engineering in various species. This technology can be used to investigate the function of a gene of interest or to correct gene mutations in cells via genome editing, paving the way for future gene therapy approaches. Improvements to the efficiency of CRISPR repair, in particular to increase the rate of gene correction and to reduce undesired off-target effects, and the development of more effective delivery methods will be required for its broad therapeutic application.


Glucocorticoid feedback increases the sensitivity of the limbic system to stress.
In the hypothalamus, corticotropin-releasing hormone (CRH) has a well-described role initiating the hypothalamic-pituitary-adrenal (HPA) axis response to stress. Cortisol, released from the adrenal gland, exerts negative feedback on this axis. The role of extrahypothalamic CRH in stress responses is less well known. The purpose of this study was to measure the response of CRH in the amygdala to acute and repeated stress and to examine if cortisol had any effect on this response. Immunosensor-based microdialysis probes were used to measure CRH and cortisol in the amygdala and cortisol systemically in sheep exposed to a predator stress (a dog). Upon presentation of a dog, CRH increased in the amygdala of the sheep and then fell off. Cortisol levels rose both systemically and in the amygdala, and as they peaked, a second CRH response was observed. Repeated stress changed this response, with the magnitude of the first CRH peak decreasing while the second peak increased. Repeated stress also produced an exaggeration in both of the CRH peaks to presentation of a subsequent novel stress (a forelimb electric shock). Animals that had an escape route from the repeated dog stress did not show this exaggeration when faced subsequently with the novel stress. Administration of mifepristone, a glucocorticoid receptor antagonist, prior to the delivery of the repeat stress prevented subsequent changes in the CRH response. The data suggest that the amygdala shows a CRH response to presentation of a stressor acutely and repeatedly and that repeated stress can alter subsequent amygdala responsiveness to the same or a different stressor. This alteration appears dependent on circulatory glucocorticoids.


The effects of music listening on pain and stress in the daily life of patients with fibromyalgia syndrome.
Music listening is associated with both pain- and stress-reducing effects. However, the effects of music listening in daily life remain understudied, and the psycho-biological mechanisms underlying the health-beneficial effect of music listening remain unknown. We examined the effects of music listening on pain and stress in daily life in a sample of women with fibromyalgia syndrome (FMS; i.e., a condition characterized by chronic pain) and investigated whether a potentially pain-reducing effect of music listening was mediated by biological stress-responsive systems. Thirty women (mean age: 50.7 ± 9.9 years) with FMS were examined using an ecological momentary assessment design. Participants rated their current pain intensity, perceived control over pain, perceived stress level, and music listening behavior five times per day for 14 consecutive days. At each assessment, participants provided a saliva sample for the later analysis of cortisol and alpha-amylase as biomarkers of stress-responsive systems. Hierarchical linear modeling revealed that music listening increased perceived control over pain, especially when the music was positive in valence and when it was listened to for the reason of 'activation' or 'relaxation'. In contrast, no effects on perceived pain intensity were observed. The effects of music listening on perceived control over pain were not mediated by biomarkers of stress-responsive systems. Music listening in daily life improved perceived control over pain in female FMS patients. Clinicians using music therapy should become aware of the potential adjuvant role of music listening in daily life, which has the potential to improve symptom control in chronic pain patients. In order to study the role of underlying biological mechanisms, it might be necessary to use more intensive engagement with music (i.e., collective singing or music-making) rather than mere music listening.


Can urinary nerve growth factor be a biomarker for overactive bladder?
The clinical diagnosis of overactive bladder (OAB) greatly varies and is based on subjective symptoms. A more objective method to diagnose and assess therapeutic outcome in OAB patients, especially for health care providers not trained in urology, needs to be found. Evidence has shown that urinary proteins such as nerve growth factor (NGF) and prostaglandin E(2) levels increase in patients with OAB, bladder outlet obstruction, and detrusor overactivity. Urinary NGF level increases physiologically in normal subjects at urge to void, but increases pathologically in OAB patients at a small bladder volume and with a sensation of urgency. Recent studies have shown that patients with OAB dry and OAB wet have significantly higher urinary NGF levels compared with control groups and patients with increased bladder sensation. Urinary NGF levels decrease after antimuscarinic therapy and further decrease after detrusor botulinum toxin injections in refractory OAB. Urinary NGF level could be a potential biomarker for diagnosis of OAB and assessment of the therapeutic effect of antimuscarinic therapy. The latest medical advances in this field are reviewed herein.


Growth phase regulation of flaA expression in Helicobacter pylori is luxS dependent.
LuxS plays a role in the synthesis of an extracellular signaling molecule, autoinducer 2 (AI-2). To analyze a possible role of AI-2 in regulating Helicobacter pylori gene expression, we constructed a panel of transcriptional reporter strains. We show that the expression of H. pylori flaA is growth phase dependent and that flaA transcription increases in association with increased culture density. Mutating the luxS gene eliminates growth-phase-dependent control of flaA, and this growth phase dependence is restored when the luxS mutant strain is complemented with the wild-type luxS gene.


