Triggers of eating in everyday life.
Understanding the triggers of eating in everyday life is crucial for the creation of interventions to promote healthy eating and to prevent overeating. Here, the proximal predictors of eating are explored in a natural setting. Research from laboratory settings suggests that restrained eaters overeat after experiencing anxiety, distraction, and the presence of positive or negative moods, but not hunger; whereas the only factor that triggers eating in unrestrained eaters is hunger. In this study, 137 female participants reported hourly for 2 days on these potential predictors and their eating using electronic diaries, allowing us to establish the relationships between these factors while participants went about their normal daily activities. The main outcome variables were the number of servings eaten and whether or not food was eaten. Contrary to findings from laboratory settings, in everyday life restrained eaters (1) did not overeat in response to anxiety; (2) ate less in the presence of positive or negative moods; and (3) ate more in response to hunger. The relationships between these factors and eating among unrestrained eaters were closer to those found in laboratory settings. In conclusion, predictors of eating must be studied in everyday life to develop successful interventions.


Mice lacking EFA6C/Psd2, a guanine nucleotide exchange factor for Arf6, exhibit lower Purkinje cell synaptic density but normal cerebellar motor functions.
ADP ribosylation factor 6 (Arf6) is a small GTPase that regulates various neuronal events including formation of the axon, dendrites and dendritic spines, and synaptic plasticity through actin cytoskeleton remodeling and endosomal trafficking. EFA6C, also known as Psd2, is a guanine nucleotide exchange factor for Arf6 that is preferentially expressed in the cerebellar cortex of adult mice, particularly in Purkinje cells. However, the roles of EFA6C in cerebellar development and functions remain unknown. In this study, we generated global EFA6C knockout (KO) mice using the CRISPR/Cas9 system and investigated their cerebellar phenotypes by histological and behavioral analyses. Histological analyses revealed that EFA6C KO mice exhibited normal gross anatomy of the cerebellar cortex, in terms of the thickness and cellularity of each layer, morphology of Purkinje cells, and distribution patterns of parallel fibers, climbing fibers, and inhibitory synapses. Electron microscopic observation of the cerebellar molecular layer revealed that the density of asymmetric synapses of Purkinje cells was significantly lower in EFA6C KO mice compared with wild-type control mice. However, behavioral analyses using accelerating rotarod and horizontal optokinetic response tests failed to detect any differences in motor coordination, learning or adaptation between the control and EFA6C KO mice. These results suggest that EFA6C plays ancillary roles in cerebellar development and motor functions.


Regulated expression of telomerase activity in human T lymphocyte development and activation.
Telomerase, a ribonucleoprotein that is capable of synthesizing telomeric repeats, is expressed in germline and malignant cells, and is absent in most normal human somatic cells. The selective expression of telomerase has thus been proposed to be a basis for the immortality of the germline and of malignant cells. In the present study, telomerase activity was analyzed in normal human T lymphocytes. It was found that telomerase is expressed at a high level in thymocyte subpopulations, at an intermediate level in tonsil T lymphocytes, and at a low to undetectable level in peripheral blood T lymphocytes. Moreover, telomerase activity is highly inducible in peripheral T lymphocytes by activation through CD3 with or without CD28 costimulation, or by stimulation with phorbol myristate acetate (PMA)/ionomycin. The induction of telomerase by anti-CD3 plus anti-CD28 (anti-CD3/CD28) stimulation required RNA and protein synthesis, and was blocked by herbimycin A, an inhibitor of S pi protein tyrosine kinases. The immunosuppressive drug cyclosporin A selectively inhibited telomerase induction by PMA/ionomycin and by anti-CD3, but not by anti-CD3/CD28. Although telomerase activity in peripheral T lymphocytes was activation dependent and correlated with cell proliferation, it was not cell cycle phase restricted. These results indicate that the expression of telomerase in normal human T lymphocytes is both developmentally regulated and activation induced. Telomerase may thus play a permissive role in T cell development and in determining the capacity of lymphoid cells for cell division and clonal expansion.


Dual beneficial effects of (-)-epigallocatechin-3-gallate on levodopa methylation and hippocampal neurodegeneration: in vitro and in vivo studies.
A combination of levodopa (L-DOPA) and carbidopa is the most commonly-used treatment for symptom management in Parkinson's disease. Studies have shown that concomitant use of a COMT inhibitor is highly beneficial in controlling the wearing-off phenomenon by improving L-DOPA bioavailability as well as brain entry. The present study sought to determine whether (-)-epigallocatechin-3-gallate (EGCG), a common tea polyphenol, can serve as a naturally-occurring COMT inhibitor that also possesses neuroprotective actions. Using both in vitro and in vivo models, we investigated the modulating effects of EGCG on L-DOPA methylation as well as on chemically induced oxidative neuronal damage and degeneration. EGCG strongly inhibited human liver COMT-mediated O-methylation of L-DOPA in a concentration-dependent manner in vitro, with an average IC50 of 0.36 microM. Oral administration of EGCG moderately lowered the accumulation of 3-O-methyldopa in the plasma and striatum of rats treated with L-DOPA+carbidopa. In addition, EGCG also reduced glutamate-induced oxidative cytotoxicity in cultured HT22 mouse hippocampal neuronal cells through inactivation of the nuclear factor kappaB-signaling pathway. Under in vivo conditions, administration of EGCG exerted a strong protective effect against kainic acid-induced oxidative neuronal death in the hippocampus of rats. These observations suggest that oral administration of EGCG may have significant beneficial effects in Parkinson's patients treated with L-DOPA and carbidopa by exerting a modest inhibition of L-DOPA methylation plus a strong neuroprotection against oxidative damage and degeneration.


Water safety education among primary school children in Grenada.
Drowning is a common cause of death among children. Successful prevention interventions currently used in developed countries are often not transferable into developing countries due to differences in both environment and resources. In this study, we adapted a water safety education programme developed by the American Red Cross for primary school students in Grenada. Water safety knowledge before and after the training session was assessed using a nine-question evaluation tool. Following the training, a survey was administered to all teachers to assess the adaptability and effectiveness of the WHALE Tales training. Fifty-six students (30% males) completed the training. The age range was between 5 and 12 years old. Participants' water safety knowledge increased 15% (p < 0.01). Mean scores of correct answers increased for every grade level, ranging from a 5% increase for first graders to 33% increase for second graders. The findings from this study suggested that implementation of such a programme is effective. With cultural modifications and outsourcing, we believe this adapted programme would be successful in Grenada and other similar settings.


Detection of drugs of abuse in saliva by surface-enhanced Raman spectroscopy (SERS).
Eighty drugs of abuse and metabolites were successfully measured by surface-enhanced Raman spectroscopy (SERS) using gold- and silver-doped sol-gels immobilized in glass capillaries. A method was developed that provided consistent detection of 50 ppb cocaine in saliva in a focused study. This general method was successfully applied to the detection of a number of additional drugs in saliva, such as amphetamine, diazepam, and methadone.


The Swedish Blood Pass project.
Manipulation of the blood's oxygen carrying capacity (CaO(2)) through reinfusion of red blood cells, injections of recombinant erythropoietin or by other means results in an increased maximal oxygen uptake and concomitantly enhanced endurance performance. Therefore, there is a need to establish a system--"A Blood Pass"--through which such illegal and unethical methods can be detected. Venous blood samples were taken under standardized conditions from 47 male and female Swedish national and international elite endurance athletes four times during the athletic year of the individual sport (beginning and end of the preparation period and at the beginning and during peak performance in the competition period). In these samples, different hematological values were determined. ON(hes) and OFF(hre) values were calculated according to the formula of Gore et al. A questionnaire regarding training at altitude, alcohol use and other important factors for hematological status was answered by the athletes. There were some individual variations comparing hematological values obtained at different times of the athletic year or at the same time in the athletic year but in different years. However, the median values of all individual hematological, ON(hes) and OFF(hre), values taken at the beginning and the end of the preparation or at the beginning and the end of the competition period, respectively, as well as median values for the preparation and competition periods in the respective sport, were all within the 95% confidence limit (CI) of each comparison. It must be mentioned that there was no gender difference in this respect. This study shows that even if there are some individual variations in different hematological values between different sampling times in the athletic year, median values of important hematological factors are stable over time. It must be emphasized that for each blood sample, the 95% CI in each athlete will be increasingly narrower. The conclusion is that there is a physiological basis for establishing an individual-based "Blood Pass" system, mainly for athletes competing at the international level. On indications of manipulations of hemoglobin concentration and red cell mass by deviations from established "Blood Pass" data, more specific methods can be applied.


Cloud identification in atmospheric trace molecule spectroscopy infrared occultation measurements.
High-resolution infrared nongas absorption spectra derived from the Atmospheric Trace Molecule Spectroscopy (ATMOS) experiment are analyzed for evidence of the presence of cirrus clouds. Several nonspherical ice extinction models based on realistic size distributions and crystal habits along with a stratospheric sulfate aerosol model are fit to the spectra, and comparisons are made with different model combinations. Nonspherical ice models often fit observed transmission spectra better than a spherical Mie ice model, and some discrimination among nonspherical models is noted. The ATMOS lines of sight for eight occultations are superimposed on coincident geostationary satellite infrared imagery, and brightness temperatures along the lines of sight are compared with retrieved vertical temperature profiles. With these comparisons, studies of two cases of clear sky, three cases of opaque cirrus, and three cases of patchy cirrus are discussed.


