Search

We report the discovery of a rare isolated group of five dwarf galaxies located at z = 0.0086 ( D = 36 Mpc). All member galaxies are star forming, blue, and gas rich, with g − r indices ranging from 0.2 to 0.6 mag, and two of them show signs of ongoing mutual interaction. The most massive member of the group has a stellar mass that is half of the Small Magellanic Cloud stellar mass, and the median stellar mass of the group members is 7.87 × 10 ^7 M _☉ . The derived total dynamical mass of the group is M _dyn = 6.02 × 10 ^10 M _☉ , whereas its total baryonic mass (stellar + H i ) is 2.6 × 10 ^9 M _☉ , which gives us the dynamical to baryonic mass ratio of 23. Interestingly, all galaxies found in the group are aligned along a straight line in the plane of the sky. The observed spatial extent of the member galaxies is 154 kpc, and their relative line-of-sight velocity span is within 75 km s ^−1 . Using the spatially resolved optical spectra provided by the Dark Energy Spectroscopic Instrument early data release, we find that three group members share a common rotational direction. With these unique properties of the group and its member galaxies, we discuss the possible importance of such a system in the formation and evolution of dwarf galaxy groups and in testing the theory of large-scale structure formation.

One intriguing approach for studying the dynamical evolution of galaxy clusters is to compare the spatial distributions among various components such as dark matter, member galaxies, gas, and intracluster light (ICL). Utilizing the recently introduced weighted overlap coefficient (WOC), we analyze the spatial distributions of components within 174 galaxy clusters ( M _tot > 5 × 10 ^13 M _⊙ , z = 0.625) at varying dynamical states in the cosmological hydrodynamical simulation Horizon Run 5. We observe that the distributions of gas and the combination of ICL with the brightest cluster galaxy (BCG) closely resembles the dark matter distribution, particularly in more relaxed clusters, characterized by the half-mass epoch. The similarity in spatial distribution between dark matter and BCG+ICL mimics the changes in the dynamical state of clusters during a major merger. Notably, at redshifts >1, BCG+ICL traced dark matter more accurately than the gas. Additionally, we examined the one-dimensional radial profiles of each component, which show that the BCG+ICL is a sensitive component revealing the dynamical state of clusters. We propose a new method that can approximately recover the dark matter profile by scaling the BCG+ICL radial profile. Furthermore, we find a recipe for tracing dark matter in unrelaxed clusters by including the most massive satellite galaxies together with the BCG+ICL distribution. Combining the BCG+ICL and the gas distribution enhances the dark matter tracing ability. Our results imply that the BCG+ICL distribution is an effective tracer for the dark matter distribution, and the similarity of the spatial distribution may be a useful probe of the dynamical state of a cluster.

We present a new simulated galaxy cluster catalog based on the IllustrisTNG simulation. We use the Mulguisin (MGS) algorithm to identify galaxy overdensities. Our cluster identification differs from the previous friends-of-friends (FoF) cluster identification in two aspects: (1) we identify cluster halos based on the galaxy subhalos instead of unobservable dark matter particles, and (2) we use the MGS algorithm, which separates galaxy overdensities hosted by massive galaxies. Our approach provides a cluster catalog constructed in a way similar to the construction of observed cluster catalogs using spectroscopic surveys. The MGS cluster catalog lists 303 halos with M _200 > 10 ^14 M _⊙ , including ∼10% more than the FoF catalog. The MGS catalog includes more systems because we separate some independent massive MGS cluster halos that are bundled into a single FoF halo. These independent MGS halos are apparently distinguishable in the galaxy spatial distribution and the phase-space diagram. Because we construct a refined cluster catalog that identifies local galaxy overdensities, we evaluate the effect of MGS clusters on the evolution of galaxies better than when using the FoF cluster catalog. The MGS halo identification also enables effective identifications of merging clusters by selecting systems with neighboring galaxy overdensities. We thus highlight the fact that the MGS cluster catalog is a useful tool for studying clusters in cosmological simulations and for comparing with observed cluster samples.

