Mutational signatures and increased retrotransposon insertions in xeroderma pigmentosum variant skin tumors.

Xeroderma pigmentosum variant (XP-V) is an autosomal recessive disease with an increased risk of developing cutaneous neoplasms in sunlight-exposed regions. These cells are deficient in the translesion synthesis (TLS) DNA polymerase eta, responsible for bypassing different types of DNA lesions. From the exome sequencing of 11 skin tumors of a genetic XP-V patients' cluster, classical mutational signatures related to sunlight exposure, such as C>T transitions targeted to pyrimidine dimers, were identified. However, basal cell carcinomas also showed distinct C>A mutation spectra reflecting a mutational signature possibly related to sunlight-induced oxidative stress. Moreover, four samples carry different mutational signatures, with C>A mutations associated with tobacco chewing or smoking usage. Thus, XP-V patients should be warned of the risk of these habits. Surprisingly, higher levels of retrotransposon somatic insertions were also detected when the tumors were compared with non-XP skin tumors, revealing other possible causes for XP-V tumors and novel functions for the TLS polymerase eta in suppressing retrotransposition. Finally, the expected high mutation burden found in most of these tumors renders these XP patients good candidates for checkpoint blockade immunotherapy.

Ballroom dance and body size perception.

Ballroom dancing consists in the performance of rhythmic movements guided by music, which provide sensorimotor integration and stimulate feelings. The body schema is the unconscious sensorimotor representation that allows the individual to perceive his anatomical body in space. Comprising tactile, proprioceptive, kinesthetic, and environmental information, it is directly related to movement. The aim of this study was to investigate the influence of non-competitive practice of ballroom dancing on body perception. The projection point test was applied to 30 volunteers before and after a period of 3 mo.; 15 controls attended lectures on body perception and 15 participants took dance lessons. It was observed that ballroom dancing brought perceptual benefits for those who practiced it.

Ancient mitogenomes from the Southern Pampas of Argentina reflect local differentiation and limited extra-regional linkages after rapid initial colonization.

OBJECTIVE: This study aims to contribute to the recovery of Indigenous evolutionary history in the Southern Pampas region of Argentina through an analysis of ancient complete mitochondrial genomes. MATERIALS AND METHODS: We generated DNA data for nine complete mitogenomes from the Southern Pampas, dated to between 2531 and 723 cal BP. In combination with previously published ancient mitogenomes from the region and from throughout South America, we documented instances of extra-regional lineage-sharing, and estimated coalescent ages for local lineages using a Bayesian method with tip calibrations in a phylogenetic analysis. RESULTS: We identified a novel mitochondrial haplogroup, B2b16, and two recently defined haplogroups, A2ay and B2ak1, as well as three local haplotypes within founder haplogroups C1b and C1d. We detected lineage-sharing with ancient and contemporary individuals from Central Argentina, but not with ancient or contemporary samples from North Patagonian or Littoral regions of Argentina, despite archeological evidence of cultural interactions with the latter regions. The estimated coalescent age of these shared lineages is ~10,000 years BP. DISCUSSION: The history of the human populations in the Southern Pampas is temporally deep, exhibiting long-term continuity of mitogenome lineages. Additionally, the identification of highly localized mtDNA clades accords with a model of relatively rapid initial colonization of South America by Indigenous communities, followed by more local patterns of limited gene flow and genetic drift in various South American regions, including the Pampas.

An isoniazid analogue promotes Mycobacterium tuberculosis-nanoparticle interactions and enhances bacterial killing by macrophages.

Nanoenabled drug delivery systems against tuberculosis (TB) are thought to control pathogen replication by targeting antibiotics to infected tissues and phagocytes. However, whether nanoparticle (NP)-based carriers directly interact with Mycobacterium tuberculosis and how such drug delivery systems induce intracellular bacterial killing by macrophages is not defined. In the present study, we demonstrated that a highly hydrophobic citral-derived isoniazid analogue, termed JVA, significantly increases nanoencapsulation and inhibits M. tuberculosis growth by enhancing intracellular drug bioavailability. Importantly, confocal and atomic force microscopy analyses revealed that JVA-NPs associate with both intracellular M. tuberculosis and cell-free bacteria, indicating that NPs directly interact with the bacterium. Taken together, these data reveal a nanotechnology-based strategy that promotes antibiotic targeting into replicating extra- and intracellular mycobacteria, which could actively enhance chemotherapy during active TB.

