Scotin, a novel p53-inducible proapoptotic protein located in the ER and the nuclear membrane

p53 is a transcription factor that induces growth arrest or apoptosis in response to cellular stress. To identify new p53-inducible proapoptotic genes, we compared, by differential display, the expression of genes in spleen or thymus of normal and p53 nullizygote mice after γ-irradiation of whole animals. We report the identification and characterization of human and mouse Scotin homologues, a novel gene directly transactivated by p53. The Scotin protein is localized to the ER and the nuclear membrane. Scotin can induce apoptosis in a caspase-dependent manner. Inhibition of endogenous Scotin expression increases resistance to p53-dependent apoptosis induced by DNA damage, suggesting that Scotin plays a role in p53-dependent apoptosis. The discovery of Scotin brings to light a role of the ER in p53-dependent apoptosis

Unital quantum operators on the Bloch ball and Bloch region

For one qubit systems, we present a short, elementary argument characterizing unital quantum operators in terms of their action on Bloch vectors. We then show how our approach generalizes to multi-qubit systems, obtaining inequalities that govern when a ``diagonal'' superoperator on the Bloch region is a quantum operator. These inequalities are the n-qubit analogue of the Algoet-Fujiwara conditions. Our work is facilitated by an analysis of operator-sum decompositions in which negative summands are allowed.Comment: Revised and corrected, to appear in Physical Review

Weighted composition operators on Korenblum type spaces of analytic functions

[EN] We investigate the continuity, compactness and invertibility of weighted composition operators W-psi,W-phi: f -> psi(f circle phi) when they act on the classical Korenblum space A(-infinity) and other related Frechet or (LB)-spaces of analytic functions on the open unit disc which are defined as intersections or unions of weighted Banach spaces with sup-norms. Some results about the spectrum of these operators are presented in case the self-map phi has a fixed point in the unit disc. A precise description of the spectrum is obtained in this case when the operator acts on the Korenblum space.This research was partially supported by the research project MTM2016-76647-P and the grant BES-2017-081200.Gomez-Orts, E. (2020). Weighted composition operators on Korenblum type spaces of analytic functions. Revista de la Real Academia de Ciencias Exactas Físicas y Naturales Serie A Matemáticas. 114(4):1-15. https://doi.org/10.1007/s13398-020-00924-1S1151144Abramovich, Y.A., Aliprantis, C.D.: An invitation to operator theory. Graduate Studies in Mathematics. Amer. Math. Soc., 50 (2002)Albanese, A.A., Bonet, J., Ricker, W.J.: The Cesàro operator in the Fréchet spaces $$\ell ^{p+}$$ and $$L^{p-}$$. Glasgow Math. J. 59, 273–287 (2017)Albanese, A.A., Bonet, J., Ricker, W.J.: The Cesàro operator on Korenblum type spaces of analytic functions. Collect. Math. 69(2), 263–281 (2018)Albanese, A.A., Bonet, J., Ricker, W.J.: Operators on the Fréchet sequence spaces $$ces(p+), 1\le p\le \infty$$. Rev. R. Acad. Cienc. Exactas Fís. Nat. Ser. A Mat. RACSAM 113(2), 1533–1556 (2019)Albanese, A.A., Bonet, J., Ricker, W.J.: Linear operators on the (LB)-sequence spaces $$ces(p-), 1\le p\le \infty$$. Descriptive topology and functional analysis. II, 43–67, Springer Proc. Math. Stat., 286, Springer, Cham (2019)Arendt, W., Chalendar, I., Kumar, M., Srivastava, S.: Powers of composition operators: asymptotic behaviour on Bergman, Dirichlet and Bloch spaces. J. Austral. Math. Soc. 1–32. https://doi.org/10.1017/S1446788719000235Aron, R., Lindström, M.: Spectra of weighted composition operators on weighted Banach spaces of analytic funcions. Israel J. Math. 141, 263–276 (2004)Bierstedt, K.D., Summers, W.H.: Biduals of weighted Banach spaces of analytic functions. J. Austral. Math. Soc., Ser. A, 54(1), 70–79 (1993)Bonet, J.: A note about the spectrum of composition operators induced by a rotation. RACSAM 114, 63 (2020). https://doi.org/10.1007/s13398-020-00788-5Bonet, J., Domański, P., Lindström, M., Taskinen, J.: Composition operators between weighted Banach spaces of analytic functions. J. Austral. Math. Soc., Ser. A, 64(1), 101–118 (1998)Bourdon, P.S.: Essential angular derivatives and maximum growth of Königs eigenfunctions. J. Func. Anal. 160, 561–580 (1998)Bourdon, P.S.: Invertible weighted composition operators. Proc. Am. Math. Soc. 142(1), 289–299 (2014)Carleson, L., Gamelin, T.: Complex Dynamics. Springer, Berlin (1991)Cowen, C., MacCluer, B.: Composition Operators on Spaces of Analytic Functions. CRC Press, Boca Raton, FL (1995)Contreras, M., Hernández-Díaz, A.G.: Weighted composition operators in weighted Banach spacs of analytic functions. J. Austral. Math. Soc., Ser. A 69, 41–60 (2000)Eklund, T., Galindo, P., Lindström, M.: Königs eigenfunction for composition operators on Bloch and $$H^\infty$$ spaces. J. Math. Anal. Appl. 445, 1300–1309 (2017)Hedenmalm, H., Korenblum, B., Zhu, K.: Theory of Bergman Spaces. Grad. Texts in Math. 199. Springer, New York (2000)Jarchow, H.: Locally Convex Spaces. Teubner, Stuttgart (1981)Kamowitz, H.: Compact operators of the form $$uC_{\varphi }$$. Pac. J. Math. 80(1) (1979)Korenblum, B.: An extension of the Nevanlinna theory. Acta Math. 135, 187–219 (1975)Köthe, G.: Topological Vector Spaces II. Springer, New York Inc (1979)Lusky, W.: On the isomorphism classes of weighted spaces of harmonic and holomophic functions. Stud. Math. 75, 19–45 (2006)Meise, R., Vogt, D.: Introduction to functional analysis. Oxford Grad. Texts in Math. 2, New York, (1997)Montes-Rodríguez, A.: Weighted composition operators on weighted Banach spaces of analytic functions. J. Lond. Math. Soc. 61(3), 872–884 (2000)Queffélec, H., Queffélec, M.: Diophantine Approximation and Dirichlet series. Hindustain Book Agency, New Delhi (2013)Shapiro, J.H.: Composition Operators and Classical Function Theory. Springer, New York (1993)Shields, A.L., Williams, D.L.: Bounded projections, duality and multipliers in spaces of analytic functions. Trans. Amer. Math. Soc. 162, 287–302 (1971)Zhu, K.: Operator Theory on Function Spaces, Math. Surveys and Monographs, Amer. Math. Soc. 138 (2007

