Biosecurity and biosafety measures are designed to mitigate intentional and accidental biological risks that pose potentially catastrophic consequences to a country's health system, security, and ...political and economic stability. Unfortunately, biosecurity and biosafety are often under-prioritized nationally, regionally, and globally. Security leaders often deemphasize accidental and deliberate biological threats relative to other challenges to peace and security. Given emerging biological risks, including those associated with rapid technological advances and terrorist and state interest in weapons of mass destruction, biosecurity deserves stronger emphasis in health and security fora. The Global Biosecurity Dialogue (GBD) was initiated to align national and regional donor initiatives toward a common set of measurable targets. The GBD was launched by the Nuclear Threat Initiative (NTI), with support from Global Affairs Canada's Weapons Threat Reduction Program and the Open Philanthropy Project, and in coordination with the government of The Netherlands as the 2018-19 Chair of the Global Health Security Agenda (GHSA) Action Package Prevent-3 (APP3) on Biosafety and Biosecurity. The GBD provides a multisectoral forum for sharing models, enabling new actions to achieve biosecurity-related targets, and promoting biosecurity as an integral component of health security. The GBD has contributed to new national and continent-wide actions, including the African Union and Africa Centres for Disease Control and Prevention's new regional Initiative to Strengthen Biosafety and Biosecurity in Africa. Here we present the GBD as a model for catalyzing action within APP3. We describe how the benefits of this approach could expand to other GHSA Action Packages and international health security initiatives.
There are three isoforms of dimeric nitric oxide synthases (NOS) that convert arginine to citrulline and nitric oxide. Inducible NOS is implicated in numerous inflammatory diseases and, more ...recently, in neuropathic pain states. The majority of existing NOS inhibitors are either based on the structure of arginine or are substrate competitive. We describe the identification from an ultra high-throughput screen of a novel series of quinolinone small molecule, nonarginine iNOS dimerization inhibitors. SAR studies on the screening hit, coupled with an in vivo lipopolysaccharide (LPS) challenge assay measuring plasma nitrates and drug levels, rapidly led to the identification of compounds 12 and 42potent inhibitors of the human and mouse iNOS enzyme that were highly selective over endothelial NOS (eNOS). Following oral dosing, compounds 12 and 42 gave a statistical reduction in pain behaviors in the mouse formalin model, while 12 also statistically reduced neuropathic pain behaviors in the chronic constriction injury (Bennett) model.
It is very desirable to design dual-mode nanocomposites for diagnostic applications via flexible strategies. Herein, we proposed to synthesize one type of multifunctional magnetic resonance ...(MR)/optic nanocomposites based on manganese ferrite magnetic nanoparticles (MFNPs) modified by fluorescent podoplanin (PDPN) antibodies. MFNPs were synthesized using a thermal decomposition method and were modified by the fluorescent PDPN antibodies on their surfaces. The fluorescent PDPN antibody-conjugated MFNPs enabled strong MR imaging and fluorescence imaging due to the antibodies that targeted brain tumors. These results demonstrate that MR/optic nanocomposites have potential as precision diagnostic systems for brain cancer.
The purpose of this research was to determine if prior activity affected the shape of a plaster cast taken of a trans-tibial residual limb. Plaster casts were taken twice within a day on 24 ...participants with trans-tibial limb loss, with 5 s between doffing and casting in one trial (PDI-5s), and 20 min in the other trial (PDI-20m). The ordering of the trials was randomized. The mean radial difference between PDI-20m and PDI-5s was 0.34mm (s.d. 0.21) when PDI-5s was conducted first and −0.02mm (s.d. 02.0) when PDI-20m was conducted first. Ordering of the trials had a statistically significant influence on the mean radial difference between the two shapes (p=0.008). The result shows that prior activity influenced the residual limb cast shape. Practitioners should be mindful of prior activity and doffing history when casting an individual’s limb for socket design and prosthetic fitting.
