Toward a Symbiotic Perspective on Public Health: Recognizing the Ambivalence of Microbes in the Anthropocene

Microbes evolve in complex environments that are often fashioned, in part, by human desires. In a global perspective, public health has played major roles in structuring how microbes are perceived, cultivated, and destroyed. The germ theory of disease cast microbes as enemies of the body and the body politic. Antibiotics have altered microbial development by providing stringent natural selection on bacterial species, and this has led to the formation of antibiotic-resistant bacterial strains. Public health perspectives such as “Precision Public Health” and “One Health” have recently been proposed to further manage microbial populations. However, neither of these take into account the symbiotic relationships that exist between bacterial species and between bacteria, viruses, and their eukaryotic hosts. We propose a perspective on public health that recognizes microbial evolution through symbiotic associations (the hologenome theory) and through lateral gene transfer. This perspective has the advantage of including both the pathogenic and beneficial interactions of humans with bacteria, as well as combining the outlook of the “One Health” model with the genomic methodologies utilized in the “Precision Public Health” model. In the Anthropocene, the conditions for microbial evolution have been altered by human interventions, and public health initiatives must recognize both the beneficial (indeed, necessary) interactions of microbes with their hosts as well as their pathogenic interactions

On-shell approach to neutrino oscillations

In the usual quantum field theoretical approach, neutrino oscillations are studied diagonalizing either the mass or matter Hamiltonians. In this paper we analyze the problem from an on-shell amplitude perspective, where Lagrangians or Hamiltonians are not available. We start by studying in detail how flavor enters in the amplitudes and how the Pontecorvo-Maki-Nakagawa-Sakata (PMNS) matrix emerges. We then analyze the elastic amplitude of two neutrinos and two charged leptons that induce matter effects and propose a strategy to obtain the known results of the standard oscillation theory without Hamiltonians. Finally, we extend the previously proposed procedure and use the most general elastic 4-point amplitude to study beyond the Standard Model effects on oscillations

Criminalidade organizada nas prisões e os ataques do PCC

The advent of organized crime in Brazilian prisons, especially in the state of São Paulo, constitutes the object of this article. The waves of attack unleashed by the Capital's First Command (PCC - Primeiro Comando da Capital), in May 2006, which resulted in countless deaths, brought cities to a halt, and cornered authorities in charge preventing them from applying law and order are the starting as well as reference points taken. The advent of organized criminality is analyzed under the light of determined axes: the international scenario and the Brazilian context, the historical antecedents, the taking root of crime in society and the role of penitentiary public policies.A emergência da criminalidade organizada nas prisões brasileiras, em especial no Estado de São Paulo, constitui objeto deste artigo. Tomam-se como ponto de partida e referência para análise as ondas de ataques desencadeadas pelo Primeiro Comando da Capital (PCC), de maio a agosto de 2006, que resultaram em inúmeros mortos, paralisaram cidades e acuaram as autoridades encarregadas de aplicar lei e ordem. A emergência da criminalidade organizada é analisada sob eixos determinados: cenário internacional e contexto brasileiro, antecedentes históricos, enraizamento do crime na sociedade e papel das políticas públicas penitenciárias

Structure and dynamics of a human myelin protein P2 portal region mutant indicate opening of the β barrel in fatty acid binding proteins

Abstract Background Myelin is a multilayered proteolipid sheath wrapped around selected axons in the nervous system. Its constituent proteins play major roles in forming of the highly regular membrane structure. P2 is a myelin-specific protein of the fatty acid binding protein (FABP) superfamily, which is able to stack lipid bilayers together, and it is a target for mutations in the human inherited neuropathy Charcot-Marie-Tooth disease. A conserved residue that has been proposed to participate in membrane and fatty acid binding and conformational changes in FABPs is Phe57. This residue is thought to be a gatekeeper for the opening of the portal region upon ligand entry and egress. Results We performed a structural characterization of the F57A mutant of human P2. The mutant protein was crystallized in three crystal forms, all of which showed changes in the portal region and helix α2. In addition, the behaviour of the mutant protein upon lipid bilayer binding suggested more unfolding than previously observed for wild-type P2. On the other hand, membrane binding rendered F57A heat-stable, similarly to wild-type P2. Atomistic molecular dynamics simulations showed opening of the side of the discontinuous β barrel, giving important indications on the mechanism of portal region opening and ligand entry into FABPs. The results suggest a central role for Phe57 in regulating the opening of the portal region in human P2 and other FABPs, and the F57A mutation disturbs dynamic cross-correlation networks in the portal region of P2. Conclusions Overall, the F57A variant presents similar properties to the P2 patient mutations recently linked to Charcot-Marie-Tooth disease. Our results identify Phe57 as a residue regulating conformational changes that may accompany membrane surface binding and ligand exchange in P2 and other FABPs

