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1. Relationship Between Pregnancy-Associated Malaria and Adverse Pregnancy Outcomes: a Systematic Review and Meta-Analysis

   https://doi.org/10.1093/tropej/fmz068  

   Thompson, Julie M. ; Eick, Stephanie M. ; Dailey, Cody ; Dale, Ariella P. ; Mehta, Mansi ; Nair, Anjali ; Cordero, José F. ; Welton, Michael ( October 2019 , Journal of Tropical Pediatrics)

   Pregnancy-associated malaria (PAM) has been associated with adverse pregnancy outcomes like preterm birth (PTB) and low birthweight (LBW), which are among the leading causes of infant mortality globally. Rates of PTB and LBW are high in countries with a high burden of malaria. PAM may be a contributing factor to PTB and LBW, but is not well understood.

   We conducted a systematic review and meta-analysis of studies examining the relationship between PAM and PTB or LBW using PubMed. The title and abstract of all studies were screened by two reviewers, and the full text of selected studies was reviewed to ensure they met inclusion criteria. Information regarding study characteristics and of PTB and LBW births among women with and without PAM was abstracted for included studies.

   Our search terms yielded 2237 articles, of which 18 met our final inclusion criteria. Eight studies examined associations between PAM and PTB, and 10 examined associations between PAM and LBW (population size ranging from 35 to 9956 women). The overall risk of LBW was 63% higher among women with PAM compared with women without PAM (95% CI = 1.48–1.80) and the risk of PTB was 23% higher among women with PAM compared with women without PAM (95% CI = 1.07–1.41).

   These results indicate that infection with PAM is associated with PTB and LBW. Further understanding of the pathogenesis of disease and the immunologic changes that occur during pregnancy is essential for reducing the disproportional effects this disease has on this vulnerable population.

    

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2. Prenatal and early-life exposure to the Great Chinese Famine increased the risk of tuberculosis in adulthood across two generations

   https://doi.org/10.1073/pnas.2008336117  

   Cheng, Qu ; Trangucci, Robert ; Nelson, Kristin N. ; Fu, Wenjiang ; Collender, Philip A. ; Head, Jennifer R. ; Hoover, Christopher M. ; Skaff, Nicholas K. ; Li, Ting ; Li, Xintong ; et al ( October 2020 , Proceedings of the National Academy of Sciences)

   Global food security is a major driver of population health, and food system collapse may have complex and long-lasting effects on health outcomes. We examined the effect of prenatal exposure to the Great Chinese Famine (1958–1962)—the largest famine in human history—on pulmonary tuberculosis (PTB) across consecutive generations in a major center of ongoing transmission in China. We analyzed >1 million PTB cases diagnosed between 2005 and 2018 in Sichuan Province using age–period–cohort analysis and mixed-effects metaregression to estimate the effect of the famine on PTB risk in the directly affected birth cohort (F1) and their likely offspring (F2). The analysis was repeated on certain sexually transmitted and blood-borne infections (STBBI) to explore potential mechanisms of the intergenerational effects. A substantial burden of active PTB in the exposed F1 cohort and their offspring was attributable to the Great Chinese Famine, with more than 12,000 famine-attributable active PTB cases (>1.23% of all cases reported between 2005 and 2018). An interquartile range increase in famine intensity resulted in a 6.53% (95% confidence interval [CI]: 1.19–12.14%) increase in the ratio of observed to expected incidence rate (incidence rate ratio, IRR) in the absence of famine in F1, and an 8.32% (95% CI: 0.59–16.6%) increase in F2 IRR. Increased risk of STBBI was also observed in F2. Prenatal and early-life exposure to malnutrition may increase the risk of active PTB in the exposed generation and their offspring, with the intergenerational effect potentially due to both within-household transmission and increases in host susceptibility.

    

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3. A novel peptide inhibitor of Dll4‐Notch1 signalling and its pro‐angiogenic functions

   https://doi.org/10.1111/bph.15743  

   Zhu, Guofu ; Lin, Ying ; Ge, Tandi ; Singh, Shekhar ; Liu, Hao ; Fan, Linlin ; Wang, Shumin ; Rhen, Jordan ; Jiang, Dongyang ; Lyu, Yuyan ; et al ( January 2022 , British Journal of Pharmacology)

   The Dll4‐Notch1 signalling pathway plays an important role in sprouting angiogenesis, vascular remodelling and arterial or venous specificity. Genetic or pharmacological inhibition of Dll4‐Notch1 signalling leads to excessive sprouting angiogenesis. However, transcriptional inhibitors of Dll4‐Notch1 signalling have not been described.

