Effects of curcumin on TTX-R sodium currents of dorsal root ganglion neurons in type 2 diabetic rats with diabetic neuropathic pain.
Type 2 diabetic mellitus (T2DM) has reached pandemic status and shows no signs of abatement. Diabetic neuropathic pain (DNP) is generally considered to be one of the most common complications of T2DM, which is also recognized as one of the most difficult types of pain to treat. As one kind of peripheral neuropathic pain, DNP manifests typical chronic neuralgia symptoms, including hyperalgesia, allodynia, autotomy, and so on. The injured dorsal root ganglion (DRG) is considered as the first stage of the sensory pathway impairment, whose neurons display increased frequency of action potential generation and increased spontaneous activities. These are mainly due to the changed properties of voltage-gated sodium channels (VGSCs) and the increased sodium currents, especially TTX-R sodium currents. Curcumin, one of the most important phytochemicals from turmeric, has been demonstrated to effectively prevent and/or ameliorate diabetic mellitus and its complications including DNP. The present study demonstrates that the TTX-R sodium currents of small-sized DRG neurons isolated from DNP rats are significantly increased. Such abnormality can be efficaciously ameliorated by curcumin.


Correlation of lung collapse and gas exchange - a computer tomographic study in sheep and pigs with atelectasis in otherwise normal lungs.
Atelectasis can provoke pulmonary and non-pulmonary complications after general anaesthesia. Unfortunately, there is no instrument to estimate atelectasis and prompt changes of mechanical ventilation during general anaesthesia. Although arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt have both been suggested to correlate with atelectasis, studies yielded inconsistent results. Therefore, we investigated these correlations. Shunt, PaO2 and atelectasis were measured in 11 sheep and 23 pigs with otherwise normal lungs. In pigs, contrasting measurements were available 12 hours after induction of acute respiratory distress syndrome (ARDS). Atelectasis was calculated by computed tomography relative to total lung mass (Mtotal). We logarithmically transformed PaO2 (lnPaO2) to linearize its relationships with shunt and atelectasis. Data are given as median (interquartile range). Mtotal was 768 (715-884) g in sheep and 543 (503-583) g in pigs. Atelectasis was 26 (16-47) % in sheep and 18 (13-23) % in pigs. PaO2 (FiO2 = 1.0) was 242 (106-414) mmHg in sheep and 480 (437-514) mmHg in pigs. Shunt was 39 (29-51) % in sheep and 15 (11-20) % in pigs. Atelectasis correlated closely with lnPaO2 (R2 = 0.78) and shunt (R2 = 0.79) in sheep (P-values<0.0001). The correlation of atelectasis with lnPaO2 (R2 = 0.63) and shunt (R2 = 0.34) was weaker in pigs, but R2 increased to 0.71 for lnPaO2 and 0.72 for shunt 12 hours after induction of ARDS. In both, sheep and pigs, changes in atelectasis correlated strongly with corresponding changes in lnPaO2 and shunt. In lung-healthy sheep, atelectasis correlates closely with lnPaO2 and shunt, when blood gases are measured during ventilation with pure oxygen. In lung-healthy pigs, these correlations were significantly weaker, likely because pigs have stronger hypoxic pulmonary vasoconstriction (HPV) than sheep and humans. Nevertheless, correlations improved also in pigs after blunting of HPV during ARDS. In humans, the observed relationships may aid in assessing anaesthesia-related atelectasis.


First Report of Limonomyces roseipellis Causing Pink Patch on Bermudagrass in South China.
Hybrid bermudagrass (Cynodon dactylon (L.) Pers. × C. transvaalensis Burtt-Davy) is widely used on golf course putting greens in southern China. In September 2011, circular pink patches ranging from 10 to 20 cm in diameter were observed on putting greens established with cv. 'Tifgreen' on a golf course in Haikou, Hainan Province. There were approximately 50 pink patches on a putting green. Infected leaves were covered with pink, gelatinous fungal mycelium, which resulted in the production of chlorotic lesions. Lesions expanded, became water-soaked, and leaves died basipetally. A pink fungus, characterized by the presence of clamp connections, was consistently isolated from leaves of infected plants on a potato dextrose agar amended with 0.01% gentamicin sulfate. Based on morphological characteristics, the fungus was preliminary identified as Limonomyces roseipellis Stalpers & Loerakker, the causal agent of pink patch of turfgrass (2,3). To verify the identity, the internal transcribed spacer (ITS) of rDNA was amplified and sequenced using primers ITS1 and ITS4. Comparison with sequences in the GenBank database revealed that the ITS sequence (Accession No. KC193592) showed 98% homology with the sequence of L. roseipellis (EU622846). For pathogenicity tests, inoculum was prepared by culturing the fungus on an autoclaved mixture of 100 g of rye grain and 20 ml water for 3 weeks at 25°C. Six-week-old C. dactylon plants in 10-cm pots were inoculated by placing 2 g of infested grain in the center of the turf canopy, or 2 g sterilized, uninfested grain as a control, with four replications of each treatment. After inoculation, pots were covered with translucent plastic bags and placed in a greenhouse at 24 ± 2°C with a 12-h photoperiod (1). After 3 weeks, more than 70% of leaves in the infested pots showed symptoms identical to those observed under natural conditions while control plants remained asymptomatic. The fungus was reisolated from symptomatic plants. To our knowledge, this is the first report of L. roseipellis causing pink patch on hybrid bermudagrass in China. References: (1) L. L. Burpee and L. G. Goulty. Phytopathology 74:692, 1986. (2) J. D. Kaplan and N. Jackson. Plant Dis. 67:159, 1983. (3) J. A. Stalpers and W. M. Loerakker. Can. J. Bot. 60:529, 1982.


Gold mining impact on riverine heavy metal transport in a sparsely monitored region: the upper Lake Baikal Basin case.
Mining and ore excavation can cause the acidification and heavy metal pollution of downstream water systems. It can be difficult to assess the load contributions from individual mining areas, which is commonly required for environmental impact assessments. In the current study, we quantified the net impact of the unmonitored mining activities in the Zaamar Goldfield (Mongolia) on heavy metal transport in the downstream Tuul River-Selenga River-Lake Baikal water systems. We also noted that the Zaamar site shares the conditions of limited monitoring with many rapidly developing regions of the world. The heavy metal concentrations and flow data were obtained from historical measurement campaigns, long-term monitoring, and a novel field campaign. The results indicate that natural mass flows of heavy metals in dissolved form increased by an order of magnitude because of mining. Prevailing alkaline conditions in the vicinity of Zaamar can limit the dissolution, maintaining the on-site concentrations below health-risk based guideline values. However, suspended river concentrations are much higher than the dissolved concentrations. The placer gold mining at the Zaamar site has increased the total riverine mass flows of Al, As, Cu, Fe, Mn, Pb and Zn by 44.300, 30.1, 65.7, 47.800, 1.480, 76.0 and 65.0 tonnes per year respectively. We suggest that local to regional transformation and enrichment processes in combination with suspended sediment transport from numerous existing upstream mining areas contribute to high concentrations of dissolved heavy metals in downstream parts of the Selenga River, including its delta area at Lake Baikal. Furthermore, single hydrological events can increase the suspended load concentrations by at least one order of magnitude. Overall, the Selenga River Basin, which drains into Lake Baikal, should be recognised as one of the world's most impacted areas with regard to heavy metal loads, and it contributes to 1% and 3% of the world flux of dissolved Fe and Pb, respectively.


Solid-state NMR identification and quantification of newly formed aluminosilicate phases in weathered kaolinite systems.
The weathering of a specimen kaolinite clay was studied over the course of 369 d via solid-state 29Si magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy and high-field 27Al MAS NMR. The chosen baseline solution conditions (0.05 mol kg-1 of Al, 2 mol kg-1 of Na+, 1 mol kg-1 of NO3-, 1 mol kg-1 of OH-, and pH approximately 13.8) approximate those of solutions leaking from waste tanks at the Hanford Site in Richland, WA. Nonradioactive Cs and Sr cations were added to this synthetic tank waste leachate (STWL) solution at concentrations of 10(-3), 10(-4), and 10(-5) molal (m) to represent their radionuclide counterparts. The transformations of silicon- and aluminum-containing solid phase species were monitored quantitatively by using NMR spectroscopy, with the resulting spectra directly reporting the influence of the initial Cs and Sr on formation and transformation of the neo-formed solids. At the lowest concentration of Cs and Sr employed (10(-5) m in each cation) peaks consistent with the formation of zeolite-like minerals were detected via 29Si and 27Al MAS NMR as early as 33 d. At concentrations of 10(-3) m in each cation, new silicon species are not detected until 93 d, although neophases containing four-coordinate aluminum were detectable at earlier reaction times via 27Al MAS NMR. At the highest magnetic field strengths employed in this NMR study, deconvolutions of resonances detected in the tetrahedral region of the 27Al MAS spectra yielded multiple components, indicating the existence of at least four new aluminum-containing phases. Two of these phases are identified as sodalite and cancrinite through comparison with diffuse-reflectance infrared (DRIFT) spectra and powder X-ray diffraction (XRD) results, while a third phase may correlate with a previously detected aluminum-rich chabazite phase. All measurable solid reaction products have been quantified via their 27Al MAS resonances acquired at high magnetic field strengths (17.6 T), and the quantitative nature of the 27Al NMR data shows that cancrinite growth increases while sodalite reaches a steady state with respect to total aluminum in the solid phases. The data also relate the coupling of Cs sorption to the ripening of feldspathoid phases in this heterogeneous system as a function of time, and illustrate the important influence of co-contaminants on the environmental reaction kinetics studied here.


Role of the capsular polysaccharide-like serotype-specific antigen in resistance of Actinobacillus actinomycetemcomitans to phagocytosis by human polymorphonuclear leukocytes.
Serotype b-specific polysaccharide antigen (SPA) of Actinobacillus actinomycetemcomitans Y4 consists of D-fucose and L-rhamnose. To clarify the role of SPA in phagocytosis of the organism by human polymorphonuclear leukocytes (PMNs), monoclonal antibodies (MAbs) against SPA and SPA-defective mutants, which were constructed by inserting the transposon Tn916 into strain Y4, were used in a chemiluminescence (CL) assay and a phagocytic killing assay. The CL responses of human PMNs to strain Y4 were very low, and the organism was not killed by PMNs. In contrast, SPA-defective mutants induced strong CL responses. The addition of immunoglobulin G MAbs against Y4 SPA enhanced significantly both the CL responses to strain Y4 and the killing of the organism in the presence of complement. The CL responses to SPA-defective mutants were little affected by the addition of these MAbs. We conclude that SPA of A. actinomycetemcomitans plays an important role in the resistance to host defenses by PMNs.


