c-di-AMP determines the hierarchical organization of bacterial RCK proteins.

In bacteria, intracellular K+ is involved in the regulation of membrane potential, cytosolic pH, and cell turgor as well as in spore germination, environmental adaptation, cell-to-cell communication in biofilms, antibiotic sensitivity, and infectivity. The second messenger cyclic-di-AMP (c-di-AMP) has a central role in modulating the intracellular K+ concentration in many bacterial species, controlling transcription and function of K+ channels and transporters. However, our understanding of how this regulatory network responds to c-di-AMP remains poor. We used the RCK (Regulator of Conductance of K+) proteins that control the activity of Ktr channels in Bacillus subtilis as a model system to analyze the regulatory function of c-di-AMP with a combination of in vivo and in vitro functional and structural characterization. We determined that the two RCK proteins (KtrA and KtrC) are neither physiologically redundant or functionally equivalent. KtrC is the physiologically dominant RCK protein in the regulation of Ktr channel activity. In explaining this hierarchical organization, we found that, unlike KtrA, KtrC is very sensitive to c-di-AMP inactivation and lack of c-di-AMP regulation results in RCK protein toxicity, most likely due to unregulated K+ flux. We also found that KtrC can assemble with KtrA, conferring c-di-AMP regulation to the functional KtrA/KtrC heteromers and potentially compensating KtrA toxicity. Altogether, we propose that the central role of c-di-AMP in the control of the K+ machinery, by modulating protein levels through gene transcription and by regulating protein activity, has determined the evolutionary selection of KtrC as the dominant RCK protein, shaping the hierarchical organization of regulatory components of the K+ machinery.

Fostering the social and physical challenges of female recreational or professional athletes in pregnancy and postpartum.

Combining pregnancy and parenthood with sporting activities or a professional athletic career can be challenging. The objective of this Collection is to gain a deeper understanding of the effects of pregnancy and postpartum on female athletes, both recreational and professional, in order to improve their health and fitness outcomes and support their continued success in sports.

Development and validation of the physical exercise program "Active Mums" for postpartum recovery: application of the CReDECI-2 guidelines.

Postpartum physical activity is a public health issue. Reporting on the quality of exercise interventions designs must be ensured in view of the reproducibility and successful implementation of such studies. The objective was to develop and preliminary validate a physical exercise program for postpartum recovery, aiming to promote physical fitness and health of the new mothers. The study was carried out through the three stages of development, piloting, and evaluation. The Consensus on Exercise Reporting Template (CERT) was used to describe the postpartum exercise program. The Criteria for Reporting the Development and Evaluation of Complex Interventions in Healthcare (CReDECI2) was followed to develop and preliminary validate the program. A tailored postpartum exercise program was developed based on evidence-based international recommendations to be implemented by qualified exercise professionals. A pilot intervention of 16 weeks was carried out, engaging a group of postpartum women. The viability of the program was subsequently evaluated by all participants. The present work provided guidance to develop a study protocol with a larger sample in order to prove the effectiveness of a supervised postpartum exercise program on selected parameters of health.

Demographic expansion of an African opportunistic carnivore during the Neolithic revolution.

The diffusion of Neolithic technology together with the Holocene Climatic Optimum fostered the spread of human settlements and pastoral activities in North Africa, resulting in profound and enduring consequences for the dynamics of species, communities and landscapes. Here, we investigate the demographic history of the African wolf (Canis lupaster), a recently recognized canid species, to understand if demographic trends of this generalist and opportunistic carnivore reflect the increase in food availability that emerged after the arrival of the Neolithic economy in North Africa. We screened nuclear and mitochondrial DNA in samples collected throughout Algeria and Tunisia, and implemented coalescent approaches to estimate the variation of effective population sizes from present to ancestral time. We have found consistent evidence supporting the hypothesis that the African wolf population experienced a meaningful expansion concurring with a period of rapid population expansion of domesticates linked to the advent of agricultural practices.

Characterization of the molecular properties of KtrC, a second RCK domain that regulates a Ktr channel in Bacillus subtilis.