Abstract Laparoscopic rectosigmoid resection for endometriosis is usually performed with the section of the inferior mesenteric artery (IMA) distal to the left colic artery (low-tie ligation). This study was to determine outcomes in IMA-sparing surgery in endometriosis cases. A single-center retrospective study based on the analysis of clinical notes of women who underwent laparoscopic rectosigmoid segmental resection and IMA-sparing surgery for deep infiltrating endometriosis with bowel involvement between March the 1st, 2018 and February the 29th, 2020 in a referral hospital. During the study period, 1497 patients had major gynecological surgery in our referral center, of whom 253 (17%) for endometriosis. Of the 100 patients (39%) who had bowel endometriosis, 56 underwent laparoscopic nerve-sparing rectosigmoid segmental resection and IMA-sparing surgery was performed in 53 cases (95%). Short-term complications occurred in 4 cases (7%) without any case of anastomotic leak. Preservation of the IMA in colorectal surgery for endometriosis is feasible, safe and enables a tension-free anastomosis without an increase of postoperative complication rates.

The Piper species are a recognized botanical source of a broad structural diversity of lignans and its derivatives. For the first time, Piper tectoniifolium Kunth is presented as a promising natural source of the bioactive (−)-grandisin. Phytochemical analyses of extracts from its leaves, branches and inflorescences showed the presence of the target compound in large amounts, with leaf extracts found to contain up to 52.78% in its composition. A new HPLC-DAD-UV method was developed and validated to be selective for the identification of (−)-grandisin being sensitive, linear, precise, exact, robust and with a recovery above 90%. The absolute configuration of the molecule was determined by X-ray diffraction. Despite the identification of several enantiomers in plant extracts, the major isolated substance was characterized to be the (−)-grandisin enantiomer. In vascular reactivity tests, it was shown that the grandisin purified from botanical extracts presented an endothelium-dependent vasorelaxant effect with an IC50 of 9.8 ± 1.22 μM and around 80% relaxation at 30 μM. These results suggest that P. tectoniifolium has the potential to serve as a renewable source of grandisin on a large scale and the potential to serve as template for development of new drugs for vascular diseases with emphasis on disorders related to endothelial disfunction.

Purpose The treatment of urinary tract infections (UTI) with antibiotics is commonly used, but recurrence and antibiotic resistance have been growing and concerning clinicians. We studied whether the rapid onset of a protective biofilm may be responsible for the lack of effectiveness of antibiotics against selected bacteria. Materials and Methods Two established uropathogenic Escherichia coli strains, UTI89 and CFT073, and two Pseudomonas aeruginosa strains, PA01 and Boston-41501, were studied to establish a reliable biofilm formation process. Bacterial growth (BG) was determined by optical density at 600 nm (OD 600) using a spectrophotometer, while biofilm formation (BF) using crystal violet staining was measured at OD 550. Next, these bacterial strains were treated with clinically relevant antibiotics, ciprofloxacin HCl (200 ng/mL and 2 μg/mL), nitrofurantoin (20 μg/mL and 40 μg/mL) and ampicillin (50 μg/mL) at time points of 0 (T0) or after 6 hours of culture (T6). All measurements, including controls (bacteria -1% DMSO), were done in triplicates and repeated three times for consistency. Results The tested antibiotics effectively inhibited both BG and BF when administered at T0 for UPEC strains, but not when the antibiotic administration started 6 hours later. For Pseudomonas strains, only Ciprofloxacin was able to significantly inhibit bacterial growth at T0 but only at the higher concentration of 2 μg/mL for T6. Conclusion When established UPEC and Pseudomonas bacteria were allowed to culture for 6 hours before initialization of treatment, the therapeutic effect of selected antibiotics was greatly suppressed when compared to immediate treatment, probably as a result of the protective nature of the biofilm.