Microfluidics in microbiology: putting a magnifying glass on microbes.
Microfluidic technologies enable unique studies in the field of microbiology to facilitate our understanding of microorganisms. Using miniaturized and high-throughput experimental capabilities in microfluidics, devices with controlled microenvironments can be created for microbial studies in research fields such as healthcare and green energy. In this research highlight, we describe recently developed tools for diagnostic assays, high-throughput mutant screening, and the study of human disease development as well as a future outlook on microbes for renewable energy.


Anthropometric and lifestyle characteristics of active and inactive Saudi and British adolescents.
To compare the anthropometric and lifestyle characteristics of active and inactive adolescents in Saudi Arabia and Britain. A school-based cross-sectional study was conducted at four cities in Saudi Arabia (Riyadh and Al-Khobar; N = 1,648) and Britain (Birmingham and Coventry; N = 1,158). The participants (14- to 18-year-olds) were randomly selected using a multistage stratified cluster sampling. Measurements included anthropometric [BMI, Waist circumference (WC), Waist to height ratio], screen time, validated physical activity questionnaire and dietary habits. British males were lighter (P = 0.04, 64.4 vs. 68.2 kg), and had lower values for WC (P = 0.003, 77.1 vs. 78.7 cm) than Saudi males. Males (P = 0.0001) were significantly more active than females but the difference between inactive Saudi and British females was greater than that between inactive Saudi and British males. Being female was significantly (P < 0.001) associated with lower activity levels in both the Saudi and British adolescents. Having lower frequency of fruit intake was significantly (P < 0.001) associated with lower activity levels, whereas increased frequency of consumption of French fries/potato chips was significantly (P = 0.008) associated with increased activity levels in Saudi adolescents. Among British adolescents, lower frequency of breakfast was (P = 0.045) associated with lower activity levels, increased frequency of consumption of sweetened beverages was significantly (P = 0.005) associated with higher activity levels. Higher energy drinks intake frequency was significantly (P = 0.007) associated with higher activity levels. The present study identifies crosscultural differences and similarities in lifestyle habits in adolescents from Britain and Saudi Arabia. Activity status (active vs. inactive) appears to play an important role in other lifestyle related behaviors, with active adolescent more likely to engage in healthy dietary behavior than their inactive peers, irrespective of country of origin.


Evaluation of productivity of sexually precocious Nelore heifers.
The objectives of the present study were to investigate the influence of yearling weight on the occurrence of early pregnancy and to determine differences between precocious and non-precocious heifers in terms of pre- and postnatal calf mortality, calf weight and height, mature cow weight, and stayability of the cow in the herd. Data from 26 977 females of a Nelore herd that participated in the breeding season between 1986 and 2004 were analyzed. The influence of yearling weight on sexual precocity and differences between precocious and non-precocious heifers in pre- and postnatal calf mortality and stayability were analyzed using the GENMOD procedure of the SAS program. Differences in the growth traits between precocious and non-precocious animals were estimated by contrast analysis. Three groups were analyzed for postnatal mortality: first calving of the heifers, calves born from the third calving and all offspring of the cow. In order to have a standardized calving to conception period for all females (precocious and non-precocious), calves born from the second calving were not included in the analysis. This was necessary because the first calving to conception period (days open) of precocious heifers was longer than for non-precocious due to farm reproductive management. No differences in postnatal mortality rates, from the third calving, were observed between the two groups of heifers studied. Analysis of all offspring of the dams showed a 9% higher probability of death of calves born to precocious heifers compared with calves born to non-precocious heifers. With respect to stayability, precocious heifers presented 33% greater odds to remain in the herd until 5 and 6 years of age and 28% greater odds to remain in the herd until 7 years when compared with non-precocious heifers. Precocious heifers weaned calves (205 days) significantly heavier than non-precocious ones, 1.410 and 0.797 kg considering the weaning weights of all offspring and of the third calving, respectively. With respect to sexual precocity, the results suggest that the probability of heifers to become pregnant at 16 months of age increases with increasing weight. However, heifers weighing more than 240 kg present practically the same pregnancy probability. Nevertheless, exposure of heifers during the early breeding season is recommended for beef cattle herds raised in tropical regions in view of the numerous benefits demonstrated here.


The comparative cellular architecture of the female gonoduct among tylenchoidea (nematoda: tylenchina).
The cellular architecture of the female gonoduct of 68 nematode populations representing 42 species belonging to Tylenchidae, Belonolaimidae, Hoplolaimidae and Meloinema is shown to have an overall similarity in cellular gonoduct structure. The oviduct consists of two rows of four cells; the spermatheca is comprised of 10 to 20 cells, and the uterus cells, except in the case of Psilenchus, are arranged in four (Tylenchidae) or three (Belonolaimidae, Hoplolaimidae and Meloinema) regular rows. Although the genus Meloinema is classified within Meloidogynidae, its spermatheca is clearly hoplolaimid-like and lacks the spherical shape with lobe-like protruding cells typical of Meloidogyne. Detailed morphology of expelled gonoducts may provide a valuable character set in phylogenetic analysis, and the cellular morphology of the spermatheca appears to be a distinguishing feature at species level, especially in the genera Tylenchus and Geocenamus. Ultrastructural data on the oviduct-spermatheca region of Meloidogyne incognita complement light-microscopic (LM) results. The combination of LM of expelled organs and transmission electron microscopy (TEM) on selected sections is put forward as a powerful tool to combine three-dimensional knowledge with ultrastructural detail.


Knowledge and behaviors related to dietary salt and sources of dietary sodium in north India.
Sodium, an element needed for the normal human physiology is known to be associated with high blood pressure and other consequences if consumed in excess. The assessment of knowledge and behavior related to sodium that is consumed in the form of salt plays an important role in the control of cardiovascular diseases. To control the intake of sodium, dietary sources of sodium need to be identified. To address this, a community-based cross-sectional study was conducted among women aged 20 to 59 years in north India, where knowledge, attitude, and behavior questionnaire given by the World Health Organization and 24-h dietary recall were used. The mean age of the participants was 34.5 years, and the majority of them were homemakers. Approximately, 80% of the participants believed that high salt diet causes serious health problems, and only 5% of the participants were aware of the existence of a recommendation for daily salt intake. Less than 20% of the participants took measures to control their salt intake. Vegetable-based dishes were found to be the major contributors to the daily salt intake followed by pulse-based and cereal-based dishes. This is because of the high quantity in which they are consumed. Food cooked at home contributed to 90% of the daily salt intake. To control the salt intake, we should cut- down the discretionary salt use. Dietary advice should be customized to the individual, and the family physician plays an important role in this. Behavioral change is the need of the hour to control the epidemic of non-communicable diseases.


Sustained attention is associated with right superior longitudinal fasciculus and superior parietal white matter microstructure in children.
Sustained attention develops during childhood and has been linked to the right fronto-parietal cortices in functional imaging studies; however, less is known about its relation to white matter (WM) characteristics. Here we investigated whether the microstructure of the WM underlying and connecting the right fronto-parietal cortices was associated with sustained attention performance in a group of 76 typically developing children aged 7-13 years. Sustained attention was assessed using a rapid visual information processing paradigm. The two behavioral measures of interest were the sensitivity index d' and the coefficient of variation in reaction times (RTCV ). Diffusion-weighted imaging was performed. Mean fractional anisotropy (FA) was extracted from the WM underlying right dorsolateral prefrontal (DLPFC) and parietal cortex (PC), and the right superior longitudinal fasciculus (SLF), as well as equivalent anatomical regions-of-interest (ROIs) in the left hemisphere and mean global WM FA. When analyzed collectively, right hemisphere ROIs FA was significantly associated with d' independently of age. Follow-up analyses revealed that only FA of right SLF and the superior part of the right PC contributed significantly to this association. RTCV was significantly associated with right superior PC FA, but not with right SLF FA. Observed associations remained significant after controlling for FA of equivalent left hemisphere ROIs or global mean FA. In conclusion, better sustained attention performance was associated with higher FA of WM in regions connecting right frontal and parietal cortices. Further studies are needed to clarify to which extent these associations are driven by maturational processes, stable characteristics and/or experience.


Agree or Agree to Disagree? Assessing the Convergence between Parents and Observers on Infant Temperament.
The assessment of infant temperament has been typically accomplished with parent questionnaires. When compared with temperament behaviours observed in the laboratory, parents and observers generally do not agree, leading some researchers to question the validity of parent report. This paper reports on a representative sample of infants whose families resided in non-metropolitan counties and whose temperament was measured in three ways: (1) standard parent report (Infant Behavior Questionnaire); (2) observer ratings across two lengthy home visits; and (3) observer coding of second-by-second reactions to specific emotion-eliciting tasks. In order to account for both trait and method variance, structural equation modelling was applied to a sample of 955 infants (M age = 7.3 months) using variables from the three methods that reflected the dimensions of positivity and negativity. Although models based solely on method factors and trait factors fit the data well, results indicated that a model that included method and trait factors provided the best fit. Results also indicated that parents and observers (either across the home visit or to specific tasks) converge, to a degree, on ratings of the positivity dimension but diverge on the negativity dimension.


Multi-omic characterization of laboratory-evolved Saccharomyces cerevisiae HJ7-14 with high ability of algae-based ethanol production.
In this study, an evolved Saccharomyces cerevisiae HJ7-14 with high ability of algae-based ethanol production was characterized by multi-omic approaches. Genome sequencing of the HJ7-14 revealed a point mutation in the GAL83 gene (G703A) involved in the catabolite repression as well as the galactose metabolism. Cultural and transcriptional analyses of a S. cerevisiae mutant with chromosomal GAL83(G703A) indicated that the catabolite repression onto the galactose metabolism was considerably relieved in all cell growth stages. Untargeted metabolomic approach revealed that metabolic phenotypes between the control D452-2 and HJ7-14 strains were clearly discriminated in time-dependent manner. Especially in early growth stage at 6 h, the HJ7-14 showed dramatic and coordinated alteration in central carbon and amino acid metabolisms. Through metabolomic re-organization, fold changes in fatty acid metabolism and metabolites related to stress response system were also found upon glucose depletion and active galactose utilization. Multi-omic characterization using genome sequencing, transcription, and metabolome profiling clearly unveiled that the GAL83 gene mutation partially relieved glucose-dependent catabolite repression and allowed the evolved HJ7-14 to efficiently convert algal sugars to ethanol. Our finding could be applicable for engineering of S. cerevisiae able to covert red algal biomass to other biofuels and biochemicals.