Isolation and characterization of an acquired antithrombin antibody.
A 68-year-old man, following mitral valve replacement, presented with a low-grade chronic consumptive coagulopathy. Laboratory analysis showed mild fibrinolysis, minimal effect of coumadin therapy, and a prolonged thrombin time (greater than 150 seconds using bovine IIa). When purified human IIa was used the thrombin time normalized to within 17 seconds of controls, suggesting a possible inhibitor of bovine IIa. An anti-IIa antibody was isolated by protein A-Sepharose (Sigma, St Louis, MO) chromatography followed by affinity chromatography using a bovine IIa-Sepharose column. The effects of this purified anti-IIa antibody on both bovine and human IIa procoagulant and anticoagulant functions were studied. The isolated immunoglobulin G (IgG) was observed to inhibit bovine IIa in all assays tested. This IgG was also able to slightly prolong fibrinogen clotting by human IIa. Using an enzyme-linked immunosorbent assay it was observed that the IgG bound to bovine IIa, bovine II, human IIa, but not to human II. Further, binding was detectable at approximately 50-fold lower concentrations to bovine IIa (1 nmol/L IgG concentration) than to human IIa (50 nmol/L IgG concentration). The effect of the antibody on the reaction between IIa and AT III/heparin was investigated. Human IIa was found to be protected from AT III/heparin neutralization in the presence of this antibody. These results suggest that this patient developed an antibody that strongly binds to and inhibits the bovine IIa in all assays tested. However, the antibody only significantly affects human IIa neutralization by AT III/heparin, and has little effect on the human IIa procoagulant activity. These data suggest that the decreased effect of AT III/heparin on this patient's IIa may have been a contributing factor in his coagulopathy. The exact cause of this antibody development is unclear, but the role of bovine topical thrombin used during cardiac valve replacement surgery is suspect.


Convenient methods for ingestion of molecular hydrogen: drinking, injection, and inhalation.
Molecular hydrogen (H2) is clinically administered; however, in some hospitals, H2 is given to patients without consideration of its safe use. In the present study, we prepared convenient and safe devices for the drinking of super-saturated H2 water, for intravenous drip infusion of H2-rich saline, and for the inhalation of H2 gas. In order to provide useful information for researchers using these devices, the changes in H2 concentration were studied. Our experimental results should contribute to the advance of non-clinical and clinical research in H2 medicine.


Hemicallotasis open-wedge osteotomy for osteoarthritis of the knee. Complications in 308 operations.
We studied the complications after open-wedge osteotomy by hemicallotasis in 308 consecutive patients, most of whom had osteoarthritis of the knee. The participating surgeons, who worked at 17 hospitals, used their discretion in selecting patients, operating techniques and external fixators. The general complications included 11 cases of deep-vein thrombosis (4%), six of nonunion (2%) and one of septic arthritis of the knee. There were technical complications in 13 patients (4%). In 157 patients (51%) pin-site infections were recorded; of these, 96% were minor and responded to wound toilet and antibiotic treatment. A total of 18 revision procedures was carried out.


The Impact of COVID-19 on Emergent Large-Vessel Occlusion: Delayed Presentation Confirmed by ASPECTS.
Our hypothesis is that the COVID-19 pandemic led to delayed presentations for patients with acute ischemic stroke. This study evaluates the impact of the coronavirus disease 2019 pandemic on presentation, treatment, and outcomes of patients with emergent large-vessel occlusion using data from a large health system in the Bronx, New York. We performed a retrospective cohort study of 2 cohorts of consecutive patients with emergent large-vessel occlusion admitted to 3 Montefiore Health System hospitals in the Bronx from January 1 to February 17, 2020, (prepandemic) and March 1 to April 17, 2020 (pandemic). We abstracted data from the electronic health records on presenting biomarker profiles, admission and postprocedural NIHSS scores, time of symptom onset, time of hospital presentation, time of start of the thrombectomy procedure, time of revascularization, presenting ASPECTS, TICI recanalization score, mRS, functional outcomes, and mortality. Of 179 patients admitted with ischemic stroke during the study periods, 80 had emergent large-vessel occlusion, of whom 36 were in the pandemic group. Patients in the pandemic group were younger (66 versus 72 years, P < .061) and had lower ASPECTS (7 versus 9, P < .001) and took longer to arrive at the hospital (361 versus 152 minutes, P < .004) with no other major differences. There was a decreased rate of thrombolysis administration (22% versus 43%, P < .049) and a decreased number of patients treated with mechanical thrombectomy (33% versus 61%, P < .013). The pandemic led to delays in patients arriving at hospitals, leading to decreased patients eligible for treatment, while in-hospital evaluation and treatment times remain unchanged.


Maternal investment, sibling competition, and offspring survival with increasing litter size and parity in pigs (Sus scrofa).
The aim of this study was to examine the effects of litter size and parity on sibling competition, piglet survival, and weight gain. It was predicted that competition for teats would increase with increasing litter size, resulting in a higher mortality due to maternal infanticide (i.e., crushing) and starvation, thus keeping the number of surviving piglets constant. We predicted negative effects on weight gain with increasing litter size. Based on maternal investment theory, we also predicted that piglet mortality would be higher for litters born late in a sow's life and thus that the number of surviving piglets would be higher in early litters. As predicted, piglet mortality increased with increasing litter size both due to an increased proportion of crushed piglets, where most of them failed in the teat competition, and due to starvation caused by increased sibling competition, resulting in a constant number of survivors. Piglet weight at day 1 and growth until weaning also declined with increasing litter size. Sows in parity four had higher piglet mortality due to starvation, but the number of surviving piglets was not affected by parity. In conclusion, piglet mortality caused by maternal crushing of piglets, many of which had no teat success, and starvation caused by sibling competition, increased with increasing litter size for most sow parities. The constant number of surviving piglets at the time of weaning suggests that 10 to 11 piglets could be close to the upper limit that the domestic sow is capable of taking care of.


[Isoniazid induced neuropathy: consider prevention].
Antituberculous treatment is effective but has numerous side effects. Among these isoniazid induced neuropathy is easily preventable. A female patient of 42 years, infected with HIV, presented with general deterioration associated with an interstitial pulmonary infiltrate and mediastinal lymphadenopathy. Tuberculosis was not confirmed bacteriologically but she responded to antituberculous treatment. Three months later she developed distal leg pains extending proximally. There was superficial sensory impairment up to the groins and loss of the ankle reflexes. The dose of isoniazid was reduced from 5 to 2.5 mg/kg/day on account of slow acetylator status and treatment with pyridoxine 250 mg/day commenced. The clinical signs resolved in a few weeks. Isoniazid neuropathy develops in the presence of risk factors (HIV, alcoholism, diabetes, renal failure, malnutrition, pregnancy and lactation, neurotoxic medication) and manifests itself initially by burning feet. Pyridoxine is preventative in low dosage and curative in high dosage. The development of symptoms should lead to measurement of acetylator status, and a reduction of the isoniazid dose to 3 mg/kg/day or even less in slow acetylators.


Development of an algorithm to link electronic health record prescriptions with pharmacy dispense claims.
Medication adherence is an important aspect of chronic disease management. Electronic health record (EHR) data are often not linked to dispensing data, limiting clinicians' understanding of which of their patients fill their medications, and how to tailor care appropriately. We aimed to develop an algorithm to link EHR prescribing to claims-based dispensing data and use the results to quantify how often patients with diabetes filled prescribed chronic disease medications. We developed an algorithm linking EHR prescribing data (RxNorm terminology) to claims-based dispensing data (NDC terminology), within sample of adult (19-64) community health center (CHC) patients with diabetes from a network of CHCs across 12 states. We demonstrate an application of the method by calculating dispense rates for a set of commonly prescribed diabetes and cardio-protective medications. To further inform clinical care, we computed adjusted odds ratios of dispense by patient-, encounter-, and clinic-level characteristics. Seventy-six percent of cardio-protective medication prescriptions and 74% of diabetes medications were linked to a dispensing record. Age, income, ethnicity, insurance, assigned primary care provider, comorbidity, time on EHR, and clinic size were significantly associated with odds of dispensing. EHR prescriptions and pharmacy dispense data can be linked at the record level across different terminologies. Dispensing rates in this low-income population with diabetes were similar to other populations. Record linkage resulted in the finding that CHC patients with diabetes largely had their chronic disease medications dispensed. Understanding factors associated with dispensing rates highlight barriers and opportunities for optimal disease management.


Quantitative trait loci that modulate trabecular bone's risk of failure during unloading and reloading.
Genetic makeup of an individual is a strong determinant of the morphologic and mechanical properties of bone. Here, in an effort to identify quantitative trait loci (QTLs) for changes in the simulated mechanical parameters of trabecular bone during altered mechanical demand, we subjected 352 second generation female adult (16 weeks old) BALBxC3H mice to 3 weeks of hindlimb unloading followed by 3 weeks of reambulation. Longitudinal in vivo microcomputed tomography (μCT) scans tracked trabecular changes in the distal femur. Tomographies were directly translated into finite element (FE) models and subjected to a uniaxial compression test. Apparent trabecular stiffness and components of the Von Mises (VM) stress distributions were computed for the distal metaphysis and associated with QTLs. At baseline, five QTLs explained 20% of the variation in trabecular peak stresses across the mouse population. During unloading, three QTLs accounted for 14% of the variability in peak stresses. During reambulation, one QTL accounted for 5% of the variability in peak stresses. QTLs were also identified for mechanically induced changes in stiffness, median stress values and skewness of stress distributions. There was little overlap between QTLs identified for baseline and QTLs for longitudinal changes in mechanical properties, suggesting that distinct genes may be responsible for the mechanical response of trabecular bone. Unloading related QTLs were also different from reambulation related QTLs. Further, QTLs identified here for mechanical properties differed from previously identified QTLs for trabecular morphology, perhaps revealing novel gene targets for reducing fracture risk in individuals exposed to unloading and for maximizing the recovery of trabecular bone's mechanical properties during reambulation.


p21-activated kinase 1: PAK'ed with potential.
The p21-activated kinases (PAKs) are central players in growth factor signaling networks and morphogenetic processes that control proliferation, cell polarity, invasion and actin cytoskeleton organization. This raises the possibility that interfering with PAK activity may produce significant anti-tumor activity. In this perspective, we summarize recent data concerning the contribution of the PAK family member, PAK1, in growth factor signaling and tumorigenesis. We further discuss mechanisms by which inhibition of PAK1 can arrest tumor growth and promote cell apoptosis, and the types of cancers in which PAK1 inhibition may hold promise.