El reciente desarrollo en tecnologías de almacenamiento de energía eléctrica e iluminación de eficiencia energética hace viable, tanto desde el punto de vista técnico como económico, la utilización de dispositivos de iluminación energéticamente autónomos. Este tipo de dispositivos no sólo son de gran utilidad en aquellas regiones en donde no existe la red eléctrica sino también en aquellos espacios en donde se desea evitar construir instalaciones eléctricas por razones estéticas, ambientales o económicas. Si bien es cierto existen dispositivos comerciales de iluminación energéticamente autónomos, su costo, vida útil y desempeño no los hacen atractivos o competitivos con respecto a los sistemas de iluminación convencionales. Análisis basados en ingeniería inversa realizados por el Laboratorio de Sistemas Electrónicos para la Sostenibilidad (SESLab), de la Escuela de Ingeniería en Electrónica del Tecnológico de Costa Rica, se ha encontrado que el subsistema electrónico de muchas luminarias comerciales se puede modificar para ampliar significativamente su desempeño y vida útil. En este artículo se presenta el proceso de diseño de un dispositivo de iluminación LED energéticamente autónomo, en el cual se toman en cuenta las características eléctricas del sistema de iluminación, el sistema de almacenamiento y las características ópticas de la luminaria. De esta forma, se logra identificar formas en las cuales se puede extender la vida útil del sistema y mejorar su desempeño.

Recurrent urinary tract infections (RUTI) are prevalent and pose significant clinical challenges. Although the term RUTI has long been vaguely defined, a consensus definition has emerged in recent years. The exact etiology behind RUTI remains under debate, with valid arguments for both ascending reinfections as well as persistent infection inside the bladder. These persistent infections exist in the form of quiescent intracellular reservoirs in the mouse model and may represent a novel concept to explain UTI recurrence in humans. Manageable risk factors such as behavioral patterns alongside nonmanageable risk factors including genetic susceptibility are growing fields of investigation. Acute UTI have been studied through two model bacterial strains: Escherichia coli UTI89 and CFT073. However, the clinical relevance to RUTI of these two strains has not been firmly established. Current treatment strategies for RUTI are limited and remain dominated by antibiotic usage despite variable efficacy. The majority of studies in humans have focused on younger groups of women with little information available about the postmenopausal population despite a heightened risk of RUTI in this age group.

ABSTRACT Enteric pathogens such as enterohemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium, which is largely used as a surrogate EHEC model for murine infections, are exposed to several host neurotransmitters in the gut. An important chemical exchange within the gut involves the neurotransmitters epinephrine and/or norepinephrine, extensively reported to increase virulence gene expression in EHEC, acting through two bacterial adrenergic sensors: QseC and QseE. However, EHEC is unable to establish itself and cause its hallmark lesions, attaching and effacing (AE) lesions, on murine enterocytes. To address the role of these neurotransmitters during enteric infection, we employed C. rodentium. Both EHEC and C. rodentium harbor the locus of enterocyte effacement (LEE) that is necessary for AE lesion formation. Here we show that expression of the LEE, as well as that of other virulence genes in C. rodentium, is also activated by epinephrine and/or norepinephrine. Both QseC and QseE are required for LEE gene activation in C. rodentium, and the qseC and qseE mutants are attenuated for murine infection. C. rodentium has a decreased ability to colonize dopamine β-hydroxylase knockout (Dbh−/−) mice, which do not produce epinephrine and norepinephrine. Both adrenergic sensors are required for C. rodentium to sense these neurotransmitters and activate the LEE genes during infection. These data indicate that epinephrine and norepinephrine are sensed by bacterial adrenergic receptors during enteric infection to promote activation of their virulence repertoire. This is the first report of the role of these neurotransmitters during mammalian gastrointestinal (GI) infection by a noninvasive pathogen. IMPORTANCE The epinephrine and norepinephrine neurotransmitters play important roles in gut physiology and motility. Of note, epinephrine and norepinephrine play a central role in stress responses in mammals, and stress has profound effects on GI function. Bacterial enteric pathogens exploit these neurotransmitters as signals to coordinate the regulation of their virulence genes. The bacterial QseC and QseE adrenergic sensors are at the center of this regulatory cascade. C. rodentium is a noninvasive murine pathogen with a colonization mechanism similar to that of EHEC, enabling the investigation of host signals in mice. The presence of these neurotransmitters in the gut is necessary for C. rodentium to fully activate its virulence program, in a QseC/QseE-dependent manner, to successfully colonize its murine host. Our study data provide the first example of epinephrine and norepinephrine signaling within the gut to stimulate infection by a bacterial pathogen in a natural animal infection.