RCK (regulating conductance of K+) domains are common regulatory domains that control the activity of eukaryotic and prokaryotic K+ channels and transporters. In bacteria these domains play roles in osmoregulation, regulation of turgor and membrane potential and in pH homeostasis. Whole-genome sequencing unveiled RCK gene redundancy, however the biological role of this redundancy is not well understood. In Bacillus subtilis, there are two closely related RCK domain proteins (KtrA and KtrC) that regulate the activity of the Ktr cation channels. KtrA has been well characterized but little is known about KtrC. We have characterized the structural and biochemical proprieties of KtrC and conclude that KtrC binds ATP and ADP, just like KtrA. However, in solution KtrC exist in a dynamic equilibrium between octamers and non-octameric species that is dependent on the bound ligand, with ATP destabilizing the octameric ring relative to ADP. Accordingly, KtrC-ADP crystal structures reveal closed octameric rings similar to those in KtrA, while KtrC-ATP adopts an open assembly with RCK domains forming a super-helix. In addition, both KtrC-ATP and -ADP octamers are stabilized by the signaling molecule cyclic-di-AMP, which binds to KtrC with high affinity. In contrast, c-di-AMP binds with 100-fold lower affinity to KtrA. Despite these differences we show with an E. coli complementation assay that KtrC and KtrA are interchangeable and able to form functional transporters with both KtrB and KtrD. The distinctive properties of KtrC, in particular ligand-dependent assembly/disassembly, suggest that this protein has a specific physiological role that is distinct from KtrA.

Alternated selection mechanisms maintain adaptive diversity in different demographic scenarios of a large carnivore.

BACKGROUND: Different population trajectories are expected to impact the signature of neutral and adaptive processes at multiple levels, challenging the assessment of the relative roles of different microevolutionary forces. Here, we integrate adaptive and neutral variability patterns to disentangle how adaptive diversity is driven under different demographic scenarios within the Iberian wolf (Canis lupus) range. We studied the persistent, the expanding and a small, isolated group within the Iberian wolf population, using 3 MHC class II genes (DRB1, DQA1, and DQB1), which diversity was compared with 39 microsatellite loci. RESULTS: Both the persistent and the expanding groups show evidence of balancing selection, revealed by a significant departure from neutrality at MHC loci, significant higher observed and expected heterozygosity and lower differentiation at MHC than at neutral loci, and signs of positive selection. However, despite exhibiting a significantly higher genetic diversity than the isolated group, the persistent group did not show significant excess of MHC heterozygotes. The expanding group, while showing a similar level of genetic diversity than the persistent group, displays by contrast a significant excess of MHC heterozygotes, which is compatible with the heterozygote advantage mechanism. Results are not clear regarding the role of drift and selection in the isolated group due to the small size of this population. Although diversity indices of MHC loci correspond to neutral expectations in the isolated group, accelerated MHC divergence, revealed by a higher differentiation at MHC than neutral loci, may indicate diversifying selection. CONCLUSION: Different selective pressures were observed in the three different demographic scenarios, which are possibly driven by different selection mechanisms to maintain adaptive diversity.

Dissecting the Molecular Mechanism of Nucleotide-Dependent Activation of the KtrAB K+ Transporter.

KtrAB belongs to the Trk/Ktr/HKT superfamily of monovalent cation (K+ and Na+) transport proteins that closely resemble K+ channels. These proteins underlie a plethora of cellular functions that are crucial for environmental adaptation in plants, fungi, archaea, and bacteria. The activation mechanism of the Trk/Ktr/HKT proteins remains unknown. It has been shown that ATP stimulates the activity of KtrAB while ADP does not. Here, we present X-ray structural information on the KtrAB complex with bound ADP. A comparison with the KtrAB-ATP structure reveals conformational changes in the ring and in the membrane protein. In combination with a biochemical and functional analysis, we uncover how ligand-dependent changes in the KtrA ring are propagated to the KtrB membrane protein and conclude that, despite their structural similarity, the activation mechanism of KtrAB is markedly different from the activation mechanism of K+ channels.

Neotropical forest expansion during the last glacial period challenges refuge hypothesis.

The forest refuge hypothesis (FRH) has long been a paradigm for explaining the extreme biological diversity of tropical forests. According to this hypothesis, forest retraction and fragmentation during glacial periods would have promoted reproductive isolation and consequently speciation in forest patches (ecological refuges) surrounded by open habitats. The recent use of paleoclimatic models of species and habitat distributions revitalized the FRH, not by considering refuges as the main drivers of allopatric speciation, but instead by suggesting that high contemporary diversity is associated with historically stable forest areas. However, the role of the emerged continental shelf on the Atlantic Forest biodiversity hotspot of eastern South America during glacial periods has been ignored in the literature. Here, we combined results of species distribution models with coalescent simulations based on DNA sequences to explore the congruence between scenarios of forest dynamics through time and the genetic structure of mammal species cooccurring in the central region of the Atlantic Forest. Contrary to the FRH predictions, we found more fragmentation of suitable habitats during the last interglacial (LIG) and the present than in the last glacial maximum (LGM), probably due to topography. We also detected expansion of suitable climatic conditions onto the emerged continental shelf during the LGM, which would have allowed forests and forest-adapted species to expand. The interplay of sea level and land distribution must have been crucial in the biogeographic history of the Atlantic Forest, and forest refuges played only a minor role, if any, in this biodiversity hotspot during glacial periods.