Effect of different regimens of gut decontamination on bacterial translocation and mortality in experimental acute pancreatitis.
To assess the effect of four regimens of antibiotics (compared with a control regimen of distilled water) given orally on gut decontamination, bacterial translocation, and mortality in acute necrotising pancreatitis in mice. Randomised experimental study. University hospitals, USA and Italy. 150 young Swiss Webster mice. All mice were fed a diet deficient in choline and supplemented with ethionine. They were then randomised to be given by gavage (36 hours after starting the diet): distilled water (controls, group 1); aztreonam along (group 2); neomycin, erythromycin, metronidazole (group 3); polymyxin B and amikacin (group 4); polymyxin B, amikacin, amphotericin B (group 5). 20 Mice in each group were treated for 10 days, and the remaining 10 in each group were killed after 3 days. Survival, and qualitative and quantitative cultures of the liver, lungs, pancreas and caecum. The best survival rate during the first 7 days was in group 5, but by day 10 there was no difference among the groups. All the antibiotic regimens reduced the number of bacteria in the caecum and all but aztreonam alone (group 2) reduced the rate of translocation of both Gram negative and Gram positive bacteria to all organs studied. Translocation of yeast occurred in those animals in groups 2, 3, and 4 in which there was overgrowth of fungi in the caecum. Gram negative and Gram positive organisms and fungi may have an important role in infective morbidity and mortality in acute pancreatitis, and selective decontamination with polymyxin B, amikacin, amphotericin B reduced the incidence of translocation related infections and early mortality in mice with acute necrotising pancreatitis.


Characterization of factors that direct transcription of rat ribosomal DNA.
The protein components that direct and activate accurate transcription by rat RNA polymerase I were studied in extracts of Novikoff hepatoma ascites cells. A minimum of at least two components, besides RNA polymerase I, that are necessary for efficient utilization of templates were identified. The first factor, rat SL-1, is required for species-specific recognition of the rat RNA polymerase I promoter and may be sufficient to direct transcription by pure RNA polymerase I. Rat SL-1 directed the transcription of templates deleted to -31, the 5' boundary of the core promoter element (+1 being the transcription initiation site). The second factor, rUBF, increased the efficiency of template utilization. Transcription of deletion mutants indicated that the 5' boundary of the domain required for rUBF lay between -137 and -127. Experiments using block substitution mutants confirmed and extended these observations. Transcription experiments using those mutants demonstrated that two regions within the upstream promoter element were required for optimal levels of transcription in vitro. The first region was centered on nucleotides -129 and -124. The 5' boundary of the second domain mapped to between nucleotides -106 and -101. DNase footprint experiments using highly purified rUBF indicated that rUBF bound between -130 and -50. However, mutation of nucleotides -129 and -124 did not affect the rUBF footprint. These results indicate that basal levels of transcription by RNA polymerase I may require only SL-1 and the core promoter element. However, higher transcription levels are mediated by additional interactions of rUBF, and possibly SL-1, bound to distal promoter elements.


A review on the occurrence of micropollutants in the aquatic environment and their fate and removal during wastewater treatment.
Micropollutants are emerging as a new challenge to the scientific community. This review provides a summary of the recent occurrence of micropollutants in the aquatic environment including sewage, surface water, groundwater and drinking water. The discharge of treated effluent from WWTPs is a major pathway for the introduction of micropollutants to surface water. WWTPs act as primary barriers against the spread of micropollutants. WWTP removal efficiency of the selected micropollutants in 14 countries/regions depicts compound-specific variation in removal, ranging from 12.5 to 100%. Advanced treatment processes, such as activated carbon adsorption, advanced oxidation processes, nanofiltration, reverse osmosis, and membrane bioreactors can achieve higher and more consistent micropollutant removal. However, regardless of what technology is employed, the removal of micropollutants depends on physico-chemical properties of micropollutants and treatment conditions. The evaluation of micropollutant removal from municipal wastewater should cover a series of aspects from sources to end uses. After the release of micropollutants, a better understanding and modeling of their fate in surface water is essential for effectively predicting their impacts on the receiving environment.


Evaluation of aerial photography for predicting trends in structural attributes of Australian woodland including comparison with ground-based monitoring data.
The accurate assessment of trends in the woody structure of savannas has important implications for greenhouse accounting and land-use industries such as pastoralism. Two recent assessments of live woody biomass change from north-east Australian eucalypt woodland between the 1980s and 1990s present divergent results. The first estimate is derived from a network of permanent monitoring plots and the second from woody cover assessments from aerial photography. The differences between the studies are reviewed and include sample density, spatial scale and design. Further analyses targeting potential biases in the indirect aerial photography technique are conducted including a comparison of basal area estimates derived from 28 permanent monitoring sites with basal area estimates derived by the aerial photography technique. It is concluded that the effect of photo-scale; or the failure to include appropriate back-transformation of biomass estimates in the aerial photography study are not likely to have contributed significantly to the discrepancy. However, temporal changes in the structure of woodlands, for example, woodlands maturing from many smaller trees to fewer larger trees or seasonal changes, which affect the relationship between cover and basal area could impact on the detection of trends using the aerial photography technique. It is also possible that issues concerning photo-quality may bias assessments through time, and that the limited sample of the permanent monitoring network may inadequately represent change at regional scales.


Bees can be trained to identify SARS-CoV-2 infected samples.
The COVID-19 pandemic has illustrated the need for the development of fast and reliable testing methods for novel, zoonotic, viral diseases in both humans and animals. Pathologies lead to detectable changes in the volatile organic compound (VOC) profile of animals, which can be monitored, thus allowing the development of a rapid VOC-based test. In the current study, we successfully trained honeybees (Apis mellifera) to identify SARS-CoV-2 infected minks (Neovison vison) thanks to Pavlovian conditioning protocols. The bees can be quickly conditioned to respond specifically to infected mink's odours and could therefore be part of a wider SARS-CoV-2 diagnostic system. We tested two different training protocols to evaluate their performance in terms of learning rate, accuracy and memory retention. We designed a non-invasive rapid test in which multiple bees are tested in parallel on the same samples. This provided reliable results regarding a subject's health status. Using the data from the training experiments, we simulated a diagnostic evaluation trial to predict the potential efficacy of our diagnostic test, which yielded a diagnostic sensitivity of 92% and specificity of 86%. We suggest that a honeybee-based diagnostics can offer a reliable and rapid test that provides a readily available, low-input addition to the currently available testing methods. A honeybee-based diagnostic test might be particularly relevant for remote and developing communities that lack the resources and infrastructure required for mainstream testing methods.