Sex chromosome meiotic drive in stalk-eyed flies Presgraves, D.C. (University of Maryland, College Park, MD.); Severance, E; Wilkinson, G.S
Genetics (Austin),
(Nov 1997), 1997-Nov, Letnik:
147, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Meiotically driven sex chromosomes can quickly spread to fixation and cause population extinction unless balanced by selection or suppressed by genetic modifiers. We report results of genetic ...analyses that demonstrate that extreme female-biased sex ratios in two sister species of stalk-eyed flies, Cyrtodiopsis dalmanni and C. whitei, are due to a meiotic drive element on the X chromosome (Xd). Relatively high frequencies of Xd in C. dalmanni and C. whitei (13-17% and 29%, respectively) cause female-biased sex ratios in natural populations of both species. Sex ratio distortion is associated with spermatid degeneration in male carriers of Xd. Variation in sex ratios is caused by Y-linked and autosomal factors that decrease the intensity of meiotic drive. Y-linked polymorphism for resistance to drive exists in C. dalmanni in which a resistant Y chromosome reduces the intensity and reverses the direction of meiotic drive. When paired with Xd, modifying Y chromosomes (Ym) cause the transmission of predominantly Y-bearing sperm, and on average, production of 63% male progeny. The absence of sex ratio distortion in closely related monomorphic outgroup species suggests that this meiotic drive system may predate the origin of C. whitei and C. dalmanni. We discuss factors likely to be involved in the persistence of these sex-linked polymorphisms and consider the impact of Xd on the operational sex ratio and the intensity of sexual selection in these extremely sexually dimorphic flies.
A functional cell-based screen identified 3-(4-chlorophenyl)-3-(2-(dimethylamino)ethyl)isochroman-1-one hydrochloride (AC-7954, 1) as a nonpeptidic agonist of the urotensin-II receptor. Racemic 1 had ...an EC50 of 300 nM at the human UII receptor and was highly selective. Testing of the enantiopure (+)- and (−)- 1 revealed that the UII receptor activity of racemic 1 resides primarily in (+)-1. Being a selective nonpeptidic druglike UII receptor agonist, (+)-1 will be useful as a pharmacological research tool and a potential drug lead.
Resampling or simulation techniques are now frequently used in applied economic analyses. However, significance tests for differences between empirical distributions have either invoked normality ...assumptions or have used nonoverlapping confidence interval criteria. We demonstrate that such methods generally will not be appropriate, and we present an empirical test, based on the method of convolutions, for assessing the statistical significance between approximate empirical distributions created by resampling techniques. The proposed convolutions approach is illustrated in a case study involving empirical distributions from dichotomous choice contingent valuation data.
Immune aberrations in schizophrenia and bipolar disorder have led to the hypotheses that infectious agents or corresponding immune responses might contribute to psychiatric etiopathogeneses. We ...investigated case-control differences in exposure to the opportunistic fungal pathogen, Candida albicans, and examined associations with cognition, medication, lifestyle, and somatic conditions. We quantified C. albicans IgG antibodies in two cohorts totaling 947 individuals and evaluated odds ratios (OR) of exposure with psychiatric disorder using multivariate regressions. The case-control cohort included 261 with schizophrenia, 270 with bipolar disorder, and 277 non-psychiatric controls; the second included 139 with first-episode schizophrenia, 78 of whom were antipsychotic naive. No differences in C. albicans exposures were found until diagnostic groups were stratified by sex. In males, C. albicans seropositivity conferred increased odds for a schizophrenia diagnosis (OR 2.04-9.53, P⩽0.0001). In females, C. albicans seropositivity conferred increased odds for lower cognitive scores on Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in schizophrenia (OR 1.12, P⩽0.004), with significant decreases on memory modules for both disorders (P⩽0.0007-0.03). C. albicans IgG levels were not impacted by antipsychotic medications. Gastrointestinal (GI) disturbances were associated with elevated C. albicans in males with schizophrenia and females with bipolar disorder (P⩽0.009-0.02). C. albicans exposure was associated with homelessness in bipolar males (P⩽0.0015). In conclusion, sex-specific C. albicans immune responses were evident in psychiatric disorder subsets. Inquiry regarding C. albicans infection or symptoms may expedite amelioration of this treatable comorbid condition. Yeast exposure as a risk factor for schizophrenia and its associated cognitive and GI effects require further investigation including the possible contribution of gut-brain mechanisms.
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