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We explore the dynamics and evolution of the Universe at early and late times, focusing on both dark energy and extended gravity models and their astrophysical and cosmological consequences. Modified theories of gravity not only provide an alternative explanation for the recent expansion history of the universe, but they also offer a paradigm fundamentally distinct from the simplest dark energy models of cosmic acceleration. In this review, we perform a detailed theoretical and phenomenological analysis of different modified gravity models and investigate their consistency. We also consider the cosmological implications of well motivated physical models of the early universe with a particular emphasis on inflation and topological defects. Astrophysical and cosmological tests over a wide range of scales, from the solar system to the observable horizon, severely restrict the allowed models of the Universe. Here, we review several observational probes—including gravitational lensing, galaxy clusters, cosmic microwave background temperature and polarization, supernova and baryon acoustic oscillations measurements—and their relevance in constraining our cosmological description of the Universe.

Objetivou-se avaliar a distribuição e a magnitude da deficiência de vitamina A e o consumo dietético de 161 crianças de 6 a 72 meses de idade, de áreas rurais do Município de Cansanção-Bahia, Brasil. Os níveis de retinol sérico foram medidos pelo método espectrofotométrico (Bessey-Lowry modificado por Araújo e Flores, 1978). A média do retinol sérico distribuiuse homogeneamente entre as diferentes faixas etárias. Níveis inadequados de retinol sérico (deficiente

Com o objetivo de conhecer p estabelecimento e duração do aleitamento materno total e exclusivo em comunidades rurais do Semi-Árido Baiano, Brasil, foram estudadas 226 crianças de O a 2 anos de idade, filhas de pequenos produtores rurais que vivem numa das regiões mais secas do nordeste brasileiro, de pobreza absoluta. Os dados referem-se a todas as crianças da família que à data do estudo tinham até 2 anos de idade. Os dados foram coletados por meio de formulários aplicados às mães ou responsáveis pelo menor, no período de 1988 a 1989. A tábua de vida foi o recurso estatístico utilizado para o cálculo da duração mediana do evento. Das 226 crianças que integraram o estudo, 91,6 iniciaram a amamentação ao peito. A duração mediana do aleitamento total foi de 90,28 dias e o aleitamento exclusivo apresentou duração mediana de 0,1 dia. Ainda que o estabelecimento da amamentação ao peito possa ser considerado alto, a duração mediana do aleitamento total foi extrememente curta, e o aleitamento exclusivo foi desprezível.

Como parte de um estudo para avaliar as relações entre mudanças ambientais e ocorrência de infecções, estudou-se a prevalência e intensidade de parasitas intestinais em uma amostra de crianças em idade escolar, residentes em Salvador. A prevalência de infectados por pelo menos um protozoário/helminto foi 66,1%. A prevalência da infecção por helmintos, se eleva com o aumento da idade das crianças, sendo os meninos mais intensamente infectados.

Abstract Background The causation of asthma is poorly understood. Risk factors for atopic and non-atopic asthma may be different. This study aimed to analyze the associations between markers of poverty, dirt and infections and wheezing in atopic and non-atopic children. Methods 1445 children were recruited from a population-based cohort in Salvador, Brazil. Wheezing was assessed using the ISAAC questionnaire and atopy defined as allergen-specific IgE ≥0.70 kU/L. Relevant social factors, environmental exposures and serological markers for childhood infections were investigated as risk factors using multivariate multinomial logistic regression. Results Common risk factors for wheezing in atopic and non-atopic children, respectively, were parental asthma and respiratory infection in early childhood. No other factor was associated with wheezing in atopic children. Factors associated with wheezing in non-atopics were low maternal educational level (OR 1.49, 95% CI 0.98-2.38), low frequency of room cleaning (OR 2.49, 95% CI 1.27-4.90), presence of rodents in the house (OR 1.48, 95% CI 1.06-2.09), and day care attendance (OR 1.52, 95% CI 1.01-2.29). Conclusions Non-atopic wheezing was associated with risk factors indicative of poverty, dirt and infections. Further research is required to more precisely define the mediating exposures and the mechanisms by which they may cause non-atopic wheeze.

Abstract Background There is evidence that poverty, health and nutrition affect children's cognitive development. This study aimed to examine the relative contributions of both proximal and distal risk factors on child cognitive development, by breaking down the possible causal pathways through which poverty affects cognition. Methods This cohort study collected data on family socioeconomic status, household and neighbourhood environmental conditions, child health and nutritional status, psychosocial stimulation and nursery school attendance. The effect of these on Wechsler Pre-School and Primary Scale of Intelligence scores at five years of age was investigated using a multivariable hierarchical analysis, guided by the proposed conceptual framework. Results Unfavourable socioeconomic conditions, poorly educated mother, absent father, poor sanitary conditions at home and in the neighbourhood and low birth weight were negatively associated with cognitive performance at five years of age, while strong positive associations were found with high levels of domestic stimulation and nursery school attendance. Conclusion Children's cognitive development in urban contexts in developing countries could be substantially increased by interventions promoting early psychosocial stimulation and preschool experience, together with efforts to prevent low birth weight and promote adequate nutritional status.