Spectroscopy research at the McLennan physical laboratories of the University of Toronto.
Recent research of the Spectroscopy and Molecular Physics Research Group at the Department of Physics, University of Toronto, has been in the general areas: spectroscopy of compressed gases, low temperature spectroscopy, Raman spectra of low pressure gases, optical pumping, applications of lasers to light scattering, and interference spectroscopy in the laboratory and from high altitude balloons. Topics discussed in some detail in this communication are: bound states of hydrogen-foreign gas Van der Waals complexes, intensity anomalies in the Raman effect of solid hydrogen, pressure broadening in the Raman spectra of simple diatomic molecules, a synopsis of work on high resolution rotation and rotation-vibrational Raman spectra of gases, recent results on Brillouin scattering and Raman line widths using lasers, and collision broadening in the spectrum of zinc by optical pumping.


Upset Over Sexual versus Emotional Infidelity Among Gay, Lesbian, Bisexual, and Heterosexual Adults.
One hypothesis derived from evolutionary perspectives is that men are more upset than women by sexual infidelity and women are more upset than men by emotional infidelity. The proposed explanation is that men, in contrast to women, face the risk of unwittingly investing in genetically unrelated offspring. Most studies, however, have relied on small college or community samples of heterosexual participants. We examined upset over sexual versus emotional jealousy among 63,894 gay, lesbian, bisexual, and heterosexual participants. Participants imagined which would upset them more: their partners having sex with someone else (but not falling in love with them) or their partners falling in love with someone else (but not having sex with them). Consistent with this evolutionary perspective, heterosexual men were more likely than heterosexual women to be upset by sexual infidelity (54 vs. 35 %) and less likely than heterosexual women to be upset by emotional infidelity (46 vs. 65 %). This gender difference emerged across age groups, income levels, history of being cheated on, history of being unfaithful, relationship type, and length. The gender difference, however, was limited to heterosexual participants. Bisexual men and women did not differ significantly from each other in upset over sexual infidelity (30 vs. 27 %), regardless of whether they were currently dating a man (35 vs. 29 %) or woman (28 vs. 20 %). Gay men and lesbian women also did not differ (32 vs. 34 %). The findings present strong evidence that a gender difference exists in a broad sample of U.S. adults, but only among heterosexuals.


Diffuse large B-cell lymphoma presenting with neurolymphomatosis and intravascular lymphoma: a unique autopsy case with diverse neurological symptoms.
A 78-year-old Japanese male noticed a difficulty in the beginning of standing up, followed by 7a progressive numbness of extremities with pain, Bell's palsy, dysarthria, and difficulty in swallowing. A clinician had suspected cancer of unknown primary origin, accompanied by the diverse and elusive neurological symptoms, likely presenting as painful mononeuropathy simplex and cranial neuropathy. He developed dysbasia over weeks and died 1 month after the symptom onset. At autopsy, an ill-defined large and soft tumor mass in the right lobe of the liver with direct invasion into the right adrenal gland was observed. The left adrenal gland or right iliopsoas muscle was also involved. Microscopic findings showed a monotonous proliferation of medium-sized to large atypical lymphoid cells, which were diffusely positive for CD20 in immunohistochemistry, consistent with diffuse large B-cell lymphoma (DLBL). Furthermore, the lymphoma cells aggressively infiltrated endoneurial and subperineurial spaces not only in the peripheral nerves and plexuses, but partly in the spinal nerve roots, and intravascular spaces in various tissues. Therefore, systemic lymphoma (DLBL) complicated with neurolymphomatosis (NL) and intravascular lymphoma (IVL) was diagnosed. Very early diagnosis and treatment are necessary for the NL patients with poor prognosis. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5862472377020448.


Extrapyramidal epilepsy.
Non-epileptic paroxysmal movement disorders are rare extrapyramidal diseases. The clinical signs are often excluded from differential diagnosis due to their paucity on clinical examination and low prevalence. The paroxysmal, stereotypical nature of non-epileptic paroxysmal movement disorders, as well as the potential response to benzodiazepines, renders these disorders susceptible to misdiagnosis as epileptic seizures. We report a case of paroxysmal non-kinesigenic dyskinesia which was misdiagnosed and treated as epilepsy for decades. The major pathophysiological, diagnostic and therapeutic hallmarks of the disease are summarised. Familiarity and inclusion of the disease in the list of conditions that mimic epilepsy, as well as prolonged video-EEG recordings, may prevent diagnostic delays and unnecessary or belated treatments. [Published with video sequences].


Diabetic nephropathy: lessons from the mouse.
A fundamental problem in the identification of new molecular targets for therapeutic intervention in diabetic nephropathy has been the lack of an experimental mouse model that faithfully recapitulates human diabetic nephropathy. Our laboratory, in collaboration with Drs Kakoki and Smithies at the University of North Carolina-Chapel Hill, has developed novel strains of Akita diabetic mice in which the p66 longevity gene has been deleted by homologous recombination. We chose to delete p66 because p66 controls mitochondrial metabolism and cellular responses to oxidative stress, aging, and apoptosis. The redox function of p66 is indispensable for the exponential increase in reactive oxygen species (ROS) associated with diabetes. p66 null Akita mice express a protection phenotype in kidneys that includes marked attenuation of oxidative stress and glomerular/tubular injury and a striking reduction in urine albumin excretion. Furthermore, the p66 null mutation not only confers a survival advantage to podocytes but also prevents foot process effacement and retains the stationary phenotype. Sirtuin 1 (SIRT1) deacetylase and p66 share overlapping biological functions but induce divergent phenotypes, including opposite effects on longevity, ROS metabolism, cell senescence, and apoptosis. Exciting new data from our laboratory show that SIRT1 is upregulated in the kidneys of p66 null Akita mice and decreases acetylation of p53, which destabilizes the p53 protein and prevents the transcription of p53 proapoptosis genes. Conversely, SIRT1 activates the transcription of FOXO3a-dependent stress gene programs that detoxify ROS and promote the survival phenotype. We will focus future research on translating these experimental findings in the mouse to clinical diabetic nephropathy.


Mammalian oocyte development: checkpoints for competence.
During the lifespan of the female, biochemical changes occur in the ovarian environment. These changes are brought about by numerous endogenous and exogenous factors, including husbandry practices, production demands and disease, and can have a profound effect on ovarian oocyte quality and subsequent embryo development. Despite many investigations, there is no consensus regarding the time or period of follicular oocyte development that is particularly sensitive to insult. Here, the key molecular and morphological events that occur during oocyte and follicle growth are reviewed, with a specific focus on identifying critical checkpoints in oocyte development. The secondary follicle stage appears to be a key phase in follicular oocyte development because major events such as activation of the oocyte transcriptome, sequestration of the zona pellucida, establishment of bidirectional communication between the granulosa cells and the oocyte and cortical granule synthesis occur during this period of development. Several months later, the periovulatory period is also characterised by the occurrence of critical events, including appropriate degradation or polyadenylation of mRNA transcripts, resumption of meiosis, spindle formation, chromosome alignment and segregation, and so should also be considered as a potential checkpoint of oocyte development.


A New Stethoscope Design with Unique Characteristics and Development in Medical Device.
As regards the significant role of stethoscopes in the diagnosis of congenital and adventitious heart diseases and prevention of irreparable complications of these diseases, the quality of hearing sound of these stethoscopes by a physician has a significant impact on the disease diagnosis. This device plays an important role in the early diagnosis of congenital heart and respiratory diseases and provides this feasibility since birth. Also, the importance of this device performance in the diagnosis of heart, cardiovascular and respiratory diseases at different age periods is not a secret. This new invented device, in comparison to a variety of available stethoscopes in the field of diagnosis, is capable of hearing the sound of a very high quality and cancelling the noise of sound that sometimes leads to wrong diagnosis or misdiagnosis. This new invented stethoscope is approved by cardiologists, lung and Infectious disease specialists as well as being registered under No. 78382 in Patent Islamic Republic of Iran.


Conditions for inducing T helper cells in vitro.
Lymphoid cells of CBA mice were triggered to act as specific helper cells by incubation with protein antigen (usually keyhole limpet haemocyanin (KLH)) in Marbrook cultures in vitro. After optimum priming, these helper cells, at optimal numbers, stimulated B cells (from unprimed spleens) to respond to trinitrophenyl-KLH in vitro. The in vitro-induced helper cells were carrier-specific. B cell depletion before helper cell induction increased the efficiency of helper cell induction and thus provided further proof of the T-cell nature of in vitro helper cells. Heterogeneity within T helper cell precursors is suggested on the basis of differences in antigen dose requirements of precursor cells in cortisone-resistant thymocytes, spleen, or lymph nodes.


Spinal sumatriptan inhibits capsaicin-induced canine external carotid vasodilatation via 5-HT1B rather than 5-HT1D receptors.
Migraine is a neurovascular disorder associated with trigeminal activation, vasodilatation and trigeminal release of calcitonin gene-related peptide (CGRP). The antimigraine properties of triptans may be due to: i) vasoconstriction of the carotid arterial bed via 5-HT(1B) receptors; and ii) inhibition of CGRP release from trigeminal nerves, via 5-HT(1B/1D) receptors. This study investigated the effects of intrathecally administered sumatriptan (a 5-HT(1B/1D) receptor agonist) and PNU-142633 (a 5-HT(1D) receptor agonist) on the canine external carotid vasodilator responses to capsaicin, alpha-CGRP and acetylcholine. For this purpose, 42 mongrel dogs were anaesthetised with sodium pentobarbitone and, subsequently, vagosympathectomized. The animals were prepared to measure arterial blood pressure, heart rate and external carotid blood flow; the thyroid artery was cannulated for infusion of agonists. 1-min intracarotid (i.c.) continuous infusions of capsaicin, alpha-CGRP and acetylcholine produced dose-dependent increases in external carotid blood flow without affecting arterial blood pressure or heart rate. These vasodilator responses remained unaffected after intrathecal (i.t.) administration of physiological saline (0.5 ml) or PNU-142633 (300-1000 microg); in contrast, i.t. sumatriptan (300-1000 microg) significantly inhibited the vasodilator responses to capsaicin, but not those to alpha-CGRP or acetylcholine. Furthermore, i.t. administration of SB224289 (a 5-HT(1B) receptor antagonist), but not of BRL15572 (a 5-HT(1D) receptor antagonist), abolished the above inhibition by sumatriptan. These results suggest that sumatriptan-induced inhibition of the external carotid vasodilatation to capsaicin involves a central mechanism mainly mediated by 5-HT(1B) receptors.