Pyruvate ferredoxin oxidoreductase from the hyperthermophilic archaeon, Pyrococcus furiosus, functions as a CoA-dependent pyruvate decarboxylase.
Pyruvate ferredoxin oxidoreductase (POR) has been previously purified from the hyperthermophilic archaeon, Pyrococcus furiosus, an organism that grows optimally at 100 degrees C by fermenting carbohydrates and peptides. The enzyme contains thiamine pyrophosphate and catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA and CO2 and reduces P. furiosus ferredoxin. Here we show that this enzyme also catalyzes the formation of acetaldehyde from pyruvate in a CoA-dependent reaction. Desulfocoenzyme A substituted for CoA showing that the cofactor plays a structural rather than a catalytic role. Ferredoxin was not necessary for the pyruvate decarboxylase activity of POR, nor did it inhibit acetaldehyde production. The apparent Km values for CoA and pyruvate were 0.11 mM and 1.1 mM, respectively, and the optimal temperature for acetaldehyde formation was above 90 degrees C. These data are comparable to those previously determined for the pyruvate oxidation reaction of POR. At 80 degrees C (pH 8.0), the apparent Vm value for pyruvate decarboxylation was about 40% of the apparent Vm value for pyruvate oxidation rate (using P. furiosus ferredoxin as the electron acceptor). Tentative catalytic mechanisms for these two reactions are presented. In addition to POR, three other 2-keto acid ferredoxin oxidoreductases are involved in peptide fermentation by hyperthermophilic archaea. It is proposed that the various aldehydes produced by these oxidoreductases in vivo are used by two aldehyde-utilizing enzymes, alcohol dehydrogenase and aldehyde ferredoxin oxidoreductase, the physiological roles of which were previously unknown.


Nanoscale chirality in metal and semiconductor nanoparticles.
The field of chirality has recently seen a rejuvenation due to the observation of chirality in inorganic nanomaterials. The advancements in understanding the origin of nanoscale chirality and the potential applications of chiroptical nanomaterials in the areas of optics, catalysis and biosensing, among others, have opened up new avenues toward new concepts and design of novel materials. In this article, we review the concept of nanoscale chirality in metal nanoclusters and semiconductor quantum dots, then focus on recent experimental and theoretical advances in chiral metal nanoparticles and plasmonic chirality. Selected examples of potential applications and an outlook on the research on chiral nanomaterials are additionally provided.


Social support as a health resource in Germany.
Social support is a psychosocial resource that results from social ties and networks. It has a significant impact on health and can improve mental well-being, reduce stress and mitigate the impact of unfavourable living conditions. The GEDA 2014/2015-EHIS survey undertaken by the Robert Koch Institute (RKI) is used to examine the extent and distribution of perceived social support among the adult population in Germany (n=23,617). The results show that both women and men largely feel supported by the people they are close to and their neighbours. However, perceived social support is not distributed equally across the population: the elderly, people with low levels of education and the unemployed report relatively frequently that they receive low levels of social support. As such, the sections of the population that are more frequently affected by health problems are also less likely to be able to rely on social support.


Submicrometer digital in-line holographic microscopy at 32 nm with high-order harmonics.
Soft-x-ray digital in-line microscopic holography is achieved using a fully coherent high-order harmonic source emitting at 32 nm. Combination of commercial-grade soft-x-ray optics and a back-illuminated CCD detector allows a compact and versatile holographic setup. Different experimental geometries have been tested by imaging calibrated 50 nm tips and 1 microm wires. Spatial resolution of 800 nm is measured with magnifications ranging from 30 to 110 and a numerical aperture around 0.01. Finally, the potentiality of three-dimensional numerical reconstruction from a single hologram acquisition is shown experimentally.


Effects of Pueraria mirifica and miroestrol on the antioxidation-related enzymes in ovariectomized mice.
The influences of Pueraria candollei var. mirifica (PM), a Thai medicinal plant with long tradition of medicinal consumption among menopausal women for rejuvenation and estrogen hormone replacement, on oxidative status in ovariectomized (OVX) mice were determined. The crude extract of PM and its active phytoestrogen, miroestrol (MR), were given to OVX mice. The effect of them on antioxidation enzymes and glutathione (GSH) levels in livers and uteri were examined in OVX mice and compared with the synthetic estradiol hormone. Ovariectomy significantly decreased total GSH content, reduced GSH content, and the ratio of GSH to oxidized glutathione (GSSG) in both the livers and the uteri of mice. Moreover, an ovariectomy reduced the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). The crude extract of PM as well as MR significantly increased levels of GSH, levels of reduced GSH, and the ratio of GSH/GSSG in both the livers and the uteri, while estradiol did not. In addition, the potential of PM and MR to return the activities of GPx, SOD, and CAT to normal levels was noted. These observations support using PM and MR as promising alternative medicine candidates for hormone replacement therapy of estradiol because of their ability to improve GSH levels and the activities of antioxidative enzymes, especially in OVX mice.