Oligomeric α-Synuclein induces skin degeneration in reconstructed human epidermis.

Aged and photoaged skin exhibit fine wrinkles that are signs of epidermal inflammation and degeneration. It has been shown that healthy elderly skin expresses amyloidogenic proteins, including α-Synuclein, which are known to oligomerize and trigger inflammation and neurodegeneration. However, little is known about their putative role in skin physiology and sensitivity. To unravel this possible role, we investigated the impact of oligomeric α-Synuclein (Oα-Syn) in 2D and 3D keratinocyte human models. Exogenous Oα-Syn caused degeneration of reconstructed human epidermis (RHE) by diminishing proliferation and thickness of the stratum basale. Oα-Syn also increased NF-kB nuclear translocation in keratinocytes and triggered inflammation in the RHE, by increasing expression of interleukin-1ß and tumor necrosis factor-alpha, and the release of tumor necrosis factor-alpha in a time-dependent manner. Dexamethasone and an IL-1ß inhibitor partially diminished RHE degeneration caused by Oα-Syn. These findings suggest that Oα-Syn induces epidermal inflammation and decreases keratinocyte proliferation, and therefore might contribute to epidermal degeneration observed in human skin aging.

Ancient genomes in South Patagonia reveal population movements associated with technological shifts and geography.

Archaeological research documents major technological shifts among people who have lived in the southern tip of South America (South Patagonia) during the last thirteen millennia, including the development of marine-based economies and changes in tools and raw materials. It has been proposed that movements of people spreading culture and technology propelled some of these shifts, but these hypotheses have not been tested with ancient DNA. Here we report genome-wide data from 20 ancient individuals, and co-analyze it with previously reported data. We reveal that immigration does not explain the appearance of marine adaptations in South Patagonia. We describe partial genetic continuity since ~6600 BP and two later gene flows correlated with technological changes: one between 4700-2000 BP that affected primarily marine-based groups, and a later one impacting all <2000 BP groups. From ~2200-1200 BP, mixture among neighbors resulted in a cline correlated to geographic ordering along the coast.

Modern guanaco (Lama guanicoe, Camelidae) bezoars: An approach towards identification in the fossil record.

OBJECTIVE: Provide a frame of reference for the recognition and interpretation of bezoars recovered from archeological and paleontological sites. MATERIALS: 49 bezoars from extant guanaco (Lama guanicoe) were analyzed and compared with five objects previously identified as bezoars, recovered from Holocene archeological sites of the Argentine Pampas. METHODS: Size, shape, weight, external and internal features, and mineralogical composition were evaluated in both modern and archeological bezoars using nondestructive and destructive methods. RESULTS: Modern and archeological bezoars are formed by calcium phosphate and display great morphological variability linked to ante-mortem processes, taphonomic alterations, and anthropic activity. CONCLUSIONS: Morphometry, along with external and internal features and mineral composition, are useful tools for the identification and interpretation of bezoars in the fossil record. SIGNIFICANCE: This study offers new information on the etiology, mechanisms of formation, and means of interpreting the presence of bezoars, a common pathology in South American camelids, in the fossil record. LIMITATIONS: The features of fossil bezoars do not provide accurate identification of the animal that produced them. SUGGESTIONS FOR FURTHER RESEARCH: Further analyses on modern bezoars belonging to other species of mammals are needed in order to enhance the interpretation of bezoars in the fossil record.

Using wearable devices for assessing the impacts of hair exposome in Brazil.