OBJETIVO: Identificar os fatores de risco associados à hepatopatia da fibrose cística. MÉTODOS: Dos 106 pacientes acompanhados regularmente no ano de 1999, 10 preencheram os critérios clínicos, bioquímicos e/ou ultra-sonográficos para hepatopatia (9,4%). Foram obtidos dos pacientes, no protocolo do serviço à admissão, fatores relacionados aos dados demográficos, genótipo, idade e manifestações ao diagnóstico da fibrose cística, estado nutricional e dados laboratoriais. As variáveis associadas à hepatopatia foram inicialmente identificadas pelo método de Kaplan-Meier. Os fatores significativos na análise univariada foram incluídos na análise multivariada, utilizando o modelo de regressão de Cox. RESULTADOS: Os fatores associados à hepatopatia na análise univariada foram: sexo masculino, idade ao diagnóstico da fibrose cística, insuficiência pancreática, escore z de peso à admissão, escore de Shwachman e bioquímica à admissão. Após o ajustamento pelo modelo de Cox, duas variáveis demonstraram estar independentemente associadas ao desenvolvimento de hepatopatia: escore de Shwachman (p = 0,0057) e idade ao diagnóstico da fibrose cística (p = 0,014). CONCLUSÃO:O risco de hepatopatia é maior entre os pacientes que apresentam diagnóstico mais precoce e entre aqueles com pior estado clínico avaliado pelo escore de Shwachman, evidenciando que a hepatopatia parece fazer parte de uma forma mais grave da doença. Esses pacientes merecem mais atenção quanto ao screening para hepatopatia e instituição mais precoce do ácido ursodesoxicólico na ocorrência de alterações.OBJECTIVE: To identify the risk factors for cystic fibrosis related liver disease. METHODS: Ten patients out of a total of 106 patients regularly followed-up during 1999 met the clinical, biochemical and/or ultrasound criteria for liver disease (9.4%). Using information from the admissions records at the service, we collected data on demography, genotype, age and manifestations at diagnosis of cystic fibrosis, nutritional status and laboratory findings. Variables associated with liver disease were initially identified by the Kaplan-Meier method. Those factors that were significant in the univariate analysis were included in the multivariate analysis by means of a Cox regression model. RESULTS: Under univariate analysis the following factors were associated with liver disease: male sex, age at diagnosis of cystic fibrosis, pancreatic insufficiency, z score for weight at admission, Shwachman score and biochemistry at admission. After adjustment by Cox model, two variables were independently associated with liver disease: Shwachman score (p = 0.0057) and age at diagnosis of cystic fibrosis (p = 0.014). CONCLUSION: The risk of developing liver disease is higher among patients diagnosed at an early age and those with worse clinical status as assessed by the Shwachman score, indicating that liver involvement might be part of a more severe form of the condition. These patients merit greater attention in terms of screening for liver disease and should be given treatment with ursodeoxycholic acid earlier in the event of abnormal findings.