The air-liquid flow in a microfluidic airway tree.
Microfluidic techniques are employed to investigate air-liquid flows in the lung. A network of microchannels with five generations is made and used as a simplified model of a section of the pulmonary airway tree. Liquid plugs are injected into the network and pushed by a flow of air; they divide at every bifurcation until they reach the exits of the network. A resistance, associated with the presence of one plug in a given generation, is defined to establish a linear relation between the driving pressure and the total flow rate in the network. Based on this resistance, good predictions are obtained for the flow of two successive plugs in different generations. The total flow rate of a two-plug flow is found to depend not only on the driving pressure and lengths of the plugs, but also the initial distance between them. Furthermore, long range interactions between daughters of a dividing plug are observed and discussed, particularly when the plugs are flowing through the bifurcations. These interactions lead to different flow patterns for different forcing conditions: the flow develops symmetrically when subjected to constant pressure or high flow rate forcing, while a low flow rate driving yields an asymmetric flow.


Effect of prepolymerized composite megafiller on the marginal adaptation of composite restorations in cavities with different C-factors: an SEM study.
To evaluate the effect of prepolymerized custom-made composite megafiller and configuration factors (C-factor) on marginal adaptation of resin composite restorations. Forty extracted human mandibular molars were divided into four experimental groups consisting of 10 samples each. In groups I and III, class V (configuration factor 5) and in groups II and IV, class II box-shaped cavities (configuration factor 2) were prepared. Groups I and II were restored with a nanofilled composite (Filtek™ Z350 3M ESPE, St Paul, MN, USA) placed in horizontal increments. In groups III and IV, preformed composite megafiller was placed and cavities were restored with nanofilled composite Z-350. After curing, the samples were finished and prepared for examination under low vacuum scanning electron microscope. The data were analyzed with one-way analysis of variance. The significance between the individual groups was calculated by Post hoc test using the Holm-Sidak method ( P≤0.05). The marginal gap values in groups III and IV were significantly lower than in groups I and II, respectively ( P≤0.05). Minimum gap values were seen in group IV. Use of prepolymerized composite megafiller and a lower C-factor decreased the marginal gaps between the tooth and composite restorations.


The impact of exposure to antidepressant medications during pregnancy on neonatal outcomes: a review of retrospective database cohort studies.
Concerns with prescription antidepressant use in pregnant women have instigated the examination of potential associations between fetal exposure to antidepressant medication and outcomes including preterm delivery, congenital malformations, perinatal and post-natal adverse events, persistent pulmonary hypertension, and mortality. The retrospective cohort model is an often utilized study design. The objective of this review is to evaluate the literature on antidepressant use in pregnancy conducted as retrospective cohorts in national/regional medical, or claims databases that assess neonatal and infant outcomes for agreement between studies, ultimately providing a methodological and outcomes summary for future scientific endeavors. PubMed was searched for literature relating to antidepressant use and infant outcomes from the earliest available date through July 15, 2016. Studies with a retrospective cohort design and conducted in national/regional medical or claims databases were included. Searched outcomes included preterm delivery, congenital malformations, low birth weight, small for gestational age, persistent pulmonary hypertension of the newborn, and other select adverse events comprising low Apgar score (5 min), convulsions/seizures, respiratory distress/problems, fetal mortality, and infant mortality. Of the 784 studies identified, 36 retrospective cohort studies met eligibility criteria. An increase in preterm delivery and respiratory distress/problems and no increase in congenital malformation or fetal and infant death were associated with prenatal use of prescription antidepressants by majority consensus (at least 2/3 [67%] of studies). While consensus indicates that perinatal prescription antidepressant use has consequences for the fetus and infant, there are notable inconsistencies in the literature. More investigations that address prenatal exposure to depression and other important covariates are needed.


The main sources of intersubject variability in neuronal activation for reading aloud.
The aim of this study was to find the most prominent source of intersubject variability in neuronal activation for reading familiar words aloud. To this end, we collected functional imaging data from a large sample of subjects (n = 76) with different demographic characteristics such as handedness, sex, and age, while reading. The subject-by-subject error variance was estimated from a one-sample t test (on all 76 subjects) and was reduced to a lower dimension using principal components decomposition. A Gaussian Mixture Model was then applied to dissociate different subgroups of subjects that explained the main sources of variability in the data. This resulted in the identification of four different subject groups. The comparison of these subgroups to the subjects' demographic details showed that age had a significant effect on the subject partitioning. In addition, a region-by-group dissociation in the dorsal and the ventral inferior frontal cortex was consistent with previously reported dissociations in semantic and nonsemantic reading strategies. In contrast to these significant findings, the groupings did not differentiate subjects on the basis of either sex or handedness, nor did they segregate the subjects with right- versus left-lateralized reading activation. We therefore conclude that, of the variables tested, age and reading strategy were the most prominent source of variability in activation for reading familiar words aloud.


The Heterosexual Script on Tween, Teen, and Young-Adult Television Programs: A Content Analytic Update and Extension.
In a well-cited 2007 paper in Journal of Sex Research, Kim and colleagues proposed and documented a heterosexual script on primetime television. In the present study, we provide a 15-year update on the portrayal of the heterosexual script, and we further examine how it relates to three contextual variables: target age of the audience, age of the characters, and relational context of the script. Drawing from a 2016 sample of television programs that featured tween, teen, or young-adult characters, we documented three complementary sexual scripts: the sexual double standard (sexuality is equated with masculinity, women's virtue is tied to their sexuality), commitment (men avoid commitment, women seek it), and homophobia (men must avoid homosexuality, female homosexuality is voyeuristically appealing to men). Like the Kim et al. study, the dominant heterosexual script was sex as masculinity; this script was equally represented in tween, teen, and young-adult shows. The second most common script was that men prioritize sex over commitment, followed by the notion that women's virtue is tied to their sexuality. The commitment scripts were most often invoked by young-adult and adult characters, while the sexual double standard scripts were more pronounced in hookups than in committed relationships.