Psychometric properties of the Spanish version of the Clinical Outcomes in Routine Evaluation Outcome Measure

Objective: The objective of this paper is to assess the reliability and validity of the Spanish translation of the Clinical Outcomes in Routine Evaluation – Outcome Measure, a 34-item selfreport questionnaire that measures the client’s status in the domains of Subjective well-being, Problems/Symptoms, Life functioning, and Risk. Method: Six hundred and forty-four adult participants were included in two samples: the clinical sample (n=192) from different mental health and primary care centers; and the nonclinical sample (n=452), which included a student and a community sample. Results: The questionnaire showed good acceptability and internal consistency, appropriate test–retest reliability, and acceptable convergent validity. Strong differentiation between clinical and nonclinical samples was found. As expected, the Risk domain had different characteristics than other domains, but all findings were comparable with the UK referential data. Cutoff scores were calculated for clinical significant change assessment. Conclusion: The Spanish version of the Clinical Outcomes in Routine Evaluation – Outcome Measure showed acceptable psychometric properties, providing support for using the questionnaire for monitoring the progress of Spanish-speaking psychotherapy clients

Moringa oleifera na alimentação de bezerros lactentes da raça Pantaneira.

Objetivou-se avaliar o desempenho de bezerros da raça Pantaneira durante o período de amamentação. Para tanto, foram utilizados 10 bezerros do nascimento aos 84 dias de vida, com peso corpóreo médio de 23,3Kg, e divididos em dois tratamentos: C - animais que receberam concentrado (grupo controle); e CFM - animais que receberam o concentrado e feno de Moringa Oleifera (Moringa oleífera). O desempenho foi avaliado por meio do ganho de peso médio diário; do crescimento corpóreo, via medições do perímetro torácico e da altura de cernelha e de garupa; do consumo de matéria seca expresso em kg/dia, da porcentagem do peso corpóreo e em função do peso metabólico; dos consumos de proteína bruta e de fibra em detergente neutro; e da conversão alimentar. Adotou-se o delineamento experimental em blocos inteiramente casualizados, com dois tratamentos e cinco repetições, sendo cada unidade experimental representada por um animal. Foram realizadas análises de variância, e teste de Tukey para a comparação de médias, considerando-se um nível de significância de 5% de probabilidade. Os animais apresentaram um consumo de matéria seca, ganho de peso médio diário, porcentagem de peso corpóreo e de peso metabólico semelhantes; para ambos os tratamentos. Do mesmo modo ocorreu para a conversão alimentar e a proteína bruta, exceto para fibra em detergente neutro onde os animais alimentados com feno apresentaram um maior consumo. O desempenho dos bezerros lactentes Pantaneiros não foi influenciado com a inclusão do feno de moringa. Abstract: The present study aimed to evaluate the performance of calves of the Pantaneira breed during the breastfeeding period. For this, were used ten calves, from birth to 84 days of life, with a mean body weight of 23.3Kg, divided into two treatments: C - animals receiving concentrate, and CMH animals receiving concentrate and moringa hay (Moringa oleifera). The performance was evaluated by the average daily weight gain; body growth, via measurements of heart girth and height of the withers and the rump; the dry matter intake, expressed as kg/day, percentage of body weight and as function of metabolic weight; consumption of crude protein and neutral detergent fiber; and feed conversion. The experimental design was a randomized block with two treatments and five replications, each experimental unit represented by an animal. Were realized analyses of variance and Tukey test considering a significance level of 5 % probability. The animals presented a dry matter intake, average daily weight gain, percentage of body weight and similar metabolic weight; for both treatments. Likewise, it occurred for feed conversion and crude protein, except for neutral detergent fiber where hay fed animals showed higher intake. The performance of the suckling calves was not affected by the inclusion of moringa hay

Multiplexing with three-primer PCR for rapid and economical microsatellite validation

The next generation sequencing revolution has enabled rapid discovery of genetic markers, however, development of fully functioning new markers still requires a long and costly process of marker validation. This study reports a rapid and economical approach for the validation and deployment of polymorphic microsatellite markers obtained from a 454 pyrosequencing library of Atlantic cod, Gadus morhua, Linnaeus 1758. Primers were designed from raw reads to amplify specific amplicon size ranges, allowing effective PCR multiplexing. Multiplexing was combined with a three-primer PCR approach using four universal tails to label amplicons with separate fluorochromes. A total of 192 primer pairs were tested, resulting in 73 polymorphic markers. Of these, 55 loci were combined in six multiplex panels each containing between six and eleven markers. Variability of the loci was assessed on G. morhua from the Celtic Sea (n = 46) and the Scotian Shelf (n = 46), two locations that have shown genetic differentiation in previous studies. Multilocus FST between the two samples was estimated at 0.067 (P = 0.001). After three loci potentially under selection were excluded, the global FST was estimated at 0.043 (P = 0.001). Our technique combines three-primer and multiplex PCR techniques, allowing simultaneous screening and validation of relatively large numbers of microsatellite loci