Quantifying Heterogeneity in Host-Vector Contact: Tsetse (Glossina swynnertoni and G. pallidipes) Host Choice in Serengeti National Park, Tanzania.
Identifying hosts of blood-feeding insect vectors is crucial in understanding their role in disease transmission. Rhodesian human African trypanosomiasis (rHAT), also known as acute sleeping sickness is caused by Trypanosoma brucei rhodesiense and transmitted by tsetse flies. The disease is commonly associated with wilderness areas of east and southern Africa. Such areas hold a diverse range of species which form communities of hosts for disease maintenance. The relative importance of different wildlife hosts remains unclear. This study quantified tsetse feeding preferences in a wilderness area of great host species richness, Serengeti National Park, Tanzania, assessing tsetse feeding and host density contemporaneously. Glossina swynnertoni and G. pallidipes were collected from six study sites. Bloodmeal sources were identified through matching Cytochrome B sequences amplified from bloodmeals from recently fed flies to published sequences. Densities of large mammal species in each site were quantified, and feeding indices calculated to assess the relative selection or avoidance of each host species by tsetse. The host species most commonly identified in G. swynnertoni bloodmeals, warthog (94/220), buffalo (48/220) and giraffe (46/220), were found at relatively low densities (3-11/km2) and fed on up to 15 times more frequently than expected by their relative density. Wildebeest, zebra, impala and Thomson's gazelle, found at the highest densities, were never identified in bloodmeals. Commonly identified hosts for G. pallidipes were buffalo (26/46), giraffe (9/46) and elephant (5/46). This study is the first to quantify tsetse host range by molecular analysis of tsetse diet with simultaneous assessment of host density in a wilderness area. Although G. swynnertoni and G. pallidipes can feed on a range of species, they are highly selective. Many host species are rarely fed on, despite being present in areas where tsetse are abundant. These feeding patterns, along with the ability of key host species to maintain and transmit T. b. rhodesiense, drive the epidemiology of rHAT in wilderness areas.


Endothelin ETA receptor blockade with darusentan increases sodium and potassium excretion in aging rats.
This study investigated whether intrarenal endothelin-1(ET-1) contributes to sodium excretion in aged rats. Metabolic function studies were performed in male Wistar rats (3 and 24 months) treated with placebo or the orally active ET(A) receptor antagonist darusentan (20 mg/kg/d) for 4 weeks. Mean arterial pressure was measured using an intra-arterial catheter. Electrolytes, aldosterone levels, renin activity, and angiotensin converting enzyme activity were determined in plasma, and mRNA expression of epithelial sodium channel (ENaC) and Na(+), K(+)-ATPase subunits was measured in the renal cortex and medulla. Aging was associated with a marked decrease in urinary excretion of sodium, chloride, and potassium (all P < 0.001) as well as renin activity (P < 0.05), but had no significant effect on gene expression of ENaC or Na(+), K(+)-ATPase subunits. In aged rats, darusentan treatment increased ion excretion (P < 0.05), reduced cortical gene expression of alphaENaC and alpha(1)-Na(+), K(+)-ATPase (both P < 0.05), and increased plasma aldosterone levels (P < 0.01). These data demonstrate a decrease of sodium and potassium excretion in aged rats, changes that are partly sensitive to ETA receptor blockade. Treatment with darusentan also reduced cortical expression of alphaENaC and alpha(1)-Na(+), K(+)-ATPase and increased plasma aldosterone levels independently of blood pressure, electrolytes, renin activity, or angiotensin converting enzyme activity. These findings may provide new pathogenetic links between aging and sodium sensitivity.


Cell Biology and Microbiology: A Continuous Cross-Feeding.
Microbiology and cell biology both involve the study of cells, albeit at different levels of complexity and scale. Interactions between both fields during the past 25 years have led to major conceptual and technological advances that have reshaped the whole biology landscape and its biomedical applications.


Raising the barrier for photoinduced DNA charge injection with a cyclohexyl artificial base pair.
The effects of an artificial cyclohexyl base pair on the quantum yields of fluorescence and dynamics of charge separation and charge recombination have been investigated for several synthetic DNA hairpins. The hairpins possess stilbenedicarboxamide, perylenediimide, or naphthalenediimide linkers and base-paired stems. In the absence of the artificial base pair hole injection into both adenine and guanine purine bases is exergonic and irreversible, except in the case of stilbene with adenine for which it is slightly endergonic and reversible. Insertion of the artificial base pair renders hole injection endergonic or isoergonic except in the case of the powerful naphthalene acceptor for which it remains exergonic. Both hole injection and charge recombination are slower for the naphthalene acceptor in the presence of the artificial base pair than in its absence. The effect of an artificial base pair on charge separation and charge recombination in hairpins possessing stilbene and naphthalene acceptor linkers and a stilbenediether donor capping group has also been investigated. In the case of the stilbene acceptor-stilbene donor capped hairpins photoinduced charge separation across six base pairs is efficient in the absence of the artificial base pair but does not occur in its presence. In the case of the naphthalene acceptor-stilbene donor capped hairpins the artificial base pair slows but does not stop charge separation and charge recombination, leading to the formation of long-lived charge separated states.


Sources of diversity in a grassland metacommunity: quantifying the contribution of dispersal to species richness.
Metacommunity theory suggests a potentially important role for dispersal in diversity maintenance at local, as well as regional, scales. In addition, propagule addition experiments have shown that dispersal often limits local diversity. However, actual dispersal rates into local communities and the contribution of immigrants to observed local diversity are poorly known. We present a new approach that partitions the diversity of a target community into dispersal-maintained and dispersal-independent components. Specifically, we quantify distances through space and time to the nearest potential seed source for naturally occurring recruits in target communities by using hierarchical data on species pools (local, site, region, and seed bank). Using this "recruit tag" approach, we found that dispersal contributed 29%-57% of the seedling diversity in perennial grasslands with different successional histories. However, both dispersal and seedling mortality remained remarkably constant, in absolute terms, over succession. The considerable loss of diversity over secondary succession (66%), therefore, could be understood only by considering how these processes interact with the decreasing disturbance rate (i.e., frequency of gaps) in later-successional sites. We conclude that a metacommunity perspective is relevant and necessary to understand the diversity and community assembly of this study system.


Use of echocardiography for the diagnosis of heartworm disease in cats: 43 cases (1985-1997).
To determine the usefulness of echocardiography in the diagnosis of heartworm disease in cats and to compare this modality with other tests. Retrospective study. 43 cats with heartworm infection that had echocardiographic examinations at 2 veterinary teaching hospitals between 1985 and 1997. Twenty-two of these 43 cats also underwent radiography of the thorax and heartworm antibody and heartworm antigen testing. Cats were determined to be infected with Dirofilaria immitis infection on the basis of 1 or more of the following findings: positive modified Knott or antigen test result, echocardiographic evidence of heartworm disease, or confirmation of the disease on postmortem examination. The percentage of echocardiographs in which heartworms were evident was compared with the percentage of radiographs in which pulmonary artery enlargement was evident and results of antigen or antibody tests in cats in which all tests were performed. Overall, heartworms were detectable by use of echocardiography in 17 of 43 cats, most often in the pulmonary arteries. In the 22 cats in which all tests were performed, antibody test results were positive in 18, antigen test results were positive in 12, and pulmonary artery enlargement was evident radiographically and heartworms were identifiable echocardiographically in 14. Heartworm infection was diagnosed exclusively by use of echocardiography in 5 cats in which the antigen test result was negative. Although echocardiography was less sensitive than antigen testing, it was a useful adjunctive test in cats that had negative antigen test results in which there was a suspicion of heartworm disease. The pulmonary arteries should be evaluated carefully to increase the likelihood of detection of heartworms echocardiographically.


Conformational differences of human IgE on hydrophobic and hydrophilic solid phases detected by monoclonal antibodies.
Very sensitive assays of IgE are required for determining prevalence of allergic reactions in children. In order to develop a sensitive two-site IRMA two kinds of mAb were produced. Antibodies specific for D epsilon 1 determinants were derived from immunization with a 40 kDa papain Fc fragment. They bound equally native and 56 degrees C heated IgE. D epsilon 2 specific mAb were obtained after immunization with IgE anti-D epsilon 1 complex and were selected on the basis of their inability to bind heated IgE. In a two-site assay on plastic plates, D epsilon 1 specific mAb led to the binding of IgE but always prevented further binding of anti-D epsilon 1 mAb, anti-human kappa chain mAb or allergen on bound IgE. This was not true when CNBr activated cellulose was used. The influence of the nature of the solid phase disappeared when D epsilon 2 specific mAb were coated on plastic tubes. In this case, the binding of a second mAb with identical or different fine specificity was observed. The best matched pair was E 164 (anti-D epsilon 2) on the solid phase and 6H10 (anti-D epsilon 1) as a tracer. As little as 0.2 UI/ml of IgE could be detected in a 2 hr test.


Listeria comet tails: the actin-based motility machinery at work.
Listeria monocytogenes is a master of mimicry that uses the host cell actin system both to move within the cytoplasm of infected cells and for cell-to-cell spread. Recent studies of Listeria and similarly acting pathogens have generated leaps in our understanding of the actin-based force producing machinery. This machinery is essential for most motile properties of cells, not least for cell migration. In a minimal configuration, it consists of the Arp2/3-complex, Ena-VASP proteins, cofilin, capping protein and a nucleation-promoting factor. In this review, we discuss current models of pseudopodial protrusions and describe how the road to more complex models lies open and is already paved by recent studies using Listeria-based biomimetic motility assays.