The density of anthropogenic features explains seasonal and behaviour-based functional responses in selection of linear features by a social predator.
Anthropogenic linear features facilitate access and travel efficiency for predators, and can influence predator distribution and encounter rates with prey. We used GPS collar data from eight wolf packs and characteristics of seismic lines to investigate whether ease-of-travel or access to areas presumed to be preferred by prey best explained seasonal selection patterns of wolves near seismic lines, and whether the density of anthropogenic features led to functional responses in habitat selection. At a broad scale, wolves showed evidence of habitat-driven functional responses by exhibiting greater selection for areas near low-vegetation height seismic lines in areas with low densities of anthropogenic features. We highlight the importance of considering landscape heterogeneity and habitat characteristics, and the functional response in habitat selection when investigating seasonal behaviour-based selection patterns. Our results support behaviour in line with search for primary prey during summer and fall, and ease-of-travel during spring, while patterns of selection during winter aligned best with ease-of-travel for the less-industrialized foothills landscape, and with search for primary prey in the more-industrialized boreal landscape. These results highlight that time-sensitive restoration actions on anthropogenic features can affect the probability of overlap between predators and threatened prey within different landscapes.


Chronic liver inflammation and hepatocellular carcinoma: persistence matters.
Inflammatory responses in the liver--a central constituent of hepatic wound healing--can be self-limited or persistent depending on the aetiology, liver health state, concentration of toxins or pathogens, and the time frame of exposure to toxins or infection. In case the immune system eradicates a pathogen or in case toxin-exposure is transient, acute hepatitis resolves and the affected liver tissue regenerates ad integrum. However, in many cases liver damage remains chronic. Irrespective of the aetiology, chronic liver damage drives chronic hepatitis and hepatocyte death as well as compensatory proliferation, reflecting liver regeneration. Over time this potentially promotes further hepatic damage, fibrosis, cirrhosis and liver cancer. Here, we review the current knowledge on how chronic liver injury and inflammation is triggered and maintained, and how inflammation is linked to liver cancer. We also discuss the most frequently used animal models for damage or inflammation induced liver cancer and their suitability for conducting clinically relevant research.


Cerebrovascular effects of selective serotonin reuptake inhibitors: a systematic review.
An understanding of cerebro-vascular effects of selective serotonin reuptake inhibitors (SSRIs) is essential, since SSRIs are a widely used antidepressant, serotonin is a vasoactive and thrombostatic amine, and there is a bidirectional relationship between depression and cerebrovascular disease. A MEDLINE search was performed to identify published reports over the period of 1966 through 2003, using the terms SSRIs and antidepressants matched with the terms platelets, coagulation, anticoagulation, bleeding, fibrinolysis, thrombosis, embolism, cerebral ischemia, stroke, cerebrovascular accident, acute and chronic cerebrovascular disease, intracranial hemorrhage, cerebrovascular disorder, and cerebral circulation. Adverse event reports collected from the World Health Organization (WHO), manufacturers, and the Physicians' Desk Reference (PDR) were also examined. Two case-control studies failed to show an association between SSRI use and intracranial hemorrhage, and of these, 1 showed no association with ischemic stroke. Sixteen studies of SSRI treatment in poststroke patients found no significant cerebrovascular adverse reactions. The WHO data have shown several hundred cases of SSRI-associated cerebrovascular disease, but definitive causal relationships remain undetermined. Four cases of vasoconstrictive stroke related to drug interactions between SSRIs and other serotonergic drugs have been reported. PDR and manufacturer reference sources categorized cerebrovascular reaction as an infrequent or rare adverse event related to SSRI use. Available evidence suggests that SSRI treatment has a very low rate of cerebrovascular adverse reaction. Pharmacovigilance is required in the use of SSRIs in high-risk populations for bleeding and vasoconstrictive stroke. More research is warranted to examine the variability of pharmacologic and genetic factors, depressive illness, and stroke on the antiplatelet and vasospastic effects of SSRIs and their significance to cerebrovascular protection or adverse reactions.


Cohort Profile: The Mexican American Mano a Mano Cohort.
Hispanic Americans comprise the largest and fastest-growing ethnic minority in the USA. In Houston, Texas, 44% of the population is of Hispanic descent, with the majority being Mexican Americans (78%). This population is under-represented in health-related research despite their high prevalence of obesity and diabetes, which may predispose them to cancer and other chronic conditions. Recognizing the need for a greater research effort into the health risks of Hispanic Americans, the population-based Mexican American (Mano a Mano) Cohort study was launched in 2001. This is an open cohort with enrolment ongoing to 2019, and as of 30 June 2014, 23 606 adult participants from over 16 600 households were enrolled. Bilingual interviewers elicit information in person on demographics, acculturation, lifestyle, occupation, medical history, family cancer history, self-reported and measured height and weight, and other exposures. Urine, blood and saliva samples have been collected at baseline from 43%, 56% and 63% of participants, respectively. DNA samples are available for about 90% of participants. Incident cancers and other chronic diseases are ascertained through annual telephone re-contact and linkage to the Texas Cancer Registry and/or medical records. Molecular data such as genetic ancestry markers, blood telomere length and HbA1c, a marker of impaired glucose tolerance, are available for a substantial proportion of the participants. Data access is provided on request [email@example.com]. For further information please visit [www.mano-mano.us].