Preferences and skills of Indian public sector teachers

With a sample of 700 future public sector primary teachers in India, a Discrete Choice Experiment is used to measure job preferences, particularly regarding location. General skills are also tested. Urban origin teachers and women are more averse to remote locations than rural origin teachers and men respectively. Women would require a 26-73 percent increase in salary for moving to a remote location. The results suggest that existing caste and gender quotas can be detrimental for hiring skilled teachers willing to work in remote locations. The most preferred location is home, which supports decentralised hiring, although this could compromise skills

Antirhea borbonica Aqueous Extract Protects Albumin and Erythrocytes from Glycoxidative Damages

Diabetes constitutes a major health problem associated with severe complications. In hyperglycemic conditions, chronically increased oxidation and glycation of circulating components lead to advanced glycation end-products (AGEs) formation, a key contributor in diabetes complication progression. In line with literature documenting the beneficial properties of herbal teas, this study evaluates the antioxidant/glycant properties of Antirhea borbonica (Ab). Ab aqueous extract effects were tested on human albumin or erythrocytes submitted to methyl glyoxal-mediated glycoxidative damages. By using mass spectrometry, Ab aqueous extracts revealed to be rich in polyphenols. All tested biomarkers of oxidation and glycation, such as AGE, ketoamine, oxidized thiol groups, were decreased in albumin when glycated in the presence of Ab aqueous extract. Ab extract preserve erythrocyte from methylglyoxal (MGO)-induced damages in terms of restored membrane deformability, reduced oxidative stress and eryptosis phenomenon. Antioxidant capacities of Ab extract on erythrocytes were retrieved in vivo in zebrafish previously infused with MGO. These results bring new evidences on the deleterious impacts of glycation on albumin and erythrocyte in diabetes. Furthermore, it reveals antioxidant and antiglycant properties of Ab that could be used for the dietary modulation of oxidative stress and glycation in hyperglycemic situations

