Resilience of rotifers and cladocerans communities in four reservoirs with eutrophication pollution and lead concentrations in Aguascalientes, Mexico.

Pollution in aquatic ecosystems has been increasing drastically worldwide changing their water quality. Therefore, species must be adapted to these new scenarios. In Aguascalientes City, four representative urban reservoirs contain lead in the water column and extremely high concentrations of sediments. Therefore, an analysis was conducted to evaluate the resilience of zooplankton species to lead exposure in each reservoir using dormant and organisms. Results demonstrated a decrease range from 57.5 to 22.5% in overall diapausing egg hatching rate, while survivorship rate also decreased from 98 to 54% when organisms were exposed to the water of the four reservoirs and increasing lead concentrations. When Pb exposure increased, results showed a global negative effect on both hatching rate (decreasing from 58 to 30% at 0.09 mg L-1) and survivorship levels (decreasing from 100% to 0.07% at 0.09 mg L-1). We provide Species Sensitivity Distribution for both water reservoir dilutions and lead concentration to analyze diapausing eggs hatching and survivorship of offspring in the presence of same polluted conditions or lead of the autochthonous species found in reservoirs. Furthermore, specific analysis with two populations of the cladoceran Moina macrocopa showed clear dissimilar hatching patterns that suggested a different adaptive mechanism. Niagara population shows a hatching rate of approximately 25% in the first two days of reservoir water exposure, while UAA population drastically increased hatching rate to 75% on exposure at day seven. We provide the first record of bioaccumulation in ephippia of M. macrocopa.

[Comparative analysis of bleed volume with visual technique]. / Análisis comparativo de volumen de sangrado mediante técnica visual.

Background: Blood loss estimation in a surgery is made by anesthesiologists by means of visual technique, which is not reliable because it can change depending on the judgement of every person, or his/her work experience, which is why it is considered something subjective. Therefore, the results obtained could lead to make mistakes with the exact amount of bleeding, mismanaging unnecessary hemoderived transfusions or administering unnecessary drugs. Objective: To compare the blood volume and its visual calculation between Anesthesiology residents and anesthesiologists. Material and methods: Prolective cross-sectional study which included 85 Anesthesiology residents and anesthesiologists. Diverse scenarios of bleeding were set, divided into gauze pads, compresses and jars, and each participant was asked to answer the poll. Results: There is no significant difference in the estimate of bleeding between the estimation made by residents and anesthesiologists. Conclusions: The grade of studies or experience is not significant for the exact estimation of bleeding with visual technique.

Introducción: la estimación de sangrado en las cirugías se realiza por medio de la técnica de cálculo visual, que es llevada a cabo por parte del servicio de anestesiología. Se trata de una técnica poco confiable, que puede variar dependiendo del juicio de cada persona y de su experiencia laboral, por lo que es considerada algo subjetivo. Por lo tanto, los datos arrojados hacen que se cometan errores en la cantidad exacta del sangrado y llevan a transfusiones de paquetes globulares o a la administración probablemente innecesaria de medicamentos. Objetivo: comparar la cantidad de un volumen de sangrado determinado y su cálculo visual realizada por residentes de Anestesiología y anestesiólogos. Material y métodos: estudio transversal prolectivo en el cual se incluyeron 85 médicos residentes de Anestesiología y anestesiólogos. Se dispusieron diversos escenarios con sangrado, los cuales se dividieron en gasas, compresas y frascos, y se le pidió a cada médico que contestara la encuesta correspondiente según su criterio. Resultados: de acuerdo con los resultados, no hay diferencia significativa en la estimación realizada del sangrado entre residentes y anestesiólogos para las muestras estudiadas. Conclusiones: el grado de estudios o experiencia no es significativo para la exacta estimación de sangrado con técnica visual.

Ultrastructural skin alterations of healthy subjects with anti-desmoglein 1 antibodies in endemic areas to pemphigus foliaceus: A case series.