OBJETIVOS: Descrever as alterações hepáticas observadas ao exame ultra-sonográfico de fibrocísticos do Ambulatório de Fibrose Cística do Hospital das Clínicas da UFMG, comparar os achados ultra-sonográficos com critérios clínicos e bioquímicos e validar o escore de Williams para o diagnóstico de hepatopatia associada à fibrose cística. MÉTODOS: Setenta fibrocísticos foram acompanhados prospectivamente e submetidos a exame clínico, bioquímico e ultra-sonográfico. Os achados ultra-sonográficos foram comparados com os resultados do exame clínico e bioquímico. Para a validação do escore ultra-sonográfico de Williams, os critérios clínicos e bioquímicos foram utilizados como padrão-ouro. Foram calculados sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo do escore de Williams. Para os cálculos, os pacientes foram divididos em dois grupos: normal ao exame ultra-sonográfico (escore = 3) ou alterado (escore > 3). RESULTADOS: Dez pacientes preencheram os critérios clínicos e/ou bioquímicos para hepatopatia (14,3%). Todos os pacientes hepatopatas segundo os critérios clínicos e/ou bioquímicos apresentavam alguma alteração ao exame ultra-sonográfico. As alterações do parênquima hepático, borda hepática e fibrose periportal foram encontradas mais freqüentemente entre os hepatopatas, com diferença estatisticamente significativa. O escore de Williams apresentou alta especificidade (91,7%; IC 80,9-96,9), mas baixa sensibilidade (s = 50%; IC 20,1-79,9) para o diagnóstico da hepatopatia. CONCLUSÕES: O escore de Williams não constituiu um bom exame de triagem quando comparado ao exame clínico e bioquímico. Uma vez que ainda não há nenhum teste que, utilizado isoladamente, apresente sensibilidade adequada, é recomendável a utilização conjunta dos exames clínico, bioquímico e ultra-sonográfico no diagnóstico da hepatopatia associada à fibrose cística, sempre em avaliações seqüenciais.OBJECTIVES: To describe the hepatic abnormalities revealed by ultrasound examination of cystic fibrosis (CF) patients followed at the CF Outpatient Clinic at the Federal University of Minas Gerais; to compare ultrasound data with clinical and biochemical parameters; to validate the Williams ultrasound score for the diagnosis of liver disease in CF. METHODS: Seventy cystic fibrosis patients were followed prospectively and underwent clinical, biochemical and ultrasound examinations. The ultrasound findings were compared to the results of the clinical and biochemical examinations. Clinical and biochemical criteria were used as the gold standard for the validation of the Williams ultrasound score. We calculated the sensitivity, specificity, and positive and negative predictive values for the Williams score. The patients were divided into two groups: normal (score = 3) or abnormal (score > 3) ultrasound examination. RESULTS: Ten patients met the clinical and/or biochemical criteria for liver disease (14.3%). All of them presented some abnormality on ultrasound examination of the liver. Abnormalities of the hepatic parenchyma, edge and periportal fibrosis were statistically more frequent in these patients. The Williams ultrasound score showed high specificity (91.7%; CI 80,9-96,9), but low sensitivity (50%; CI 20,1-79,9) for the diagnosis of liver disease. CONCLUSIONS: The Williams ultrasound score was not a good screening tool when compared to the clinical and biochemical examinations. Since there are currently no adequate tests that can be used to diagnose liver disease, we recommend a sequential evaluation combining clinical, biochemical and ultrasound examinations for the diagnosis of liver disease in CF.

