A Closer Look at Type I Left-Handed β-Helices Provides a Better Understanding in Their Sequence-Structure Relationship: Toward Their Rational Design.

Understanding the sequence-structure relationship in protein is of fundamental interest, but has practical applications such as the rational design of peptides and proteins. This relationship in the Type I left-handed β-helix containing proteins is updated and revisited in this study. Analyzing the available experimental structures in the Protein Data Bank, we could describe, further in detail, the structural features that are important for the stability of this fold, as well as its nucleation and termination.

An Effective Health System Approach to End TB: Implementing the Double X Strategy in Vietnam.

Countries that are high burden for TB must reverse the COVID-19 pandemic's devastating effects to accelerate progress toward ending TB. Vietnam's Double X (2X) strategy uses chest radiography (CXR) and GeneXpert (Xpert) rapid diagnostic testing to improve early detection of TB disease. Household contacts and vulnerable populations (e.

Quest for a stable Cu-ligand complex with a high catalytic activity to produce reactive oxygen species.

Metal ion-catalyzed overproduction of reactive oxygen species (ROS) is believed to contribute significantly to oxidative stress and be involved in several biological processes, from immune defense to development of diseases. Among the essential metal ions, copper is one of the most efficient catalysts in ROS production in the presence of O2 and a physiological reducing agent such as ascorbate. To control this chemistry, Cu ions are tightly coordinated to biomolecules.

Computer-Aided Detection for Chest Radiography to Improve the Quality of Tuberculosis Diagnosis in Vietnam's District Health Facilities: An Implementation Study.

In Vietnam, chest radiography (CXR) is used to refer people for GeneXpert (Xpert) testing to diagnose tuberculosis (TB), demonstrating high yield for TB but a wide range of CXR abnormality rates. In a multi-center implementation study, computer-aided detection (CAD) was integrated into facility-based TB case finding to standardize CXR interpretation. CAD integration was guided by a programmatic framework developed for routine implementation.

Tuberculin skin testing and QuantiFERON™-TB Gold Plus positivity among household contacts in Vietnam.

Setting: TB infection (TBI) is diagnosed using the technique-dependent tuberculin skin test (TST) or costly, more accurate interferon-gamma release assays. The TST (⩾10 mm) threshold was indicated by previous research among household contacts in Vietnam, but routine implementation with a different tuberculin reagent showed unexpectedly low TST positivity.

Objective: TST (⩾5 mm and ⩾10 mm) results were compared to QuantiFERON™-TB Gold Plus (QFT) results in household contacts during community campaigns in 2020 and 2021.

Revisiting the pro-oxidant activity of copper: interplay of ascorbate, cysteine, and glutathione.

Copper (Cu) is essential for most organisms, but it can be poisonous in excess, through mechanisms such as protein aggregation, trans-metallation, and oxidative stress. The latter could implicate the formation of potentially harmful reactive oxygen species (O2•-, H2O2, and HO•) via the redox cycling between Cu(II)/Cu(I) states in the presence of dioxygen and physiological reducing agents such as ascorbate (AscH), cysteine (Cys), and the tripeptide glutathione (GSH). Although the reactivity of Cu with these reductants has been previously investigated, the reactions taking place in a more physiologically relevant mixture of these biomolecules are not known.

Liver Fetuin-A at Initiation of Insulin Resistance.

Hepatokines (liver secreted proteins with possible distant action) are emerging potential players in insulin resistance in type 2 diabetic patients. Here, we explored the effect of a high-fat diet on the expression of fetuin-A, one of those candidate liver proteins, and its relationship with liver macrophage activation. Mice were fed a normal diet or a high-fat diet for 3 days, known to initiate steatosis and liver insulin resistance.

Fetuin-A in Activated Liver Macrophages Is a Key Feature of Non-Alcoholic Steatohepatitis.

Fetuin-A, a plasma multifunctional protein known to play a role in insulin resistance, is usually presented as a liver secreted protein. However, fetuin-A adipose tissue production has been also described. Here, we evaluated fetuin-A production by the liver and the adipose tissue during metabolic dysfunction-associated fatty liver disease (MAFLD)-non-alcoholic steatohepatitis (NASH) development.

Treatment of 120 adult osteosarcoma patients with metachronous and synchronous metastases: A retrospective series of the French Sarcoma Group.

Treatment options for metastatic osteosarcomas are scarce. Following failure of standard first line therapy, patients who relapse present a challenging treatment dilemma, and have a poor prognosis. Surgical removal of all metastases is essential.

Optimizing the design of a contraceptive microarray patch: a discrete choice experiment on women's preferences in India and Nigeria.

Background: Efforts are underway to develop an easy-to-use contraceptive microarray patch (MAP) that could expand the range of self-administrable methods. This paper presents results from a discrete choice experiment (DCE) designed to support optimal product design.

Methods: We conducted a DCE survey of users and non-users of contraception in New Delhi, India (496 women) and Ibadan, Nigeria (two versions with 530 and 416 women, respectively) to assess stated preferences for up to six potential product attributes: effect on menstruation, duration of effectiveness, application pain, location, rash after application, and patch size.

Copper-binding motifs Xxx-His or Xxx-Zzz-His (ATCUN) linked to an antimicrobial peptide: Cu-binding, antimicrobial activity and ROS production.

Depending on the coordination, copper ions can have a very high activity in catalyzing the production of reactive oxygen species. Thus interest arose in increasing the activity of antimicrobial peptides (AMPs) by equipping them with a Cu-binding unit. Several examples, native and engineered, have been investigated with the motif Xxx-Zzz-His, called Amino Terminal Cu(II)- and Ni(II)-binding (ATCUN) motif.

