Large amplitude and multiple stable periodic oscillations in treatment–donation–stockpile dynamics

A transmission–treatment–donation–stockpile model was originally formulated for the 2014–2015 West Africa Ebola outbreak in order to inform policy complication of large scale use and collection of convalescent blood as an empiric treatment. Here we reduce this model to a three dimensional system with a single delay counting for the duration between two consecutive donations. The blood unit reproduction number R0 is calculated and interpreted biologically. Using the LaSalle’s invariance principle we show that the zero blood bank storage equilibrium is globally asymptotically stable if R0 1, the system has a non-zero equilibrium with potential occurrence of Hopf bifurcations. The geometric approach previously developed is applied to guide the location of critical bifurcation points. Numerical analysis shows that variations of the single delay parameter can trigger bi-stable large amplitude periodic solutions. We therefore suggest that this time lag must be carefully chosen and maintained to attain stable treatment availability during outbreaks

Large amplitude and multiple stable periodic oscillations in treatment-donation-stockpile dynamics

A transmission-treatment-donation-stockpile model was originally formulated for the 2014-2015 West Africa Ebola outbreak in order to inform policy complication of large scale use and collection of convalescent blood as an empiric treatment. Here we reduce this model to a three dimensional system with a single delay counting for the duration between two consecutive donations. The blood unit reproduction number $R_0$ is calculated and interpreted biologically. Using the LaSalle's invariance principle we show that the zero blood bank storage equilibrium is globally asymptotically stable if $R_01$, the system has a non-zero equilibrium with potential occurrence of Hopf bifurcations. The geometric approach previously developed is applied to guide the location of critical bifurcation points. Numerical analysis shows that variations of the single delay parameter can trigger bi-stable large amplitude periodic solutions. We therefore suggest that this time lag must be carefully chosen and maintained to attain stable treatment availability during outbreaks

Association of whole-genome and NETRIN1 signaling pathway-derived polygenic risk scores for Major Depressive Disorder and white matter microstructure in UK Biobank

Background: Major depressive disorder is a clinically heterogeneous psychiatric disorder with a polygenic architecture. Genome-wide association studies have identified a number of risk-associated variants across the genome and have reported growing evidence of NETRIN1 pathway involvement. Stratifying disease risk by genetic variation within the NETRIN1 pathway may provide important routes for identification of disease mechanisms by focusing on a specific process, excluding heterogeneous risk-associated variation in other pathways. Here, we sought to investigate whether major depressive disorder polygenic risk scores derived from the NETRIN1 signaling pathway (NETRIN1-PRSs) and the whole genome, excluding NETRIN1 pathway genes (genomic-PRSs), were associated with white matter microstructure. Methods: We used two diffusion tensor imaging measures, fractional anisotropy (FA) and mean diffusivity (MD), in the most up-to-date UK Biobank neuroimaging data release (FA: n = 6401; MD: n = 6390). Results: We found significantly lower FA in the superior longitudinal fasciculus (β = −.035, p =.029) and significantly higher MD in a global measure of thalamic radiations (β =.029, p =.021), as well as higher MD in the superior (β =.034, p =.039) and inferior (β =.029, p =.043) longitudinal fasciculus and in the anterior (β =.025, p =.046) and superior (β =.027, p =.043) thalamic radiation associated with NETRIN1-PRS. Genomic-PRS was also associated with lower FA and higher MD in several tracts. Conclusions: Our findings indicate that variation in the NETRIN1 signaling pathway may confer risk for major depressive disorder through effects on a number of white matter tracts

A conceptual model for optimizing vaccine coverage to reduce vector-borne infections in the presence of antibody-dependent enhancement

Abstract Background Many vector-borne diseases co-circulate, as the viruses from the same family are also transmitted by the same vector species. For example, Zika and dengue viruses belong to the same Flavivirus family and are primarily transmitted by a common mosquito species Aedes aegypti. Zika outbreaks have also commonly occurred in dengue-endemic areas, and co-circulation and co-infection of both viruses have been reported. As recent immunological cross-reactivity studies have confirmed that convalescent plasma following dengue infection can enhance Zika infection, and as global efforts of developing dengue and Zika vaccines are intensified, it is important to examine whether and how vaccination against one disease in a large population may affect infection dynamics of another disease due to antibody-dependent enhancement. Methods Through a conceptual co-infection dynamics model parametrized by reported dengue and Zika epidemic and immunological cross-reactivity characteristics, we evaluate impact of a hypothetical dengue vaccination program on Zika infection dynamics in a single season when only one particular dengue serotype is involved. Results We show that an appropriately designed and optimized dengue vaccination program can not only help control the dengue spread but also, counter-intuitively, reduce Zika infections. We identify optimal dengue vaccination coverages for controlling dengue and simultaneously reducing Zika infections, as well as the critical coverages exceeding which dengue vaccination will increase Zika infections. Conclusion This study based on a conceptual model shows the promise of an integrative vector-borne disease control strategy involving optimal vaccination programs, in regions where different viruses or different serotypes of the same virus co-circulate, and convalescent plasma following infection from one virus (serotype) can enhance infection against another virus (serotype). The conceptual model provides a first step towards well-designed regional and global vector-borne disease immunization programs