An mHealth intervention programme to promote healthy behaviours and prevent adolescent obesity (TeenPower): A study protocol.

AIM: This paper describes the design and rationale of multicenter practice-based research that aims to develop and evaluate an innovative mobile health (mHealth) intervention programme directed to promote healthy behaviours and prevent adolescent obesity. DESIGN: This study is designed as a non-randomized controlled trial with a three-arm structure. METHODS: Twelve to 16 years old participants will be recruited from schools, with access to the Internet and smartphone/tablet devices. The intervention group will be invited to engage in the TeenPower mHealth programme and divided into two subgroups: Group A (additionally engaged in a structured school-based intervention programme) and Group B (only engaged in the mHealth programme). The mHealth app includes educational resources, self-monitoring, social support, interactive training modules and motivational tools. The control group will only follow the structured school-based intervention programme. The intervention length will be 3 months, including the direct support of an interdisciplinary team (nursing, nutrition, sports, psychology, among others). This research was approved and funded in August 2017. DISCUSSION: The positive evaluation of the intervention programme will stimulate the inclusion of technologies in the promotion of salutogenic behaviours and obesity prevention. IMPACT: Adolescent obesity reached epidemic proportions. It is urgent to find effective prevention strategies to induce change at the individual, family and community level. If effective, this protocol can be used by health and exercise professionals in improving community interventions tailored to teenagers.

Community-Based Exercise Intervention for Gait and Functional Fitness Improvement in an Older Population: Study Protocol.

Functional fitness (FF) and gait ability in older populations have been associated with increased survival rates, fall prevention, and quality of life. One possible intervention for the improvement of FF is well-structured exercise programs. However, there are inconsistent findings regarding the effects of exercise interventions in the maintenance of gait parameters. The aim of this protocol is to develop a community-based exercise intervention targeting an older population. The intervention aim is the improvement of gait parameters and FF. A control trial with follow-up will be performed. The primary outcome variables will be plantar pressure gait parameters. The secondary outcome variables will be aerobic endurance, lower limb strength, agility, and balance. These variables will be recorded at baseline and after 12, 24, and 36 weeks, in the intervention and control groups. If effective, this protocol can be used by exercise professionals in improving community exercise programs.

The Araguaia River as an Important Biogeographical Divide for Didelphid Marsupials in Central Brazil.

The riverine barrier model suggests that rivers play a significant role in separating widespread organisms into isolated populations. In this study, we used a comparative approach to investigate the phylogeography of 6 didelphid marsupial species in central Brazil. Specifically, we evaluate the role of the mid-Araguaia River in differentiating populations and estimate divergence time among lineages to assess the timing of differentiation of these species, using mitochondrial DNA sequence data. The 6 didelphid marsupials revealed different intraspecific genetic patterns and structure. The 3 larger and more generalist species, Didelphis albiventris, Didelphis marsupialis, and Philander opossum, showed connectivity across the Araguaia River. In contrast the genetic structure of the 3 smaller and specialist species, Gracilinanus agilis, Marmosa (Marmosa) murina, and Marmosa (Micoureus) demerarae was shaped by the mid-Araguaia. Moreover, the split of eastern and western bank populations of the 2 latter species is consistent with the age of Araguaia River sediments formation. We hypothesize that the role of the Araguaia as a riverine barrier is linked to the level of ecological specialization among the 6 didelphid species and differences in their ability to cross rivers or disperse through the associated habitat types.

Review on Dynamic Contour Tonometry and Ocular Pulse Amplitude.

Intraocular pressure (IOP) measurement is the cornerstone of the management of glaucoma patients. The gold standard for assessing IOP is Goldmann applanation tonometry (GAT). Recently, the dynamic contour tonometer (DCT) has become available. While both devices provide reliable IOP measurements, the results are not interchangeable. DCT has the advantage of measuring an additional parameter: ocular pulse amplitude (OPA). OPA is defined as the difference between systolic and diastolic IOP and represents the pulsatile wave front produced by the varying amount of blood in the eye during the cardiac cycle. It has been shown to vary with ocular structural parameters, such as axial length, corneal thickness, and ocular rigidity, as well as with systemic variables like heart rate, blood pressure, and left ventricular ejection fraction. Although the existence of some of these associations is still controversial, the clinical relevance of OPA has been consistently suggested, especially in glaucoma. Further research on this intriguing parameter could not only provide insight into glaucoma pathophysiology but also help integrate this variable into clinical practice.