How trimerization of CTR1 N-terminal model peptides tunes Cu-binding and redox-chemistry.

Employing peptide-based models of copper transporter 1 (CTR1), we show that the trimeric arrangement of its N-terminus tunes its reactivity with Cu, promoting Cu(ii) reduction and stabilizing Cu(i). Hence, the employed multimeric models of CTR1 provide an important contribution to studies on early steps of Cu uptake by cells.

Feasibility and Acceptability of an Adapted Mobile Phone Message Program and Changes in Maternal and Newborn Health Knowledge in Four Provinces of Afghanistan: Single-Group Pre-Post Assessment Study.

Background: Mobile phone apps for health promotion have expanded in many low- and middle-income countries. Afghanistan, with high maternal and newborn morbidity and mortality rates, a fragile health infrastructure, and high levels of mobile phone ownership, is an ideal setting to examine the utility of such programs. We adapted messages of the Mobile Alliance for Maternal Action (MAMA) program, which was designed to promote healthy behaviors during pregnancy and a newborn's first year of life, to the Afghan context.

Reversible turn-on fluorescent Cu(ii) sensors: rather dream than reality?

Reversible turn-on fluorescent sensors of Cu(ii) are of high interest for biological studies. We re-investigate a reported sensor, showing that turn-on occurs via irreversible Cu(ii)-induced sensor oxidation only in the presence of acetonitrile. This prevents its application in biological studies and highlights the challenge of establishing a reversible Cu(ii) turn-on sensor.

Hypoxia protects the liver from Small For Size Syndrome: A lesson learned from the associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure in rats.

Portal hyperperfusion and "dearterialization" of the liver remnant are the main pathogenic mechanisms for Small For Size syndrome (SFSS). Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) induces rapid remnant hypertrophy. We hypothesized a similar increase in portal pressure/flow into the future liver remnant in ALPPS and SFSS-setting hepatectomies.

Model peptide for anti-sigma factor domain HHCC zinc fingers: high reactivity toward O leads to domain unfolding.

All organisms have to cope with the deleterious effects of reactive oxygen species. Some of them are able to mount a transcriptional response to various oxidative stresses, which involves sensor proteins capable of assessing the redox status of the cell or to detect reactive oxygen species. In this article, we describe the design, synthesis and characterization of Zn·L(HHCC), a model for the Zn(Cys)(His) zinc finger site of ChrR, a sensor protein involved in the bacterial defence against singlet oxygen that belongs to the family of zinc-binding anti-sigma factors possessing a characteristic H/C-X-H-X-C-X-C motif.

Referral patterns through the lens of health facility readiness to manage obstetric complications: national facility-based results from Ghana.

Introduction: Countries with high maternal and newborn mortality can benefit from national facility level data that describe intra-facility emergency referral patterns for major obstetric complications. This paper assesses the relationship between referral and facilities' readiness to treat complications at each level of the health system in Ghana. We also investigate other facility characteristics associated with referral.

Associating liver partition and portal vein ligation for staged hepatectomy: establishment of an animal model with insufficient liver remnant.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) allows extended hepatectomy in patients with an extremely small future liver remnant (FLR). Current rodent models of ALPPS do not include resection resulting in insufficient-for-survival FLR, or they do incorporate liver mass reduction prior to ALPPS. Differences in FLR volume and surgical procedures could bias our understanding of physiological and hemodynamic mechanisms.

Artificial Metalloenzymes: Reaction Scope and Optimization Strategies.

The incorporation of a synthetic, catalytically competent metallocofactor into a protein scaffold to generate an artificial metalloenzyme (ArM) has been explored since the late 1970's. Progress in the ensuing years was limited by the tools available for both organometallic synthesis and protein engineering. Advances in both of these areas, combined with increased appreciation of the potential benefits of combining attractive features of both homogeneous catalysis and enzymatic catalysis, led to a resurgence of interest in ArMs starting in the early 2000's.

Towards Cellular Activation of an Artificial Metalloenzyme: Development of an Artificial Zymogen.

Regulation of enzymatic activity is essential for living organisms. Nowadays, with the emergence of synthetic biology, there is a rising interest in placing the activity of synthetic catalysts under the control of a cell. This short review aims at summarizing the regulation strategies developed to date, and at presenting the development of an artificial zymogen, which is upregulated by a natural protease.

Aging enhances liver fibrotic response in mice through hampering extracellular matrix remodeling.

Unlabelled: Clinical data identify age as a factor for severe liver fibrosis. We evaluate whether and how aging modulates the fibrotic response in a mouse model. Liver fibrosis was induced by CCl injections (thrice weekly for 2 weeks) in 7 weeks- and 15 months-old mice (young and old, respectively).

Upregulation of an Artificial Zymogen by Proteolysis.

Regulation of enzymatic activity is vital to living organisms. Here, we report the development and the genetic optimization of an artificial zymogen requiring the action of a natural protease to upregulate its latent asymmetric transfer hydrogenase activity.

Near diffusion-controlled reaction of a Zn(Cys) zinc finger with hypochlorous acid.

Hypochlorous acid (HOCl) is one of the strongest oxidants produced in mammals to kill invading microorganisms. The bacterial response to HOCl involves proteins that are able to sense HOCl using methionine, free cysteines or zinc-bound cysteines of zinc finger sites. Although the reactivity of methionine or free cysteine with HOCl is well documented at the molecular level, this is not the case for zinc-bound cysteines.