Loss of proteostasis is well documented during physiological aging and depends on the progressive decline in the activity of two major degradative mechanisms: the ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway. This decline in proteostasis is exacerbated in age-associated neurodegenerative diseases, such as Parkinson's Disease (PD). In PD, patients develop an accumulation of aggregated proteins and dysfunctional mitochondria, which leads to ROS production, neuroinflammation and neurodegeneration. We recently reported that inhibition of the deubiquitinating enzyme USP14, which is known to enhance both the UPS and autophagy, increases lifespan and rescues the pathological phenotype of two Drosophila models of PD. Studies on the effects of USP14 inhibition in mammalian neurons have not yet been conducted. To close this gap, we exploited iNeurons differentiated from human embryonic stem cells (hESCs), and investigated the effect of inhibiting USP14 in these cultured neurons. Quantitative global proteomics analysis performed following genetic ablation or pharmacological inhibition of USP14 demonstrated that USP14 loss of function specifically promotes mitochondrial autophagy in iNeurons. Biochemical and imaging data also showed that USP14 inhibition enhances mitophagy. The mitophagic effect of USP14 inhibition proved to be PINK1/Parkin- independent, instead relying on expression of the mitochondrial E3 Ubiquitin Ligase MITOL/MARCH5. Notably, USP14 inhibition normalized the mitochondrial defects of Parkin KO human neurons., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elena Ziviani reports financial support was provided by Michael J Fox Foundation for Parkinson’s Research. Elena Ziviani reports a relationship with Michael J Fox Foundation for Parkinson’s Research that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The mining and metallurgical industry represents one of the leading causes of environmental pollution. In this context, the optimization of mineral waste management and the efficient extraction of metals of interest becomes an imperative priority for a sustainable future. Microorganisms such as Acidithiobacillus thiooxidans have represented a sustainable and economical alternative in recent years due to their capacity for environmental remediation in bioleaching processes because of their sulfur-oxidizing capacity and sulfuric acid generation. However, its use has been limited due to the reluctance of mine operators because of the constant reproduction of the bacterial culture in suitable media and the care that this entails. In this work, the central objective was to evaluate the functional characteristics of A. thiooxidans, microencapsulated and stored at room temperature for three years in vacuum bags, using a spray drying process with gum arabic as a wall vector. Growth kinetics showed a survival of 80 ± 0.52% after this long period of storage. Also, a qualitative fluorescence technique with a 5-cyano-2-3 ditolyl tetrazolium (CTC) marker was used to determine the respiratory activity of the microorganisms as soon as it was resuspended. On the other hand, the consumption of resuspended sulfur was evaluated to corroborate the correct metabolic functioning of the bacteria, with results of up to 50% sulfur reduction in 16 days and sulfate generation of 513.85 ± 0.4387 ppm and 524.15 ± 0.567 ppm for microencapsulated and non-microencapsulated cultures, respectively. These results demonstrate the success after three years of the microencapsulation process and give guidelines for its possible application in the mining-metallurgical industry., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Imbalances in protein homeostasis affect human brain development, with the ubiquitin-proteasome system (UPS) and autophagy playing crucial roles in neurodevelopmental disorders (NDD). This study explores the impact of biallelic USP14 variants on neurodevelopment, focusing on its role as a key hub connecting UPS and autophagy., Methods: Here, we identified biallelic USP14 variants in 4 individuals from 3 unrelated families: 1 fetus, a newborn with a syndromic NDD and 2 siblings affected by a progressive neurological disease. Specifically, the 2 siblings from the latter family carried 2 compound heterozygous variants c.8T>C p.(Leu3Pro) and c.988C>T p.(Arg330∗), whereas the fetus had a homozygous frameshift c.899_902del p.(Lys300Serfs∗24) variant, and the newborn patient harbored a homozygous frameshift c.233_236del p.(Leu78Glnfs∗11) variant. Functional studies were conducted using sodium dodecyl-sulfate polyacrylamide gel electrophoresis, western blotting, and mass spectrometry analyses in both patient-derived and CRISPR-Cas9-generated cells., Results: Our investigations indicated that the USP14 variants correlated with reduced N-terminal methionine excision, along with profound alterations in proteasome, autophagy, and mitophagy activities., Conclusion: Biallelic USP14 variants in NDD patients perturbed protein degradation pathways, potentially contributing to disorder etiology. Altered UPS, autophagy, and mitophagy activities underscore the intricate interplay, elucidating their significance in maintaining proper protein homeostasis during brain development., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Phosphoinositide-3-kinase-γ (PI3Kγ) is implicated as a target to repolarize tumour-associated macrophages and promote antitumour immune responses in solid cancers 1-4 . However, cancer cell-intrinsic roles of PI3Kγ are unclear. Here, by integrating unbiased genome-wide CRISPR interference screening with functional analyses across acute leukaemias, we define a selective dependency on the PI3Kγ complex in a high-risk subset that includes myeloid, lymphoid and dendritic lineages. This dependency is characterized by innate inflammatory signalling and activation of phosphoinositide 3-kinase regulatory subunit 5 (PIK3R5), which encodes a regulatory subunit of PI3Kγ 5 and stabilizes the active enzymatic complex. We identify p21 (RAC1)-activated kinase 1 (PAK1) as a noncanonical substrate of PI3Kγ that mediates this cell-intrinsic dependency and find that dephosphorylation of PAK1 by PI3Kγ inhibition impairs mitochondrial oxidative phosphorylation. Treatment with the selective PI3Kγ inhibitor eganelisib is effective in leukaemias with activated PIK3R5. In addition, the combination of eganelisib and cytarabine prolongs survival over either agent alone, even in patient-derived leukaemia xenografts with low baseline PIK3R5 expression, as residual leukaemia cells after cytarabine treatment have elevated G protein-coupled purinergic receptor activity and PAK1 phosphorylation. Together, our study reveals a targetable dependency on PI3Kγ-PAK1 signalling that is amenable to near-term evaluation in patients with acute leukaemia., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Aging is a prominent risk factor for Alzheimer's disease (AD), but the cellular mechanisms underlying neuronal phenotypes remain elusive. Both accumulation of amyloid plaques and neurofibrillary tangles in the brain 1 and age-linked organelle deficits 2-7 are proposed as causes of AD phenotypes but the relationship between these events is unclear. Here, we address this question using a transdifferentiated neuron (tNeuron) model directly from human dermal fibroblasts. Patient-derived tNeurons retain aging hallmarks and exhibit AD-linked deficits. Quantitative tNeuron proteomic analyses identify aging and AD-linked deficits in proteostasis and organelle homeostasis, particularly affecting endosome-lysosomal components. The proteostasis and lysosomal homeostasis deficits in aged tNeurons are exacerbated in sporadic and familial AD tNeurons, promoting constitutive lysosomal damage and defects in ESCRT-mediated repair. We find deficits in neuronal lysosomal homeostasis lead to inflammatory cytokine secretion, cell death and spontaneous development of Aß and phospho-Tau deposits. These proteotoxic inclusions co-localize with lysosomes and damage markers and resemble inclusions in brain tissue from AD patients and APP-transgenic mice. Supporting the centrality of lysosomal deficits driving AD phenotypes, lysosome-function enhancing compounds reduce AD-associated cytokine secretion and Aβ deposits. We conclude that proteostasis and organelle deficits are upstream initiating factors leading to neuronal aging and AD phenotypes., Competing Interests: Competing interests: R.V., J.L. and T.W.-C. are co-founders of Qinotto Inc.