A molecular phylogeny of the Indo-West Pacific species of Haloa sensu lato gastropods (Cephalaspidea: Haminoeidae): Tethyan vicariance, generic diversity, and ecological specialization.
The cephalaspidean gastropod genus Haminoea has been considered a worldwide radiation with species living in intertidal and shallow areas with algae, seagrass sandy-mud, mangroves, and coral reefs. Recently this monophyletic status was questioned and it was suggested that Haminoea proper only included Atlantic plus eastern Pacific species, whereas the Indo-West Pacific species were a separate radiation belonging to the genus Haloa. In this work we used an extended dataset of Haminoea sensu lato including to our best knowledge representatives of all Indo-West Pacific species, plus a large representation of Atlantic and eastern Pacific species. Bayesian and maximum likelihood molecular phylogenetic analyses using three mitochondrial (COI, 12S rRNA, 16S rRNA) and two nuclear genes (28S rRNA and Histone-3) were employed to study relationships and diversification including also the closely related genus Smaragdinella. Our results support a monophyletic Atlantic + eastern Pacific Haminoea clade and a monophyletic Indo-West Pacific radiation with five genera all defined by unique morphological characters and ecological requirements, namely Haloa proper with tropical and sub-tropical species spread across the Indo-West Pacific, Lamprohaminoea including only colourful species of tropical and sub-tropical affinity, Bakawan gen. nov. with species associated with mangrove habitats across the tropical eastern Indian Ocean and western Pacific, Papawera gen. nov. restricted to temperate waters of Australasia, and Smaragdinella the only cephalaspidean genus inhabiting intertidal hard substrates across sub-tropical and tropical regions of the Indo-West Pacific. This result suggests the role of the closure of the Tethys seaway structuring the phylogeny of worldwide "Haminoea" snails and of ecology driving the phylogenetic structure of the Indo-West Pacific radiation.


Role of the RNA/DNA kinase Grc3 in transcription termination by RNA polymerase I.
Transcription termination by RNA polymerase I in Saccharomyces cerevisiae is mediated by a 'torpedo' mechanism: co-transcriptional RNA cleavage by Rnt1 at the ribosomal DNA 3'-region generates a 5'-end that is recognized by the 5'-3' exonuclease Rat1; this degrades the downstream transcript and eventually causes termination. In this study, we identify Grc3 as a new factor involved in this process. We demonstrate that GRC3, an essential gene of previously unknown function, encodes a polynucleotide kinase that is required for efficient termination by RNA polymerase I. We propose that it controls the phosphorylation status of the downstream Rnt1 cleavage product and thereby regulates its accessibility to the torpedo Rat1.


A new hynobiid-like salamander (Amphibia, Urodela) from Inner Mongolia, China, provides a rare case study of developmental features in an Early Cretaceous fossil urodele.
A new fossil salamander, Nuominerpeton aquilonaris (gen. et sp. nov.), is named and described based on specimens from the Lower Cretaceous Guanghua Formation of Inner Mongolia, China. The new discovery documents a far northern occurrence of Early Cretaceous salamanders in China, extending the geographic distribution for the Mesozoic fossil record of the group from the Jehol area (40th-45th parallel north) to near the 49th parallel north. The new salamander is characterized by having the orbitosphenoid semicircular in shape; coracoid plate of the scapulocoracoid greatly expanded with a convex ventral and posterior border; ossification of two centralia in carpus and tarsus; and first digit being about half the length of the second digit in both manus and pes. The new salamander appears to be closely related to hynobiids, although this inferred relationship awaits confirmation by research in progress by us on a morphological and molecular combined analysis of cryptobranchoid relationships. Comparison of adult with larval and postmetamorphic juvenile specimens provides insights into developmental patterns of cranial and postcranial skeletons in this fossil species, especially resorption of the palatine and anterior portions of the palatopterygoid in the palate and the coronoid in the mandible during metamorphosis, and postmetamorphic ossification of the mesopodium in both manus and pes. Thus, this study provides a rare case study of developmental features in a Mesozoic salamander.


A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis.
Oral fingolimod, a sphingosine-1-phosphate-receptor modulator that prevents the egress of lymphocytes from lymph nodes, significantly improved relapse rates and end points measured on magnetic resonance imaging (MRI), as compared with either placebo or intramuscular interferon beta-1a, in phase 2 and 3 studies of multiple sclerosis. In our 24-month, double-blind, randomized study, we enrolled patients who had relapsing-remitting multiple sclerosis, were 18 to 55 years of age, had a score of 0 to 5.5 on the Expanded Disability Status Scale (which ranges from 0 to 10, with higher scores indicating greater disability), and had had one or more relapses in the previous year or two or more in the previous 2 years. Patients received oral fingolimod at a dose of 0.5 mg or 1.25 mg daily or placebo. End points included the annualized relapse rate (the primary end point) and the time to disability progression (a secondary end point). A total of 1033 of the 1272 patients (81.2%) completed the study. The annualized relapse rate was 0.18 with 0.5 mg of fingolimod, 0.16 with 1.25 mg of fingolimod, and 0.40 with placebo (P<0.001 for either dose vs. placebo). Fingolimod at doses of 0.5 mg and 1.25 mg significantly reduced the risk of disability progression over the 24-month period (hazard ratio, 0.70 and 0.68, respectively; P=0.02 vs. placebo, for both comparisons). The cumulative probability of disability progression (confirmed after 3 months) was 17.7% with 0.5 mg of fingolimod, 16.6% with 1.25 mg of fingolimod, and 24.1% with placebo. Both fingolimod doses were superior to placebo with regard to MRI-related measures (number of new or enlarged lesions on T(2)-weighted images, gadolinium-enhancing lesions, and brain-volume loss; P<0.001 for all comparisons at 24 months). Causes of study discontinuation and adverse events related to fingolimod included bradycardia and atrioventricular conduction block at the time of fingolimod initiation, macular edema, elevated liver-enzyme levels, and mild hypertension. As compared with placebo, both doses of oral fingolimod improved the relapse rate, the risk of disability progression, and end points on MRI. These benefits will need to be weighed against possible long-term risks. (ClinicalTrials.gov number, NCT00289978.)


