Oncogenic enhancers prime quiescent metastatic cells to escape NK immune surveillance by eliciting transcriptional memory.

Metastasis arises from disseminated tumour cells (DTCs) that are characterized by intrinsic phenotypic plasticity and the capability of seeding to secondary organs. DTCs can remain latent for years before giving rise to symptomatic overt metastasis. In this context, DTCs fluctuate between a quiescent and proliferative state in response to systemic and microenvironmental signals including immune-mediated surveillance. Despite its relevance, how intrinsic mechanisms sustain DTCs plasticity has not been addressed. By interrogating the epigenetic state of metastatic cells, we find that tumour progression is coupled with the activation of oncogenic enhancers that are organized in variable interconnected chromatin domains. This spatial chromatin context leads to the activation of a robust transcriptional response upon repeated exposure to retinoic acid (RA). We show that this adaptive mechanism sustains the quiescence of DTCs through the activation of the master regulator SOX9. Finally, we determine that RA-stimulated transcriptional memory increases the fitness of metastatic cells by supporting the escape of quiescent DTCs from NK-mediated immune surveillance. Overall, these findings highlight the contribution of oncogenic enhancers in establishing transcriptional memories as an adaptive mechanism to reinforce cancer dormancy and immune escape, thus amenable for therapeutic intervention.

May the force be with you: Nuclear condensates function beyond transcription control: Potential nongenetic functions of nuclear condensates in physiological and pathological conditions.

Over the past decade, research has revealed biomolecular condensates' relevance in diverse cellular functions. Through a phase separation process, they concentrate macromolecules in subcompartments shaping the cellular organization and physiology. In the nucleus, biomolecular condensates assemble relevant biomolecules that orchestrate gene expression. We here hypothesize that chromatin condensates can also modulate the nongenetic functions of the genome, including the nuclear mechanical properties. The importance of chromatin condensates is supported by the genetic evidence indicating that mutations in their members are causative of a group of rare Mendelian diseases named chromatinopathies (CPs). Despite a broad spectrum of clinical features and the perturbations of the epigenetic machinery characterizing the CPs, recent findings highlighted negligible changes in gene expression. These data argue in favor of possible noncanonical functions of chromatin condensates in regulating the genome's spatial organization and, consequently, the nuclear mechanics. In this review, we discuss how condensates may impact nuclear mechanical properties, thus affecting the cellular response to mechanical cues and, eventually, cell fate and identity. Chromatin condensates organize macromolecules in the nucleus orchestrating the transcription regulation and mutations in their members are responsible for rare diseases named chromatinopathies. We argue that chromatin condensates, in concert with the nuclear lamina, may also govern the nuclear mechanical properties affecting the cellular response to external cues.

LINE1 are spliced in non-canonical transcript variants to regulate T cell quiescence and exhaustion.

How gene expression is controlled to preserve human T cell quiescence is poorly understood. Here we show that non-canonical splicing variants containing long interspersed nuclear element 1 (LINE1) enforce naive CD4+ T cell quiescence. LINE1-containing transcripts are derived from CD4+ T cell-specific genes upregulated during T cell activation. In naive CD4+ T cells, LINE1-containing transcripts are regulated by the transcription factor IRF4 and kept at chromatin by nucleolin; these transcripts act in cis, hampering levels of histone 3 (H3) lysine 36 trimethyl (H3K36me3) and stalling gene expression. T cell activation induces LINE1-containing transcript downregulation by the splicing suppressor PTBP1 and promotes expression of the corresponding protein-coding genes by the elongating factor GTF2F1 through mTORC1. Dysfunctional T cells, exhausted in vitro or tumor-infiltrating lymphocytes (TILs), accumulate LINE1-containing transcripts at chromatin. Remarkably, depletion of LINE1-containing transcripts restores TIL effector function. Our study identifies a role for LINE1 elements in maintaining T cell quiescence and suggests that an abundance of LINE1-containing transcripts is critical for T cell effector function and exhaustion.

Wastewater-Based Epidemiology for Managing the COVID-19 Pandemic.