Introduction/aim: Hyperphosphatemia is a mortality risk factor in dialysis patients; however, low phosphorus levels too. Diabetes and malnutrition are strongly associated with mortality and with reduced serum phosphorus. This study analyzed the pattern of serum phosphorus in patients on Peritoneal Dialysis (PD) and its association with mortality., Methods: A Secondary analysis was performed on a multicenter cohort study in peritoneal dialysis patients from two previous studies done by our group., Results: Six hundred fifty-four patients were included. Serum phosphorus was <3.6 mg/dL in 28.29% of patients, 3.6 to 5.2 mg/dL in 48.16%, and >5.2 mg/dL in 23.55%. In logistic regression analysis; education, age, and hypoalbuminemia were risk factors for low P levels. In multivariate Cox analysis P < 3.6 mg/dL, age, and low albumin were predictors for all-cause mortality. When lower P and lower albumin were combined, this group had the highest risk for all cause and cardiovascular mortality., Conclusion: The frequency of patients with reduced serum phosphorus was higher in the Mexican population than in Europe or Asia. Low serum phosphorus levels, older age and hypoalbuminemia were risk factors for all-cause mortality. Low phosphorus combined with low albumin levels were the highest risk factor for all-cause and cardiovascular mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ávila, Prado, Cuevas-Budhart and Paniagua.)

Background: Screening and treatment guidance for somatic sequalae of eating disorders typically include specifics such as laboratory testing, observable physical signs, and treatment interventions. Oral health guidance is notably sparse or absent from many guidelines. Often, the only mention of oral health is the potential erosion caused by self-induced vomiting and suggests a referral to an oral health professional. The guidelines generally do not include information about education and training of oral health professionals., Objective: The objective of this research was to explore the literature on eating disorders and oral health including the effects of eating disordered behaviors on oral health and training of oral health professionals to increase their capacity to recognize and appropriately address clinical care needs of individuals with eating disorders., Methods: A comprehensive scoping review was conducted to investigate what is known about the relationship between eating disorders and oral health and training provided to oral health professionals in recognition and treatment of individuals with eating disorders. The search was completed using PubMed, Embase, Science Direct, Google Scholar, and the Journal of the American Dental Association., Results: Of 178 articles returned in the initial search, 72 full texts were read, and 44 were included based on eligibility criteria. The retained articles were categorized thematically into articles related to (1) oral health professional education and training, (2) the oral health effects of eating disorders, and (3) patient experiences of oral health care., Conclusion: Most of the research on the relationship between eating disorders and oral health examines the impact of eating disordered behaviors. There is a significantly smaller literature on the knowledge and training of oral health professionals related to eating disorders and individuals with eating disorders' experiences of oral health care. Research on education and training of oral health professionals should be expanded globally, taking into consideration the suitability of interventions for diverse models of oral health education and service delivery. Further, there is an opportunity for eating disorder professionals and professional organizations to improve understanding and care of eating disorders by building relationships with oral health providers and professional organizations in their local communities., (© 2023. The Author(s).)

Myeloproliferative neoplasms (MPNs) are characterized by the activated JAK2/STAT pathway. Pleckstrin-2 (Plek2) is a downstream target of the JAK2/STAT5 pathway and is overexpressed in patients with MPNs. We previously revealed that Plek2 plays critical roles in the pathogenesis of JAK2-mutated MPNs. The nonessential roles of Plek2 under physiologic conditions make it an ideal target for MPN therapy. Here, we identified first-in-class Plek2 inhibitors through an in silico high-throughput screening approach and cell-based assays, followed by the synthesis of analogs. Plek2-specific small-molecule inhibitors showed potent inhibitory effects on cell proliferation. Mechanistically, Plek2 interacts with and enhances the activity of Akt through the recruitment of downstream effector proteins. The Plek2-signaling complex also includes Hsp72, which protects Akt from degradation. These functions were blocked by Plek2 inhibitors via their direct binding to the Plek2 dishevelled, Egl-10 and pleckstrin (DEP) domain. The role of Plek2 in activating Akt signaling was further confirmed in vivo using a hematopoietic-specific Pten-knockout mouse model. We next tested Plek2 inhibitors alone or in combination with an Akt inhibitor in various MPN mouse models, which showed significant therapeutic efficacies similar to that seen with the genetic depletion of Plek2. The Plek2 inhibitor was also effective in reducing proliferation of CD34-positive cells from MPN patients. Our studies reveal a Plek2/Akt complex that drives cell proliferation and can be targeted by a class of antiproliferative compounds for MPN therapy.

RNA alternative splicing (AS) expands the regulatory potential of eukaryotic genomes. The mechanisms regulating liver-specific AS profiles and their contribution to liver function are poorly understood. Here, we identify a key role for the splicing factor RNA-binding Fox protein 2 (RBFOX2) in maintaining cholesterol homeostasis in a lipogenic environment in the liver. Using enhanced individual-nucleotide-resolution ultra-violet cross-linking and immunoprecipitation, we identify physiologically relevant targets of RBFOX2 in mouse liver, including the scavenger receptor class B type I (Scarb1). RBFOX2 function is decreased in the liver in diet-induced obesity, causing a Scarb1 isoform switch and alteration of hepatocyte lipid homeostasis. Our findings demonstrate that specific AS programmes actively maintain liver physiology, and underlie the lipotoxic effects of obesogenic diets when dysregulated. Splice-switching oligonucleotides targeting this network alleviate obesity-induced inflammation in the liver and promote an anti-atherogenic lipoprotein profile in the blood, underscoring the potential of isoform-specific RNA therapeutics for treating metabolism-associated diseases., (© 2022. The Author(s).)