   We designed a new peptide targeting Notch signalling, referred to as TAT‐ANK, and assessed its effects on angiogenesis. In vitro, tube formation and fibrin gel bead assay were carried out, using human umbilical vein endothelial cells (HUVECs). In vivo, Matrigel plug angiogenesis assay, a developmental retinal model and tumour models in mice were used. The mechanisms underlying TAT‐ANK activity were investigated by immunochemistry, western blotting, immunoprecipitation, RT‐qPCR and luciferase reporter assays.

   The amino acid residues 179–191 in the G‐protein‐coupled receptor‐kinase‐interacting protein‐1 (GIT1‐ankyrin domain) are crucial for GIT1 binding to the Notch transcription repressor, RBP‐J. We designed the peptide TAT‐ANK, based on residues 179–191 in GIT1. TAT‐ANK significantly inhibited Dll4 expression and Notch 1 activation in HUVECs by competing with activated Notch1 to bind to RBP‐J. The analyses of biological functions showed that TAT‐ANK promoted angiogenesis in vitro and in vivo by inhibiting Dll4‐Notch1 signalling.

   We synthesized and investigated the biological actions of TAT‐ANK peptide, a new inhibitor of Notch signalling. This peptide will be of significant interest to research on Dll4‐Notch1 signalling and to clinicians carrying out clinical trials using Notch signalling inhibitors. Furthermore, our findings will have important conceptual and therapeutic implications for angiogenesis‐related diseases.

    

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4. Tit-for-tat dynamics and market volatility

   https://doi.org/10.1088/1361-6544/ad1e26  

   Brânzei, Simina ( January 2024 , Nonlinearity)

   We consider tit-for-tat dynamics in production markets, where there is a set ofnplayers connected via a weighted graph. Each playerican produce an eponymous good using its linear production function, given as input various amounts of goods in the system. In the tit-for-tat dynamic, each playerishares its good with its neighbours in fractions proportional to how much they helped playeri’s production in the last round. Our contribution is to characterize the asymptotic behaviour of the dynamic as a function of the graph structure, finding that the fortune of a player grows in the long term if and only if the player has a good self loop (i.e. the player works well alone) or works well with at least one other player. We also consider a generalized damped update, where the players may update their strategies with different speeds, and obtain a lower bound on their rate of growth by identifying a function that gives insight into the behaviour of the dynamical system. The model can capture circular economies, where players use each other’s products, and organizational partnerships, where fostering long-term growth of an organization hinges on creating relationships in which reciprocal exchanges between the agents in the organization are paramount.

    

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5. TatC2 is Important for Growth of Acinetobacter baylyi Under Stress Conditions

   Langro, J. ( October 2019 , Fine focus)

   Protein export pathways are important for bacterial physiology among pathogens and non-pathogens alike. This includes the Twin-Arginine Translocation (Tat) pathway, which transports fully folded proteins across the bacterial cytoplasmic membrane. Some Tat substrates are virulence factors, while others are important for cellular processes like peptidoglycan remodeling. Some bacteria encode more than one copy of each Tat component, including the Gram-negative soil isolate Acinetobacter baylyi. One of these Tat pathways is essential for growth, while the other is not. We constructed a loss-of-function mutation to disrupt the non-essential tatC2 gene and assessed its contribution to cell growth under different environmental conditions. While the tatC2 mutant grew well under standard laboratory conditions, it displayed a growth defect and an aberrant cellular morphology when subjected to high temperature stress including an aberrant cellular morphology. Furthermore, increased sensitivities to detergent suggested a compromised cell envelope. Lastly, using an in vitro co-culture system, we demonstrate that the non-essential Tat pathway provides a growth advantage. The findings of this study establish the importance of the non-essential Tat pathway for optimal growth of A. baylyi in stressful environmental conditions. 

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