Unveiling the structural basis for translational ambiguity tolerance in a human fungal pathogen.

In a restricted group of opportunistic fungal pathogens the universal leucine CUG codon is translated both as serine (97%) and leucine (3%), challenging the concept that translational ambiguity has a negative impact in living organisms. To elucidate the molecular mechanisms underlying the in vivo tolerance to a nonconserved genetic code alteration, we have undertaken an extensive structural analysis of proteins containing CUG-encoded residues and solved the crystal structures of the two natural isoforms of Candida albicans seryl-tRNA synthetase. We show that codon reassignment resulted in a nonrandom genome-wide CUG redistribution tailored to minimize protein misfolding events induced by the large-scale leucine-to-serine replacement within the CTG clade. Leucine or serine incorporation at the CUG position in C. albicans seryl-tRNA synthetase induces only local structural changes and, although both isoforms display tRNA serylation activity, the leucine-containing isoform is more active. Similarly, codon ambiguity is predicted to shape the function of C. albicans proteins containing CUG-encoded residues in functionally relevant positions, some of which have a key role in signaling cascades associated with morphological changes and pathogenesis. This study provides a first detailed analysis on natural reassignment of codon identity, unveiling a highly dynamic evolutionary pattern of thousands of fungal CUG codons to confer an optimized balance between protein structural robustness and functional plasticity.

Biomechanics of gait during pregnancy.

INTRODUCTION: During pregnancy women experience several changes in the body's physiology, morphology, and hormonal system. These changes may affect the balance and body stability and can cause discomfort and pain. The adaptations of the musculoskeletal system due to morphological changes during pregnancy are not fully understood. Few studies clarify the biomechanical changes of gait that occur during pregnancy and in postpartum period. PURPOSES: The purpose of this review was to analyze the available evidence on the biomechanical adaptations of gait that occur throughout pregnancy and in postpartum period, specifically with regard to the temporal, spatial, kinematic, and kinetic parameters of gait. METHODS: Three databases were searched and 9 studies with a follow-up design were retrieved for analysis. RESULTS: Most studies performed temporal, spatial, and kinematic analysis. Only three studies performed kinetic analysis. CONCLUSION. The adaptation strategies to the anatomical and physiological changes throughout pregnancy are still unclear, particularly in a longitudinal perspective and regarding kinetic parameters.

Changes in Foot Biomechanics during Pregnancy and Postpartum: Scoping Review.

(1) Background: During pregnancy, changes in foot biomechanics affect structural stability and gait. (2) Objective: To map the available evidence for changes in foot biomechanics during pregnancy and the postpartum period. (3) Methods: Scoping review according to the methodology of the Joanna Briggs Institute through the relevant databases via EBSCO, MEDLINE with full text, BioOne Complete, CINAHL Plus with full text, Academic Search Complete, and SPORT Discus with full text. The search was conducted in SCOPUS and PubMed. (4) Results: Eight studies were included in the scoping review. Two independent reviewers performed data extraction and synthesized data in narrative form. We found that changes in the length and volume of the foot occur during pregnancy and remain in the postpartum period. (5) Conclusions: During pregnancy, anatomical and biomechanical changes occur in the pregnant woman's foot, potentially contributing to the risk of musculoskeletal disorders. However, more research is needed to determine whether these biomechanical changes can lead to the risk of musculoskeletal disorders.

Nutritional Knowledge about Maternal and Newborn Health among Physiotherapists during the COVID-19 Pandemic in Minas Gerais, Brazil.

Adequate nutrition before and during pregnancy, as well as postpartum, is among the major contributors to maternal and newborn health. Physiotherapists' knowledge of this area is still scarce, although their clinical practice has been linked to newborns' neuropsychomotor development, which, in turn, is influenced by maternal health and nutritional status. Therefore, this study aimed to evaluate the nutritional knowledge of physiotherapists regarding maternal and newborn health. A total of 70 Brazilian physiotherapists (32.2 ± 6.0 years; 72.9% females) were evaluated between November 2019 and February 2020 for their sociodemographic characteristics, professional experience, and nutritional knowledge about maternal and newborn health through a validated questionnaire personally administered by the same trained researcher. Most of the physiotherapists had graduated but had no specialization in maternal and child physiotherapy (96.1% of the females and all the males). The nutritional knowledge about maternal and newborn health was significantly different between the female and male health professionals, as well as between the less and more experienced participants, i.e., female physiotherapists and the more experienced ones had more correct answers on the nutritional questionnaire than the male and less experienced physiotherapists, respectively (p < 0.05). Our results open an interesting window for the future education and training of Brazilian physiotherapists in nutrition.