SARS-CoV-2 is shed by COVID-19 patients and can be detected in wastewater. Thus, testing wastewater for the virus provides a depiction of disease prevalence in a community. Virus concentration data can be utilized to monitor infection trends, identify hot spots, and inform decision makers regarding reopening efforts and directing resources. This perspective aims to shed light on the current situation relating to SARS-CoV-2 in the wastewater system and the opportunity to utilize wastewater to collect useful epidemiological data. First, the survivability of SARS-CoV-2 in different water matrices is examined through the lens of surrogate viruses. Second, the effect of wastewater treatment processes on SARS-CoV-2 is investigated. Current standards for sufficient reduction of the virus and the risk of exposure that arises at each stage in the wastewater treatment process are discussed. Third, the immense potential of wastewater-based epidemiology (WBE) for managing the ongoing COVID-19 pandemic is analyzed. Studies that have tested wastewater or sludge for SARS-CoV-2 are discussed, and results are tabulated. Lastly, the current limitations of WBE and opportunities of future research are explored. Using the wealth of knowledge that the scientific community now has about WBE, wastewater testing should be considered by regional governments and private institutions.

Yield and Water Quality Impacts of Field-Scale Integration of Willow into a Continuous Corn Rotation System.

Agricultural landscape design has gained recognition by the international environmental and development community as a strategy to address multiple goals in land, water, and ecosystem service management; however, field research is needed to quantify impacts on specific local environments. The production of bioenergy crops in specific landscape positions within a grain-crop field can serve the dual purpose of producing cellulosic biomass (nutrient recovery) while also providing regulating ecosystem services to improve water quality (nutrient reduction). The effectiveness of such a landscape design was evaluated by the strategic placement of a 0.8-ha short-rotation shrub willow ( Seemen) bioenergy buffer along marginal soils in a 6.5-ha corn ( L.) field in a 6-yr field study in central Illinois. The impact of willow integration on water quality (soil water, shallow groundwater leaching, and crop nutrient uptake) and quantity (soil moisture and transpiration) was monitored in comparison with corn in the willow's first cycle of growth. Willows significantly reduced nitrate leachate in shallow subsurface water by 88% while maintaining adequate nutrient and water usage. Results suggest that willows offer an efficient nutrient-reduction strategy and may provide additional ecosystem services and benefits, including enhanced soil health. However, low values for calculated willow biomass will need to be readdressed in the future as harvest data become available to understand contributing factors that affected productivity beyond nutrient availability.

Evaluación de enfermedades cardiovasculares subclínicas en pacientes con diabetes mellitus tipo 1 / Evaluation of subclinical cardiovascular disease in patients with diabetes mellitus type 1

Pacientes con diabetes mellitus tipo 1 (DM1) poseen mayor riesgo de enfermedad cardiovascular (ECV). Existen estudios en los que se observó que en pacientes con DM1 la ECV aparece en edades más tempranas comparado con la población general. La asociación de anomalías vasculares y aterosclerosis es muy frecuente en DM1, siendo la detección del engrosamiento de la íntima media carotidea un método útil para realizar el diagnóstico de enfermedad aterosclerótica subclínica

Descripción de una serie de casos de pacientes con diabetes secundaria a acromegalia e hipercortisolismo endógeno: características clínicas y de laboratorio / Description of a series of patients with diabetes secondary to acromegaly and endogenous hypercortisolism: clinical and laboratory features

La regulación de la glucemia requiere el accionar de distintas hormonas, además de insulina. A través de mecanismos de insulinopenia o insulinorresistencia (IR), como en la acromegalia (Acro) o el síndrome de Cushing, las endocrinopatías pueden precipitar estados de hiperglucemia. La presencia de diabetes mellitus (DM) aumenta la morbimortalidad de estos pacientes, por lo cual es fundamental tanto el tratamiento como el seguimiento de la enfermedad subyacente

Modifications of the cell wall of yeasts grown on hexadecane and under starvation conditions.