Descriptors of magnetic anisotropy revisited.
The recently discovered thermal elasticity of magnetic anisotropy is not at all an exotic phenomenon. For many lanthanide complexes the qualitative nature of their magnetic anisotropy changes as a function of temperature and magnetic field; for some, even multiple times. The theoretically predicted existence of such multi-switch compounds is experimentally corroborated.


Charge transfer-induced photoluminescence in ZnO nanoparticles.
The quality of solution-processed zinc oxide (ZnO) nanoparticles (NPs) is often correlated with their photoluminescence (PL) spectral characteristics. However, the reported PL spectral characteristics lack consistency and remain controversial. Here we report that "defect-emission free" PL spectra can even be obtained in thin films composed of as-synthesized ZnO NPs. It is found that both the PL spectral line-shape and intensity are extremely sensitive to nitrogen and oxygen. By conducting time-dependent PL (t-PL) and photothermal deflection spectroscopy (PDS) measurements under vacuum and different gases, it is proposed that both inert (N2) and reactive (O2) molecules can be absorbed on the ZnO NP surface and induce charge transfer (CT). The CT states induced by N2 are non-radiative which significantly reduces the band emission. Whereas the CT states induced by O2 are radiative at the visible region, and the exciton transfer is efficient which increases the overall PL quantum yield. Owing to such effects, the previously reported correlation between defects and PL emission becomes questionable and needs to be revisited. Particularly, the visible emission from the ZnO NPs is proved to be facilitated by external effects, instead of direct recombination from defect states.


Macrophage phenotypic subtypes diametrically regulate epithelial-mesenchymal plasticity in breast cancer cells.
Metastatic progression of breast cancer involves phenotypic plasticity of the carcinoma cells moving between epithelial and mesenchymal behaviors. During metastatic seeding and dormancy, even highly aggressive carcinoma cells take on an E-cadherin-positive epithelial phenotype that is absent from the emergent, lethal metastatic outgrowths. These phenotypes are linked to the metastatic microenvironment, though the specific cells and induction signals are still to be deciphered. Recent evidence suggests that macrophages impact tumor progression, and may alter the balance between cancer cell EMT and MErT in the metastatic microenvironment. Here we explore the role of M1/M2 macrophages in epithelial-mesenchymal plasticity of breast cancer cells by coculturing epithelial and mesenchymal cells lines with macrophages. We found that after polarizing the THP-1 human monocyte cell line, the M1 and M2-types were stable and maintained when co-cultured with breast cancer cells. Surprisingly, M2 macrophages may conferred a growth advantage to the epithelial MCF-7 cells, with these cells being driven to a partial mesenchymal phenotypic as indicated by spindle morphology. Notably, E-cadherin protein expression is significantly decreased in MCF-7 cells co-cultured with M2 macrophages. M0 and M1 macrophages had no effect on the MCF-7 epithelial phenotype. However, the M1 macrophages impacted the highly aggressive mesenchymal-like MDA-MB-231 breast cancer cells to take on a quiescent, epithelial phenotype with re-expression of E-cadherin. The M2 macrophages if anything exacerbated the mesenchymal phenotype of the MDA-MB-231 cells. Our findings demonstrate M2 macrophages might impart outgrowth and M1 macrophages may contribute to dormancy behaviors in metastatic breast cancer cells. Thus EMT and MErT are regulated by selected macrophage phenotype in the liver metastatic microenvironment. These results indicate macrophage could be a potential therapeutic target for limiting death due to malignant metastases in breast cancer.


Esophageal squamous cell dysplasia and delayed differentiation with deletion of krüppel-like factor 4 in murine esophagus.
Krüppel-like factor 4 (Klf; previously known a gut-enriched Krüppel-like factor) is a DNA-binding transcriptional regulator highly expressed in skin and gastrointestinal epithelia, specifically in regions of cellular differentiation. Homozygous null mice for Klf4 die shortly after birth from skin defects, precluding their analysis at later stages. The aim of this study was to analyze the function of Klf4 in keratinocyte biology and epithelial homeostasis in the adult by focusing on the squamous lined esophagus. By using the ED-L2 promoter of Epstein-Barr virus to drive Cre, we obtained tissue-specific ablation of Klf4 in the squamous epithelia of the tongue, esophagus, and forestomach. Mice with loss of Klf4 in esophageal epithelia survived to adulthood, bypassing the early lethality. Tissue-specific Klf4 knockout mice had increased basal cell proliferation and a delay in cellular maturation; these mice developed epithelial hypertrophy and subsequent dysplasia by 6 months of age. Moreover, loss of Klf4 in vivo was associated with increased expression of the pro-proliferative Klf5, and Klf4 down-regulated Klf5 both transcriptionally and posttranscriptionally. By using gene expression profiling, we also showed decreased expression of critical late-stage differentiation factors and identified alterations of several genes important in cellular differentiation. Klf4 is essential for squamous epithelial differentiation in vivo and interacts with Klf5 to maintain normal epithelial homeostasis.


The Tromsø heart study: coffee consumption and serum lipid concentrations in men with hypercholesterolaemia: an randomised intervention study.
In a 10 week trial to assess the effects of coffee consumption and coffee brewing methods on serum cholesterol concentrations 33 men with hypercholesterolaemia were randomly assigned to: continue with their usual coffee intake; stop drinking coffee altogether; or stop drinking coffee for five weeks, thereafter drinking either boiled or filter coffee. Cholesterol concentrations fell significantly in all subjects abstaining for the first five weeks compared with subjects not giving up and continued to fall in those abstaining for 10 weeks. Cholesterol concentrations rose again in subjects returning to boiled coffee but remained the same in those returning to filter coffee. Abstention from heavy coffee drinking is an efficient way of reducing serum cholesterol concentrations in men with hypercholesterolaemia. The extent to which the brewing method affects this relation requires further study.


The roles of phospholipase D and a GTP-binding protein in guanosine 5'-[gamma-thio]triphosphate-stimulated hydrolysis of phosphatidylcholine in rat liver plasma membranes.
1. Guanosine 5'-[gamma-thio]triphosphate (GTP[S]) stimulated by 50% the rate of release of [3H]choline and [3H]phosphorylcholine in rat liver plasma membranes labelled with [3H]choline. About 70% of the radioactivity released in the presence of GTP[S] was [3H]choline and 30% was [3H]phosphorylcholine. 2. The hydrolysis of phosphorylcholine to choline and the conversion of choline to phosphorylcholine did not contribute to the formation of [3H]choline and [3H]phosphorylcholine respectively. 3. The release of [3H]choline from membranes was inhibited by low concentrations of SDS or Triton X-100. Considerably higher concentrations of the detergents were required to inhibit the release of [3H]phosphorylcholine. 4. Guanosine 5'-[beta gamma-imido]triphosphate and guanosine 5'-[alpha beta-methylene]triphosphate, but not adenosine 5'-[gamma-thio]-triphosphate, stimulated [3H]choline release to the same extent as did GTP[S]. The GTP[S]-stimulated [3H]choline release was inhibited by guanosine 5'-[beta-thio]diphosphate, GDP and GTP but not by GMP. 5. It is concluded that, in rat liver plasma membranes, (a) GTP[S]-stimulated hydrolysis of phosphatidylcholine is catalysed predominantly by phospholipase D with some contribution from phospholipase C, and (b) the stimulation of phosphatidylcholine hydrolysis by GTP[s] occurs via a GTP-binding regulatory protein.


Models of mild traumatic brain injury: translation of physiological and anatomic injury.
Mild traumatic brain injury (TBI) has become a rising epidemic, affecting millions of people each year. Even though it is the most common type of brain injury, our understanding of the science underlying mild TBI is just in its infancy. There has been an explosion of basic science research interest in mild TBI, as emerging clinical evidence is suggestive that concussion and subconcussion may result in detrimental long-term neurological sequelae, particularly when occurring repetitively. Many animal models have been developed to study the different pathological mechanisms implicated in TBI, and more recently there has been a heightened focus on modeling mild TBI in the laboratory as well. The most widely used models of TBI have been adapted for experimental mild TBI research, although more work still remains. The ability to create improved diagnostic measures and treatment approaches for concussion depend on the development and characterization of clinically relevant models of mild TBI. This review aims to provide a broad general overview of the current efforts to model mild TBI in animals and the challenges and limitations that exist in translating this behavioral, physiological, and anatomic knowledge from the bench to the clinical arena.


Using exercise to protect physical and mental health in youth at risk for psychosis.
A large body of literature has demonstrated that exercise interventions can improve a broad range of outcomes in people with established schizophrenia, including reducing psychiatric symptoms, increasing cognitive functioning, and improving physical health. Furthermore, these benefits seem just as pronounced in first-episode psychosis. However, there have been few clinical studies to date examining the effects of exercise in those found to be 'at-risk' of psychosis, particularly for those meeting the criteria for 'Clinical High Risk' (CHR) state (a classification which includes both those meeting the 'ultra-high risk for psychosis' criteria and/or those with 'atrisk mental states'). This is surprising, as a proportion of those in the CHR state go on to develop psychotic disorders, and a growing body of evidence suggests that early interventions in this period have significant potential to improve the course of illness. In this article, we shall review the existing literature for i) exercise as an adjunctive intervention for those treated for psychosis; ii) exercise as a standalone intervention in CHR groups; and iii) the rationale and supportive evidence for widescale use of exercise to preserve physical and mental health in those identified as at risk for psychosis. From this, we will put forth how the CHR phase represents an under-researched but highly-suitable timepoint for administering structured exercise interventions, in order to improve physical, psychological and neurocognitive outcomes; while also potentially reducing the odds of transition to full-threshold psychotic disorders. Following this, directions, recommendations and considerations around both the clinical implementation and future research around exercise in CHR individuals will be discussed.