Autophagy Dances with Phytohormones upon Multiple Stresses

Autophagy is an evolutionarily conserved process for turning over unwanted cellular components, thus promoting nutrient recycling and maintaining cellular homeostasis, which eventually enables plants to survive unfavorable growth conditions. In addition to plant growth and development, previous studies have demonstrated that autophagy is involved in the responses to various environmental challenges through interplaying with multiple phytohormones, including abscisic acid (ABA), jasmonic acid (JA), and salicylic acid (SA). In this review, we summarize the advances made in their synergistic interactions in response to multiple abiotic and biotic stresses; we also discuss the remaining issues and perspectives regarding their crosstalk

Berberine-Induced Apoptosis in Human Breast Cancer Cells is Mediated by Reactive Oxygen Species Generation and Mitochondrial-Related Apoptotic Pathway

Berberine has drawn extensive attention toward their wide range of biochemical and pharmacological effects, including antineoplastic effect in recent years, but the precise mechanisms remain unclear. Treatment of human breast cancer cells (MCF-7 and MDA-MB-231 cells) with berberine induced inhibition of cell viability in concentration- and time-dependent manner irrespective of their estrogen receptor (ER) expression. Hoechst33342 staining confirmed berberine induced breast cancer cell apoptosis in time-dependent manner. Because apoptosis induction is considered to be a crucial strategy for cancer prevention and therapy, berberine may be an effective chemotherapeutic agent against breast cancer. To explore the precise mechanism, berberine-induced oxidative stress and mitochondrial-related apoptotic pathway in human breast cancer cells were investigated in this study. In both MCF-7 and MDA-MB-231 cells, berberine increased the production of reactive oxygen species (ROS), which activated the pro-apoptotic JNK signaling. Phosphorylated JNK triggered mitochondria membrane potential (ΔΨm) depolarization and downregulation expression of anti-apoptotic protein Bcl-2 concomitant with the upregulation expression of pro-apoptotic protein Bax. Downregulation of anti-apoptotic Bcl-2 family protein in parallel with loss of ΔΨm, leading to increased the release of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria, and eventually triggered the caspase-dependent and caspase-independent apoptosis. Taken together, our study reveled that berberine exerted an antitumor activity in breast cancer cells by reactive oxygen species generation and mitochondrial-related apoptotic pathway. These finding provide an insight into the potential of berberine for breast cancer therapy

Clinical observation of factors in the efficacy of blood component transfusion in patients following hematopoietic stem cell transplantation.

BACKGROUND: Factors affecting the efficacy of platelet and red blood cell (RBC) transfusion in patients undergoing hematopoietic stem cell transplantation (HSCT) have not been studied extensively. We aimed to evaluate platelet and RBC transfusion efficacy by measuring the platelet corrected count increment and the hemoglobin increment, respectively, 24 h after transfusion in 105 patients who received HSCT. METHODOLOGY/PRINCIPAL FINDINGS: Using retrospective analysis, we studied whether factors, including gender, time of transplantation, the compatibility of ABO group between HSC donors and recipients, and autologous or allogenic transplantation, influence the efficacy of blood component transfusion. We found that the infection rate of HSCT patients positively correlated with the transfusion amount, and the length of stay in the laminar flow room was associated with transfusion. We found that platelet transfusion performed during HSCT showed significantly better efficacy than that performed before HSCT. The effect of platelet transfusion in auto-transplantation was significantly better than that in allo-transplantation. The efficacy of RBC transfusion during HSCT was significantly lower than that performed before HSCT. The efficacy of RBC transfusion in auto-transplantation was significantly higher than that in allo-transplantation. Allo-transplantation patients who received HSCs from compatible ABO groups showed significantly higher efficacy during both platelet and RBC transfusion. CONCLUSIONS: We conclude that the efficacy of platelet and RBC transfusions does not correlate with the gender of patients, while it significantly correlates with the time of transplantation, type of transplantation, and ABO compatibility between HSC donors and recipients. During HSCT, the infection rate of patients positively correlates with the transfusion amount of RBCs and platelets. The total volume of RBC units transfused positively correlates with the length of the patients' stay in the laminar flow room

