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Plasma membrane damage occurs in healthy cells and more frequently in cancer cells where high growth rates and metastasis result in frequent membrane damage. The annexin family of proteins plays a key role in membrane repair. Annexins are recruited at the membrane injury site by Ca +2 and repair the damaged membrane in concert with several other proteins. Annexin A4 (ANXA4) and ANXA5 form trimers at the bilayer surface, and previous simulations show that the trimers induce high local negative membrane curvature on a flat bilayer. The membrane-curvature-inducing property of ANXA5 is presumed to be vital to the membrane repair mechanism. A previously proposed descriptive model hypothesizes that ANXA5-mediated curvature force is utilized at the free edge of the membrane at a wound site to pull the wound edges together, resulting in the formation of a "neck"-shaped structure, which, when combined with a constriction force exerted by ANXA6, leads to membrane repair. The molecular details and mechanisms of repair remain unknown, in part because the membrane edge is a transient structure that is difficult to investigate both experimentally and computationally. For the first time, we investigate the impact of ANXA5 near a membrane edge, which is modeled by a bicelle under periodic boundary conditions. ANXA5 trimers induce local curvature on the membrane leading to global bending of the bicelle. The global curvature depends on the density of annexins on the bicelle, and the curvature increases with the ANXA5 concentration until it reaches a plateau. The simulations suggest that not only do annexins induce local membrane curvature, but they can change the overall shape of a free-standing membrane. We also demonstrate that ANXA5 trimers reduce the rate of phosphatidylserine lipid diffusion from the cytoplasmic to the exoplasmic leaflet along the edge of the bicelle. In this way, membrane-bound annexins can potentially delay the apoptotic signal triggered by the presence of phosphatidylserine lipids in the outer leaflet, thus biding time for repair of the membrane hole. Our findings provide new insights into the role of ANXA5 at the edges of the membrane (the injury site) and support the curvature-constriction model of membrane repair., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Micronutrient malnutrition has affected over two billion people worldwide and continues to be a health risk. A growing human population, poverty, and the prevalence of low dietary diversity are jointly responsible for malnutrition, particularly in developing nations. Inadequate bioavailability of key micronutrients, such as iron (Fe), zinc (Zn), and vitamin A, can be improved through agronomic and/or genetic interventions. The Consultative Group on International Agricultural Research prioritizes developing biofortified food crops that are rich in minerals and vitamins through the HarvestPlus initiative on biofortification. The objective of this review is to provide an overview of biofortified food crops along with evidence supporting their acceptability and adoption. Between 2004 and 2019, 242 biofortified varieties belonging to 11 major crops were released in 30 countries across Asia, Africa, and Latin America. These conventionally bred biofortified crops include Fe-enriched beans, pearl millet, and cowpea; Zn-enriched rice, wheat, and maize; both Fe- and Zn-enriched lentil and sorghum; and varieties with improved vitamin A in orange-fleshed sweet potato, maize, cassava, and banana/plantain. In addition to ongoing efforts, breeding innovations, such as speed breeding and CRISPR-based gene editing technologies, will be necessary for the next decade to reach two billion people with biofortified crops., (© 2022 New York Academy of Sciences.)

Efficient plasma membrane repair (PMR) is required to repair damage sustained in the cellular life cycle. The annexin family of proteins, involved in PMR, are activated by Ca 2+ influx from extracellular media at the site of injury. Mechanistic studies of the annexins have been overwhelmingly performed using a single annexin, despite the recruitment of multiple annexins to membrane damage sites in living cells. Hence, we investigate the effect of the presence of the crosslinking annexins, annexin A1, A2 and A6 (ANXA1, ANXA2 and ANXA6) on the membrane curvature induction of annexin A4 (ANXA4) in model membrane systems. Our data support a mechanistic model of PMR where ANXA4 induced membrane curvature and ANXA6 crosslinking promotes wound closure. The model now can be expanded to include ANXA1 and ANXA2 as specialist free edge membrane crosslinkers that act in concert with ANXA4 induced curvature and ANXA6 crosslinking., (© 2022. The Author(s).)

Hydrotropes are small amphiphilic compounds that increase the aqueous solubility of hydrophobic molecules. Recent evidence suggests that adenosine triphosphate (ATP), which is the primary energy carrier in cells, also assumes hydrotropic properties to prevent the aggregation of hydrophobic proteins, but the mechanism of hydrotropy is unknown. Here, we compare the hydrotropic behavior of all four biological nucleoside triphosphates (NTPs) using molecular dynamics (MD) simulations. We launch all atom MD simulations of aqueous solutions of NTPs [ATP, guanosine triphosphate (GTP), cytidine triphosphate (CTP), and uridine triphosphate (UTP)] with pyrene, which acts both as a model hydrophobic compound and as a spectroscopic reporter for aggregation. GTP prevents pyrene aggregation effectively. Dissolution is not achieved in the presence of CTP and UTP. The higher stability of the base stacking in guanine is responsible for the higher hydrotropic efficiency of GTP. Consistent with the simulations, spectroscopic measurements also suggest that the hydrotropic activity of GTP is higher than ATP. Stacking of aromatic pyrene with the aromatic base of NTPs is a characteristic feature of this hydrotropic property. Both ATP and GTP also dissolve clusters of di- and tripeptides containing tryptophan but with equal potency. Importantly, the presence of aromatic amino acids is a necessary condition for the hydrotropic potency of ATP and GTP. Our results can have broad implications for hydrotrope design in the pharmaceutical industry, as well as the possibility of cells employing GTP as a hydrotrope to regulate the hydrophobic protein aggregation in membrane-less biological condensates.