Hemileia vastatrix (HV) is the pathogen responsible for the coffee leaf rust (CLR) disease that has spread globally. CLR causes losses of up to a billion dollars annually and affects all types of crops regardless of their production regime (organic or inorganic). Additionally, smallholders produce approximately 80% of coffee in developing countries. The condition causes losses of up to a billion dollars annually. It affects all types of crops regardless of their production regime (organic or inorganic). Approximately 80% of coffee is produced by smallholders in developing countries. Until the 90s, shaded-production systems and native varieties were encouraged; however, the rapid spread of CLR has forced farmers to migrate towards inorganic schemes, mainly due to a lack of knowledge about natural alternatives to pesticides that can be implemented to control HV. Therefore, the purpose of this article is to compile the currently existing options, emphasizing two key factors that guarantee efficient rust control: selective fungicidal activity against HV and the nutrition of coffee crops. Thus, by comprehending how these natural compounds (such as plant, bacteria, fungi, animals, or algae metabolites) impact coffee rust proliferation. Furthermore, since a various range of biochar effects contributes to the control of foliar fungal pathogens through modification of root exudates, soil properties, and nutrient availability, which influence the growth of antagonist microorganisms, we present a review of the pathogen-suppressive effects of biochar, and new control strategies suitable for organic schemes can be developed.

Wastewater-Based Epidemiology (WBE) is a novel community-wide monitoring tool that provides comprehensive real-time data of the public and environmental health status and can contribute to public health interventions, including those related to infectious disease outbreaks (e.g., the ongoing COVID-19 pandemic). Nonetheless, municipalities without centralized laboratories are likely still not able to process WBE samples. Biosensors are a potentially cost-effective solution to monitor the development of diseases through WBE to prevent local outbreaks. This review discusses the economic and technical feasibility of eighteen recently developed biosensors for the detection and monitoring of infectious disease agents in wastewater, prospecting the prevention of future pandemics., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier B.V. All rights reserved.)

In the last decade, algae applications have generated considerable interest among research organizations and industrial sectors. Bioactive compounds, such as carotenoids, and Mycosporine-like amino acids (MAAs) derived from microalgae may play a vital role in the bio and non-bio sectors. Currently, commercial sunscreens contain chemicals such as oxybenzone and octinoxate, which have harmful effects on the environment and human health; while microalgae-based sunscreens emerge as an eco-friendly alternative to provide photo protector agents against solar radiation. Algae-based exploration ranges from staple foods to pharmaceuticals, cosmetics, and biomedical applications. This review aims to identify the effects of UV and UV-vis irradiation on the production of microalgae bioactive compounds through the assistance of different techniques and extraction methods for biomass characterization. The efficiency and results focus on the production of a blocking agent that does not damage the aquifer, being beneficial for health and possible biomedical applications.

Bionanocomposites based on natural bioactive entities have gained importance due to their abundance; renewable and environmentally benign nature; and outstanding properties with applied perspective. Additionally, their formulation with biological molecules with antimicrobial, antioxidant, and anticancer activities has been produced nowadays. The present review details the state of the art and the importance of this pyrrolic compound produced by microorganisms, with interest towards Serratia marcescens , including production strategies at a laboratory level and scale-up to bioreactors. Promising results of its biological activity have been reported to date, and the advances and applications in bionanocomposites are the most recent strategy to potentiate and to obtain new carriers for the transport and controlled release of prodigiosin. Prodigiosin, a bioactive secondary metabolite, produced by Serratia marcescens , is an effective proapoptotic agent against bacterial and fungal strains as well as cancer cell lines. Furthermore, this molecule presents antioxidant activity, which makes it ideal for treating wounds and promoting the general improvement of the immune system. Likewise, some of the characteristics of prodigiosin, such as hydrophobicity, limit its use for medical and biotechnological applications; however, this can be overcome by using it as a component of a bionanocomposite. This review focuses on the chemistry and the structure of the bionanocomposites currently developed using biorenewable resources. Moreover, the work illuminates recent developments in pyrrole-based bionanocomposites, with special insight to its application in the medical area.

Rapid industrialization and manufacturing expansion have caused heavy metal pollution, which is a critical environmental issue faced by global population. In addition, the disadvantages presented by conventional detection methods such as the requirement of sophisticated instruments and qualified personnel have led to the development of novel nanosensors. Recently, carbon dots (CDs) have been presented as a multifunctional nanomaterial alternative for the accurate detection of heavy metal ions in water systems. The capacity of CDs to detect contaminants in wastewater -including heavy metals- can be found in the literature; however, to the best of our knowledge, none of them discusses the most recent strategies to enhance their performance. Therefore, in this review, beyond presenting successful examples of the use of CDs for the detection of metal ions, we further discuss the strategies to enhance their photoluminescence properties and their performance for environmental monitoring. In this manner, strategies such as heteroatom-doping and surface passivation are reviewed in detail, as well as describing the mechanisms and the effect of precursors and synthesis methods. Finally, the current challenges are described in detail to propose some recommendations for further research., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

UBQLN2 mutations cause amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD), but the pathogenic mechanisms by which they cause disease remain unclear. Proteomic profiling identified 'mitochondrial proteins' as comprising the largest category of protein changes in the spinal cord (SC) of the P497S UBQLN2 mouse model of ALS/FTD. Immunoblots confirmed P497S animals have global changes in proteins predictive of a severe decline in mitochondrial health, including oxidative phosphorylation (OXPHOS), mitochondrial protein import and network dynamics. Functional studies confirmed mitochondria purified from the SC of P497S animals have age-dependent decline in nearly all steps of OXPHOS. Mitochondria cristae deformities were evident in spinal motor neurons of aged P497S animals. Knockout (KO) of UBQLN2 in HeLa cells resulted in changes in mitochondrial proteins and OXPHOS activity similar to those seen in the SC. KO of UBQLN2 also compromised targeting and processing of the mitochondrial import factor, TIMM44, resulting in accumulation in abnormal foci. The functional OXPHOS deficits and TIMM44-targeting defects were rescued by reexpression of WT UBQLN2 but not by ALS/FTD mutant UBQLN2 proteins. In vitro binding assays revealed ALS/FTD mutant UBQLN2 proteins bind weaker with TIMM44 than WT UBQLN2 protein, suggesting that the loss of UBQLN2 binding may underlie the import and/or delivery defect of TIMM44 to mitochondria. Our studies indicate a potential key pathogenic disturbance in mitochondrial health caused by UBQLN2 mutations., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Porphyridium purpureum is a well-known Rhodophyta that recently has attracted enormous attention because of its capacity to produce many high-value metabolites such as the pigment phycoerythrin and several high-value fatty acids. Phycoerythrin is a fluorescent red protein-pigment commercially relevant with antioxidant, antimicrobial activity, and fluorescent properties. The volumetric mass transfer coefficient (k L a) was kept constant within the different scaling-up stages in the present study. This scaling-up strategy was sought to maintain phycoerythrin production and other high-value metabolites by Porphyridium purpureum , using hanging-bag photobioreactors. The k L a was monitored to ensure the appropriate mixing and CO 2 diffusion in the entire culture during the scaling process (16, 80, and 400 L). Then, biomass concentration, proteins, fatty acids, carbohydrates, and phycoerythrin were determined in each step of the scaling-up process. The k L a at 16 L reached a level of 0.0052 s -1 , while at 80 L, a value of 0.0024 s -1 was achieved. This work result indicated that at 400 L, 1.22 g L -1 of biomass was obtained, and total carbohydrates (117.24 mg L -1 ), proteins (240.63 mg L -1 ), and lipids (17.75% DW) were accumulated. Regarding fatty acids production, 46.03% palmitic, 8.03% linoleic, 22.67% arachidonic, and 2.55% eicosapentaenoic acid were identified, principally. The phycoerythrin production was 20.88 mg L -1 with a purity of 2.75, making it viable for food-related applications. The results of these experiments provide insight into the high-scale production of phycoerythrin via the cultivation of P. purpureum in an inexpensive and straightforward culture system.