Comparative Genomic Analysis of a <i>Methylorubrum rhodesianum</i> MB200 Isolated from Biogas Digesters Provided New Insights into the Carbon Metabolism of Methylotrophic Bacteria

Methylotrophic bacteria are widely distributed in nature and can be applied in bioconversion because of their ability to use one-carbon source. The aim of this study was to investigate the mechanism underlying utilization of high methanol content and other carbon sources by Methylorubrum rhodesianum strain MB200 via comparative genomics and analysis of carbon metabolism pathway. The genomic analysis revealed that the strain MB200 had a genome size of 5.7 Mb and two plasmids. Its genome was presented and compared with that of the 25 fully sequenced strains of Methylobacterium genus. Comparative genomics revealed that the Methylorubrum strains had closer collinearity, more shared orthogroups, and more conservative MDH cluster. The transcriptome analysis of the strain MB200 in the presence of various carbon sources revealed that a battery of genes was involved in the methanol metabolism. These genes are involved in the following functions: carbon fixation, electron transfer chain, ATP energy release, and resistance to oxidation. Particularly, the central carbon metabolism pathway of the strain MB200 was reconstructed to reflect the possible reality of the carbon metabolism, including ethanol metabolism. Partial propionate metabolism involved in ethyl malonyl-CoA (EMC) pathway might help to relieve the restriction of the serine cycle. In addition, the glycine cleavage system (GCS) was observed to participate in the central carbon metabolism pathway. The study revealed the coordination of several metabolic pathways, where various carbon sources could induce associated metabolic pathways. To the best of our knowledge, this is the first study providing a more comprehensive understanding of the central carbon metabolism in Methylorubrum. This study provided a reference for potential synthetic and industrial applications of this genus and its use as chassis cells

Microbe-mediated transformation of metal sulfides: Mechanisms and environmental significance

Highlights • Microbe-mediated transformation of metal sulfide has enormous environmental impact. • Microbes provide templates for mineralization of metal sulfide crystals. • Sulfate reducing bacteria recover metal ions through metal sulfide precipitation. • Biosynthetic metal sulfide nanoparticles play a big role in pollutant sensing and treatment. • Metal sulfide-microbe biohybrid system has greater prospects in environmental field. Microorganisms play a key role in the natural circulation of various constituent elements of metal sulfides. Some microorganisms (such as Thiobacillus ferrooxidans) can promote the oxidation of metal sulfides to increase the release of heavy metals. However, other microorganisms (such as Desulfovibrio vulgaris) can transform heavy metals into metal sulfides crystals. Therefore, insight into the metal sulfides transformation mediated by microorganisms is of great significance to environmental protection. In this review, first, we discuss the mechanism and influencing factors of microorganisms transforming heavy metals into metal sulfides crystals in different environments. Then, we explore three microbe-mediated transformation forms of heavy metals to metal sulfides and their environmental applications: (1) transformation to metal sulfides precipitation for metal resource recovery; (2) transformation to metal sulfides nanoparticles (NPs) for pollutant treatment; (3) transformation to “metal sulfides-microbe” biohybrid system for clean energy production and pollutant remediation. Finally, we further provide critical views on the application of microbe-mediated metal sulfides transformation in the environmental field and discuss the need for future research

Prognostic Significance of CD56 Antigen Expression in Patients with De Novo Non-M3 Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a heterogeneous group of disorders with distinct characteristics and prognoses. Although cytogenetic changes and gene mutations are associated with AML prognosis, there is a need to identify further factors. CD56 is considered a prognostic factor for AML, which is abnormally expressed in leukemia cells. However, a clear consensus for this surface molecule is lacking, which has prompted us to investigate its prognostic significance. Bone marrow samples of de novo non-M3 AML were collected to detect CD56 expression using multiparameter flow cytometry (FCM). As a result, the CD56 expression in de novo non-M3 AML was found to be significantly higher than that in acute lymphoma leukemia (ALL, P=0.017) and healthy controls (P=0.02). The X-Tile program produced a CD56 cutoff point at a relative expression level of 24.62%. Based on this cutoff point, high CD56 expression was observed in 29.21% of de novo non-M3 AML patients. CD56-high patients had a poor overall survival (OS, P=0.015) compared to CD56-low patients. Bone marrow transplantation (BMT) improved OS (P=0.004), but a poor genetic risk was associated with an inferior OS (P=0.002). Compared with CD56-low patients, CD56-high patients had lower peripheral blood platelet (PLT) counts (P=0.010). Our research confirmed that high CD56 expression is associated with adverse clinical outcomes in de novo non-M3 AML patients, indicating that CD56 could be used as a prognostic marker for a more precise stratification of de novo non-M3 AML patients