Background: Endemic pemphigus foliaceus and endemic pemphigus vulgaris are autoimmune dermatologic disorders endemic to the Peruvian Amazon. Objective: To determine the ultrastructural skin alterations of three healthy subjects with anti DSG-1 antibodies in areas endemic to pemphigus foliaceus and pemphigus vulgaris in the Peruvian Amazon. Patients and methods: Case series carried out from data of three clinically healthy subjects positive to anti DSG-1 antibodies, from Peru. This study consists of a sub-analysis of data gathered in a previous study. Results: Ultrastructural results are presented from the skin biopsies of three clinically healthy patients positive to anti-desmoglein 1 (DSG-1) antibodies. High Resolution Optical Microscopy (HROM) showed the absence of acantholysis. Transmission Electron Microscopy (TEM) showed the widening of intercellular space between keratinocytes, the presence of vacuoles in intercellular space with granular material and cytoplasmic vacuolization, loss of desmosome structure, loss of normal distribution among tonofilaments and lateral separation among cells in the stratum basale. Conclusion: According to our results, healthy subjects that present anti-desmoglein 1 antibodies can develop ultrastructural alterations that are visible through transmission electron microscopy but not through conventional optical microscopy.

Noncanonical function of Capicua as a growth termination signal in Drosophila oogenesis.

Capicua (Cic) proteins are conserved HMG-box transcriptional repressors that control receptor tyrosine kinase (RTK) signaling responses and are implicated in human neurological syndromes and cancer. While Cic is known to exist as short (Cic-S) and long (Cic-L) isoforms with identical HMG-box and associated core regions but distinct N termini, most previous studies have focused on Cic-S, leaving the function of Cic-L unexplored. Here we show that Cic-L acts in two capacities during Drosophila oogenesis: 1) as a canonical sensor of RTK signaling in somatic follicle cells, and 2) as a regulator of postmitotic growth in germline nurse cells. In these latter cells, Cic-L behaves as a temporal signal that terminates endoreplicative growth before they dump their contents into the oocyte. We show that Cic-L is necessary and sufficient for nurse cell endoreplication arrest and induces both stabilization of CycE and down-regulation of Myc. Surprisingly, this function depends mainly on the Cic-L-specific N-terminal module, which is capable of acting independently of the Cic HMG-box-containing core. Mirroring these observations, basal metazoans possess truncated Cic-like proteins composed only of Cic-L N-terminal sequences, suggesting that this module plays unique, ancient roles unrelated to the canonical function of Cic.

Cross-species analysis of LZTR1 loss-of-function mutants demonstrates dependency to RIT1 orthologs.

RAS GTPases are highly conserved proteins involved in the regulation of mitogenic signaling. We have previously described a novel Cullin 3 RING E3 ubiquitin ligase complex formed by the substrate adaptor protein LZTR1 that binds, ubiquitinates, and promotes proteasomal degradation of the RAS GTPase RIT1. In addition, others have described that this complex is also responsible for the ubiquitination of classical RAS GTPases. Here, we have analyzed the phenotypes of Lztr1 loss-of-function mutants in both fruit flies and mice and have demonstrated a biochemical preference for their RIT1 orthologs. Moreover, we show that Lztr1 is haplosufficient in mice and that embryonic lethality of the homozygous null allele can be rescued by deletion of Rit1. Overall, our results indicate that, in model organisms, RIT1 orthologs are the preferred substrates of LZTR1.

Trombosis venosa cerebral en paciente embarazada. A propósito de un caso / Brain venous thrombosis in pregnant patient. About a case / Trombose venosa cerebral em paciente gestante. Relato de um caso

Resumen: Introducción: La trombosis venosa cerebral (TVC) es una enfermedad grave que afecta con mayor frecuencia a adultos jóvenes, con una incidencia de tres casos por cada 1'000,000 de habitantes en edad adulta. Aproximadamente se reporta 0.5% de los eventos vasculares cerebrales, siendo más frecuente en el género femenino, como factores de riesgo importante está el embarazo, parto, puerperio y uso de anticonceptivos orales (ACO). Caso clínico: Femenino de 34 años, con 8.2 semanas de gestación (SDG) normoevolutivo, que inicia siete días previos a su ingreso con cefalea occipital de intensidad moderada, que se intensifica progresivamente y empeoraba al estar acostada, agregándose náuseas y vómitos, sugestivos de cráneo hipertensivo, por lo que acude a hospital, donde ingresa con Glasgow de 15 puntos, se realiza resonancia magnética (RM), que muestra trombosis del seno venoso transverso izquierdo y hemorragia intraparenquimatosa temporoparietal izquierda, presenta deterioro del estado neurológico, requiere manejo avanzado de vía aérea y traslado a Unidad de Cuidados Intensivos (UCI). La tomografía de cráneo (TC) de ingreso a UCI con hematoma parenquimatoso temporoparietal izquierdo, edema cerebral, colapso de sistema ventricular lateral ipsilateral y desviación de la línea media, valorada por neurocirugía, quien descarta procedimiento quirúrgico y se inicia terapia osmolar con soluciones hipertónicas al 7.5%. La TC cinco días después muestra infarto cerebral en hemisferio izquierdo y sangrado intraparenquimatoso antiguo, el cual se encuentra en procesos de reabsorción; sin embargo, edema cerebral severo, que requiere de craniectomía parietofrontal izquierda. La TC de control con disminución del edema, logrando progresar y destetar de la ventilación mecánica, egresándose a piso de ginecología con Glasgow de 14 puntos y embarazo de 10.2 SDG normoevolutivo. Conclusiones: Esta patología es potencialmente reversible con un diagnóstico precoz y atención médica adecuada. La RM es el estudio de elección.