Childhood acute illness and nutrition (CHAIN) network: A protocol for a multi-site prospective cohort study to identify modifiable risk factors for mortality among acutely ill children in Africa and Asia

Introduction: Children admitted to hospitals in resource-poor settings remain at risk of both inpatient and post-discharge mortality. While known risk factors such as young age and nutritional status can identify children at risk, they do not provide clear mechanistic targets for intervention. The Childhood Acute Illness and Nutrition (CHAIN) cohort study aims to characterise the biomedical and social risk factors for mortality in acutely ill children in hospitals and after discharge to identify targeted interventions to reduce mortality.Methods and analysis: The CHAIN network is currently undertaking a multi-site, prospective, observational cohort study, enrolling children aged 1 week to 2 years at admission to hospitals at nine sites located in four African and two South Asian countries. The CHAIN Network supports the sites to provide care according to national and international guidelines. Enrolment is stratified by anthropometric status and children are followed throughout hospitalisation and for 6 months after discharge. Detailed clinical, demographic, anthropometric, laboratory and social exposures are assessed. Scheduled visits are conducted at 45, 90 and 180 days after discharge. Blood, stool and rectal swabs are collected at enrolment, hospital discharge and follow-up. The primary outcome is inpatient or post-discharge death. Secondary outcomes include readmission to hospital and nutritional status after discharge. Cohort analysis will identify modifiable risks, children with distinct phenotypes, relationships between factors and mechanisms underlying poor outcomes that may be targets for intervention. A nested case-control study examining infectious, immunological, metabolic, nutritional and other biological factors will be undertaken.Ethics and dissemination: This study protocol was reviewed and approved primarily by the Oxford Tropical Research Ethics Committee, and the institutional review boards of all partner sites. The study is being externally monitored. Results will be published in open access peer-reviewed scientific journals and presented to academic and policy stakeholders

Quantifying loopy network architectures

Biology presents many examples of planar distribution and structural networks having dense sets of closed loops. An archetype of this form of network organization is the vasculature of dicotyledonous leaves, which showcases a hierarchically-nested architecture containing closed loops at many different levels. Although a number of methods have been proposed to measure aspects of the structure of such networks, a robust metric to quantify their hierarchical organization is still lacking. We present an algorithmic framework, the hierarchical loop decomposition, that allows mapping loopy networks to binary trees, preserving in the connectivity of the trees the architecture of the original graph. We apply this framework to investigate computer generated graphs, such as artificial models and optimal distribution networks, as well as natural graphs extracted from digitized images of dicotyledonous leaves and vasculature of rat cerebral neocortex. We calculate various metrics based on the Asymmetry, the cumulative size distribution and the Strahler bifurcation ratios of the corresponding trees and discuss the relationship of these quantities to the architectural organization of the original graphs. This algorithmic framework decouples the geometric information (exact location of edges and nodes) from the metric topology (connectivity and edge weight) and it ultimately allows us to perform a quantitative statistical comparison between predictions of theoretical models and naturally occurring loopy graphs.Comment: 17 pages, 8 figures. During preparation of this manuscript the authors became aware of the work of Mileyko at al., concurrently submitted for publicatio

Proof of concept of a personalized genetic risk tool to promote smoking cessation:High acceptability and reduced cigarette smoking