Determining Clinically Meaningful Thresholds for the Hip Outcome Score Sport-Specific Subscale in Athletes Undergoing Hip Arthroscopy for Femoroacetabular Impingement Syndrome.
The minimal clinically important difference (MCID), Patient Acceptable Symptom State (PASS), substantial clinical benefit (SCB), and maximum outcome improvement (MOI) satisfaction threshold for the Hip Outcome Score Sport-Specific Subscale (HOS-SSS) have not been established in athletes undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS). To determine threshold MCID, PASS, SCB, and MOI satisfaction threshold values for the HOS-SSS in athletes undergoing hip arthroscopy for FAIS at minimum 2-year follow-up. Cohort study (Diagnosis); Level of evidence, 3. Anchor questions were administered to recreational, organized amateur, high school, college, and professional athletes who underwent primary hip arthroscopy for FAIS between May 2015 and March 2019. Patients were included if they were younger than 50 years, answered the anchor questions, and had preoperative and minimum 2-year follow-up for the HOS-SSS, modified Harris Hip Score (mHHS), Non-Arthritic Hip Score (NAHS), and visual analog scale (VAS) for pain. Exclusion criteria were Tönnis grade >1, hip dysplasia (lateral center-edge angle <18°), and previous ipsilateral hip surgery or conditions. Receiver operating characteristic (ROC) analysis was used to determine PASS, SCB, and MOI satisfaction for the HOS-SSS. Two distribution methods were used to calculate MCID for HOS-SSS. A total of 225 athletes who underwent primary hip arthroscopy met the inclusion criteria. Of those athletes, 200 (88.9%) who had minimum 2-year follow-up and information regarding return to sport (RTS) were included. The cohort included 124 (62.0%) women and 76 (38.0%) men with a mean ± standard deviation age of 29.4 ± 10.4 years, body mass index of 25.6 ± 5.4, and follow-up of 29.5 ± 5.1 months. Athletes experienced significant improvements in HOS-SSS, mHHS, NAHS, and VAS from preoperative to latest postoperative follow-up (P < .001), and mean satisfaction was 8.2. The RTS rate was 83.7%. ROC analysis determined that the PASS, MOI satisfaction threshold, SCB absolute score, SCB change score, and MCID (baseline/change score methods) for the HOS-SSS were 77.0, 44.6%, 92.7, 30.6, and 10.6, respectively, with athletes achieving thresholds at high rates (80.0%, 80.5%, 45.0%, 54.0%, and 79.5%, respectively). This study identified values for the HOS-SSS that can be used to define clinically meaningful outcomes in athletes after primary hip arthroscopy for FAIS. The PASS, MOI satisfaction threshold, SCB absolute score, SCB change score, and MCID for the HOS-SSS at minimum 2-year follow-up in athletes after primary hip arthroscopy were 77.0, 44.6%, 92.7, 30.6, and 10.6, respectively.


A novel SRY missense mutation affecting nuclear import in a 46,XY female patient with bilateral gonadoblastoma.
Patients with disorders of sex development (DSD), especially those with gonadal dysgenesis and hypovirilization, are at risk of developing the so-called type II germ cell tumors (GCTs). Both carcinoma in situ and gonadoblastoma (GB) can be the precursor lesion, resulting in a seminomatous or non-seminomatous invasive cancer. SRY mutations residing in the HMG domain are found in 10-15% of 46,XY gonadal dysgenesis cases. This domain contains two nuclear localization signals (NLSs). In this study, we report a unique case of a phenotypical normal woman, diagnosed as a patient with 46,XY gonadal dysgenesis, with an NLS missense mutation, on the basis of the histological diagnosis of a unilateral GB. The normal role of SRY in gonadal development is the upregulation of SOX9 expression. The premalignant lesion of the initially removed gonad was positive for OCT3/4, TSPY and stem cell factor in germ cells, and for FOXL2 in the stromal component (ie, granulosa cells), but not for SOX9. On the basis of these findings, prophylactical gonadectomy of the other gonad was performed, also showing a GB lesion positive for both FOXL2 (ovary) and SOX9 (testis). The identified W70L mutation in the SRY gene resulted in a 50% reduction in the nuclear accumulation of the mutant protein compared with wild type. This likely explains the diminished SOX9 expression, and therefore the lack of proper Sertoli cell differentiation during development. This case shows the value of the proper diagnosis of human GCTs in identification of patients with DSD, which allows subsequent early diagnosis and prevention of the development of an invasive cancer, likely to be treated by chemotherapy at young age.


Induction of c-Met proto-oncogene by Epstein-Barr virus latent membrane protein-1 and the correlation with cervical lymph node metastasis of nasopharyngeal carcinoma.
Nasopharyngeal carcinoma (NPC) is distinctive in head and neck carcinomas for its close association with Epstein-Barr virus and its highly metastatic nature. Up-regulation of cell motility is essential for enhancement of metastatic potential. The expression of c-Met proto-oncogene, a high-affinity receptor for hepatocyte growth factor/scatter factor, has been reported to correlate with metastatic ability of the tumor cell. We observed close association of c-Met expression with cervical lymph node metastasis (P = 0.0272) in 39 NPC specimens studied immunohistochemically. Epstein-Barr virus-encoding latent membrane protein-1 (LMP-1) is a primary oncogene and is suggested to enhance the metastatic property of NPC. Previously, we reported that LMP-1 enhanced the motility of Madin-Darby canine kidney (MDCK) epithelial cells that was mediated by activation of Ets-1 transcription factor. Therefore, we examined the interrelationships of LMP-1, Ets-1, and c-Met. In immunohistochemical studies, the expression of LMP-1, Ets-1, and c-Met correlated significantly with each other in NPC (LMP-1 versus Ets-1, P < 0.0001; Ets-1 versus c-Met, P = 0.0012; LMP-1 versus Met, P = 0.0005). Transfection of LMP-1-expressing plasmid in MDCK cells induced c-Met protein expression. The c-Met protein was also induced by Ets-1 expression, and induction of c-Met by LMP-1 was suppressed by introducing a dominant-negative form of Ets-1 in LMP-1-expressing MDCK cells. These results suggest that LMP-1 induces c-Met through the activation of Ets-1, which may contribute in part to the highly metastatic potential of NPC.


EZH2 is overexpressed in adrenocortical carcinoma and is associated with disease progression.
Adrenal Cortex Carcinoma (ACC) is an aggressive tumour with poor prognosis. Common alterations in patients include constitutive WNT/β-catenin signalling and overexpression of the growth factor IGF2. However, the combination of both alterations in transgenic mice is not sufficient to trigger malignant tumour progression, suggesting that other alterations are required to allow development of carcinomas. Here, we have conducted a study of publicly available gene expression data from three cohorts of ACC patients to identify relevant alterations. Our data show that the histone methyltransferase EZH2 is overexpressed in ACC in the three cohorts. This overexpression is the result of deregulated P53/RB/E2F pathway activity and is associated with increased proliferation and poorer prognosis in patients. Inhibition of EZH2 by RNA interference or pharmacological treatment with DZNep inhibits cellular growth, wound healing and clonogenic growth and induces apoptosis of H295R cells in culture. Further growth inhibition is obtained when DZNep is combined with mitotane, the gold-standard treatment for ACC. Altogether, these observations suggest that overexpression of EZH2 is associated with aggressive progression and may constitute an interesting therapeutic target in the context of ACC.


Ordered mesoporous materials from metal nanoparticle-block copolymer self-assembly.
The synthesis of ordered mesoporous metal composites and ordered mesoporous metals is a challenge because metals have high surface energies that favor low surface areas. We present results from the self-assembly of block copolymers with ligand-stabilized platinum nanoparticles, leading to lamellar CCM-Pt-4 and inverse hexagonal (CCM-Pt-6) hybrid mesostructures with high nanoparticle loadings. Pyrolysis of the CCM-Pt-6 hybrid produces an ordered mesoporous platinum-carbon nanocomposite with open and large pores (>/=10 nanometers). Removal of the carbon leads to ordered porous platinum mesostructures. The platinum-carbon nanocomposite has very high electrical conductivity (400 siemens per centimeter) for an ordered mesoporous material fabricated from block copolymer self-assembly.


Toxicity hazard of organophosphate insecticide malathion identified by in vitro methods.
Malathion is generally not classified as toxic. However, the toxicity seems to be species-dependent. Local and systemic toxicity data for birds are rare, but a decrease of wild bird densities in areas where malathion was applied was reported. Aim of the study was to extend knowledge on malathion toxicity on cellular and organ level and to evaluate embryotoxicity and genotoxicity for birds using the chick embryo model HET-CAM. Skin and eye irritation was determined using reconstructed skin and eye cornea tissues and the chorioallantoic membrane of chick embryo to simulate conjunctiva. Cytotoxicity in 3T3 Balb/c fibroblast culture was determined to estimate acute systemic toxicity. Chick embryo model was further employed to evaluate acute embryotoxicity for birds (mortality and genotoxicity). Data were analysed by means of general linear models. Malathion is not a skin and eye irritant. Cytotoxicity in vitro test provided LD50 value of 616 mg/kg suggesting higher toxic potential than is generally published based on in vivo tests on laboratory rodents. Embryotoxicity studies revealed dose and age dependent mortality of chick embryos. Genotoxicity was identified by means of micronucleus test in erythroid cells isolated from chorioallantois vascular system of chick embryos. Using in vitro alternative toxicological methods, a higher toxic potential of malathion was demonstrated than is generally declared. An increased health and environmental hazard may occur in areas with intensive agricultural production. The environmental consequences of delayed effects and embryotoxicity for bird populations in areas exposed to organophosphate insecticides, such as malathion, are obvious.


Physical Activity Participation and Preferences: Developmental and Oncology-Related Transitions in Adolescents Treated for Cancer.
To describe motor function and participation in, barriers to, and preferences for physical activity (PA) in adolescents during and after treatment of cancer and to discuss PA promotion in the context of developmental and cancer transitions. A cross-sectional survey study used the Transfer and Basic Mobility and Sports/Physical Functioning self-report and parent-report scales of the Pediatric Outcomes Data Collection Instrument (PODCI) and questions about PA participation and preferences to collect information from 80 adolescents and 63 parents. PODCI scores for adolescents receiving treatment were more variable and significantly lower than those of adolescents who had been off treatment for more than 2 years. Fatigue, pain, general health, and doctor's orders were frequently identified as barriers to PA for adolescents receiving treatment. Many did not achieve recommended levels of PA. The adolescents expressed preferences for being active with friends and family, at home or in school, in the afternoon or evening, and through daily recreational and sports activities typical of teenagers. Physical abilities and participation in and barriers to PA vary across the cancer journey. Interventions should be sensitive to variability and acknowledge individual preferences and environments throughout the trajectories and transitions of cancer treatment and youth development to achieve lifelong healthy lifestyles.