Objetivo: o presente estudo foi realizado com o objetivo de comparar a eficácia de uma fórmula infantil pré-espessada (Nan AR) com fórmula convencional, de espessamento caseiro, com amido de milho, na redução de episódios de regurgitações e vômitos de lactentes com refluxo gastroesofágico (RGE). Métodos: foram estudadas 100 crianças, menores de 12 meses de idade, que não faziam uso de leite materno exclusivo. Por sorteio, 48 receberam fórmula convencional, e 52 receberam fórmula infantil pré-espessada (Nan AR), com comparação dos resultados clínicos após 3 meses. Resultados: não houve diferença estatisticamente significativa na melhora ou cura dos sintomas entre os dois grupos, tendo sido ambos os tratamentos eficazes. Conclusões: o espessamento dietético, seja com fórmulas infantis especiais, seja com medidas caseiras, tem eficácia semelhante no tratamento do refluxo gastroesofágico do lactente.Objective: the purpose of this study was to compare the effectiveness of a pre-thickened infant formula (Nan AR) with a conventional homemade formula in the reduction of regurgitation and vomiting in infants with gastroesophageal reflux. Methods: a hundred children, under 12 months, not exclusively breast feeding, were select for the study. Forty-eight were treated with conventional formula with starch and 52 with pre-thickened infant formula. Results: there was no statistically significant difference between the two groups in the improvement or cure of symptoms, each treatment having been effective. Conclusions: thickened formulas, pre-thickened or home-thickened, have shown the same efficacy in the management of gastroesophageal reflux in children.

Objetivo: determinar a prevalência de alterações clínicas e bioquímicas sugestivas de hepatopatia na população de fibrocísticos atendidos no ambulatório de fibrose cística do Hospital das Clínicas da Universidade Federal de Minas Gerais, descrever o grupo de hepatopatas e compará-lo com o de não-hepatopatas, em relação a diversas variáveis clínicas e laboratoriais. Métodos: estudo descritivo, resultante da avaliação prospectiva e, parcialmente, retrospectiva de 106 fibrocísticos. A doença hepática foi definida pela presença de hepatomegalia (>2,5cm da reborda costal direita) firme, e/ou esplenomegalia, e/ou aumento persistente e significativo (>1,5 vezes o limite superior da normalidade, por pelo menos seis meses) de pelo menos duas das enzimas hepáticas (AST, ALT, GGT e FA). Resultados: hepatomegalia foi verificada em sete pacientes (6,6%), e esplenomegalia em cinco (4,7%). A atividade da AST mostrou-se alterada em 18,9% dos pacientes, ALT em 9,4%, GGT em 11,3% e FA em 46,2%. Elevações significativas e persistentes das enzimas hepáticas ocorreram em nove pacientes (8,5%). Dez fibrocísticos (9,4%) preencheram os critérios de hepatopatia. Foram excluídas outras causas de doença hepática. A média de idade dos pacientes com alterações sugestivas de hepatopatia foi de 7,7 anos. Houve predominância absoluta do sexo masculino. Todos os pacientes permanecem assintomáticos. Conclusões: a prevalência da hepatopatia associada à fibrose cística foi de 9,4%. A maior freqüência de elevações transitórias e pouco significativas das enzimas hepáticas é bem documentada na literatura. A sua significância como preditor de hepatopatia ainda não foi determinada. No entanto, esses achados ressaltam a necessidade de avaliações seqüenciais para a definição dos casos de hepatopatia na fibrose cística.Objective: to determine the prevalence of clinical and biochemical abnormalities suggestive of liver disease in the population of patients with cystic fibrosis (CF) seen at the CF Outpatient Clinic of the Federal University of Minas Gerais; to describe the group of patients with liver disease and to compare it with the group without liver disease, regarding several clinical and laboratory variables. Methods: descriptive study, resultant of a prospective, and partially retrospective assessment of 106 patients with CF. Liver disease was defined by the presence of firm hepatomegaly (>2.5 cm from the right costal margin), and/or splenomegaly, and/or persistent and significant increase (>1.5 times the upper limit of normality, over six months) of at least two serum liver enzymes (alanine aminotransferase - ALT, aspartate aminotransferase - AST, alkaline phosphatase - ALP, -glutamyl transpeptidase - GGT). Results: hepatomegaly was verified in seven patients (6.6%) and splenomegaly in five (4.7%). AST activity was altered in 18.9% of the patients, ALT in 9.4%, GGT in 11.3%, and ALP in 46.2%. Significant and persistent increase in liver enzyme activities was verified in nine patients (8.5%). Ten patients with CF (9.4%) fulfill the criteria for liver disease. Other causes of liver disease were excluded. The mean age of the patients with liver disease was 7.7 years. There was absolute predominance of the male sex. All the patients are without symptoms. Conclusions: The prevalence of liver disease associated with CF was 9.4%. The frequent and transitory insignificant elevations of liver enzymes are well documented in the literature. Its significance as a predictor of liver disease has not been determined yet. However, the results of this study enhance the need for longitudinal assessment in order to define cases of liver disease in CF.