Background: Maternal iron deficiency (ID) is associated with poor pregnancy and fetal outcomes. The effect is thought to be mediated by the placenta but there is no comprehensive assessment of placental responses to maternal ID. Additionally, whether the influence of maternal ID on the placenta differs by fetal sex is unknown., Objectives: To identify gene and protein signatures of ID mouse placentas at mid-gestation. A secondary objective was to profile the expression of iron genes in mouse placentas across gestation., Methods: We used a real-time PCR-based array to determine the mRNA expression of all known iron genes in mouse placentas at embryonic day (E) 12.5, E14.5, E16.5, and E19.5 (n = 3 placentas/time point). To determine the effect of maternal ID, we performed RNA sequencing and proteomics in male and female placentas from ID and iron-adequate mice at E12.5 (n = 8 dams/diet)., Results: In female placentas, 6 genes, including transferrin receptor (Tfrc) and solute carrier family 11 member 2, were significantly changed by maternal ID. An additional 154 genes were altered in male ID placentas. A proteomic analysis quantified 7662 proteins in the placenta. Proteins translated from iron-responsive element (IRE)-containing mRNA were altered in abundance; ferritin and ferroportin 1 decreased, while TFRC increased in ID placentas. Less than 4% of the significantly altered genes in ID placentas occurred both at the transcriptional and translational levels., Conclusions: Our data demonstrate that the impact of maternal ID on placental gene expression in mice is limited in scope and magnitude at mid-gestation. We provide strong evidence for IRE-based transcriptional and translational coordination of iron gene expression in the mouse placenta. Finally, we discover sexually dimorphic effects of maternal ID on placental gene expression, with more genes and pathways altered in male compared with female mouse placentas., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

The proteasome mediates most selective protein degradation. Proteolysis occurs within the 20S core particle (CP), a barrel-shaped chamber with an α 7 β 7 β 7 α 7 configuration. CP biogenesis proceeds through an ordered multistep pathway requiring five chaperones, Pba1-4 and Ump1. Using Saccharomyces cerevisiae, we report high-resolution structures of CP assembly intermediates by cryogenic-electron microscopy. The first structure corresponds to the 13S particle, which consists of a complete α-ring, partial β-ring (β2-4), Ump1 and Pba1/2. The second structure contains two additional subunits (β5-6) and represents a later pre-15S intermediate. These structures reveal the architecture and positions of Ump1 and β2/β5 propeptides, with important implications for their functions. Unexpectedly, Pba1's N terminus extends through an open CP pore, accessing the CP interior to contact Ump1 and the β5 propeptide. These results reveal how the coordinated activity of Ump1, Pba1 and the active site propeptides orchestrate key aspects of CP assembly.

The final stages of mammalian erythropoiesis involve enucleation, membrane and proteome remodeling, and organelle clearance. Concomitantly, the erythroid membrane skeleton establishes a unique pseudohexagonal spectrin meshwork that is connected to the membrane through junctional complexes. The mechanism and signaling pathways involved in the coordination of these processes are unclear. The results of our study revealed an unexpected role of the membrane skeleton in the modulation of proteome remodeling and organelle clearance during the final stages of erythropoiesis. We found that diaphanous-related formin mDia2 is a master regulator of the integrity of the membrane skeleton through polymerization of actin protofilament in the junctional complex. The mDia2-deficient terminal erythroid cell contained a disorganized and rigid membrane skeleton that was ineffective in detaching the extruded nucleus. In addition, the disrupted skeleton failed to activate the endosomal sorting complex required for transport-III (ESCRT-III) complex, which led to a global defect in proteome remodeling, endolysosomal trafficking, and autophagic organelle clearance. Chmp5, a component of the ESCRT-III complex, is regulated by mDia2-dependent activation of the serum response factor and is essential for membrane remodeling and autophagosome-lysosome fusion. Mice with loss of Chmp5 in hematopoietic cells in vivo resembled the phenotypes in mDia2-knockout mice. Furthermore, overexpression of Chmp5 in mDia2-deficient hematopoietic stem and progenitor cells significantly restored terminal erythropoiesis in vivo. These findings reveal a formin-regulated signaling pathway that connects the membrane skeleton to proteome remodeling, enucleation, and organelle clearance during terminal erythropoiesis., (© 2021 by The American Society of Hematology.)