Epidemiologic Data, Tumor Size, Histologic Tumor Type and Grade, Pathologic Staging and Follow Up in Cancers of the Ampullary Region and Head of Pancreas in 311 Whipple Resection Specimens of Pakistani Patients.
To report the histologic findings on Whipple resection specimens and thus determine the extent and spread of carcinomas of ampullary region and head of pancreas in our population. Section of Histopathology, Department of Pathology, Aga Khan University Hospital (AKUH), Karachi, Pakistan. A case series of 311 consecutive Whipple resection specimens received between January 1,2003 and December 31, 2014. Specimens processed for histologic sections and representative sections submitted and histologically examined as per established and standard protocols. All relevant tumor parameters including histologic type, histologic grade, pathologic T and N stage and tumor size were assessed. Epidemiologic data were also recorded. All findings were analysed using SPSS 19.0 software. Ampullary (periampullary) carcinomas were much more common than carcinomas of the head of the pancreas, especially in males, with an average age of 53 years. Mean tumor size was 2.5 cms, over 54% were well differentiated. A large majority were pT2 or pT3 and N0. Carcinomas of pancreatic head were also more common in males, mean age was 55 years, mean tumor size was 3.5 cms, and over 65% were moderately differentiated. The majority were T2 or T3 and pN1. Prognostically, significant statistical correlation was seen with tumor grade and pathologic T and N stage (p values statistically significant). However, tumor size was not statistically significant. Ampullary carcinomas are more common compared to pancreatic carcinomas. Majority of ampullary carcinomas were well differentiated while majority of pancreatic carcinomas were moderately differentiated. Large majority of both types of cases were pT2 or T3. Histologic tumor grade and pathologic T and N stage are significantly related to prognosis in Pakistani patients with ampullary and pancreatic cancers.


Evolutionary history of Otophysi (Teleostei), a major clade of the modern freshwater fishes: Pangaean origin and Mesozoic radiation.
Freshwater harbors approximately 12,000 fish species accounting for 43% of the diversity of all modern fish. A single ancestral lineage evolved into about two-thirds of this enormous biodiversity (≈ 7900 spp.) and is currently distributed throughout the world's continents except Antarctica. Despite such remarkable species diversity and ubiquity, the evolutionary history of this major freshwater fish clade, Otophysi, remains largely unexplored. To gain insight into the history of otophysan diversification, we constructed a timetree based on whole mitogenome sequences across 110 species representing 55 of the 64 families. Partitioned maximum likelihood analysis based on unambiguously aligned sequences (9923 bp) confidently recovered the monophyly of Otophysi and the two constituent subgroups (Cypriniformes and Characiphysi). The latter clade comprised three orders (Gymnotiformes, Characiformes, Siluriformes), and Gymnotiformes was sister to the latter two groups. One of the two suborders in Characiformes (Characoidei) was more closely related to Siluriformes than to its own suborder (Citharinoidei), rendering the characiforms paraphyletic. Although this novel relationship did not receive strong statistical support, it was supported by analyzing independent nuclear markers. A relaxed molecular clock Bayesian analysis of the divergence times and reconstruction of ancestral habitats on the timetree suggest a Pangaean origin and Mesozoic radiation of otophysans. The present timetree demonstrates that survival of the ancestral lineages through the two consecutive mass extinctions on Pangaea, and subsequent radiations during the Jurassic through early Cretaceous shaped the modern familial diversity of otophysans. This evolutionary scenario is consistent with recent arguments based on biogeographic inferences and molecular divergence time estimates. No fossil otophysan, however, has been recorded before the Albian, the early Cretaceous 100-112 Ma, creating an over 100 million year time span without fossil evidence. This formidable ghost range partially reflects a genuine difference between the estimated ages of stem group origin (molecular divergence time) and crown group morphological diversification (fossil divergence time); the ghost range, however, would be filled with discoveries of older fossils that can be used as more reasonable time constraints as well as with developments of more realistic models that capture the rates of molecular sequences accurately.


Prevention of autoimmune rheumatic disease: state of the art and future perspectives.
Prevention of disease can in principle be accomplished by identification of environmental and/or lifestyle risk and protective factors followed by public health measures (such as for smoking and lung cancer), or by modification of the individual's reactions to disease-inducing factors (such as in vaccinations against microbes). This review discusses both options based on emerging understanding of aetiologies in inflammatory rheumatic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The major current opportunity for public health-based prevention lies in avoiding smoking. In RA, recent studies have calculated that, in Sweden (a country characterised by a low frequency of smoking), 20% of all RA cases and 33% of all cases of ACPA-positive RA would not have occurred in a smoke-free society. Smoking is also a major risk factor for SLE but no population attribution is yet available. New avenues for individualised and biology-based prevention are provided by the demonstration that several autoimmune rheumatic diseases are preceded by emergence of subclinical autoimmunity followed by laboratory-based signs of inflammation and finally overt disease. Examples of this process are provided from studies of autoimmunity to citrullinated proteins (in RA), to dsDNA (in SLE in general) and to Ro52 epitopes (in the case of neonatal heart block). The recognition of this sequence of events provides opportunities to intervene specifically and potentially curatively before onset of full-blown disease. Such prevention can be accomplished by modification of inciting antigens (environment), by modification of immunity (more or less specific immunomodulation) or by modification of specific gene functions. In all cases, prevention will be different in different subsets of disease and differ at different time points of disease development. Thus, the road map towards prevention of autoimmune rheumatic diseases includes increased understanding of how genes, environment and immunity interact.


Pressor response from rostral dorsomedial medulla is mediated by excitatory amino acid receptors in rostral VLM.
Excitatory amino acid (EAA) receptors in the rostral part of the ventrolateral medulla (VLM) have been shown to mediate pressor responses elicited by stimulation of various peripheral afferent fibers as well as other central nuclei. This study tested the hypothesis that these receptors are a critical component in the central pathway mediating the powerful pressor response that is produced by stimulation of a group of neurons within a circumscribed region in the rostral dorsomedial medulla (RDM). In anesthetized rabbits, the pressor response elicited by unilateral microinjection of glutamate into this RDM region was measured before and after injection of kynurenic acid (Kyn), a broad-spectrum EAA receptor antagonist, into the physiologically identified pressor region of either the ipsilateral or contralateral rostral VLM. The pressor response to RDM stimulation was greatly reduced (to 24 +/- 4% of control) 5-10 min after injection of Kyn (but not the vehicle solution) into the ipsilateral rostral VLM; this response returned completely to its control value within 30-60 min after Kyn injection. By contrast, after Kyn injection into the contralateral rostral VLM, the pressor response to RDM stimulation was not affected (106 +/- 15% of control). The results indicate that the descending pressor pathway from the RDM to the spinal cord is mediated by EAA receptors in the rostral VLM pressor region. Furthermore, the pathway from the RDM to the rostral VLM is predominantly, if not exclusively, ipsilateral.


Biologic Use Patterns and Predictors for Non-persistence and Switching of Biologics in Patients with Inflammatory Bowel Disease: A Nationwide Population-Based Study.
Data on real-life patterns of biologic use for inflammatory bowel disease (IBD) are scarce. We aimed to examine the patterns of biologic use and the factors associated with non-persistence and switching of biologics in Korean IBD patients. Using National Health Insurance claims, we collected data on patients who were diagnosed with IBD and exposed to biologics between 2010 and 2016. Among 1838 patients with Crohn's disease (CD), 1237 and 601 started with infliximab and adalimumab, respectively. Among 1125 patients with ulcerative colitis (UC), 774, 294, and 57 initiated infliximab, adalimumab, and golimumab, respectively. Rates of non-persistence and switching were higher in UC than in CD. One- and 3-year non-persistence rates were 14.2% and 26.5% in CD and 35.4% and 53.4% in UC, respectively. One- and 3-year switching rates were 3.7% and 10.1% in CD and 15.6% and 22.0% in UC, respectively. In both CD and UC, infliximab and adalimumab initiators showed similar persistence rates, whereas adalimumab initiators had a higher risk of switching than infliximab initiators. In UC, golimumab initiators had a higher risk of non-persistence and switching than infliximab initiators. Steroid use at biologic initiation was associated with an increased risk of non-persistence and switching in both CD and UC. UC patients who started biologic treatment at tertiary hospitals were more likely to continue treatment than those who started at general hospitals/community hospitals/clinics. In real-world clinical practice settings, discontinuation of biologics occurred frequently in IBD patients, and switching of biologics was common in UC patients.


Understanding regulation of metabolism through feasibility analysis.
Understanding cellular regulation of metabolism is a major challenge in systems biology. Thus far, the main assumption was that enzyme levels are key regulators in metabolic networks. However, regulation analysis recently showed that metabolism is rarely controlled via enzyme levels only, but through non-obvious combinations of hierarchical (gene and enzyme levels) and metabolic regulation (mass action and allosteric interaction). Quantitative analyses relating changes in metabolic fluxes to changes in transcript or protein levels have revealed a remarkable lack of understanding of the regulation of these networks. We study metabolic regulation via feasibility analysis (FA). Inspired by the constraint-based approach of Flux Balance Analysis, FA incorporates a model describing kinetic interactions between molecules. We enlarge the portfolio of objectives for the cell by defining three main physiologically relevant objectives for the cell: function, robustness and temporal responsiveness. We postulate that the cell assumes one or a combination of these objectives and search for enzyme levels necessary to achieve this. We call the subspace of feasible enzyme levels the feasible enzyme space. Once this space is constructed, we can study how different objectives may (if possible) be combined, or evaluate the conditions at which the cells are faced with a trade-off among those. We apply FA to the experimental scenario of long-term carbon limited chemostat cultivation of yeast cells, studying how metabolism evolves optimally. Cells employ a mixed strategy composed of increasing enzyme levels for glucose uptake and hexokinase and decreasing levels of the remaining enzymes. This trade-off renders the cells specialized in this low-carbon flux state to compete for the available glucose and get rid of over-overcapacity. Overall, we show that FA is a powerful tool for systems biologists to study regulation of metabolism, interpret experimental data and evaluate hypotheses.