Streptococcus pneumoniae damages the ciliated ependyma of the brain during meningitis.
Streptococcus pneumoniae meningitis remains a disease with a poor outcome for the patient. A region of the brain that has been neglected in the study of meningitis is the ependyma, which has been identified as a location of adult pluripotent cells. In this study we have used a rat model of meningitis to examine whether the ependymal layer is affected by S. pneumoniae. The effects included localized loss of cilia, a decrease of the overall ependymal ciliary beat frequency, and damage to the ependymal ultrastructure during meningitis. In conclusion, loss of ependymal cells and ciliary function exposes the underlying neuronal milieu to host and bacterial cytotoxins and this is likely to contribute to the neuropathology commonly observed in pneumococcal meningitis.


Reduced replication of 3TC-resistant HIV-1 variants in primary cells due to a processivity defect of the reverse transcriptase enzyme.
Human immunodeficiency virus type 1 (HIV-1) variants with resistance mutations in the reverse transcriptase (RT) gene appear during drug therapy with the nucleoside analogue 2',3'-dideoxy-3'-thiacytidine (3TC). These resistance mutations alter the methionine (Met) residue of the conserved YMDD motif, which is part of the catalytic core of the RT enzyme. Isoleucine (Ile) variants are initially observed, followed by the appearance and eventual outgrowth of viruses encoding valine (Val). Similar replication kinetics were measured for wild-type and 3TC-resistant HIV-1 viruses in tissue culture infections of a T cell line, but we measured reduced polymerase activity for the two mutant RT enzymes compared with the wild-type enzyme (Ile = 43% and Val = 67%). Gel analysis of the reverse transcription products revealed that both 3TC-resistant RT mutants produce significantly shorter cDNA molecules than the wild-type enzyme [Met (wt)>Val>Ile], indicating that 3TC-resistant RT polymerases are less processive enzymes. Interestingly, these enzyme defects were more pronounced under limiting dNTP concentrations and we therefore assayed virus replication in primary cells that contain relatively low dNTP levels. Under these conditions, we measured significantly reduced replication kinetics for the 3TC-resistant HIV-1 variants [Met (wt)>Val>Ile]. If the level of virus replication can be similarly reduced in 3TC-treated patients that develop drug-resistant HIV-1 variants, this may be of considerable clinical benefit.


Avicennia germinans (black mangrove) vessel architecture is linked to chilling and salinity tolerance in the Gulf of Mexico.
Over the last several decades, the distribution of the black mangrove Avicennia germinans in the Gulf of Mexico has expanded, in part because it can survive the occasional freeze events and high soil salinities characteristic of the area. Vessel architecture may influence mangrove chilling and salinity tolerance. We surveyed populations of A. germinans throughout the Gulf to determine if vessel architecture was linked to field environmental conditions. We measured vessel density, hydraulically weighted vessel diameter, potential conductance capacity, and maximum tensile fracture stress. At each sampling site we recorded mangrove canopy height and soil salinity, and determined average minimum winter temperature from archived weather records. At a subset of sites, we measured carbon fixation rates using a LI-COR 6400XT Portable Photosynthesis System. Populations of A. germinans from cooler areas (Texas and Louisiana) had narrower vessels, likely reducing the risk of freeze-induced embolisms but also decreasing water conductance capacity. Vessels were also narrower in regions with high soil salinity, including Texas, USA and tidal flats in Veracruz, Mexico. Vessel density did not consistently vary with temperature or soil salinity. In abiotically stressful areas, A. germinans had a safe hydraulic architecture with narrower vessels that may increase local survival. This safe architecture appears to come at a substantial physiological cost in terms of reduction in conductance capacity and carbon fixation potential, likely contributing to lower canopy heights. The current distribution of A. germinans in the Gulf is influenced by the complex interplay between temperature, salinity, and vessel architecture. Given the plasticity of A. germinans vessel characters, it is likely that this mangrove species will be able to adapt to a wide range of potential future environmental conditions, and continue its expansion in the Gulf of Mexico in response to near-term climate change.


Receptor Polymorphism and Genomic Structure Interact to Shape Bitter Taste Perception.
The ability to taste bitterness evolved to safeguard most animals, including humans, against potentially toxic substances, thereby leading to food rejection. Nonetheless, bitter perception is subject to individual variations due to the presence of genetic functional polymorphisms in bitter taste receptor (TAS2R) genes, such as the long-known association between genetic polymorphisms in TAS2R38 and bitter taste perception of phenylthiocarbamide. Yet, due to overlaps in specificities across receptors, such associations with a single TAS2R locus are uncommon. Therefore, to investigate more complex associations, we examined taste responses to six structurally diverse compounds (absinthin, amarogentin, cascarillin, grosheimin, quassin, and quinine) in a sample of the Caucasian population. By sequencing all bitter receptor loci, inferring long-range haplotypes, mapping their effects on phenotype variation, and characterizing functionally causal allelic variants, we deciphered at the molecular level how a subjects' genotype for the whole-family of TAS2R genes shapes variation in bitter taste perception. Within each haplotype block implicated in phenotypic variation, we provided evidence for at least one locus harboring functional polymorphic alleles, e.g. one locus for sensitivity to amarogentin, one of the most bitter natural compounds known, and two loci for sensitivity to grosheimin, one of the bitter compounds of artichoke. Our analyses revealed also, besides simple associations, complex associations of bitterness sensitivity across TAS2R loci. Indeed, even if several putative loci harbored both high- and low-sensitivity alleles, phenotypic variation depended on linkage between these alleles. When sensitive alleles for bitter compounds were maintained in the same linkage phase, genetically driven perceptual differences were obvious, e.g. for grosheimin. On the contrary, when sensitive alleles were in opposite phase, only weak genotype-phenotype associations were seen, e.g. for absinthin, the bitter principle of the beverage absinth. These findings illustrate the extent to which genetic influences on taste are complex, yet arise from both receptor activation patterns and linkage structure among receptor genes.


Ether lipids in cancer chemotherapy.
There is considerable evidence that certain ether lipids such as 1-0-octadecyl-2-0-methyl-rac-glycero-3-phosphocholine represent a new class of antineoplastic agents. These ether lipids have been shown to be cytotoxic for a wide variety of tumors. The site of action of ether lipids appears to be the cell membrane, where they inhibit the biosynthesis of phosphatidylcholine as well as the activity of protein kinase C. However, it remains uncertain that these effects represent the only mechanism for the cytotoxic action of these ether lipids. Further experiments to elucidate the molecular mechanisms of the cytotoxic action of these compounds are necessary. Clinical phase I pilot trials have been completed showing encouraging tumor response in a small number of patients treated. Some of these ether lipids are selectively cytotoxic to leukemic cells sparing of normal cells within a certain dose range. Thus, they are uniquely suitable for purging residual leukemic cells from remission marrow used for autologous bone marrow transplantation. A phase I/II study of autologous bone marrow transplantation in acute leukemia using bone marrow cells treated with ether lipids is in progress.


Direct evaluation of the temperature dependence of the rate constant based on the quantum instanton approximation.
A general method for the direct evaluation of the temperature dependence of the quantum-mechanical reaction rate constant in many-dimensional systems is described. The method is based on the quantum instanton approximation for the rate constant, thermodynamic integration with respect to the inverse temperature, and the path integral Monte Carlo evaluation. It can describe deviations from the Arrhenius law due to the coupling of rotations and vibrations, zero-point energy, tunneling, corner-cutting, and other nuclear quantum effects. The method is tested on the Eckart barrier and the full-dimensional H+H(2)-->H(2)+H reaction. In the temperature range from 300 to 1500 K, the error of the present method remains within 13% despite the very large deviations from the Arrhenius law. The direct approach makes the calculations much more efficient, and the efficiency is increased even further (by up to two orders of magnitude in the studied reactions) by using optimal estimators for reactant and transition state thermal energies. Which of the estimators is optimal, however, depends on the system and the strength of constraint in a constrained simulation.


Kinase and phosphatase activities intimately associated with a reconstituted calcium-dependent potassium channel.
Type-2 calcium-dependent potassium (KCa) channels from mammalian brain, reconstituted into planar phospholipid bilayers, are modulated by ATP or ATP analogs via an endogenous protein kinase activity intimately associated with the channel (Chung et al., 1991). We show here that the endogenous protein kinase activity is protein kinase C (PKC)-like because (1) modulation by ATP can be mimicked by exogenous PKC, and (2) the effects of ATP can be blocked by PKC(19-36), a specific peptide inhibitor of PKC. Furthermore, adding the PKC inhibitor peptide after the addition of ATP reverses the modulation produced by ATP, suggesting that there is a phosphoprotein phosphatase activity closely associated with type-2 KCa channels. Consistent with this idea is the finding that microcystin, a non-specific phosphatase inhibitor, enhances the modulation of KCa channel activity by ATP. Inhibitor-1, a specific protein inhibitor of phosphoprotein phosphatase-1, also enhances the effect of ATP, suggesting that the endogenous phosphatase activity is phosphatase-1-like. The results imply that type-2 KCa channels exist as part of a regulatory complex that includes a PKC-like protein kinase and a phosphatase-1-like phosphoprotein phosphatase, both of which participate in the modulation of channel function.


The importance of supplementary immunisation activities to prevent measles outbreaks during the COVID-19 pandemic in Kenya.
The COVID-19 pandemic has disrupted routine measles immunisation and supplementary immunisation activities (SIAs) in most countries including Kenya. We assessed the risk of measles outbreaks during the pandemic in Kenya as a case study for the African Region. Combining measles serological data, local contact patterns, and vaccination coverage into a cohort model, we predicted the age-adjusted population immunity in Kenya and estimated the probability of outbreaks when contact-reducing COVID-19 interventions are lifted. We considered various scenarios for reduced measles vaccination coverage from April 2020. In February 2020, when a scheduled SIA was postponed, population immunity was close to the herd immunity threshold and the probability of a large outbreak was 34% (8-54). As the COVID-19 contact restrictions are nearly fully eased, from December 2020, the probability of a large measles outbreak will increase to 38% (19-54), 46% (30-59), and 54% (43-64) assuming a 15%, 50%, and 100% reduction in measles vaccination coverage. By December 2021, this risk increases further to 43% (25-56), 54% (43-63), and 67% (59-72) for the same coverage scenarios respectively. However, the increased risk of a measles outbreak following the lifting of all restrictions can be overcome by conducting a SIA with ≥ 95% coverage in under-fives. While contact restrictions sufficient for SAR-CoV-2 control temporarily reduce measles transmissibility and the risk of an outbreak from a measles immunity gap, this risk rises rapidly once these restrictions are lifted. Implementing delayed SIAs will be critical for prevention of measles outbreaks given the roll-back of contact restrictions in Kenya.