Previous studies have shown that physicochemical properties of hair can be impacted by internal and environmental exposures ranging from chemical stressors to weather. Besides the effects on hair, these exposures, termed "exposome", can act on specific organs including skin, as a synergistic damaging effect of UV exposure and pollution on human surfaces. The combination of several environmental factors such as sun exposure, temperature, relative humidity, air pollution and photo-oxidation caused by ground level ozone impacts hair properties such as melanin oxidation, protein content, surface quality and structural components. Therefore, exposome studies can reveal new hypotheses on how epithelia and hair could be affected by daily life environment and routine. The aim of this study was to evaluate the impact of several environmental aggressors on human surfaces, using portable and wearable devices for monitoring exposome. To better understand the underlying mechanisms associated with environmental factors, two subjects wore multiple sensors to capture the meteorological conditions biking through urban areas in summer and winter. Temperature, humidity, UV radiation and ozone concentration were recorded and hair swatches of different types, including natural, bleached/colored, colored and gray, were exposed on the helmets. Silicon wristbands were used on skin to identify main chemical aggressors. After exposure, hair swatches were analyzed by surface microscopy analysis, oxidation markers and more than 1,500 chemicals were evaluated on the bracelets. Correlated with GPS and monitoring data, all these results provide insights on how environmental stressors affect the quality of different hair types and body surface according to exposure routine. Our results suggest extreme climate conditions associated with hair damage and photo-oxidative marker linked to the environmental aggressors. Polycyclic aromatic hydrocarbons (PAH) indicate possible causes of hair damages. This is the first meteorotropic study of its kind, combining environmental aggressors related to hair damage, opening new research hypothesis further studies on exposome.

Generation of iPSC-Derived Human Peripheral Sensory Neurons Releasing Substance P Elicited by TRPV1 Agonists.

Neural crest stem cells (NCPCs) have been shown to differentiate into various cell types and tissues during embryonic development, including sensory neurons. The few studies addressing the generation of NCPCs and peripheral sensory neurons (PSNs) from human induced pluripotent stem cells (hiPSCs), generated sensory cells without displaying robust activity. Here, we describe an efficient strategy for hiPSCs differentiation into NCPCs and functional PSNs using chemically defined media and factors to achieve efficient differentiation, confirmed by the expression of specific markers. After 10 days hiPSCs differentiated into NCPCs, cells were then maintained in neural induction medium containing defined growth factors for PSNs differentiation, followed by 10 days in neonatal human epidermal keratinocytes- (HEKn-) conditioned medium (CM). We observed a further increase in PSN markers expression and neurites length after CM treatment. The resulting neurons elicited action potentials after current injection and released substance P (SP) in response to nociceptive agents such as anandamide and resiniferatoxin. Anandamide induced substance P release via activation of TRPV1 and not CB1. Transcriptomic analysis of the PSNs revealed the main dorsal root ganglia neuronal markers and a transcriptional profile compatible with C fiber-low threshold mechanoreceptors. TRPV1 was detected by immunofluorescence and RNA-Seq in multiple experiments. In conclusion, the developed strategy generated PSNs useful for drug screening that could be applied to patient-derived hiPSCs, consisting in a powerful tool to model human diseases in vitro.

Dysbiotic Bacterial and Fungal Communities Not Restricted to Clinically Affected Skin Sites in Dandruff.

Dandruff is a prevalent chronic inflammatory skin condition of the scalp that has been associated with Malassezia yeasts. However, the microbial role has not been elucidated yet, and the etiology of the disorder remains poorly understood. Using high-throughput 16S rDNA and ITS1 sequencing, we characterized cutaneous bacterial and fungal microbiotas from healthy and dandruff subjects, comparing scalp and forehead (lesional and non-lesional skin sites). Bacterial and fungal communities from dandruff analyzed at genus level differed in comparison with healthy ones, presenting higher diversity and greater intragroup variation. The microbial shift was observed also in non-lesional sites from dandruff subjects, suggesting that dandruff is related to a systemic process that is not restricted to the site exhibiting clinical symptoms. In contrast, Malassezia microbiota analyzed at species level did not differ according to health status. A 2-step OTU assignment using combined databases substantially increased fungal assigned sequences, and revealed the presence of highly prevalent uncharacterized Malassezia organisms (>37% of the reads). Although clinical symptoms of dandruff manifest locally, microbial dysbiosis beyond clinically affected skin sites suggests that subjects undergo systemic alterations, which could be considered for redefining therapeutic approaches.

Triple nanoemulsion potentiates the effects of topical treatments with microencapsulated retinol and modulates biological processes related to skin aging.