Familial neurodegenerative diseases commonly involve mutations that result in either aberrant proteins or dysfunctional components of the proteolytic machinery that act on aberrant proteins. UBQLN2 is a ubiquitin receptor of the UBL/UBA family that binds the proteasome through its ubiquitin-like domain and is thought to deliver ubiquitinated proteins to proteasomes for degradation. UBQLN2 mutations result in familial amyotrophic lateral sclerosis (ALS)/frontotemporal dementia in humans through an unknown mechanism. Quantitative multiplexed proteomics was used to provide for the first time an unbiased and global analysis of the role of Ubqln2 in controlling the composition of the proteome. We studied several murine models of Ubqln2-linked ALS and also generated Ubqln2 null mutant mice. We identified impacts of Ubqln2 on diverse physiological pathways, most notably serotonergic signaling. Interestingly, we observed an upregulation of proteasome subunits, suggesting a compensatory response to diminished proteasome output. Among the specific proteins whose abundance is linked to UBQLN2 function, the strongest hits were the ubiquitin ligase TRIM32 and two retroelement-derived proteins, PEG10 and CXX1B. Cycloheximide chase studies using induced human neurons and HEK293 cells suggested that PEG10 and TRIM32 are direct clients. Although UBQLN2 directs the degradation of multiple proteins via the proteasome, it surprisingly conferred strong protection from degradation on the Gag-like protein CXX1B, which is expressed from the same family of retroelement genes as PEG10. In summary, this study charts the proteomic landscape of ALS-related Ubqln2 mutants and identifies candidate client proteins that are altered in vivo in disease models and whose degradation is promoted by UBQLN2., Competing Interests: Conflict of interest S. D., M. W., H. N., A. E., and E. J. B. are current employees of Genentech, Inc. A. M. W. is a former employee of Genentech, Inc. D. F. is a consultant for Genentech, Inc. All the other authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Cyanobacteria are essential for the vast number of compounds they produce and the possible applications in the pharmaceutical, cosmetical, and food industries. As Lyngbya species' characterization is limited in the literature, we characterize this cyanobacterium's growth and biomass. L . purpureum was grown and analyzed under different salinities, culture media, and incubation times to determine the best conditions that favor its cell growth and the general production of proteins, carbohydrates, lipids, and some pigments as phycocyanin and chlorophyll a . In this study, each analyzed biomolecule's highest content was proteins 431.69 mg g -1 , carbohydrates 301.45 mg g -1 , lipids 131.5 mg g -1 , chlorophyll a 4.09 mg g -1 , and phycocyanin 40.4 mg g -1 . These results can provide a general context of the possible uses that can be given to biomass and give an opening to investigate possible biocompounds or bio metabolites that can be obtained from it.

Dysregulation of habit formation has been recently proposed as pivotal to eating disorders. Here, we report that a subset of patients suffering from restrictive anorexia nervosa have enhanced habit formation compared with healthy controls. Habit formation is modulated by striatal cholinergic interneurons. These interneurons express vesicular transporters for acetylcholine (VAChT) and glutamate (VGLUT3) and use acetylcholine/glutamate cotransmission to regulate striatal functions. Using mice with genetically silenced VAChT (VAChT conditional KO, VAChTcKO) or VGLUT3 (VGLUT3cKO), we investigated the roles that acetylcholine and glutamate released by cholinergic interneurons play in habit formation and maladaptive eating. Silencing glutamate favored goal-directed behaviors and had no impact on eating behavior. In contrast, VAChTcKO mice were more prone to habits and maladaptive eating. Specific deletion of VAChT in the dorsomedial striatum of adult mice was sufficient to phenocopy maladaptive eating behaviors of VAChTcKO mice. Interestingly, VAChTcKO mice had reduced dopamine release in the dorsomedial striatum but not in the dorsolateral striatum. The dysfunctional eating behavior of VAChTcKO mice was alleviated by donepezil and by l-DOPA, confirming an acetylcholine/dopamine deficit. Our study reveals that loss of acetylcholine leads to a dopamine imbalance in striatal compartments, thereby promoting habits and vulnerability to maladaptive eating in mice.

We consider brain activity from an information theoretic perspective. We analyze the information processing in the brain, considering the optimality of Shannon entropy transport using the Monge-Kantorovich framework. It is proposed that some of these processes satisfy an optimal transport of informational entropy condition. This optimality condition allows us to derive an equation of the Monge-Ampère type for the information flow that accounts for the branching structure of neurons via the linearization of this equation. Based on this fact, we discuss a version of Murray's law in this context.

Background: Bartonella henselae is the etiologic agent of cat-scratch disease, which affects the entire world population. Due to how poorly characterized the child population is, the objective was to describe the clinical behavior of this disease in children younger than 16 years of age., Methods: This was a descriptive study with prospective follow-up of all children younger than 16 years with clinical and serologic diagnoses between 2013 and 2018., Results: There were 142 patients; of these, 55.6% had localized disease, 34.5% disseminated with hepatosplenic involvement and 9.8% had atypical disease. The cases of atypical disease were prolonged febrile illness, Parinaud syndrome, subacute bacterial endocarditis/glomerulonephritis and aseptic meningitis. Cervical lymphadenopathy was the most frequent, followed by inguinal adenopathy. There were no differences between the type of manifestation and laboratory values except for a higher erythrocyte sedimentation rate tendency in patients with disseminated and/or atypical disease. The serologic titers throughout were distributed as follows: titer of 1/1024, 71.7%; titer of 1/512, 10.4% and titer of 1/256, 17.9%., Conclusions: This is, to our knowledge, the largest series of cat-scratch disease published. We demonstrate that in our environment, the inguinal location is suggestive of this disease, the disseminated presentation, frequent, and that the titers are probably much higher than in other populations, which perhaps indicates the need to re-examine the cut-off point for positivity.