ABSTRACT Invasive pathogens interface with the host and its resident microbiota through interkingdom signaling. The bacterial receptor QseC, which is a membrane-bound histidine sensor kinase, responds to the host stress hormones epinephrine and norepinephrine and the bacterial signal AI-3, integrating interkingdom signaling at the biochemical level. Importantly, the QseC signaling cascade is exploited by many bacterial pathogens to promote virulence. Here, we translated this basic science information into development of a potent small molecule inhibitor of QseC, LED209. Extensive structure activity relationship (SAR) studies revealed that LED209 is a potent prodrug that is highly selective for QseC. Its warhead allosterically modifies lysines in QseC, impairing its function and preventing the activation of the virulence program of several Gram-negative pathogens both in vitro and during murine infection. LED209 does not interfere with pathogen growth, possibly leading to a milder evolutionary pressure toward drug resistance. LED209 has desirable pharmacokinetics and does not present toxicity in vitro and in rodents. This is a unique antivirulence approach, with a proven broad-spectrum activity against multiple Gram-negative pathogens that cause mammalian infections. IMPORTANCE There is an imminent need for development of novel treatments for infectious diseases, given that one of the biggest challenges to medicine in the foreseeable future is the emergence of microbial antibiotic resistance. Here, we devised a broad-spectrum antivirulence approach targeting a conserved histidine kinase, QseC, in several Gram-negative pathogens that promotes their virulence expression. The LED209 QseC inhibitor has a unique mode of action by acting as a prodrug scaffold to deliver a warhead that allosterically modifies QseC, impeding virulence in several Gram-negative pathogens.

ABSTRACT Gastrointestinal (GI) bacteria sense diverse environmental signals as cues for differential gene regulation and niche adaptation. Pathogens such as enterohemorrhagic Escherichia coli (EHEC), which causes bloody diarrhea, use these signals for the temporal and energy-efficient regulation of their virulence factors. One of the main virulence strategies employed by EHEC is the formation of attaching and effacing (AE) lesions on enterocytes. Most of the genes necessary for the formation of these lesions are grouped within a pathogenicity island, the locus of enterocyte effacement (LEE), whose expression requires the LEE-encoded regulator Ler. Here we show that growth of EHEC in glycolytic environments inhibits the expression of ler and consequently all other LEE genes. Conversely, growth within a gluconeogenic environment activates expression of these genes. This sugar-dependent regulation is achieved through two transcription factors: KdpE and Cra. Both Cra and KdpE directly bind to the ler promoter, and Cra’s affinity to this promoter is catabolite dependent. Moreover, we show that the Cra and KdpE proteins interact in vitro and that KdpE’s ability to bind DNA is enhanced by the presence of Cra. Cra is important for AE lesion formation, and KdpE contributes to this Cra-dependent regulation. The deletion of cra and kdpE resulted in the ablation of AE lesions. One of the many challenges that bacteria face within the GI tract is to successfully compete for carbon sources. Linking carbon metabolism to the precise coordination of virulence expression is a key step in the adaptation of pathogens to the GI environment. IMPORTANCE An appropriate and prompt response to environmental cues is crucial for bacterial survival. Cra and KdpE are two proteins found in both nonpathogenic and pathogenic bacteria that regulate genes in response to differences in metabolite concentration. In this work, we show that, in the deadly pathogen enterohemorrhagic Escherichia coli (EHEC) O157:H7, which causes bloody diarrhea, these two proteins influence important virulence traits. We also propose that their control of one or more of these virulence traits is due to the direct interaction of the Cra and KdpE proteins with each other, as well as with their DNA targets. This work shows how EHEC coopts established mechanisms for sensing the metabolites and stress cues in the environment, to induce virulence factors in a temporal and energy-efficient manner, culminating in disease. Understanding how pathogens commandeer nonpathogenic systems can help us develop measures to control them.