The plasma membrane surrounds every single cell and essentially shapes cell life by separating the interior from the external environment. Thus, maintenance of cell membrane integrity is essential to prevent death caused by disruption of the plasma membrane. To counteract plasma membrane injuries, eukaryotic cells have developed efficient repair tools that depend on Ca 2+ - and phospholipid-binding annexin proteins. Upon membrane damage, annexin family members are activated by a Ca 2+ influx, enabling them to quickly bind at the damaged membrane and facilitate wound healing. Our recent studies, based on interdisciplinary research synergy across molecular cell biology, experimental membrane physics, and computational simulations show that annexins have additional biophysical functions in the repair response besides enabling membrane fusion. Annexins possess different membrane-shaping properties, allowing for a tailored response that involves rapid bending, constriction, and fusion of membrane edges for resealing. Moreover, some annexins have high affinity for highly curved membranes that appear at free edges near rupture sites, a property that might accelerate their recruitment for rapid repair. Here, we discuss the mechanisms of annexin-mediated membrane shaping and curvature sensing in the light of our interdisciplinary approach to study plasma membrane repair.

Venous air embolism can be a catastrophic iatrogenic complication during operative hysteroscopy and makes this simple surgical procedure very risky, especially with the lack of knowledge about its prevention, presentation, and immediate management. Three out of 13 hysteroscopic myoma resections at our center had venous gas embolism (VGE). The prevention, diagnosis, and management of VGE are described in this report of three cases., Competing Interests: There are no conflicts of interest.

Leaf rust (Puccinia triticina Eriks.), stripe rust (Puccinia striiformis f. tritici Eriks.) and stem rust (Puccinia graminis f. sp. tritici) cause major production losses in durum wheat (Triticum turgidum L. var. durum). The objective of this research was to identify and map leaf, stripe and stem rust resistance loci from the French cultivar Sachem and Canadian cultivar Strongfield. A doubled haploid population from Sachem/Strongfield and parents were phenotyped for seedling reaction to leaf rust races BBG/BN and BBG/BP and adult plant response was determined in three field rust nurseries near El Batan, Obregon and Toluca, Mexico. Stripe rust response was recorded in 2009 and 2011 nurseries near Toluca and near Njoro, Kenya in 2010. Response to stem rust was recorded in field nurseries near Njoro, Kenya, in 2010 and 2011. Sachem was resistant to leaf, stripe and stem rust. A major leaf rust quantitative trait locus (QTL) was identified on chromosome 7B at Xgwm146 in Sachem. In the same region on 7B, a stripe rust QTL was identified in Strongfield. Leaf and stripe rust QTL around DArT marker wPt3451 were identified on chromosome 1B. On chromosome 2B, a significant leaf rust QTL was detected conferred by Strongfield, and at the same QTL, a Yr gene derived from Sachem conferred resistance. Significant stem rust resistance QTL were detected on chromosome 4B. Consistent interactions among loci for resistance to each rust type across nurseries were detected, especially for leaf rust QTL on 7B. Sachem and Strongfield offer useful sources of rust resistance genes for durum rust breeding.

The present survey aims at determining the prevalence of extreme obesity (defined as a body mass index (BMI) ≥ 99.5th percentile) for the first time in Austria and at investigating the relationship between weight status and mother tongue in a representative Viennese sample of 24,989 children and adolescents (2-16 years) with a percentage of approximately 46 % of migration background.Directly measured anthropometric data on body weight and height were collected and BMI was calculated. Prevalence of overweight, obesity and extreme obesity was determined for every subgroup according to mother tongue using the German national reference criteria by Kromeyer-Hauschild et al.In this sample, 2.1 % of all children and adolescents had to be classified as being extremely obese. More boys (2.3 %) than girls (1.9 %) suffered from extreme obesity (p = 0.048). Total 1.7 % of children and adolescents with German as their native language, 2.5 % of Turkish native speakers and 2.9 % of children and adolescents with another mother tongue were extremely obese (p ≤ 0.001). The highest prevalence of overweight or obesity was found in Turkish-native-speaking children and adolescents (p ≤ 0.001), whereas the lowest one was found in German-native-speaking children and adolescents (p ≤ 0.001).This large study clearly shows that extreme obesity is a common disease and largely neglected. Apparently, another native language than German, as an indicator for a migration background, may be associated with a substantially higher probability for the development of extreme obesity in Vienna, Austria. Thus, effective preventive measures to overcome obesity are urgently needed.