Mutations in UBQLN2 cause amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerations. However, the mechanism by which the UBQLN2 mutations cause disease remains unclear. Alterations in proteins involved in autophagy are prominent in neuronal tissue of human ALS UBQLN2 patients and in a transgenic P497S UBQLN2 mouse model of ALS/FTD, suggesting a pathogenic link. Here, we show UBQLN2 functions in autophagy and that ALS/FTD mutant proteins compromise this function. Inactivation of UBQLN2 expression in HeLa cells reduced autophagic flux and autophagosome acidification. The defect in acidification was rescued by reexpression of wild type (WT) UBQLN2 but not by any of the five different UBQLN2 ALS/FTD mutants tested. Proteomic analysis and immunoblot studies revealed P497S mutant mice and UBQLN2 knockout HeLa and NSC34 cells have reduced expression of ATP6v1g1, a critical subunit of the vacuolar ATPase (V-ATPase) pump. Knockout of UBQLN2 expression in HeLa cells decreased turnover of ATP6v1g1, while overexpression of WT UBQLN2 increased biogenesis of ATP6v1g1 compared with P497S mutant UBQLN2 protein. In vitro interaction studies showed that ATP6v1g1 binds more strongly to WT UBQLN2 than to ALS/FTD mutant UBQLN2 proteins. Intriguingly, overexpression of ATP6v1g1 in UBQLN2 knockout HeLa cells increased autophagosome acidification, suggesting a therapeutic approach to overcome the acidification defect. Taken together, our findings suggest that UBQLN2 mutations drive pathogenesis through a dominant-negative loss-of-function mechanism in autophagy and that UBQLN2 functions as an important regulator of the expression and stability of ATP6v1g1. These findings may have important implications for devising therapies to treat UBQLN2 -linked ALS/FTD., Competing Interests: The authors declare no competing interest.

This study investigated Passiflora edulis peel flour (PEPF) intake and its effect against high-fat diet-induced obesity. PEPF is a source of fiber and phenolic compounds, which can decrease oxidative stress and inflammatory cytokines, both linked to chronic inflammatory response and fat deposition in obesity. Therefore, we hypothesized that PEPF intake could decrease inflammatory cytokines and oxidative stress observed in obesity, leading to decrease of fatness and chronic inflammatory response. The aims of the study were to evaluate the lipid peroxidation, the expression of antioxidants enzymes, and inflammatory parameters in obese rats. Male Sprague-Dawley rats were divided into 3 groups (n = 8 per group) according to the diets: control (based on AIN-93G), high-fat (HF, 35% fat w/w), and HF with PEPF (HFPF), and the experiment lasted for 10 weeks. PEPF showed high dietary fiber content and bioactive compounds, such as ferulic acid, and β-carotene. PEPF intake was effective in reducing body weight gain (13.31%) and total body fat (22.58%). The lipid peroxidation in the liver and adipose tissue decreased in the HFPF group compared to HF-fed animals, whereas hepatic glutathione peroxidase and glutathione reductase activity and their expressions in the liver were higher in HFPF than HF. In addition, the PEPF intake decreased inflammatory cytokines in serum. These results suggest that PEPF intake decreases oxidative stress, possibly by the increase of antioxidant enzymes expression. Furthermore, PEPF decreases inflammatory response and protects from adiposity. Then, PEPF could act as an adjuvant to control of early parameters in obesity dysfunction., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Chromatin organization is a highly orchestrated process that influences gene expression, in part by modulating access of regulatory factors to DNA and nucleosomes. Here, we report that the chromatin accessibility regulator HMGN1, a target of recurrent DNA copy gains in leukemia, controls myeloid differentiation. HMGN1 amplification is associated with increased accessibility, expression, and histone H3K27 acetylation of loci important for hematopoietic stem cells (HSCs) and leukemia, such as HoxA cluster genes. In vivo, HMGN1 overexpression is linked to decreased quiescence and increased HSC activity in bone marrow transplantation. HMGN1 overexpression also cooperates with the AML-ETO9a fusion oncoprotein to impair myeloid differentiation and enhance leukemia stem cell (LSC) activity. Inhibition of histone acetyltransferases CBP/p300 relieves the HMGN1-associated differentiation block. These data nominate factors that modulate chromatin accessibility as regulators of HSCs and LSCs, and suggest that targeting HMGN1 or its downstream effects on histone acetylation could be therapeutically active in AML.

The proteasome, the most complex protease known, degrades proteins that have been conjugated to ubiquitin. It faces the unique challenge of acting enzymatically on hundreds and perhaps thousands of structurally diverse substrates, mechanically unfolding them from their native state and translocating them vectorially from one specialized compartment of the enzyme to another. Moreover, substrates are modified by ubiquitin in myriad configurations of chains. The many unusual design features of the proteasome may have evolved in part to endow this enzyme with a robust ability to process substrates regardless of their identity. The proteasome plays a major role in preserving protein homeostasis in the cell, which requires adaptation to a wide variety of stress conditions. Modulation of proteasome function is achieved through a large network of proteins that interact with it dynamically, modify it enzymatically, or fine-tune its levels. The resulting adaptability of the proteasome, which is unique among proteases, enables cells to control the output of the ubiquitin-proteasome pathway on a global scale., (Copyright © 2020 Cold Spring Harbor Laboratory Press; all rights reserved.)

Open Science has changed research by making data accessible and shareable, contributing to replicability to accelerate and disseminate knowledge. However, for rodent cognitive studies the availability of tools to share and disseminate data is scarce. Automated touchscreen-based tests enable systematic cognitive assessment with easily standardised outputs that can facilitate data dissemination. Here we present an integration of touchscreen cognitive testing with an open-access database public repository (mousebytes.ca), as well as a Web platform for knowledge dissemination (https://touchscreencognition.org). We complement these resources with the largest dataset of age-dependent high-level cognitive assessment of mouse models of Alzheimer's disease, expanding knowledge of affected cognitive domains from male and female mice of three strains. We envision that these new platforms will enhance sharing of protocols, data availability and transparency, allowing meta-analysis and reuse of mouse cognitive data to increase the replicability/reproducibility of datasets., Competing Interests: FB, DP, SM, DW, WL, SL, SC, BK, MC, JM, TM, CF, MA, RB, TG, SS, VP, BW, MP No competing interests declared, LS Lisa Saksida has established a series of targeted cognitive tests for animals, administered via touchscreen within a custom environment known as the “Bussey-Saksida touchscreen chamber”. Cambridge Enterprise, the technology transfer office of the University of Cambridge, supported commercialization of the Bussey-Saksida chamber, culminating in a license to Campden Instruments. Any financial compensation received from commercialization of the technology is fully invested in further touchscreen development and/or maintenance, TB Tim Bussey has established a series of targeted cognitive tests for animals, administered via touchscreen within a custom environment known as the “Bussey-Saksida touchscreen chamber”. Cambridge Enterprise, the technology transfer office of the University of Cambridge, supported commercialization of the Bussey-Saksida chamber, culminating in a license to Campden Instruments. Any financial compensation received from commercialization of the technology is fully invested in further touchscreen development and/or maintenance, (© 2019, Beraldo et al.)