Electron-microscopic examinations have demonstrated local modifications in the cell wall of the yeast Candida maltosa grown on hexadecane. In our earlier studies, these modified sites, observed in other yeasts grown on oil hydrocarbons, were conventionally called 'canals'. The biochemical and cytochemical studies of C. maltosa have revealed a correlation between the formation of 'canals' and decrease in the amount of cell wall polysaccharides, glucan and mannan. The ultrathin sections and surface replicas have shown that the 'canals' are destroyed by pronase, thus indicating that a significant proportion of their content is represented by proteins. This finding was compatible with our earlier data on the localization of oxidative enzymes in 'canals' and possible participation of the 'canals' in the primary oxidation of hydrocarbons. A completely unexpected and intriguing phenomenon has been the appearance of 'canals' in the yeast C. maltosa under starvation conditions. Unlike the yeasts grown on hexadecane, mannan almost disappears in starving cells, while the quantity of glucan first decreases and then is restored to its initial level. The role of 'canals' in starving cells is as yet unclear; it is assumed that they acquire exoenzymes involved in the utilization of products of cell lysis in the starving population. In the future, 'canals' of starving cells will be studied in connection with their possible participation in apoptosis.

Population Genetics of Franciscana Dolphins (Pontoporia blainvillei): Introducing a New Population from the Southern Edge of Their Distribution.

Due to anthropogenic factors, the franciscana dolphin, Pontoporia blainvillei, is the most threatened small cetacean on the Atlantic coast of South America. Four Franciscana Management Areas have been proposed: Espiritu Santo to Rio de Janeiro (FMA I), São Paulo to Santa Catarina (FMA II), Rio Grande do Sul to Uruguay (FMA III), and Argentina (FMA IV). Further genetic studies distinguished additional populations within these FMAs. We analyzed the population structure, phylogeography, and demographic history in the southernmost portion of the species range. From the analysis of mitochondrial DNA control region sequences, 5 novel haplotypes were found, totalizing 60 haplotypes for the entire distribution range. The haplotype network did not show an apparent phylogeographical signal for the southern FMAs. Two populations were identified: Monte Hermoso (MH) and Necochea (NC)+Claromecó (CL)+Río Negro (RN). The low levels of genetic variability, the relative constant size over time, and the low levels of gene flow may indicate that MH has been colonized by a few maternal lineages and became isolated from geographically close populations. The apparent increase in NC+CL+RN size would be consistent with the higher genetic variability found, since genetic diversity is generally higher in older and expanding populations. Additionally, RN may have experienced a recent split from CL and NC; current high levels of gene flow may be occurring between the latter ones. FMA IV would comprise four franciscana dolphin populations: Samborombón West+Samborombón South, Cabo San Antonio+Buenos Aires East, NC+CL+Buenos Aires Southwest+RN and MH. Results achieved in this study need to be taken into account in order to ensure the long-term survival of the species.

Morphological analysis of the flippers in the Franciscana dolphin, Pontoporia blainvillei, applying X-ray technique.

Pectoral flippers of cetaceans function to provide stability and maneuverability during locomotion. Directional asymmetry (DA) is a common feature among odontocete cetaceans, as well as sexual dimorphism (SD). For the first time DA, allometry, physical maturity, and SD of the flipper skeleton--by X-ray technique--of Pontoporia blainvillei were analyzed. The number of carpals, metacarpals, phalanges, and morphometric characters from the humerus, radius, ulna, and digit two were studied in franciscana dolphins from Buenos Aires, Argentina. The number of visible epiphyses and their degree of fusion at the proximal and distal ends of the humerus, radius, and ulna were also analyzed. The flipper skeleton was symmetrical, showing a negative allometric trend, with similar growth patterns in both sexes with the exception of the width of the radius (P ≤ 0.01). SD was found on the number of phalanges of digit two (P ≤ 0.01), ulna and digit two lengths. Females showed a higher relative ulna length and shorter relative digit two length, and the opposite occurred in males (P ≤ 0.01). Epiphyseal fusion pattern proved to be a tool to determine dolphin's age; franciscana dolphins with a mature flipper were, at least, four years old. This study indicates that the flippers of franciscana dolphins are symmetrical; both sexes show a negative allometric trend; SD is observed in radius, ulna, and digit two; and flipper skeleton allows determine the age class of the dolphins.

Peril in the market-classification and dosage of species used as anti-diabetics in Lima, Peru.