BACKGROUND: The sum of environmental and genetic factors affects the appearance and function of the skin as it ages. The identification of molecular changes that take place during skin aging provides biomarkers and possible targets for therapeutic intervention. Retinoic acid in different formulations has emerged as an alternative to prevent and repair age-related skin damage. OBJECTIVES: To understand the effects of different retinoid formulations on the expression of genes associated with biological processes that undergo changes during skin aging. METHODS: Ex-vivo skin samples were treated topically with different retinoid formulations. The modulation of biological processes associated with skin aging was measured by Reverse Transcription quantitative PCR (RT-qPCR). RESULTS: A formulation containing microencapsulated retinol and a blend of active ingredients prepared as a triple nanoemulsion provided the best results for the modulation of biological, process-related genes that are usually affected during skin aging. CONCLUSION: This association proved to be therapeutically more effective than tretinoin or microencapsulated retinol used singly.

Triple nanoemulsion potentiates the effects of topical treatments with microencapsulated retinol and modulates biological processes related to skin aging / Tripla nanoemulsao potencializa os efeitos do tratamento topico com retinol microencapsulado e modula processos biologicos relacionados ao envelhecimento da pele

BACKGROUND: The sum of environmental and genetic factors affects the appearance and function of the skin as it ages. The identification of molecular changes that take place during skin aging provides biomarkers and possible targets for therapeutic intervention. Retinoic acid in different formulations has emerged as an alternative to prevent and repair age-related skin damage. OBJECTIVES: To understand the effects of different retinoid formulations on the expression of genes associated with biological processes that undergo changes during skin aging. METHODS: Ex-vivo skin samples were treated topically with different retinoid formulations. The modulation of biological processes associated with skin aging was measured by Reverse Transcription quantitative PCR (RT-qPCR). RESULTS: A formulation containing microencapsulated retinol and a blend of active ingredients prepared as a triple nanoemulsion provided the best results for the modulation of biological, process-related genes that are usually affected during skin aging. CONCLUSION: This association proved to be therapeutically more effective than tretinoin or microencapsulated retinol used singly. .

FUNDAMENTOS: A soma de fatores genéticos e ambientais afeta a aparência e a funcionalidade da pele ao longo do envelhecimento. O conhecimento a respeito das mudanças moleculares durante o envelhecimento fornece biomarcadores e possíveis alvos para intervenções terapêuticas. O ácido retinoico em diferentes formulações surgiu como uma alternativa para prevenir e reparar os danos da pele associados ao envelhecimento. OBJETIVOS: Avaliar comparativamente os efeitos de diferentes formulações contendo retinoides na expressão de genes associados a processos biológicos que são alterados com o envelhecimento da pele. MÉTODOS: Peles ex vivo foram topicamente tratadas com diferentes retinoides, micro e nanoencapsulados. A modulação dos processos biológicos associados ao envelhecimento da pele foi medida por PCR quantitativa, precedida de transcrição reversa (RT-qPCR). RESULTADOS: A formulação contendo uma mistura de princípios ativos incorporados em uma tripla nanoemulsão e retinol microencapsulado apresentou os melhores resultados de modulação de genes relacionados a processos biológicos que são normalmente alterados durante o envelhecimento da pele. CONCLUSÃO: Essa associação demonstrou uma maior eficácia terapêutica quando comparada ao uso isolado de tretinoína ou retinol microencapsulado. .

A influência da dança de salão na percepção corporal / The ballroomdance influence in body perception

A dança de salão é uma forma de expressão dos sentimentos através dos movimentos. Os casais devem perceber as suas possibilidades de ação motora e o espaço disponível para interagir com o outro organizando seu corpo em um padrão espacial. Esses fatores combinados com o resgate das emoções despertadas pela dança tornam a prática potencializadora de alterações positivas na relação mente-corpo modificando a percepção corporal, tanto no seu aspecto proprioceptivo (esquema corporal), como emocional (imagem corporal). O objetivo desse estudo foi discutir a dança de salão e sua contribuição na percepção corporal dos seus praticantes. Para isso foi realizada de uma pesquisa bibliográfica de caráter descritivo e abordagem qualitativa. Sendo assim, concluímos que além da técnica na dança é necessário, também, saber utilizar os recursos como uma ferramenta e não como uma “prisão”. A beleza da dança de salão é resultado do equilíbrio entre a técnica e emoções do dançarino.