Genetic characterization of resistance to deltamethrin in Plutella xylostella (Lepidoptera: Plutellidae) from India.
The diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), is considered as one of the most difficult pests to control. It has developed resistance not only to synthetic insecticides but also to Bacillus thuringiensis-based pesticides. We tested the hypothesis that selection in a P. xylostella population, from Hosur, India, with deltamethrin would give a broad spectrum of resistance to several insecticides. We also were interested in genetically classifying resistance to deltamethrin in the selected population and in evaluating whether resistance can be suppressed using synergists. Bioassays (at generation 1, G1) using deltamethrin indicated a resistance ratio of 161-fold compared with a laboratory-susceptible population of P. xylostella (Lab-UK). At G2, the field-derived population was divided into two subpopulations; one population was selected (G1 to G8) with deltamethrin (Delta-SEL), and the second population was left unselected (UNSEL). Bioassays at G9 indicated that selection with deltamethrin gave a resistance ratio of 15-fold compared with UNSEL and 1,647-fold compared with Lab-UK. The resistance to deltamethrin in the UNSEL population was stable. The Delta-SEL population maintained resistance to lambda-cyhalothrin, but there was no cross-resistance to indoxacarb, DDT, or Cry1Ac. Crossing experiments indicated that resistance to deltamethrin in Delta-SEL was multigenic and inherited in an incompletely dominant fashion. Piperonyl butoxide (PBO) and S.S.S-tri-n-butyl phosphorotrithioate with potent inhibitory activity against esterases and/or monooxygenases significantly increased the toxicity of deltamethrin against both UNSEL and Delta-SEL, but they showed no such synergism with Lab-UK. Thus, it can be predicted that development of resistance to deltamethrin would be delayed under appropriate control strategies that favor the dilution of resistance alleles by enhanced flow of susceptible alleles. Further analysis suggested that mixing PBO and deltamethrin could eliminate the substantial resistance to deltamethrin in this population.


Cardio-visual full body illusion alters bodily self-consciousness and tactile processing in somatosensory cortex.
Prominent theories highlight the importance of bodily perception for self-consciousness, but it is currently not known whether this is based on interoceptive or exteroceptive signals or on integrated signals from these anatomically distinct systems, nor where in the brain such integration might occur. To investigate this, we measured brain activity during the recently described 'cardio-visual full body illusion' which combines interoceptive and exteroceptive signals, by providing participants with visual exteroceptive information about their heartbeat in the form of a periodically illuminated silhouette outlining a video image of the participant's body and flashing in synchrony with their heartbeat. We found, as also reported previously, that synchronous cardio-visual signals increased self-identification with the virtual body. Here we further investigated whether experimental changes in self-consciousness during this illusion are accompanied by activity changes in somatosensory cortex by recording somatosensory evoked potentials (SEPs). We show that a late somatosensory evoked potential component (P45) reflects the illusory self-identification with a virtual body. These data demonstrate that interoceptive and exteroceptive signals can be combined to modulate activity in parietal somatosensory cortex.


Thermal contribution to the inactivation of Cryptosporidium in plastic bottles during solar water disinfection procedures.
To determine the thermal contribution, independent of ultraviolet radiation, on the inactivation of Cryptosporidium parvum during solar water disinfection procedures (SODIS), oocysts were exposed for 4, 8, and 12 hours to temperatures recorded in polyethylene terephthalate bottles in previous SODIS studies carried out under field conditions. Inclusion/exclusion of the fluorogenic vital dye propidium iodide, spontaneous excystation, and infectivity studies were used to determine the inactivation of oocysts. There was a significant increase in the percentage of oocysts that took up propidium iodide and in the number of oocysts that excysted spontaneously. There was also a significant decrease in the intensity of infection elicited in suckling mice at the end of all exposure times. The results of the study demonstrate the importance of temperature in the inactivation of C. parvum oocysts during application of SODIS under natural conditions.


[Vigilance for veterinary medicinal products: declarations of suspected adverse reactions in the year 2007].
163 reports of suspected adverse reactions were received in the year 2007: 111 for veterinary medicinal (VMPs) and 52 for immunologic products. Half of the reported reactions for VMPs concerned either an antiparasitic drug (26%) or an antibiotic (24%). Reconversions (use in another target species or for another indication as registered) made the third most frequently mentioned group with 11 reports. For immunologicals, half of the declarations were related to an adverse reaction in dogs, the most frequently reported reaction in companion animals being allergies. Moreover, 272 enquiries were received by the Swiss Toxicological Information Center in Zürich. Most of these were related to dogs (73%) and the number of enquiries regarding VMPs correlated positively with the most frequently used therapeutic classes like antiparasitics (47%) and anti-inflammatory drugs (23%). The complexity of proscessing reports regarding the detection of residues in milk after prescribed withdrawal times is discussed in detail. In conclusion, the year 2007 is seen as a consolidation of the established system with a tendency towards increase in the number of complex cases.


Effects of fatty acids on expression of genes encoding subunits of cytochrome c oxidase and cytochrome c oxidase activity in HT29 human colonic adenocarcinoma cells.
As the primary and preferred energy source of normal colonic epithelial cells, fatty acids may play a unique role in the differentiation and physiology of these cells. We have shown that expression levels of COXIII, a mitochondrial gene encoding one of the 13 subunits of cytochrome c oxidase, are abnormally low in colon tumors and colonic tissue at genetic risk for developing tumors but increase following in vitro treatment of HT29 human colonic adenocarcinoma cells with the fatty acid butyrate. The present studies investigate the specificity of fatty acids in effecting cytochrome c oxidase subunit expression and enzymatic activity in HT29 cells. The data demonstrate that, depending upon their chain length, metabolizable unbranched fatty acids increase expression of two subunits encoded by mitochondrial genes (I and III) and enhance cytochrome c oxidase activity. However, none of the fatty acids had an effect on expression of two subunits encoded by nuclear genes (IV and Va). These findings suggest that the low levels of COXIII expression exhibited in colonic tumors may represent a limiting factor in the assembly of functional cytochrome c oxidase and contribute to the depressed enzyme activity reported in these tumors. By elevating expression of subunits I and III and enzymatic activity, fatty acids may enhance the potential for cellular respiration. The more differentiated phenotype which is reported in colorectal carcinoma cell lines treated with fatty acids in vitro may be, therefore, associated with correction of metabolic abnormalities in transformed cells.


Neuropsychological deficits of a U.S. Army pilot following an anoxic event as a function of cardiac arrest.
Anoxic encephalopathy occurs as a result of cardiac arrest, respiratory distress, or carbon monoxide poisoning. This is a case report on the neuropsychological deficits of anoxia in an otherwise previously healthy 36-year-old male pilot. The patient was taking an over-the-counter supplement that included an herb called Ma Huang on the day of his cardiac arrest. Ma Huang is reported to potentially present an increased risk of cardiac infarctions and central nervous system dysfunctions. Several instances of death have been linked to Ma Huang. The patient produced a neuropsychological profile that evidenced impairments in executive functioning, memory, language, attention, intellectual and academic functioning, as well as motor speed and coordination, all of which are consistent with diffuse brain damage. This case adds to the body of literature documenting the physical and neuropsychological effects of anoxia, as well as the effects of ephedrine-based supplements, such as Ma Huang.


Addressing nutritional gaps with multivitamin and mineral supplements.
A balanced and varied diet is the best source of essential vitamins and minerals; however, nutrient deficiencies occur, including in populations with bountiful food supplies and the means to procure nutrient-rich foods. For example, the typical American diet bears little resemblance to what experts recommend for fruit, vegetables, and whole grains, which serve as important sources of an array of vitamins and minerals. With time, deficiencies in one or more micronutrients may lead to serious health issues. A common reason people take multivitamin and mineral (MVM) supplements is to maintain or improve health, but research examining the effectiveness of MVMs in the prevention of certain chronic conditions is ongoing. In addition to the utility of MVMs for filling in relatively small but critical nutritional gaps, which may help prevent conditions such as anemia, neural tube defects, and osteoporosis, some evidence supports possible benefits of MVM supplementation with regard to cancer prevention (particularly in men) and prevention or delay of cataract, as well as some aspects of cognitive performance. Unlike some single-vitamin supplements, MVM supplements are generally well tolerated and do not appear to increase the risk of mortality, cerebrovascular disease, or heart failure. The potential benefits of MVM supplements likely outweigh any risk in the general population and may be particularly beneficial for older people.


Multiparametric Profiling for Identification of Chemosensitizers against Gram-Negative Bacteria.
Antibiotic resistance is now a worldwide therapeutic problem. Since the beginning of anti-infectious treatment bacteria have rapidly shown an incredible ability to develop and transfer resistance mechanisms. In the last decades, the design variation of pioneer bioactive molecules has strongly improved their activity and the pharmaceutical companies partly won the race against the clock. Since the 1980s, the new classes of antibiotics that emerged were mainly directed to Gram-positive bacteria. Thus, we are now facing to multidrug-resistant Gram-negative bacteria, with no therapeutic options to deal with them. These bacteria are mainly resistant because of their double membrane that conjointly impairs antibiotic accumulation and extrudes these molecules when entered. The main challenge is to allow antibiotics to cross the impermeable envelope and reach their targets. One promising solution would be to associate, in a combination therapy, a usual antibiotic with a non-antibiotic chemosensitizer. Nevertheless, for effective drug discovery, there is a prominent lack of tools required to understand the rules of permeation and accumulation into Gram-negative bacteria. By the use of a multidrug-resistant enterobacteria, we introduce a high-content screening procedure for chemosensitizers discovery by quantitative assessment of drug accumulation, alteration of barriers, and deduction of their activity profile. We assembled and analyzed a control chemicals library to perform the proof of concept. The analysis was based on real-time monitoring of the efflux alteration and measure of the influx increase in the presence of studied compounds in an automatized bio-assay. Then, synergistic activity of compounds with an antibiotic was studied and kinetic data reduction was performed which led to the calculation of a score for each barrier to be altered.