Relatively little is known about the possible effects of personalized genetic risk information on smoking, the leading preventable cause of morbidity and mortality. We examined the acceptability and potential behavior change associated with a personalized genetically-informed risk tool (RiskProfile) among current smokers. Current smokers (n=108) were enrolled in a pre-post study with three visits. At Visit 1, participants completed a baseline assessment and genetic testing via 23andMe. Participants’ raw genetic data (CHRNA5 variants) and smoking heaviness were used to create a tailored RiskProfile tool that communicated personalized risks of smoking-related diseases and evidence-based recommendations to promote cessation. Participants received their personalized RiskProfile intervention at Visit 2, approximately 6 weeks later. Visit 3 involved a telephone-based follow-up assessment 30 days after intervention. Of enrolled participants, 83% were retained across the three visits. Immediately following intervention, acceptability of RiskProfile was high (M=4.4; SD=0.6 on scale of 1 to 5); at 30-day follow-up, 89% of participants demonstrated accurate recall of key intervention messages. In the full analysis set of this single-arm trial, cigarettes smoked per day decreased from intervention to 30-day follow-up [11.3 vs. 9.8, difference=1.5, 95% CI (0.6—2.4), p=.001]. A personalized genetically-informed risk tool was found to be highly acceptable and associated with a reduction in smoking, although the absence of a control group must be addressed in future research. This study demonstrates proof of concept for translating key basic science findings into a genetically-informed risk tool that was used to promote progress toward smoking cessation

Probing photo-ionization: simulations of positive streamers in varying N2:O2 mixtures

Photo-ionization is the accepted mechanism for the propagation of positive streamers in air though the parameters are not very well known; the efficiency of this mechanism largely depends on the presence of both nitrogen and oxygen. But experiments show that streamer propagation is amazingly robust against changes of the gas composition; even for pure nitrogen with impurity levels below 1 ppm streamers propagate essentially with the same velocity as in air, but their minimal diameter is smaller, and they branch more frequently. Additionally, they move more in a zigzag fashion and sometimes exhibit a feathery structure. In our simulations, we test the relative importance of photo-ionization and of the background ionization from pulsed repetitive discharges, in air as well as in nitrogen with 1 ppm O2 . We also test reasonable parameter changes of the photo-ionization model. We find that photo- ionization dominates streamer propagation in air for repetition frequencies of at least 1 kHz, while in nitrogen with 1 ppm O2 the effect of the repetition frequency has to be included above 1 Hz. Finally, we explain the feather-like structures around streamer channels that are observed in experiments in nitrogen with high purity, but not in air.Comment: 12 figure

(N)-methanocarba-2MeSADP (MRS2365) is a subtype-specific agonist that induces rapid desensitization of the P2Y1 receptor of human platelets

Adenosine diphosphate (ADP) initiates and maintains sustained aggregation of platelets through simultaneous activation of both the Gq-coupled P2Y1 receptor and the Gi-coupled P2Y12 receptor. We recently described the synthesis and P2Y1 receptor-specific agonist activity of (N)-methano-carba-2MeSADP (MRS2365). Consequences of selective activation of the P2Y1 receptor by MRS2365 have been further examined in human platelets. Whereas MRS2365 alone only induced shape change, addition of MRS2365 following epinephrine treatment, which activates the Gi/z-linked, α2A-adrenergic receptor, resulted in sustained aggregation that was indistinguishable from that observed with ADP. Conversely, the platelet shape change promoted by ADP in the presence of the GPIIb/IIIa antagonist eptifibatide was similar to that promoted by MRS2365. Preaddition of the high affinity P2Y1 receptor antagonist MRS2500 inhibited the effect of MRS2365, whereas addition of MRS2500 subsequent to MRS2365 reversed the MRS2365-induced shape change. Preactivation of the P2Y1 receptor with MRS2365 for 2 min resulted in marked loss of capacity of ADP to induce aggregation as evidenced by a greater than 20-fold rightward shift in the concentration effect curve of ADP. This inhibitory effect of P2Y1 receptor activation was dependent on the concentration of MRS2365 (EC50 = 34 nM). The inhibitory effect of preincubation with MRS2365 was circumvented by activation of the Gq-coupled 5-HT2a receptor suggesting that MRS2365 induces loss of the ADP response as a consequence of desensitization of the Gq-coupled P2Y1 receptor. The time course of MRS2365-induced loss of aggregation response to epinephrine was similar to that observed with ADP. These results further demonstrate the P2Y1 receptor selectivity of MRS2365 and illustrate the occurrence of agonist-induced desensitization of the P2Y1 receptor of human platelets studied in the absence of P2Y12 receptor activation