The yeast stress-activated protein kinase Hog1 is best known for its role in mediating the response to osmotic stress, but it is also activated by various mechanistically distinct environmental stressors, including heat shock, endoplasmic reticulum stress, and arsenic. In the osmotic stress response, the signal is sensed upstream and relayed to Hog1 through a kinase cascade. Here, we identified a mode of Hog1 function whereby Hog1 senses arsenic through a direct physical interaction that requires three conserved cysteine residues located adjacent to the catalytic loop. These residues were essential for Hog1-mediated protection against arsenic, were dispensable for the response to osmotic stress, and promoted the nuclear localization of Hog1 upon exposure of cells to arsenic. Hog1 promoted arsenic detoxification by stimulating phosphorylation of the transcription factor Yap8, promoting Yap8 nuclear localization, and stimulating the transcription of the only known Yap8 targets, ARR2 and ARR3 , both of which encode proteins that promote arsenic efflux. The related human kinases ERK1 and ERK2 also bound to arsenic in vitro, suggesting that this may be a conserved feature of some members of the mitogen-activated protein kinase (MAPK) family. These data provide a mechanistic basis for understanding how stress-activated kinases can sense distinct threats and perform highly specific adaptive responses., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Primary cilia are hair-like organelles that play crucial roles in vertebrate development, organogenesis and when dysfunctional result in pleiotropic human genetic disorders called ciliopathies, characterized by overlapping phenotypes, such as renal and hepatic cysts, skeletal defects, retinal degeneration and central nervous system malformations. Primary cilia act as communication hubs to transfer extracellular signals into intracellular responses and are essential for Hedgehog (Hh) signal transduction in mammals. Despite the renewed interest in this ancient organelle of growing biomedical importance, the molecular mechanisms that trigger cilia formation, extension and ciliary signal transduction are still not fully understood. Here we provide, for the first time, evidence that the deubiquitinase ubiquitin-specific protease-14 (Usp14), a major regulator of the ubiquitin proteasome system (UPS), controls ciliogenesis, cilia elongation and Hh signal transduction. Moreover, we show that pharmacological inhibition of Usp14 positively affects Hh signal transduction in a model of autosomal dominant polycystic kidney disease. These findings provide new insight into the spectrum of action of UPS in cilia biology and may provide novel opportunities for therapeutic intervention in human conditions associated with ciliary dysfunction., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Genomic studies have recently identified RPS15 as a new driver gene in aggressive and chemorefractory cases of chronic lymphocytic leukemia (CLL). RPS15 encodes a ribosomal protein whose conserved C-terminal domain extends into the decoding center of the ribosome. We demonstrate that mutations in highly conserved residues of this domain affect protein stability, by increasing its ubiquitin-mediated degradation, and cell-proliferation rates. On the other hand, we show that mutated RPS15 can be loaded into the ribosomes, directly impacting on global protein synthesis and/or translational fidelity in a mutation-specific manner. Quantitative mass spectrometry analyses suggest that RPS15 variants may induce additional alterations in the translational machinery, as well as a metabolic shift at the proteome level in HEK293T and MEC-1 cells. These results indicate that CLL-related RPS15 mutations might act following patterns known for other ribosomal diseases, likely switching from a hypo- to a hyperproliferative phenotype driven by mutated ribosomes. In this scenario, loss of translational fidelity causing altered cell proteostasis can be proposed as a new molecular mechanism involved in CLL pathobiology., (© 2018 by The American Society of Hematology.)

Deubiquitinases are proteases with a wide functional diversity that profoundly impact multiple biological processes. Among them, the ubiquitin-specific protease 36 (USP36) has been implicated in the regulation of nucleolar activity. However, its functional relevance in vivo has not yet been fully described. Here, we report the generation of an Usp36-deficient mouse model to examine the function of this enzyme. We show that Usp36 depletion is lethal in preimplantation mouse embryos, where it blocks the transition from morula to blastocyst during embryonic development. USP36 reduces the ubiquitination levels and increases the stability of the DEAH-box RNA helicase DHX33, which is critically involved in ribosomal RNA synthesis and mRNA translation. In agreement with this finding, O- propargyl-puromycin incorporation experiments, Northern blot, and electron microscopy analyses demonstrated the role of USP36 in ribosomal RNA and protein synthesis. Finally, we show that USP36 down-regulation alters cell proliferation in human cancer cells by inducing both apoptosis and cell cycle arrest, and that reducing DHX33 levels through short hairpin RNA interference has the same effect. Collectively, these results support that Usp36 is essential for cell and organism viability because of its role in ribosomal RNA processing and protein synthesis, which is mediated, at least in part, by regulating DHX33 stability., (© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.)

The selection of topical and systemic therapies for the treatment of venous ulcers with signs of infection is challenging and should be accompanied by specific precautionary measures to protect against cross-contamination in the presence of multidrug-resistant microorganisms. However, there are still no clinical indicators for this situation, and confirmation of resistant strains occurs through culture and sensitivity, which can take up to 14 days. During this period, protective measures may no longer be taken, contributing to the spread of these pathogens. This study aimed to analyze the relationship between clinical signs and symptoms of infection in venous ulcers and the presence of antimicrobial-resistant Staphylococcus aureus and/or Pseudomonas spp. A cross-sectional study was developed including 69 patients with 98 venous ulcers. Clinical observation protocol was applied to detect infection indicators established by the European Wound Management Association and microbiological analysis of samples of the lesions. Fisher's exact test and χ 2 were used for analyses (P < 0.05). Two indicators of infection predominated (f >70%): discoloration of the opaque type and/or dark brick red and increased exudate volume; 31 (31.6%) ulcer samples showed positive culture for the bacteria studied. There was no relationship between signs and symptoms of infection and the presence of multidrug-resistant microorganisms. Taking into account the percentage of lesions with resistant strains, for safe care, contact precautionary measures should be implemented in the treatment rooms, in addition to standard precautions., (Copyright © 2017 Society for Vascular Nursing, Inc. Published by Elsevier Inc. All rights reserved.)