BACKGROUND: Peru is what Peruvian anthropologist Lupe Camino calls the "health axis" of the old Central Andean culture area stretching from Ecuador to Bolivia. In particular in the North of the country the traditional use of medicinal dates back as far as the first millennium B.C. Both healers, and the wider population, often buy their medicinal plants in local markets, but there is very little comparative information available about which plants are sold under which vernacular name at any given time, for which indication, and which dosage information and information about side effects is given by vendors. For this study we used two traditionally used species groups "Hercampuri" Gentianella spec. (Gentianaceae) and "Pasuchaca" Geranium spec. (Geraniaceae.), found in the Mercado Aviación in Lima, as small, clearly circumscribed plant group frequently used to treat symptoms of diabetes as a test case to study the taxonomy, indications, dosage, indicated side effects, and additional species used as admixtures and hypothesized that: 1. A wide variety of different species is sold under the same common name, and often several common names exist for one species. 2. There is no consistency in the dosage, or a relationship between dosage and species marketed under one name. 3. However, there is consistency in the knowledge about usage and side effects. METHODS: Surveys focusing on medicinal plants sold and their properties were conducted at the Mercado Aviaciónin Lima in December 2012. Vouchers of all specimens were deposited at the National Herbarium of Peru. RESULTS AND CONCLUSIONS: Our surveys in Mercado Aviación in Lima yielded four species of Gentianella, two of Geranium, and three additional species from three genera used as common additives that were sold as anti-diabetic. These results indicate that even in case of only a few plant species, used for a very clearly circumscribed application, patients run a considerable risk when purchasing their remedies in the market. The possible side effects in this case are the more serious because diabetes has to be treated long term, and as such the patients are ingesting possible toxic remedies over a long period of time. Much more control, and a much more stringent identification of the material sold in public markets, and entering the global supply chain via internet sales, would be needed.

Reproductive aspects of male franciscana dolphins (Pontoporia blainvillei) off Argentina.

As the first study to investigate reproductive aspects of male franciscana dolphin -Pontoporia blainvillei - in Argentine waters, the aim of this paper was to assess sexual maturity by using histological and morphometric methods. P. blainvillei was labeled as "Vulnerable" by the IUCN in 2008. The specimens analyzed were either incidentally caught in artisanal fishing nets (n=47) or found stranded on the beach (n=3). Testis weight and testicular index of maturity were reliable indicators of sexual maturity, being their values: MTW: 1.14 ± 0.60-4.49 ± 1.94; IM: 0.03 ± 0.01-0.09 ± 0.03, for immature and mature specimens' respectively. It was found that the hierarchical cluster analysis (HCA) might be appropriate for establishing sexual maturity stage, based on both the body morphometric measurements and age. The values for age, standard length and total weight at attainment sexual maturity were 2.92-3.54 years, 126.19-126.27 cm and 23.47-23.75 kg. Considering the extremely low relative testis weight, the reversed sexual length dimorphism, the absence of secondary sexual characteristics, and the lack of scars from intrasexual combats in males, the hypothesis that sperm competition does not occur in the species, and male combats for accessing female reproductive may be rare for P. blainvillei is reinforced. All these features fit the species within a serial monogamous mating system.

Peritonitis in type 2 diabetes mellitus due to Ochrobactrum anthropi complicating automated peritoneal dialysis.

Epidemiology data predict that by the year 2025, diabetes will affect about 380 million people worldwide with a significant increase in patients with chronic renal disease progressing to hemodialysis. Diabetes-related peripheral vascular disease is a major risk factor for vascular access failure in patients on extracorporeal hemodialysis. Although peritoneal dialysis is a valid option for diabetics, peritonitis is still a main complication for these patients. We report the case of a 71-year-old type 2 diabetes patient treated by subcutaneous insulin, undergoing automated peritoneal dialysis (APD) who developed peritonitis and bloodstream infection by Ochrobactrum anthropi (O. anthropi). The patient was initially shifted to continuous ambulatory peritoneal dialysis (CAPD) and treated with intraperitoneal cefotaxime and gentamicin. According to antibiogram, cefotaxime was discontinued but lasting gentamicin. Within 48 h from admission, clear peritoneal effluent was observed with reduction in white blood cells count from 580/mm³ 77.9% neutrophils to less than 10/mm³. Prompt regression of infection without catheter removal and no relapse after over 7-month follow-up allowed supposing that O. anthropi did not colonized peritoneal catheter. O. anthropi is an emerging cause of nosocomial infection in immunocompromised patients. Cases of such infection in patients undergoing CAPD and hemodialysis have been already described. However, this is the first reported case of O. anthropi in a patient undergoing APD.