Melanoma is a highly aggressive and therapy resistant tumor for which the identification of specific markers and therapeutic targets is highly desirable. We describe here the development and use of a bioinformatic pipeline tool, made publicly available under the name of EST2TSE, for the in silico detection of candidate genes with tissue-specific expression. Using this tool we mined the human EST (Expressed Sequence Tag) database for sequences derived exclusively from melanoma. We found 29 UniGene clusters of multiple ESTs with the potential to predict novel genes with melanoma-specific expression. Using a diverse panel of human tissues and cell lines, we validated the expression of a subset of three previously uncharacterized genes (clusters Hs.295012, Hs.518391, and Hs.559350) to be highly restricted to melanoma/melanocytes and named them RMEL1, 2 and 3, respectively. Expression analysis in nevi, primary melanomas, and metastatic melanomas revealed RMEL1 as a novel melanocytic lineage-specific gene up-regulated during melanoma development. RMEL2 expression was restricted to melanoma tissues and glioblastoma. RMEL3 showed strong up-regulation in nevi and was lost in metastatic tumors. Interestingly, we found correlations of RMEL2 and RMEL3 expression with improved patient outcome, suggesting tumor and/or metastasis suppressor functions for these genes. The three genes are composed of multiple exons and map to 2q12.2, 1q25.3, and 5q11.2, respectively. They are well conserved throughout primates, but not other genomes, and were predicted as having no coding potential, although primate-conserved and human-specific short ORFs could be found. Hairpin RNA secondary structures were also predicted. Concluding, this work offers new melanoma-specific genes for future validation as prognostic markers or as targets for the development of therapeutic strategies to treat melanoma.

Shortly after its discovery, General Relativity (GR) was applied to predict the behavior of our Universe on the largest scales, and later became the foundation of modern cosmology. Its validity has been verified on a range of scales and environments from the Solar system to merging black holes. However, experimental confirmations of GR on cosmological scales have so far lacked the accuracy one would hope for-its applications on those scales being largely based on extrapolation and its validity there sometimes questioned in the shadow of the discovery of the unexpected cosmic acceleration. Future astronomical instruments surveying the distribution and evolution of galaxies over substantial portions of the observable Universe, such as the Dark Energy Spectroscopic Instrument (DESI), will be able to measure the fingerprints of gravity and their statistical power will allow strong constraints on alternatives to GR. In this paper, based on a set of N-body simulations and mock galaxy catalogs, we study the predictions of a number of traditional and novel summary statistics beyond linear redshift distortions in two well-studied modified gravity models-chameleon f(R) gravity and a braneworld model-and the potential of testing these deviations from GR using DESI. These summary statistics employ a wide array of statistical properties of the galaxy and the underlying dark matter field, including two-point and higher-order statistics, environmental dependence, redshift space distortions and weak lensing. We find that they hold promising power for testing GR to unprecedented precision. The major future challenge is to make realistic, simulation-based mock galaxy catalogs for both GR and alternative models to fully exploit the statistic power of the DESI survey (by matching the volumes and galaxy number densities of the mocks to those in the real survey) and to better understand the impact of key systematic effects. Using these, we identify future simulation and analysis needs for gravity tests using DESI.