A modular attractor associative memory with patchy connectivity and weight pruning.
An important research topic in neuroscience is the study of mechanisms underlying memory and the estimation of the information capacity of the biological system. In this report we investigate the performance of a modular attractor network with recurrent connections similar to the cortical long-range connections extending in the horizontal direction. We considered a single learning rule, the BCPNN, which implements a kind of Hebbian learning and we trained the network with sparse random patterns. The storage capacity was measured experimentally for networks of size between 500 and 46 K units with a constant activity level, gradually diluting the connectivity. We show that the storage capacity of the modular network with patchy connectivity is comparable with the theoretical values estimated for simple associative memories and furthermore we introduce a new technique to prune the connectivity, which enhances the storage capacity up to the asymptotic value.


Search for anomalous production of multilepton events in pp collisions at sqrt s=1.96 TeV.
We report a search for the anomalous production of events with multiple charged leptons in pp[over] collisions at sqrt[s]=1.96 TeV using a data sample corresponding to an integrated luminosity of 346 pb(-1) collected by the CDF II detector at the Fermilab Tevatron. The search is divided into three-lepton and four-or-more-lepton data samples. We observe six events in the three-lepton sample and zero events in the > or =4-lepton sample. Both numbers of events are consistent with standard model background expectations. Within the framework of an R-parity-violating supergravity model, the results are interpreted as mass limits on the lightest neutralino (chi[over](1)(0)) and chargino (chi[over](1+/-) particles. For one particular choice of model parameters, the limits are M(chi[over](1)(0)>110 GeV/c2 and M(chi[over](1+/-)>203 GeV/c2 at 95% confidence level; the variation of these mass limits with model parameters is presented.


Spectral density-based and measure-preserving ABC for partially observed diffusion processes. An illustration on Hamiltonian SDEs.
Approximate Bayesian computation (ABC) has become one of the major tools of likelihood-free statistical inference in complex mathematical models. Simultaneously, stochastic differential equations (SDEs) have developed to an established tool for modelling time-dependent, real-world phenomena with underlying random effects. When applying ABC to stochastic models, two major difficulties arise: First, the derivation of effective summary statistics and proper distances is particularly challenging, since simulations from the stochastic process under the same parameter configuration result in different trajectories. Second, exact simulation schemes to generate trajectories from the stochastic model are rarely available, requiring the derivation of suitable numerical methods for the synthetic data generation. To obtain summaries that are less sensitive to the intrinsic stochasticity of the model, we propose to build up the statistical method (e.g. the choice of the summary statistics) on the underlying structural properties of the model. Here, we focus on the existence of an invariant measure and we map the data to their estimated invariant density and invariant spectral density. Then, to ensure that these model properties are kept in the synthetic data generation, we adopt measure-preserving numerical splitting schemes. The derived property-based and measure-preserving ABC method is illustrated on the broad class of partially observed Hamiltonian type SDEs, both with simulated data and with real electroencephalography data. The derived summaries are particularly robust to the model simulation, and this fact, combined with the proposed reliable numerical scheme, yields accurate ABC inference. In contrast, the inference returned using standard numerical methods (Euler-Maruyama discretisation) fails. The proposed ingredients can be incorporated into any type of ABC algorithm and directly applied to all SDEs that are characterised by an invariant distribution and for which a measure-preserving numerical method can be derived.


Zidovudine plus didanosine in primary HIV-1 infection.
Viraemia levels in the months following primary HIV-1 infection (PHI) predict the subsequent course of the infection. Inhibition of viral replication in PHI patients might improve their clinical prognosis. In this study, we evaluated the antiviral efficacy of the association of two reverse transcriptase inhibitors--zidovudine at 250 mg twice daily and didanosine at 200 mg twice daily--in 12 patients treated for at least 6 months (median 10 months, range 6-15 months). We compared values for viraemia, proviral DNA and CD4:CD8 ratios in these patients with two historical control groups consisting of 16 untreated patients and 15 patients on zidovudine therapy. Significantly lower viraemia was observed between 3 and 12 months in patients on zidovudine-didanosine therapy. Viraemia levels lower than 200 HIV-1 RNA copies/ml were observed in 3/12 patients on zidovudine-didanosine therapy after 3 months, in 8/12 after 6 months and in 3/5 after 12 months. Only one of the 31 historical control patients had undetectable viraemia. For proviral DNA, smaller differences between groups were observed, although with time proviral DNA became undetectable (< 1 copy/7.5 x 10(5) lymphocytes) in four patients from the zidovudine-didanosine group versus one in the control groups. Finally, the CD4:CD8 ratio was significantly higher in the zidovudine-didanosine group and none of the patients in this group developed HIV-1-associated clinical complications. These data suggest a higher efficacy of combined therapy compared with zidovudine monotherapy in PHI patients and indicate that control of viraemia for at least 1 year is achievable in PHI patients.