Ballroomdance is a feeling expression through the movements. Couples should realize their potential motor action and space available to interact appropriately one with the others leading to a correct organization of their bodies in space. Dancing with a partner, exploring perceptual diversity together, bringing the emotions aroused in a musical rhythm, makes this practice responsible for positive changes in the relationship between mind and body, modifying the body perception, both in proprioceptive (body schema), as in emotional (body image) aspects. The aim of this study was to discuss the dance and its contribution to the body perception of its practitioners. The study included a descriptive review of the literature with a qualitative approach consideration. However, more than learning the dance technique is necessary to know how to use these resources as a tool and not as a "prison." The beauty of ballroomdance achieves a balance between technique and the emotions.

Ensinar para compreensão: fundamentação teórica para a Educação Física escolar / Teaching for understanding: based theory for school physical education

Um determinado conhecimento é considerado compreendido por alguém quando pode ser transformado e adaptado a situações diferenciadas. Essa premissa é transmitida pela teoria “Teaching for Understanding” (TFU). Buscando avaliar como são desenvolvidas as aulas de Educação Física nas instituições que utilizam essa teoria na fundamentação do seu ensino, analisamos, primeiramente, três escolas em Buenos Aires. A partir desse diagnóstico, fomos analisar essa situação no Brasil. Em São Paulo, encontramos uma escola e optamos em estudá-la através de um estudo de caso. Essa pesquisa ainda se propôs apontar diretrizes para o desenvolvimento de aulas de Educação Física fundamentadas no EpC. Entre as orientações didáticas apontadas, foi sugerido que, para que um ensino objetive a compreensão doaprendiz, deve reconhecer os diferentes potenciais dos alunos, baseando-se nas experiências de vida, incentivando assim, uma aprendizagem crítica, reflexiva e autônoma, e que, através de desafios, os alunos sejam estimulados a solucionarem problemas motores.

A determined knowledge is considered understood by someone when it can be changed and adapted to different situations. This premise is transmitted by the theory “Teaching for Understanding”(TFU). Interested in evaluating how are developed the physical education’s classes that use this theory on the teaching ´s basement, doing an analyze, firstly, three schools in Buenos Aires. Through this diagnostic, we seached to analyze schools in Brazil. In São Paulo city, we found a school and opted to study it through a study case. This search proposed to point directions for the physical education based on EpC’sdevelopment. Between the pedagogical orientations pointed were suggested that for an objective teaching and a compressive learning, the different students potential must be recognized, based on the life experiences, to motivate with this form, one critical learning, reflexive and autonomous, and that through challenges the students are stimulated to through resolve motor problems.

Lifelong exposure to dietary fish oil alters macrophage responses in Walker 256 tumor-bearing rats.

Supplementation of the diet with fish oil (FO) decreases growth of the Walker 256 tumor and decreases the cachexia associated with tumor-bearing. The mechanisms by which FO inhibits tumor growth and cachexia are unknown. Macrophages are very important in host defence against tumors since they produce several anti-tumor agents which in turn have been shown to be modified by dietary FO, but rarely in the setting of tumor bearing and never in relation to lifelong exposure. In this study, we compared the effects of supplementation of the diet of pregnant and lactating rats and subsequent supplementation of the offspring with coconut fat or FO on macrophage activities involved in anti-tumor defence. FO supplementation was able to induce an increase in phagocytosis, in O2-, H2O2, nitric oxide, and TNF-alpha production by macrophages and in lysosomal volume in non-tumor-bearing rats. However, phagocytosis, production of O2- and H2O2 and lysosomal volume were not affected by the FO diet when rats were bearing tumors, although nitric oxide production was higher in these animals. It appears that tumor bearing activates the innate immune system and that dietary FO has little effect on innate immunity in the presence of Walker 256 tumors. Thus, it is still unclear how FO decreases the growth of Walker 256 tumors and the associated cachexia.