Batch and fixed-bed column study for p-nitrophenol, methylene blue, and U(VI) removal by polyvinyl alcohol-graphene oxide macroporous hydrogel bead.
There is an increasing need to explore effective and clean approaches for hazardous contamination removal from wastewaters. In this work, a novel bead adsorbent, polyvinyl alcohol-graphene oxide (PVA-GO) macroporous hydrogel bead was prepared as filter media for p-nitrophenol (PNP), dye methylene blue (MB), and heavy metal U(VI) removal from aqueous solution. Batch and fixed-bed column experiments were carried out to evaluate the adsorption capacities of PNP, MB, and U(VI) on this bead. From batch experiments, the maximum adsorption capacities of PNP, MB, and U(VI) reached 347.87, 422.90, and 327.55 mg/g. From the fixed-bed column experiments, the adsorption capacities of PNP, MB, and U(VI) decreased with initial concentration increasing from 100 to 400 mg/L. The adsorption capacities of PNP, MB, and U(VI) decreased with increasing flow rate. Also, the maximum adsorption capacity of PNP decreased as pH increased from 3 to 9, while MB and U(VI) presented opposite tendencies. Furthermore, the bed depth service Time (BDST) model showed good linear relationships for the three ions' adsorption processes in this fixed-bed column, which indicated that the BDST model effectively evaluated and optimized the adsorption process of PVA-GO macroporous hydrogel bead in fixed-bed columns for hazardous contaminant removal from wastewaters.


Activity and neuromodulatory input contribute to the recovery of rhythmic output after decentralization in a central pattern generator.
Central pattern generators (CPGs) are neuronal networks that control vitally important rhythmic behaviors including breathing, heartbeat, and digestion. Understanding how CPGs recover activity after their rhythmic activity is disrupted has important theoretical and practical implications. Previous experimental and modeling studies indicated that rhythm recovery after central neuromodulatory input loss (decentralization) could be based entirely on activity-dependent mechanisms, but recent evidence of long-term conductance regulation by neuromodulators suggest that neuromodulator-dependent mechanisms may also be involved. Here we examined the effects of altering activity and the neuromodulatory environment before decentralization of the pyloric CPG in Cancer borealis on the initial phase of rhythmic activity recovery after decentralization. We found that pretreatments altering the network activity through shifting the ionic balance or the membrane potential of pyloric pacemaker neurons reduced the delay of recovery initiation after decentralization, consistent with the recovery process being triggered already during the pretreatment period through an activity-dependent mechanism. However, we observed that pretreatment with neuromodulators GABA and proctolin, acting via metabotropic receptors, also affected the initial phase of the recovery of pyloric activity after decentralization. Their distinct effects appear to result from interactions of their metabotropic effects with their effects on neuronal activity. Thus we show that the initial phase of the recovery process can be accounted for by the existence of distinct activity-and neuromodulator-dependent pathways. We propose a computational model that includes activity- and neuromodulator-dependent mechanisms of the activity recovery process, which successfully explains the experimental observations and predicts the results of key biological experiments.


Workplace experience of radiographers: impact of structural and interpersonal interventions.
Within the framework of organisational development, an assessment of the workplace experience of radiographers (RGs) was conducted. The aims of this study were to develop structural and interpersonal interventions and to prove their effectiveness and feasibility. A questionnaire consisting of work-related factors, e.g. time management and communication, and two validated instruments (Workplace Analysis Questionnaire, Effort-Reward Imbalance Scale) was distributed to all RGs (n = 33) at baseline (T1). Interventions were implemented and a follow-up survey (T2) was performed 18 months after the initial assessment. At T1, areas with highest dissatisfaction were communication and time management for ambulant patients (bad/very bad, 57% each). The interventions addressed adaptation of work plans, coaching in developing interpersonal and team leadership skills, and regular team meetings. The follow-up survey (T2) showed significantly improved communication and cooperation within the team and improved qualification opportunities, whereas no significant changes could be identified in time management and in the workplace-related scales 'effort' expended at work and 'reward' received in return for the effort. Motivating workplace experience is important for high-level service quality and for attracting well-qualified radiographers to work at a place and to stay in the team for a longer period.


The suppression of MAD1 by AKT-mediated phosphorylation activates MAD1 target genes transcription.
MAX dimerization protein 1 (MAD1) is a transcription suppressor that antagonizes MYC-mediated transcription activation, and the inhibition mechanism occurs mainly through the competition of target genes' promoter MYC binding sites by MAD1. The promoter binding proteins switch between MYC and MAD1 affects cell proliferation and differentiation. However, little is known about MAD1's regulation process in cancer cells. Here, we present evidence that AKT inhibits MAD1-mediated transcription repression by physical interaction with and phosphorylation of MAD1. Phosphorylation reduces the binding affinity between MAD1 and its target genes' promoter and thereby abolishes its transcription suppression function. Mutation of the phosphorylation site from serine to alanine rescues the DNA-binding ability in the presence of activated AKT. In addition, AKT inhibits MAD1-mediated target genes (hTERT and ODC) transcription repression and promotes cell cycle and cell growth. However, mutated S145A MAD1 abrogates the inhibition by AKT. Thus, our results suggest that phosphorylation of MAD1 by AKT inhibits MAD1-mediated transcription suppression and subsequently activates the transcription of MAD1 target genes.


Population Modelling in Affective Disorders.
The prevalence of affective disorders is on the rise. This upward trajectory leads to a substantial personal and societal cost. There is growing body of literature demonstrating decision-making impairments associated with affective disorders, and more studies are using computational modelling methods to infer underlying mechanisms of these impairments from participant choice behaviour. However, lack of population modelling suggests that data resources may still be underutilised. A number of recent studies associated major depression with abnormal risky decision-making as well as impairments in temporal discounting and social decision-making. These domains capture relevant aspects of real-life decision-making. Consequently, data from these studies can be used to define behavioural phenotypes for major depression. The manuscript describes a detailed proposal for population modelling to capture changes in the prevalence rate of major depression. The population modelling approach can also identify which decision-making domains can account for a larger part of impairments in psychosocial functioning and how behavioural interventions built on computational principles can target these to improve real-life psychosocial functioning in patient groups.


Impact of feed additives on surface mucosal health and columnaris susceptibility in channel catfish fingerlings, Ictalurus punctatus.
One of the highest priority areas for improvement in aquaculture is the development of dietary additives and formulations which provide for complete mucosal health and protection of fish raised in intensive systems. Far greater attention has been paid to dietary impact on gut health than to protective effects at other mucosal surfaces such as skin and gill. These exterior surfaces, however, are important primary targets for pathogen attachment and invasion. Flavobacterium columnare, the causative agent of columnaris disease, is among the most prevalent of all freshwater disease-causing bacteria, impacting global aquaculture of catfish, salmonids, baitfish and aquaria-trade species among others. This study evaluated whether the feeding of a standard catfish diet supplemented with Alltech dietary additives Actigen(®), a concentrated source of yeast cell wall-derived material and/or Allzyme(®) SSF, a fermented strain of Aspergillus niger, could offer protection against F. columnare mortality. A nine-week feeding trial of channel catfish fingerlings with basal diet (B), B + Allzyme(®) SSF, B + Actigen(®) and B + Actigen(®)+Allzyme(®) SSF revealed good growth in all conditions (FCR < 1.0), but no statistical differences in growth between the treatments were found. At nine weeks, based on pre-challenge trial results, basal, B + Actigen(®), and B + Allzyme(®) SSF groups of fish were selected for further challenges with F. columnare. Replicated challenge with a virulent F. columnare strain, revealed significantly longer median days to death in B + Allzyme(®) SSF and B + Actigen(®) when compared with the basal diet (P < 0.05) and significantly higher survival following the eight day challenge period in B + Actigen(®) when compared with the other two diets (P < 0.05). Given the superior protection provided by the B + Actigen(®) diet, we carried out transcriptomic comparison of gene expression of fish fed that diet and the basal diet before and after columnaris challenge using high-throughput RNA-seq. Pathway and enrichment analyses revealed changes in mannose receptor DEC205 and IL4 signaling at 0 h (prior to challenge) which likely explain a dramatic divergence in expression profiles between the two diets soon after pathogen challenge (8 h). Dietary mannose priming resulted in reduced expression of inflammatory cytokines, shifting response patterns instead to favor resolution and repair. Our results indicate that prebiotic dietary additives may provide protection extending beyond the gut to surface mucosa.


Mutations affecting substrate specificity of the Bacillus subtilis multidrug transporter Bmr.
The Bacillus subtilis multidrug transporter Bmr, a member of the major facilitator superfamily of transporters, causes the efflux of a number of structurally unrelated toxic compounds from cells. We have shown previously that the activity of Bmr can be inhibited by the plant alkaloid reserpine. Here we demonstrate that various substitutions of residues Phe143 and Phe306 of Bmr not only reduce its sensitivity to reserpine inhibition but also significantly change its substrate specificity. Cross-resistance profiles of bacteria expressing mutant forms of the transporter differ from each other and from the cross-resistance profile of cells expressing wild-type Bmr. This result strongly suggests that Bmr interacts with its transported drugs directly, with residues Phe143 and Phe306 likely to be involved in substrate recognition.


Food-derived bioactive peptides influence gut function.
Bioactive peptides either present in foods or released from food proteins during digestion have a wide range of physiological effects, including on gut function. Many of the bioactive peptides characterized to date that influence gut motility, secretion, and absorption are opioid agonists or antagonists. The authors review a body of experimental evidence that demonstrates an effect of peptides from food proteins on endogenous (nondietary) protein flow at the terminal ileum of simple-stomached mammals, including adult humans. At least some dietary peptides (1000-5000 Da) significantly enhance the loss of protein from the small intestine, causing an increased amount of protein to enter the colon. Food-derived peptides appear to either stimulate protein secretion into the gut lumen or inhibit amino acid reabsorption or influence both processes simultaneously. The effect of dietary peptides on small-intestine secretory-protein dynamics is discussed in the context of the major components of gut endogenous protein, sloughed cells, enzymatic secretions, mucin, and bacterial protein.