Sex differences in lumbar degenerative disc disease.
A growing number of studies focus on sex differences in the pre- and postoperative setting in patients with degenerative disc disease (DDD). The exact pathomechanism behind this phenomenon, however, remains unclear. The objective of this study was to investigate pre- and postoperative sex differences in patients with lumbar DDD. In a prospective two-center study, back and leg pain (Visual Analogue Scale (VAS)), functional disability (Oswestry Disability Index (ODI) and Roland-Morris Disability Index) and health-related quality of life (HRQoL) (EuroQol 5D and Short-Form (SF12)) were collected for patients scheduled for lumbar spine surgery. In addition to the subjective functional impairment (SFI), objective functional impairment (OFI) was estimated using age- and sex-adjusted cut-off values for the timed-up-and-go (TUG) test. The 6-week responder status was defined using minimally clinically important differences of the ODI, SF12 PCS, VAS back and leg pain in all patients. Six months and one year follow-up (FU) was available in n=127 and n=87 patients, respectively. The patient cohort comprised of n=214 patients (41.6% females). Preoperatively, female patients scored significantly worse on VAS back and leg pain, ODI and SF12 PCS (p<0.033), while OFI was similar (p=0.334). At the 6 week FU, sex-related differences had resolved for SFI and OFI was similar as well (p=0.333). There were no sex differences in the mean improvement after 6 weeks for all measures of pain intensity, functional impairment and HRQoL (p>0.182). Male and female patients profited equally on measures of SFI and HRQoL up to six months and one year after surgery (p>0.091). Preoperatively, female patients scored worse in terms of SFI, while OFI was similar. Consecutively, OFI appears to be less prone to sex bias and may thus serve as a valuable surrogate-marker of disability. The disadvantageous preoperative SFI-status did not translate into worse postoperative results, as no sex differences were present at the 6-week, 6-months and 1-year follow-up.


Long-term fire resilience of the Ericaceous Belt, Bale Mountains, Ethiopia.
Fire is the most frequent disturbance in the Ericaceous Belt (ca 3000-4300 m.a.s.l.), one of the most important plant communities of tropical African mountains. Through resprouting after fire, Erica establishes a positive fire feedback under certain burning regimes. However, present-day human activity in the Bale Mountains of Ethiopia includes fire and grazing systems that may have a negative impact on the resilience of the ericaceous ecosystem. Current knowledge of Erica-fire relationships is based on studies of modern vegetation, lacking a longer time perspective that can shed light on baseline conditions for the fire feedback. We hypothesize that fire has influenced Erica communities in the Bale Mountains at millennial time-scales. To test this, we (1) identify the fire history of the Bale Mountains through a pollen and charcoal record from Garba Guracha, a lake at 3950 m.a.s.l., and (2) describe the long-term bidirectional feedback between wildfire and Erica, which may control the ecosystem's resilience. Our results support fire occurrence in the area since ca 14 000 years ago, with particularly intense burning during the early Holocene, 10.8-6.0 cal ka BP. We show that a positive feedback between Erica abundance and fire occurrence was in operation throughout the Lateglacial and Holocene, and interpret the Ericaceous Belt of the Ethiopian mountains as a long-term fire resilient ecosystem. We propose that controlled burning should be an integral part of landscape management in the Bale Mountains National Park.


Increase in cerebellar volume in Cavalier King Charles Spaniels with Chiari-like malformation and its role in the development of syringomyelia.
Previous research in Cavalier King Charles Spaniels (CKCS) has found that Chiari-like malformation and syringomyelia (CM/SM) are associated with a volume mismatch between the caudal cranial fossa (CCF) and the brain parenchyma contained within. The objectives of this study were to i) compare cerebellar volume in CKCS (a "high risk' group which frequently develops CM/SM), small breed dogs (medium risk--occasionally develop CM/SM), and Labradors (low risk--CM/SM not reported); ii) evaluate a possible association between increased cerebellar volume and CM/SM in CKCS; iii) investigate the relationship between increased cerebellar volume and crowding of the cerebellum in the caudal part of the CCF (i.e. the region of the foramen magnum). Volumes of three-dimensional, magnetic resonance imaging derived models of the CCF and cerebellum were obtained from 75 CKCS, 44 small breed dogs, and 31 Labradors. As SM is thought to be a late onset disease process, two subgroups were formed for comparison: 18 CKCS younger than 2 years with SM (CM/SM group) and 13 CKCS older than 5 years without SM (CM group). Relative cerebellar volume was defined as the volume of the cerebellum divided by the total volume of brain parenchyma. Our results show that the CKCS has a relatively larger cerebellum than small breed dogs and Labradors and provide evidence that increased cerebellar volume in CKCS is associated with crowding of cerebellum in the caudal part of the CCF. In CKCS there is an association between increased cerebellar volume and SM. These findings have implications for the understanding of the pathological mechanisms of CM/SM, and support the hypothesis that it is a multifactorial disease process governed by increased cerebellar volume and failure of the CCF to reach a commensurate size.


The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo.
The endogenous peptide apelin is differentially regulated in cardiovascular disease but the nature of its role in cardiac function remains unclear. We investigated the functional relevance of this peptide using ECG and respiration gated magnetic resonance imaging, conductance catheter pressure-volume hemodynamic measurements, and echocardiography in vivo. In addition, we carried out histology and immunohistochemistry to assess cardiac hypertrophy and to localize apelin and APJ in the adult and embryonic mouse heart. Intraperitoneal injection of apelin (300 microg/kg) resulted in a decrease in left ventricular end diastolic area (pre: 0.122+/-0.007; post: 0.104+/-0.005 cm(2), p=0.006) and an increase in heart rate (pre: 537+/-20; post: 559+/-19 beats per minute, p=0.03). Hemodynamic measurements revealed a marked increase in ventricular elastance (pre: 3.7+/-0.9; post: 6.5+/-1.4 mm Hg/RVU, p=0.018) and preload recruitable stroke work (pre: 27.4+/-8.0; post: 51.8+/-3.1, p=0.059) with little change in diastolic parameters following acute infusion of apelin. Chronic infusion (2 mg/kg/day) resulted in significant increases in the velocity of circumferential shortening (baseline: 5.36+/-0.401; 14 days: 6.85+/-0.358 circ/s, p=0.049) and cardiac output (baseline: 0.142+/-0.019; 14 days: 0.25+/-0.019 l/min, p=0.001) as determined by 15 MHz echocardiography. Post-mortem corrected heart weights were not different between apelin and saline groups (p=0.5) and histology revealed no evidence of cellular hypertrophy in the apelin group (nuclei per unit area, p=0.9). Immunohistochemistry studies revealed APJ staining of myocardial cells in all regions of the adult mouse heart. Antibody staining, as well as quantitative real time polymerase chain reaction identified expression of both APJ and apelin in embryonic myocardium as early as embryonic day 13.5. Apelin reduces left ventricular preload and afterload and increases contractile reserve without evidence of hypertrophy. These results associate apelin with a positive hemodynamic profile and suggest it as an attractive target for pharmacotherapy in the setting of heart failure.


The impact of NSAID treatment on cardiovascular risk - insight from Danish observational data.
This MiniReview describes the present evidence for the relationship between cardiovascular risk and use of non-steroidal anti-inflammatory drugs (NSAIDs) with special focus using Danish register-based data. NSAIDs are among the most widely used drugs worldwide and mainly used for management of pain and inflammatory conditions. Through the past decade, much attention has been given to the cardiovascular safety of these drugs, and several studies have shown increased risk of adverse cardiovascular effects associated with NSAID use. Current guidelines discourage any use of NSAIDs in patients with cardiovascular disease, yet over a period of 8-10 years, 35-44% of patients with myocardial infarction or heart failure were exposed to NSAIDs in Denmark. Furthermore, NSAID use was associated with an increased risk of death or myocardial infarction by up to 5 times that of non-users. There was also a clear indication for a dose-related response in risk associated with NSAID therapy, supporting a causal association. Notably, the cardiovascular risk associated with NSAID treatment was prevalent at start of treatment, suggesting no safe treatment window for NSAIDs in patients with cardiovascular disease. Thus, evidence from observational studies is accumulating, suggesting that NSAIDs are a major public health concern due to the widespread use of these drugs. Although it seems unlikely that we can completely avoid use of NSAIDs, even among high-risk patients, these results highlight the importance of balancing the benefit versus the risk of treatment before initiating NSAID treatment.


Massive osteochondritis of the lateral femoral condyle associated with discoid meniscus: management with meniscoplasty, rim stabilization and bioabsorbable screw fixation.
Discoid menisci without tears and before surgical intervention may be an aetiological factor in the development of osteochondritis dissecans (OCD). We present the case of a massive OCD lesion in the lateral femoral condyle of a 12-year-old boy who presented with relatively few symptoms despite the size of the lesion. This was treated with meniscoplasty and rim stabilization, which has become established as the gold standard treatment for symptomatic discoid menisci. This was combined with bioabsorbable screw fixation of the OCD lesion, resulting in rapid resolution of symptoms and a return to normal magnetic resonance image appearances after 6 months. It is likely that instability of discoid menisci is a key causal component when present concurrently with OCD lesions. Therefore, stabilization of this is required as well as saucerization of the meniscus. OCD lesions which are of a sufficient size such that if they became unstable or dislocated would result in a significant defect should also be stabilized. We believe that bioabsorbable screw fixation presents a good solution for fixation in these cases and this combination of treatment should result in a satisfactory outcome.


Genetic Diversity of a Brazilian Strain Collection of Xanthomonas citri subsp. citri Based on the Type III Effector Protein Genes.
Exclusion and eradication or management based on an integrated approach with less susceptible varieties, copper-based bactericides, and windbreaks are the two main strategies used to prevent or control citrus canker. Field tolerance or resistance to citrus canker is not found in the most important commercial sweet orange cultivars, and pathogen-derived resistance has been developed and applied in different crops to obtain resistant genotypes to plant pathogens. We describe the development of DNA primers and probes based on the type III effector genes avrXacE1, avrXacE2, avrXacE3, avrBs2, pthA4, hpaF, and XAC3090 (leucine rich protein), and their application in the evaluation of the genetic diversity of the pathogen. A total of 49 haplotypes were identified in 157 strains by Southern blot analysis. No genetic polymorphism was detected by BOX elements - and enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) analysis, nor with the genes avrBs2, XAC3090, and hpaF. Nei's genetic diversity indexes varied from 0.65 to 0.96 for subcollections of the pathogen. One or few haplotypes were most frequent in the strain collection, but several haplotypes were represented by solely one or few strains. The PthA4 probe resulted in the higher number of haplotypes identified in the Brazilian subcollections. Greater variation in the frequency of haplotypes occurred within subcollections (93.7%) than among subcollections. Only some haplotypes were genetically distant from all others, especially those originated from Rio Grande do Sul and Santa Catarina states. These bacterial effectors are widely spread in the collections and are useful for a better understanding of the host-pathogen interaction and the search for resistance genes in host and nonhost plants.