Uma paixão estranha / A strange passion

Neste artigo, trata-se da temática da sexualidade feminina em psicanálise, localizando sua teorização na obra de Freud, circunscrevendo-se a noção de Supereu feminino e a leitura que Lacan realiza dessa noção com base no neologismo surmoitié. Assim, por meio da surmoitié lacaniana, são realizadas elaborações sobre o encontro amoroso e a singularidade dos sujeitos diante do que Lacan chamou de "sexuação".(AU)

Mass recovery methods for trichloroethylene in plant tissue.

Monitoring expenses form a significant fraction of the costs associated with remediation of contaminated soil and groundwater sites. A novel monitoring method that could result in significant cost savings is the use of plants as monitoring devices; previous work indicates that plant tissue samples, especially trunk (core) and branch samples, can be used to delineate soil and groundwater plumes at phytoremediation sites. An important factor in reducing the uncertainty associated with this sampling method is development of a technique to analyze, both consistently and accurately, the chemicals stored in plant tissue samples. The present research presents a simple, robust, and inexpensive technique to recover most of the contaminant in plant branch tissue, irrespective of the age or species of the plant. Tricholoroethylene (TCE) was the chemical analyzed. A number of headspace and solvent extraction techniques in the literature were evaluated, including headspace extraction at different incubation times and temperatures and solvent extraction using hexane or hot methanol. Extraction using hot methanol was relatively fast, simple, and reliable; this method recovered more than 89% of the TCE present in branches of five different tree species.

Gênero e sexuação / Gender and sexuation

Abordam-se os chamados Gender Studies e suas análises sobre o conceito de gênero, assim como as problematizações inseridas nesse campo de estudos, advindas da obra da pensadora feminista Judith Butler. Ao localizar a leitura que Judith Butler faz da obra do psicanalista francês Jacques Lacan, promove-se um debate sobre a diferença sexual e suas conseqüências, confrontando os problemas dos estudos de gênero e a psicanálise(AU)

This article examines the so-called Gender Studies and their anafyses about the concept of gender, as well as the problematizations in this field of study, arising from the work of the jeminist thinker Judith Butler. After locating the reading that Judith Butler makes of the work of French psychoanalyst Jacques Lacan, thepaper discusses sexual difference and its consequences, confronting the problems of gender studies and psychoanalysis(AU)

A randomised controlled trial of moxibustion for breech presentation.

OBJECTIVES: To evaluate the efficacy of moxibustion for the correction of fetal breech presentation in a non-Chinese population. DESIGN: Single-blind randomised controlled trial (RCT). SETTING: Six obstetric departments in Italy. SAMPLE: Healthy non-Chinese nulliparous pregnant women at 32-33 weeks + 3 days of gestational age with the fetus in breech presentation. METHODS: Random assignment to treatment or observation. Treatment consisted of moxibustion (stimulation with heat from a stick of Artemisia vulgaris) at the BL 67 acupuncture point (Zhiyin) for one or two weeks. Two weeks after recruitment, each participant was subjected to an ultrasonic examination of the fetal presentation. MAIN OUTCOME MEASURE: Number of participants with cephalic presentation in the 35th week. RESULTS: The study was interrupted when 123 participants had been recruited (46% of the planned sample). Intermediate data monitoring revealed a high number of treatment interruptions. At this point no difference was found in cephalic presentation in the 35th week (treatment group: 22/65, 34%; control group: 21/58, 36%; RR 0.95; 99% CI 0.59-1.5). CONCLUSIONS: The results underline the methodological problems evaluating of a traditional treatment transferred from a different cultural context. They do not support either the effectiveness or the ineffectiveness of moxibustion in correcting fetal breech presentation.

Frequency of mutation to rifampin resistance in Streptococcus pneumoniae clinical strains: hexA and hexB polymorphisms do not account for hypermutation.

The frequency of mutation to rifampin resistance of 200 clinical Streptococcus pneumoniae isolates was examined. Two peaks were observed in the distribution, with mode frequencies of 2.5 x 10(-7) (20% of isolates) and 2.5 x 10(-8). The hexA and hexB gene entire sequences were analyzed in 13 isolates. Sequences from both hypermutable and "normomutable" strains were conserved relative to that of the R6 S. pneumoniae control strain. The phenotypic Hex system proficiency, in terms of transforming efficiency, was also maintained irrespective of the variations in mutation frequency values.