Petawatt laser absorption bounded.
The interaction of petawatt (10(15) W) lasers with solid matter forms the basis for advanced scientific applications such as table-top particle accelerators, ultrafast imaging systems and laser fusion. Key metrics for these applications relate to absorption, yet conditions in this regime are so nonlinear that it is often impossible to know the fraction of absorbed light f, and even the range of f is unknown. Here using a relativistic Rankine-Hugoniot-like analysis, we show for the first time that f exhibits a theoretical maximum and minimum. These bounds constrain nonlinear absorption mechanisms across the petawatt regime, forbidding high absorption values at low laser power and low absorption values at high laser power. For applications needing to circumvent the absorption bounds, these results will accelerate a shift from solid targets, towards structured and multilayer targets, and lead the development of new materials.


Effect of one month duration ketogenic and non-ketogenic high fat diets on mouse brain bioenergetic infrastructure.
Diet composition may affect energy metabolism in a tissue-specific manner. Using C57Bl/6J mice, we tested the effect of ketosis-inducing and non-inducing high fat diets on genes relevant to brain bioenergetic infrastructures, and on proteins that constitute and regulate that infrastructure. At the end of a one-month study period the two high fat diets appeared to differentially affect peripheral insulin signaling, but brain insulin signaling was not obviously altered. Some bioenergetic infrastructure parameters were similarly impacted by both high fat diets, while other parameters were only impacted by the ketogenic diet. For both diets, mRNA levels for CREB, PGC1α, and NRF2 increased while NRF1, TFAM, and COX4I1 mRNA levels decreased. PGC1β mRNA increased and TNFα mRNA decreased only with the ketogenic diet. Brain mtDNA levels fell in both the ketogenic and non-ketogenic high fat diet groups, although TOMM20 and COX4I1 protein levels were maintained, and mRNA and protein levels of the mtDNA-encoded COX2 subunit were also preserved. Overall, the pattern of changes observed in mice fed ketogenic and non-ketogenic high fat diets over a one month time period suggests these interventions enhance some aspects of the brain's aerobic infrastructure, and may enhance mtDNA transcription efficiency. Further studies to determine which diet effects are due to changes in brain ketone body levels, fatty acid levels, glucose levels, altered brain insulin signaling, or other factors such as adipose tissue-associated hormones are indicated.


Effects of cardiovascular angiotensin II type 1 receptor blockade on nitric oxide synthase inhibition in patients with insulin resistance syndrome.
There is evidence that in the early stages of type II diabetes, the cardiovascular system compensates by increasing endothelial nitric oxide synthase (e-NOS) expression. In the advanced stages of disease, e-NOS is diminished, and is associated with endothelial dysfunction. Angiotensin II, acting via the angiotensin II type 1 (AT(1)) receptor, is central to the development of endothelial dysfunction. The effect of AT(1) receptor blockade on NOS expression and activity in humans with early insulin resistance syndrome (INSR) has not been previously investigated. Eight subjects with INSR participated in a randomized, double-blind, placebo-controlled, crossover study. Subjects were randomized to receive telmisartan or placebo (1 month of each) in a two-period crossover study with a 1-week washout period in between. The arterial stiffness and haemodynamic response to intravenous L-nitro-monomethyl arginine (L-NMMA 3mg/kg) was assessed at baseline and at the end of each treatment phase. SI (Stiffness index, a measure of large artery stiffness) and RI (Reflection index, small- to medium-sized arterial stiffness) were measured using digital photoplethysmography. Haemodynamic parameters [Heart rate (HR), Systolic blood pressure (SBP), Diastolic BP (DBP) and systemic vascular resistance index (SVRI)] were measured non-invasively using trans-thoracic bioimpedance. Telmisartan significantly reduced baseline SI, SBP, DBP and SVRI. Infusion of L-NMMA produced a significant increase in RI and a significant reduction in HR during placebo therapy. Telmisartan therapy attenuated these responses. Telmisartan therapy reduced NOS activity and/or expression in these subjects, possibly because of improved vascular function arising from AT(1) receptor blockade.


Current and emerging screening methods to identify post-head-emergence frost adaptation in wheat and barley.
Cereal crops can suffer substantial damage if frosts occur at heading. Identification of post-head-emergence frost (PHEF) resistance in cereals poses a number of unique and difficult challenges. Many decades of research have failed to identify genotypes with PHEF resistance that could offer economically significant benefit to growers. Research and breeding gains have been limited by the available screening systems. Using traditional frost screening systems, genotypes that escape frost injury in trials due to spatial temperature differences and/or small differences in phenology can be misidentified as resistant. We believe that by improving techniques to minimize frost escapes, such 'false-positive' results can be confidently identified and eliminated. Artificial freezing chambers or manipulated natural frost treatments offer many potential advantages but are not yet at the stage where they can be reliably used for frost screening in breeding programmes. Here we describe the development of a novel photoperiod gradient method (PGM) that facilitates screening of genotypes of different phenology under natural field frosts at matched developmental stages. By identifying frost escapes and increasing the efficiency of field screening, the PGM ensures that research effort can be focused on finding genotypes with improved PHEF resistance. To maximize the likelihood of identifying PHEF resistance, we propose that the PGM form part of an integrated strategy to (i) source germplasm;(ii) facilitate high throughput screening; and (iii) permit detailed validation. PGM may also be useful in other studies where either a range of developmental stages and/or synchronized development are desired.


Salmonella colonisation of laying hens following vaccination with killed and live attenuated commercial Salmonella vaccines.
The aim of this study was to determine the efficacy of a killed Salmonella vaccine and three live vaccines in preventing caecal colonisation of Hy-line Brown pullets by Salmonella Enteritidis PT 4. The lowest number of Salmonella-positive birds following the largest challenge (10(8) cfu) was recorded for live vaccine 1. However, birds treated with the killed vaccine had a significantly lower number of salmonellae in their caeca compared with both the control group and the other vaccine groups (P<0.05).