Implications of COVID-19 for resumption of sport in South Africa: A South African Sports Medicine Association (SASMA) position statement - Part 1.
The significant impact of the coronavirus disease 2019 (COVID-19) pandemic has extended to sport with the cessation of nearly all professional and non-professional events globally. Recreational parks and fitness centres have also closed. A challenge remains to get athletes back to participation in the safest way, balancing the protection of their health while curbing the societal transmission of the virus. With this Position Statement, the South African Sports Medicine Association (SASMA) aims to guide return-to-sport as safely as possible, in an evidence-based manner, given that COVID-19 is a new illness and new information from experts in various fields continues to emerge. Clinical considerations are briefly described, focusing on a return-to-sport strategy, including education, preparation of the environment, risk stratification of sports and participants, and the practical implementation of these guidelines. The management of the potentially exposed or infected athlete is further highlighted. It is important that persons charged with managing athletes' return-to-sport in any environment must be up-to-date with local and international trends, transmission rates, regulations and sport-specific rule changes that might develop as sport resumes. Additionally, such information should be applied in a sports-specific manner, considering individual athlete's and team needs and be consistent with national legislation.


Differential responses of carbon-degrading enzyme activities to warming: Implications for soil respiration.
Extracellular enzymes catalyze rate-limiting steps in soil organic matter decomposition, and their activities (EEAs) play a key role in determining soil respiration (SR). Both EEAs and SR are highly sensitive to temperature, but their responses to climate warming remain poorly understood. Here, we present a meta-analysis on the response of soil cellulase and ligninase activities and SR to warming, synthesizing data from 56 studies. We found that warming significantly enhanced ligninase activity by 21.4% but had no effect on cellulase activity. Increases in ligninase activity were positively correlated with changes in SR, while no such relationship was found for cellulase. The warming response of ligninase activity was more closely related to the responses of SR than a wide range of environmental and experimental methodological factors. Furthermore, warming effects on ligninase activity increased with experiment duration. These results suggest that soil microorganisms sustain long-term increases in SR with warming by gradually increasing the degradation of the recalcitrant carbon pool.


Thermal dissociation of multimeric protein complexes by using nanoelectrospray mass spectrometry.
The behavior of macromolecular systems at different temperatures is often crucial to their biological activity and function. While heat-induced changes of individual proteins are readily monitored by a number of spectroscopic methods, changes in noncovalent complexes of biomolecules are more challenging to interpret. Nanoelectrospray mass spectrometry is becoming increasingly powerful in the study of large noncovalent complexes, and here we describe the design, characterization, and application of a novel probe that allows the thermocontrol of the solution in the electrospray capillary. The transition temperature for the unfolding of the protein lysozyme is readily obtained and correlates closely with that measured by fluorescence spectroscopy, thereby demonstrating the validity of this approach. We apply this technique to the study of the 200-kDa complex of the small heat shock protein TaHSP16.9, revealing both its dissociation into suboligomeric species and an increase in its size and polydispersity at elevated temperatures. In contrast, gas-phase activation of this complex is also carried out and yields a dissociation pathway fundamentally different from that observed for thermal activation in solution. As such, this probe allows the study of the reversible heat-induced changes of noncovalent complexes in a biologically relevant manner.


A Randomized Controlled Trial of Dapagliflozin Plus Once-Weekly Exenatide Versus Placebo in Individuals with Obesity and Without Diabetes: Metabolic Effects and Markers Associated with Bodyweight Loss.
The sodium-glucose cotransporter 2 inhibitor dapagliflozin and the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide reduce bodyweight via differing and complementary mechanisms. This post hoc analysis investigated the metabolic effects and baseline associations with bodyweight loss on coadministration of dapagliflozin and exenatide once weekly (QW) among adults with obesity and without diabetes. In the primary trial, adults with obesity and without diabetes [n = 50; 18-70 years; body mass index (BMI) 30-45 kg/m2] were randomized to double-blind oral dapagliflozin 10 mg (DAPA) once daily plus subcutaneous long-acting exenatide 2 mg QW (ExQW) or placebo over 24 weeks, followed by an open-label extension from 24-52 weeks during which all participants received active treatment. Primary results have been published previously. This analysis evaluated: (1) the effects of DAPA + ExQW on changes in substrates [free fatty acids (FFAs), glycerol, beta-OH-butyrate, and glucose], hormones (glucagon and insulin), and insulin secretion [insulinogenic index (IGI)] via an oral glucose tolerance test (OGTT) and (2) associations between bodyweight loss and baseline characteristics (e.g., BMI), single-nucleotide polymorphisms (SNPs) associated with the GLP-1 pathway, and markers of glucose regulation. Compared with placebo at 24 weeks, 2-h FFAs post-OGTT increased (mean difference, +20.4 μmol/l; P < 0.05), and fasting glucose, 2-h glucose post-OGTT, and glucose area under the concentration-time curve (AUC) decreased with DAPA + ExQW [mean differences, -0.68 mmol/l [P < 0.001], -2.20 mmol/l (P < 0.01), and -306 mmol/l min (P < 0.001), respectively]. Glucagon, glycerol, beta-OH-butyrate, and IGI did not differ by treatment group at 24 weeks. Over 52 weeks, DAPA + ExQW decreased fasting insulin, 2-h post-OGTT insulin, and insulin AUC. Among DAPA + ExQW-treated participants, for each copy of the SNP variant rs10010131 A allele (gene WFS1), bodyweight decreased by 2.4 kg (P < 0.05). Lower BMI and a lower IGI were also associated with greater bodyweight loss with DAPA + ExQW. Metabolic effects with DAPA + ExQW included less FFA suppression versus placebo during the OGTT, suggesting compensatory lipid mobilization for energy production when glucose availability was reduced because of glucosuria. The expected increase in glucagon with DAPA did not occur with DAPA + ExQW coadministration. Bodyweight loss with DAPA + ExQW was associated with the SNP variant rs10010131 A allele, lower baseline adiposity (BMI), and lower baseline insulin secretion (IGI). These findings require further validation. AstraZeneca.


Clinimetric properties of sacroiliac joint mobility tests: A systematic review.
Previous systematic reviews revealed poor reliability and validity for sacroiliac joint (SIJ) mobility tests. However, these reviews were published nearly 20 years ago and recent evidence has not yet been summarised. To conduct an up-to-date systematic review to verify whether recommendations regarding the clinical use of SIJ mobility tests should be revised. Systematic review. The literature was searched for relevant articles via 5 electronic databases. The review was conducted according to the PRISMA guidelines. COSMIN checklists were used to appraise the methodological quality. Studies were included if they had at least fair methodology and reported clinimetric properties of SIJ mobility tests performed in adult patients with non-specific low back pain, pelvic (girdle) pain and/or SIJ pain. Only tests that can be performed in a clinical setting were considered. Twelve relevant articles were identified, of which three were of sufficient methodological quality. These three studies evaluated the reliability of eight SIJ mobility tests and one test cluster. For the majority of individual tests, the intertester reliability showed slight to fair agreement. Although some tests and one test cluster had higher reliability, the confidence intervals around most reliability estimates were large. Furthermore, there were no validity studies of sufficient methodological quality. Considering the low and/or imprecise reliability estimates, the absence of high-quality diagnostic accuracy studies, and the uncertainty regarding the construct these tests aim to measure, this review supports the previous recommendations that the use of SIJ mobility tests in clinical practice is problematic.


The thyroid hormone receptor-beta agonist GC-1 induces cell proliferation in rat liver and pancreas.
Thyroid hormones regulate cell growth, cell differentiation, and metabolic functions via interaction with the thyroid hormone nuclear receptors (TRs). Recently, a small class of halogen-free high-affinity thyroid hormone agonists has been developed that are highly selective for the TRbeta subtype. Because of the selective hyperthyroidism generated by one of these agonists, GC-1, this compound has the potential to be developed as a new therapeutic agent for the treatment of a variety of metabolic disturbances, including lipid disorders and obesity; thus, it becomes important to determine whether GC-1 has other unknown effects on potential target organs. The purpose of this study was to investigate the effect of GC-1 on cell proliferation in rat liver and pancreas. Rats treated with GC-1 (50 or 100 mug/100 g body weight) were killed at different time points. Hepatic and pancreatic cell proliferation was monitored by immunohistochemical determination of bromodeoxyuridine incorporation. The expression of cell cycle-related genes was analyzed by Northern and Western analysis. The results show that GC-1 strongly stimulates rat hepatocyte proliferation in the absence of tissue injury. Although GC-1-induced hepatocyte proliferation was associated with a rapid increase in cyclin D1 mRNA levels, no change in the expression of c-jun and c-fos was observed. GC-1 also induced massive pancreatic cell proliferation. The results indicate that the TRbeta-selective agonist GC-1 is a strong mitogen for hepatocytes and pancreatic acinar cells. Furthermore, they suggest that the TRbeta receptor is the mediator for the mitogenic activity of thyroid hormone and other thyromimetics.


Epidemiology of complex bone and joint infections in France using a national registry: The CRIOAc network.
In France, a network of reference centers for bone and joint infections (BJI) was created in 2008, focused on the management of complex BJI (previous failure, difficult-to-treat microorganisms, heavy comorbidities or surgical procedures). A national registry was implemented from 2012, collecting decisions advised in periodic multidisciplinary meetings. We present here an epidemiological overview. All consecutive adult patients presented from 2014 to 2019 in 23/30 reference centers were included in this cohort. Characteristics of patients, BJI, and medico-surgical management advice were described. 27,483 individual patients were included, corresponding to 28,365 distinct infectious episodes, which 17,328 were complex. Median age was 65 years, with 62% of men, 1/3 patients presented more than 2 comorbidities. Prosthetic joint infections (PJI) represented 42% of all BJIs (11,812 episodes). Staphylococcus aureus, coagulase-negative staphylococci and polymicrobial PJI represented 26%, 25% and 16% respectively. DAIR (debridement, antibiotics and implant retention) was proposed for 3,157 (27%), whereas one-stage and two-stage revision for 3,683 (31%) and 1,764 (15%). An antibiotic treatment was advised in 10,493 episodes (87%), with combination therapy in 88%. This national network allows an optimized management of complex BJIs. Its cohort is a unique opportunity to draw up a detailed epidemiological picture and to follow the trends of these infrequent infections.