Understanding and Involving the Perspective of Pregnant Women as Users When Designing the Framework of e-Health and Exercise Interventions during Pregnancy: Preliminary Study.

Health and exercise technology may promote a healthy lifestyle during pregnancy. The objective of this cross-sectional study was to understand and involve the perspective of pregnant women as users in the design of a framework for future e-health and exercise interventions during pregnancy. Pregnant women replied to a questionnaire aimed at understanding their physical activity patterns, needs, and preferences regarding the use of mobile applications (apps). The main results showed that one-third of the women did not practice any type of exercise during pregnancy. Women preferred to exercise in a gym, outdoors, or at home. The majority already had or were currently using a fitness app, but never used any pregnancy-specific app. Most women agreed that it was important to have a specific app for pregnancy to improve knowledge about recommendations on lifestyle, have direct contact with health and exercise professionals, have social interaction with other mothers, and have guidance on preparation for childbirth and postpartum recovery. Understanding and involving the perspective of pregnant women as users will allow researchers to improve the design of a pregnancy-specific app and future e-health and exercise interventions during pregnancy. These preliminary results will lead to the development of the "active pregnancy app" focused on the promotion of an active and healthy lifestyle during pregnancy and postpartum.

Experience from a regional percutaneous coronary intervention center: Aiming to assess and improve quality of care.

INTRODUCTION AND OBJECTIVES: Ischemic heart disease is the single most common cause of death in Europe. Mortality in patients presenting with ST-elevation myocardial infarction (STEMI) is associated with many factors, one of which is the time delay to treatment. The purpose of this work is to analyze the coronary pathway in our region in terms of timing, taking into consideration the place of first medical contact (FMC). METHODS: Consecutive patients admitted to our center with STEMI to undergo percutaneous coronary intervention (PCI) between 2013 and 2022 were analyzed. Age, gender, and time delays were collected. Analysis was performed with IBM SPSS version 28 for a significance level of 0.05. RESULTS: We found that non-PCI centers had a significantly greater FMC to diagnosis delay and diagnosis to wire delay compared to other places of origin. Only 2.2% of patients met the 10-min FMC to diagnosis target; 44.8% met the target of 90 min from diagnosis to wire in transferred patients, while 40.6% met the 60-min target for patients admitted to a PCI center. Median patient, electrocardiogram (ECG) and logistic delays are 92.0±146.0 min, 19.0±146.0 min and 15.5±46.3 min, respectively. CONCLUSION: A significant difference between state-of-the-art targets and reality was found, depending on the place of FMC, with the worst delays in non-PCI centers. Patient delay, ECG delay, FMC to diagnosis and logistic delay are identified as key areas in which to intervene.

Translation and cross-cultural adaptation of the Get Active Questionnaire for Pregnancy (kwestionariusz "Badz Aktywna w Ciazy") to support physical activity among pregnant women in Poland.

INTRODUCTION: Physical activity during pregnancy is established to derive clinically meaningful improvements in pregnancy, childbirth, and postpartum health outcomes. Evidence-based pre-screening tools have been developed to support the implementation of physical activity programmes, and enhance communication between health care providers, exercise professionals and pregnant women. The Get Active Questionnaire for Pregnancy (GAQ-P) and the Health Care Provider Consultation Form for Prenatal Physical Activity (HCPCF) empower pregnant women to identify whether they require additional counselling from their obstetric health care provider in terms of physical activity. However, these tools are not available in Polish. This work details the process taken to translate the GAQ-P and HCPCF into Polish. MATERIAL AND METHODS: We followed the translation process outlined by the Translation and Cultural Adaptation International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines between August 2022 and August 2023. We formed an expert group that included representatives of the Polish Society of Sports Medicine, The Polish Society of Gynaecologists and Obstetricians, practitioners, and scientists in physical activity during pregnancy. We implemented 9 of the 10 steps recommended by ISOPR in the translation process. At the Cognitive Debriefing stage, we collected opinions on the Polish version of GAQ-P and HCPCF from 70 stakeholders on the clarity and cultural appropriateness of the translation. RESULTS AND CONCLUSIONS: Target users have positively evaluated the Polish version of GAQ-P and HCPCF. Thanks to the ISPOR methodology, we obtained a trustworthy, evidence-based screening tools, which can reduce the barriers for most women to be physically active during pregnancy.