Fibroblast growth factor 14 is an intracellular modulator of voltage-gated sodium channels.
Genetic ablation of the fibroblast growth factor (Fgf) 14 gene in mice or a missense mutation in Fgf14 in humans causes ataxia and cognitive deficits. These phenotypes suggest that the neuronally expressed Fgf14 gene is essential for regulating normal neuronal activity. Here, we demonstrate that FGF14 interacts directly with multiple voltage-gated Na(+) (Nav) channel alpha subunits heterologously expressed in non-neuronal cells or natively expressed in a murine neuroblastoma cell line. Functional studies reveal that these interactions result in the potent inhibition of Nav channel currents (I(Na)) and in changes in the voltage dependence of channel activation and inactivation. Deletion of the unique amino terminus of the splice variant of Fgf14, Fgf14-1b, or expression of the splice variant Fgf14-1a modifies the modulatory effects on I(Na), suggesting an important role for the amino terminus domain of FGF14 in the regulation of Na(v) channels. To investigate the function of FGF14 in neurones, we directly expressed Fgf14 in freshly isolated primary rat hippocampal neurones. In these cells, the addition of FGF14-1a-GFP or FGF14-1b-GFP increased I(Na) density and shifted the voltage dependence of channel activation and inactivation. In fully differentiated neurones, FGF14-1a-GFP or FGF14-1b-GFP preferentially colocalized with endogenous Nav channels at the axonal initial segment, a critical region for action potential generation. Together, these findings implicate FGF14 as a unique modulator of Nav channel activity in the CNS and provide a possible mechanism to explain the neurological phenotypes observed in mice and humans with mutations in Fgf14.


Description of a standardized nutrition classification plan and its relation to nutritional outcomes in children with cystic fibrosis.
Better nutrition enhances lung function and increases survival for children with cystic fibrosis (CF). Therefore, we developed a standardized strategy to evaluate nutritional status and create individualized treatment plans to ensure that all patients received the same high-quality care in a busy CF Center. A quality improvement approach was undertaken to develop a novel nutrition classification strategy to identify and treat children with subtle manifestations of nutritional deficits in addition to those with obvious nutritional issues. During the 15-month study period, the median body mass index (BMI) percentile increased from 35.2 (0-95.9) to 42.0 (0-97.7), p < .005. Additionally, the number of children with a BMI >or=50th percentile increased by 11.8%. Adoption of a standardized approach to nutritional assessment and treatment led to significant improvement in nutritional outcomes of CF patients, demonstrating that systematic changes in clinical practice can improve clinical outcomes substantially over a short period of time.


Defects in death-inducing signalling complex formation prevent JNK activation and Fas-mediated apoptosis in DU 145 prostate carcinoma cells.
Androgen-independent prostate carcinomas are resistant to chemotherapy and cell lines derived from androgen-independent prostate carcinomas such as DU 145 cells are highly resistant to Fas-mediated apoptosis. The incubation of DU 145 cells with anti-Fas IgM agonistic antibody of Fas receptor fails to activate JNK, a stress kinase involved in regulating apoptosis. We have previously shown that JNK activation is sufficient and necessary to promote Fas-mediated apoptosis in DU 145 cells. We investigate the mechanisms by which JNK activation and apoptosis are abrogated. HSP27 is overexpressed in DU 145 cells and has previously been reported to sequester DAXX and prevent JNK activation in cells treated with anti-Fas IgM. However, we find no evidence that HSP27 interacts with DAXX in DU 145 cells. Instead, we find that FADD does not interact with caspase-8 and this results in defective death-inducing signalling complex formation following Fas receptor activation.


Rethinking risk in pediatric research.
This article reviews four areas of pediatric research in which we have identified questionable levels of allowable risk, exceeding those foreseen by the Commission. They are the following: (1) the categorization of increasingly risky interventions as minimal risk in a variety of protocols; (2) the increasing number of applications for federal panel review of research not otherwise approvable because of higher projected risk levels; (3) research on asymptomatic at risk children; and (4) the inclusion of children and adolescents in placebo-controlled trials for participants of all ages without performing subgroup analysis. While embracing the imperative to include children in research is an encouraging step towards providing the pediatric population with effective medical care and finally eradicating the therapeutic orphan, we must ensure that this research does not become overly permissive.


Change in algal symbiont communities after bleaching, not prior heat exposure, increases heat tolerance of reef corals.
Mutualistic organisms can be particularly susceptible to climate change stress, as their survivorship is often limited by the most vulnerable partner. However, symbiotic plasticity can also help organisms in changing environments by expanding their realized niche space. Coral-algal (Symbiodinium spp.) symbiosis exemplifies this dichotomy: the partnership is highly susceptible to 'bleaching' (stress-induced symbiosis breakdown), but stress-tolerant symbionts can also sometimes mitigate bleaching. Here, we investigate the role of diverse and mutable symbiotic partnerships in increasing corals' ability to thrive in high temperature conditions. We conducted repeat bleaching and recovery experiments on the coral Montastraea cavernosa, and used quantitative PCR and chlorophyll fluorometry to assess the structure and function of Symbiodinium communities within coral hosts. During an initial heat exposure (32 °C for 10 days), corals hosting only stress-sensitive symbionts (Symbiodinium C3) bleached, but recovered (at either 24 °C or 29 °C) with predominantly (>90%) stress-tolerant symbionts (Symbiodinium D1a), which were not detected before bleaching (either due to absence or extreme low abundance). When a second heat stress (also 32 °C for 10 days) was applied 3 months later, corals that previously bleached and were now dominated by D1a Symbiodinium experienced less photodamage and symbiont loss compared to control corals that had not been previously bleached, and were therefore still dominated by Symbiodinium C3. Additional corals that were initially bleached without heat by a herbicide (DCMU, at 24 °C) also recovered predominantly with D1a symbionts, and similarly lost fewer symbionts during subsequent thermal stress. Increased thermotolerance was also not observed in C3-dominated corals that were acclimated for 3 months to warmer temperatures (29 °C) before heat stress. These findings indicate that increased thermotolerance post-bleaching resulted from symbiont community composition changes, not prior heat exposure. Moreover, initially undetectable D1a symbionts became dominant only after bleaching, and were critical to corals' resilience after stress and resistance to future stress.


Identification of a novel membrane protein, HP59, with therapeutic potential as a target of tumor angiogenesis.
CM101, a polysaccharide isolated from the culture medium of Group B streptococcus, a neonatal pathogen, targets pathological angiogenesis and inhibits tumor growth in mice and humans. CM101 also targets neonatal lung and adult sheep lung endothelial cells. A gene encoding a transmembrane protein that interacts with CM101 was isolated from a sheep lung endothelial cell cDNA library. The gene, termed sp55, encodes a 495-amino acid polypeptide. COS-7 cells transfected with a vector containing sp55 express the SP55 protein-bound CM101 in a concentration-dependent manner. Stably transfected CHO cells also bound CM101. The corresponding human gene, hp59, was isolated from a human fetal lung cDNA library and had a predicted identity to SP55 of 86% over 495 amino acids. HP59 protein was shown by immunohistochemistry to be present in the pathological tumor vasculature of the lung, breast, colon, and ovary, but not in the normal vasculature, suggesting that the protein may be critical to pathological angiogenesis. The hp59 gene and/or the HP59 protein was not expressed in a variety of normal tissues, but was significantly expressed in human fetal lung, consistent with the pathophysiology of Group B streptococcus infections in neonates. Mice immunized with HP59 and SP55 peptides showed significant attenuation of tumor growth. Immunization effectively inhibited both the tumor angiogenesis and vasculogenesis processes, as evidenced by lack of both HP59- and CD34-positive vessels. These results and the immunohistochemistry data suggest a therapeutic potential for the CM101 target protein HP59 both as a drug target and as a vaccine against pathoangiogenesis.


Spousal discordance on fertility preference and its effect on contraceptive practice among married couples in Jimma zone, Ethiopia.
To assess spousal agreement levels regarding fertility preference and spousal communication, and to look at how it affects contraceptive use by couples. We conducted a cross-sectional study to collect quantitative data from March to May 2010 in Jimma zone, Ethiopia, using a multistage sampling design covering six districts. In each of the 811 couples included in the survey, both spouses were interviewed. Concordance between the husband and wife was assessed using different statistics and tests including concordance rates, ANOVA, Cohen's Κ and McNemar's test for paired samples. Multivariate analysis was computed to ascertain factors associated with contraceptive use. Over half of the couples wanted more children and 27.8% of the spouses differed about the desire for more children. In terms of sex preference, there was a 48.7% discord in couples who wanted to have more children. At large, spousal concordance on the importance of family planning was positive. However, it was the husband's favourable attitude towards family planning that determined a couple's use of contraception. Overall, contraceptive prevalence was 42.9%. Among the groups with the highest level of contraceptive users, were couples where the husband does not want any more children. Spousal communication about the decision to use contraception showed a positive association with a couple's contraceptive prevalence. Family planning programs aiming to increase contraceptive uptake could benefit from findings on spousal agreement regarding fertility desire, because the characteristics of each spouse influences the couple's fertility level. Disparities between husband and wife about the desire for more children sustain the need for male consideration while analysing the unmet need for contraception. Moreover, men play a significant role in the decision making concerning contraceptive use. Accordingly, involving men in family planning programs could increase a couple's contraceptive practice in the future.


SRS2 and SGS1 prevent chromosomal breaks and stabilize triplet repeats by restraining recombination.
Several molecular mechanisms have been proposed to explain trinucleotide repeat expansions. Here we show that in yeast srs2Delta cells, CTG repeats undergo both expansions and contractions, and they show increased chromosomal fragility. Deletion of RAD52 or RAD51 suppresses these phenotypes, suggesting that recombination triggers trinucleotide repeat instability in srs2Delta cells. In sgs1Delta cells, CTG repeats undergo contractions and increased fragility by a mechanism partially dependent on RAD52 and RAD51. Analysis of replication intermediates revealed abundant joint molecules at the CTG repeats during S phase. These molecules migrate similarly to reversed replication forks, and their presence is dependent on SRS2 and SGS1 but not RAD51. Our results suggest that Srs2 promotes fork reversal in repetitive sequences, preventing repeat instability and fragility. In the absence of Srs2 or Sgs1, DNA damage accumulates and is processed by homologous recombination, triggering repeat rearrangements.