Biallelic KIF24 Variants Are Responsible for a Spectrum of Skeletal Disorders Ranging From Lethal Skeletal Ciliopathy to Severe Acromesomelic Dysplasia

Skeletal dysplasias comprise a large spectrum of mostly monogenic disorders affecting bone growth, patterning, and homeostasis, and ranging in severity from lethal to mild phenotypes. This study aimed to underpin the genetic cause of skeletal dysplasia in three unrelated families with variable skeletal manifestations. The six affected individuals from three families had severe short stature with extreme shortening of forelimbs, short long-bones, and metatarsals, and brachydactyly (family 1); mild short stature, platyspondyly, and metaphyseal irregularities (family 2); or a prenatally lethal skeletal dysplasia with kidney features suggestive of a ciliopathy (family 3). Genetic studies by whole genome, whole exome, and ciliome panel sequencing identified in all affected individuals biallelic missense variants in KIF24, which encodes a kinesin family member controlling ciliogenesis. In families 1 and 3, with the more severe phenotype, the affected subjects harbored homozygous variants (c.1457A>G; p.(Ile486Val) and c.1565A>G; p.(Asn522Ser), respectively) in the motor domain which plays a crucial role in KIF24 function. In family 2, compound heterozygous variants (c.1697C>T; p.(Ser566Phe)/c.1811C>T; p.(Thr604Met)) were found C-terminal to the motor domain, in agreement with a genotype-phenotype correlation. In vitro experiments performed on amnioblasts of one affected fetus from family 3 showed that primary cilia assembly was severely impaired, and that cytokinesis was also affected. In conclusion, our study describes novel forms of skeletal dysplasia associated with biallelic variants in KIF24. To our knowledge this is the first report implicating KIF24 variants as the cause of a skeletal dysplasia, thereby extending the genetic heterogeneity and the phenotypic spectrum of rare bone disorders and underscoring the wide range of monogenetic skeletal ciliopathies. (c) 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).Peer reviewe

Efficacy of a dilemma-focused intervention for unipolar depression : study protocol for a multicenter randomized controlled trial

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citedDepression is one of the more severe and serious health problems because of its morbidity, disabling effects and for its societal and economic burden. Despite the variety of existing pharmacological and psychological treatments, most of the cases evolve with only partial remission, relapse and recurrence. Cognitive models have contributed significantly to the understanding of unipolar depression and its psychological treatment. However, success is only partial and many authors affirm the need to improve those models and also the treatment programs derived from them. One of the issues that requires further elaboration is the difficulty these patients experience in responding to treatment and in maintaining therapeutic gains across time without relapse or recurrence. Our research group has been working on the notion of cognitive conflict viewed as personal dilemmas according to personal construct theory. We use a novel method for identifying those conflicts using the repertory grid technique (RGT). Preliminary results with depressive patients show that about 90% of them have one or more of those conflicts. This fact might explain the blockage and the difficult progress of these patients, especially the more severe and/or chronic. These results justify the need for specific interventions focused on the resolution of these internal conflicts. This study aims to empirically test the hypothesis that an intervention focused on the dilemma(s) specifically detected for each patient will enhance the efficacy of cognitive behavioral therapy (CBT) for depressionPeer reviewe

A non-DNA-binding activity for the ATHB4 transcription factor in the control of vegetation proximity

Altres ajuts: Generalitat de Catalunya through the CERCA ProgramIn plants, perception of vegetation proximity by phytochrome photoreceptors activates a transcriptional network that implements a set of responses to adapt to plant competition, including elongation of stems or hypocotyls. In Arabidopsis thaliana, the homeodomain-leucine zipper (HD-Zip) transcription factor ARABIDOPSIS THALIANA HOMEOBOX 4 (ATHB4) regulates this and other responses, such as leaf polarity. To better understand the shade regulatory transcriptional network, we have carried out structure-function analyses of ATHB4 by overexpressing a series of truncated and mutated forms and analyzing three different responses: hypocotyl response to shade, transcriptional activity and leaf polarity. Our results indicated that ATHB4 has two physically separated molecular activities: that performed by HD-Zip, which is involved in binding to DNA-regulatory elements, and that performed by the ETHYLENE-RESPONSIVE ELEMENT BINDING FACTOR-associated amphiphilic repression (EAR)-containing N-terminal region, which is involved in protein-protein interaction. Whereas both activities are required to regulate leaf polarity, DNA-binding activity is not required for the regulation of the seedling responses to plant proximity, which indicates that ATHB4 works as a transcriptional cofactor in the regulation of this response. These findings suggest that transcription factors might employ alternative mechanisms of action to regulate different developmental processes