The herpes simplex virus type 1 DNA polymerase processivity factor increases fidelity without altering pre-steady-state rate constants for polymerization or excision.
Pre-steady-state and steady-state kinetics of nucleotide incorporation and excision were used to assess potential mechanisms by which the fidelity of the herpes simplex virus type 1 DNA polymerase catalytic subunit (Pol) is enhanced by its processivity factor, UL42. UL42 had no effect on the pre-steady-state rate constant for correct nucleotide incorporation (150 s(-1)) nor on the primary rate-limiting conformational step. However, the equilibrium dissociation constant for the enzyme in a stable complex with primer-template was 44 nm for Pol and 7.0 nm for Pol/UL42. The catalytic subunit and holoenzyme both selected against incorrect nucleotide incorporation predominantly at the level of nucleotide affinity, although UL42 slowed by 4-fold the maximum rate of incorporation of incorrect, compared with correct, nucleotide. Pol, with or without UL42, cleaved matched termini at a slower rate than mismatched ones, but UL42 did not significantly alter the pre-steady-state rate constant for mismatch excision ( approximately 16 s(-1)). The steady-state rate constant for nucleotide addition was 0.09 s(-1) and 0.03 s(-1) for Pol and Pol/UL42, respectively, and enzyme dissociation was the rate-limiting step. The longer half-life for DNA complexes with Pol/UL42 (23 s) compared with that with Pol (8 s) affords a greater probability for excision when a misincorporation event does occur, accounting predominantly for the failure of Pol/UL42 to accumulate mismatched product at moderate nucleotide concentrations.


Identifying and recruiting healthy control subjects from a managed care organization: a methodology for molecular epidemiological case-control studies of cancer.
Case-control studies with stringent matching criteria require large pools of healthy subjects from which to select matched controls. This paper describes a successful method of identifying a large pool of potential control subjects to participate in two molecular epidemiological case-control studies of lung cancer, each enrolling 400 case subjects and 400 control subjects. These studies are not population based, and the study base is not well-defined. Therefore, potential control subjects are being identified and recruited through 20 area clinic sites of a large multispecialty health maintenance organization. Because the research focus is driven by genetic hypotheses and we are controlling for multiple smoking-related variables, representativeness is of lesser concern. To identify potential control subjects, a one-page questionnaire is distributed to patients in the waiting room to assess contact information as well as data relevant to the case-control matching process. An average of 2,228 questionnaires are returned monthly toward a target pool of 40,000; of these, 59% of the respondents fulfill eligibility criteria as a control subject for one of the studies and are not averse to being contacted in the future for the purpose of research. When compared to former smokers and never smokers, current smokers in the control population were least likely to refuse further contact. A collaborative arrangement with a managed care organization offers a feasible mechanism through which researchers can access a large, ethnically diverse population of potential control subjects.


An Overview of the Challenges in Designing, Integrating, and Delivering BARD: A Public Chemical-Biology Resource and Query Portal for Multiple Organizations, Locations, and Disciplines.
Recent industry-academic partnerships involve collaboration among disciplines, locations, and organizations using publicly funded "open-access" and proprietary commercial data sources. These require the effective integration of chemical and biological information from diverse data sources, which presents key informatics, personnel, and organizational challenges. The BioAssay Research Database (BARD) was conceived to address these challenges and serve as a community-wide resource and intuitive web portal for public-sector chemical-biology data. Its initial focus is to enable scientists to more effectively use the National Institutes of Health Roadmap Molecular Libraries Program (MLP) data generated from the 3-year pilot and 6-year production phases of the Molecular Libraries Probe Production Centers Network (MLPCN), which is currently in its final year. BARD evolves the current data standards through structured assay and result annotations that leverage BioAssay Ontology and other industry-standard ontologies, and a core hierarchy of assay definition terms and data standards defined specifically for small-molecule assay data. We initially focused on migrating the highest-value MLP data into BARD and bringing it up to this new standard. We review the technical and organizational challenges overcome by the interdisciplinary BARD team, veterans of public- and private-sector data-integration projects, who are collaborating to describe (functional specifications), design (technical specifications), and implement this next-generation software solution.


An assessment and monitoring program for birds in the Lower Urubamba region, Peru.
We developed an assessment and monitoring plan for birds in connection with the exploration and potential development of a large natural gas field in the Lower Urubamba drainage of Peru, a project of Shell Prospecting and Development Peru (SPDP). Our objectives were to: (1) inventory the birds in the area, including information on habitat use and abundance, and (2) devise long-term monitoring protocols for birds. We sampled birds through a combination of visual and auditory surveys and mist-netting at 4 well sites and 3 sites along the Urubamba and Camisea rivers. We recorded 420 species during 135 days of field work. We consider the highest priorities for a future monitoring program to be: (1) establish whether edge effects are occurring at well sites, along roads and along the planned pipeline route and determine the significance and extent of these effects and (2) assess the impact of increased human access to the area on game and other exploited species. The remoteness of the area, its rugged terrain and dense vegetation and the lack of trained personnel limit the choice of survey and monitoring methods. We recommend use of mist-netting and transects for monitoring edge effects and use of transects for monitoring game and other exploited species.


Novelty, uncertainty, and the looming horizon.
Novelty and uncertainty are powerful drivers of exploration that are often conflated. In this issue of Neuron, Cockburn and colleagues dissociate the two and report a key interaction: close to task termination, novel options appear much more attractive relative to uncertain options.


Relationship Between Physiologically Measured Attention and Behavioral Task Engagement in Persons With Chronic Aphasia.
Purpose Persons with aphasia (PWAs) have been shown to have impaired attention skills that may interfere with their ability to successfully participate in speech and language therapy. Fluctuations in attention can be detected using physiological measures such as electroencephalography (EEG), but these measures can be impractical for clinical use. The primary purpose of this study was to investigate observable behavioral signs of attention as a means of measuring within-session fluctuations in attention by comparing behavioral ratings to physiological changes. Other aims were to understand the relationship between observable behaviors and task performance and to determine whether syntactic complexity influences behavioral attention. Method Ten PWAs and 10 neurologically healthy adults underwent a sentence-reading task with 45 active and 45 passive sentences while video/audio and EEG data were recorded continuously. EEG data for each trial were classified into one of four levels of attention using a classification algorithm (Berka et al., 2004), and video/audio data were scored for accuracy and behavioral engagement by two trained speech-language pathologist students using a behavioral rating scale of inattention (Whyte et al., 1996). Results Results showed that behavioral engagement was significantly correlated with task performance, with higher engagement scores associated with fewer errors. Behavioral engagement did not differ based on syntactic complexity for either group, but PWAs had significantly lower behavioral engagement scores when they were in lower/distracted states of physiologically measured vigilant attention. Conclusion Behavioral observation may provide an alternative means of detecting clinically significant lapses in attention during aphasia therapy.


Trends in self-reported psychological distress among college and university students from 2010 to 2018.
An increase in reported psychological distress, particularly among adolescent girls, is observed across a range of countries. Whether a similar trend exists among students in higher education remains unknown. The aim of the current study was to describe trends in self-reported psychological distress among Norwegian college and university students from 2010 to 2018. We employed data from the Students' Health and Wellbeing Study (SHoT), a nationwide survey for higher education in Norway including full-time students aged 18-34. Numbers of participants (participation rates) were n = 6065 (23%) in 2010, n = 13 663 (29%) in 2014 and n = 49 321 (31%) in 2018. Psychological distress was measured using the Hopkins Symptom Checklist-25 (HSCL-25). Overall, a statistically significant increase in self-reported psychological distress was observed over time across gender and age-groups. HSCL-25 scores were markedly higher for women than for men at all time-points. Effect-size of the mean change was also stronger for women (time-by-gender interaction: χ2 = 70.02, df = 2, p < 0.001): in women, mean HSCL-25 score increased from 1.62 in 2010 to 1.82 in 2018, yielding a mean change effect-size of 0.40. The corresponding change in men was from 1.42 in 2010 to 1.53 in 2018, giving an effect-size of 0.26. Both the level and increase in self-reported psychological distress among Norwegian students in higher education are potentially worrying. Several mechanisms may contribute to the observed trend, including changes in response style and actual increase in distress. The relative low response rates in SHoT warrant caution when interpreting and generalising the findings.


Practical success of biomanipulation using filter-feeding Fish to control cyanobacteria blooms: a synthesis of decades of research and application in a subtropical hypereutrophic lake.
Lake Donghu is a 32-km2 shallow, subtropical lake near the Yangtze River (P.R. China) that has experienced dramatic changes in the past five decades. These changes include: (1) a trophic state change from mesotrophy to hypertrophy; (2) dense blooms of cyanobacteria during every summer from the 1970s to 1984; (3) a cessation of blooms starting in 1985, with no recurrence; and (4) an increase, coincident with bloom declines, in the production of silver and bighead carp (filter-feeders) by more than tenfold. There are several possible explanations for the disappearance of blooms, including changes in nutrient concentrations, increased zooplankton grazing, and increased grazing on algae by fish. The long-term data suggest that changes in nutrients or in zooplankton were not important, but that the remarkably increased fish densities might have played the key role. To test this hypothesis, in situ enclosure experiments were conducted in three years. The main conclusions are as follows: (1) an increased stocking of the lake with carp played a decisive role in the elimination of cyanobacteria blooms; (2) both silver and bighead carp can eliminate cyanobacteria blooms directly by grazing; (3) zooplankton cannot suppress the blooms; and (4) the lake still is vulnerable to the outbreak of blooms, should fish grazing decline. The critical biomass of carp is approximately 50 g m3. The results suggest the applicability of a new food-web manipulation (increased stocking with filter-feeding fish) for controlling cyanobacteria blooms in hypereutrophic lakes. The approach differs from traditional biomanipulation in Europe and North America, where piscivores are added to control planktivores, and this in turn increases zooplankton and decreases algae. The new biomanipulation method is being used or being tested to counteract cyanobacteria blooms in many Chinese lakes such as Lake Dianchi in Yunnan Province, Lake Chaohu in Anhui Province, and Lake Taihu in Jiangsu Province. The method has great potential as an important component of an integrated approach to counteract cyanobacteria blooms, especially in lakes where nutrient inputs cannot be reduced sufficiently, and where zooplankton cannot effectively control phytoplankton production.