Abstract: Introduction: Cerebral venous thrombosis (CVT) is a serious disease that most frequently affects young adults, with an incidence of three cases per million adult inhabitants. It is the cause of 0.5% of cerebral vascular events. It is more frequent in women, is associated with childbirth, puerperium and the use of oral contraceptives. Clinical case: Female, 34 years old, with 8.2 weeks of gestation, which began seven days prior to admission with intense headache, nausea and vomiting, suggestive of hypertensive skull; went to hospital, where he was admitted with Glasgow 15 points, MRI was performed, which showed thrombosis of the left transverse venous sinus and left parietal temporo intraparenchymal hemorrhage, showed deterioration of neurological status, and required advanced airway management and transfer to Intensive Care Unit. CT (computed tomography) of the skull on admission to the Intensive Care Unit showed parenchymal left parietal temporo hematoma, cerebral edema, collapse of the ipsilateral lateral ventricular system and deviation of the midline. Neurosurgery assessed who ruled out surgical procedure and began osmolar therapy with hypertonic solutions at 7.5%. CT scan five days later showed cerebral infarction in the left hemisphere and old intraparenchymal bleeding in reabsorption process but severe cerebral edema, which required left parietal frontal craniectomy. The control CT scan with decreased edema, achieving weaning from mechanical ventilation, graduated to the floor of gynecology with Glasgow 14 points and pregnancy of 10.2 SDG. Conclusions: It is very important the correct diagnosis and not to confuse pregnancy alterations with neurological symptoms. MR is the study of choice.

Resumo: Introdução: A trombose venosa cerebral (TVC) é uma doença grave que acomete mais frequentemente adultos jovens, com incidência de 3 casos 1'000,000 habitantes na idade adulta. Aproximadamente são relatados 0.5% dos eventos vasculares cerebrais, sendo mais frequentes no sexo feminino, como fatores de risco importantes estão a gravidez, parto, puerpério e uso de anticoncepcionais orais (AO). Caso clínico: Paciente do sexo feminino, 34 anos, com 8.2 semanas de gestação (SDG) evoluindo normalmente, que iniciou 7 dias antes da internação com cefaléia occipital de intensidade moderada, que se intensificava progressivamente e piorava ao deitar, somando-se náuseas e vômitos, sugestivos de crânio hipertenso, busca atenção hospitalar, onde é internada com um Glasgow de 15 pontos, realiza-se ressonância magnética (RM), que mostra trombose do seio venoso transverso esquerdo e hemorragia intraparenquimatosa temporomandibular esquerda, apresenta deterioração do quadro neurológico e requer manejo avançado das vias aéreas e transferência para a Unidade de Terapia Intensiva (UTI). A tomografia de crânio (TC) na admissão na UTI mostrou hematoma parietal temporal esquerdo, edema cerebral, colapso do sistema ventricular lateral ipsilateral e desvio da linha média, avaliada por neurocirurgia que descartou procedimento cirúrgico e iniciou terapia osmolar com soluções hipertônicas a 7.5%. A TC 5 dias depois mostra infarto cerebral no hemisfério esquerdo e sangramento intraparenquimatoso antigo que está em reabsorção, porém edema cerebral grave, que requer craniectomia parietofrontal esquerda. A TC de controle mostrou diminuição do edema, progredindo ao desmame da ventilação mecânica, alta para o andar de ginecologia com escore de Glasgow de 14 e gravidez de 10.2 SDG evoluindo normalmente. Conclusões: Esta patologia é potencialmente reversível com diagnóstico precoce e cuidados médicos adequados. A ressonância magnética é o estudo de eleição.

Warming and CO2 effects under oligotrophication on temperate phytoplankton communities.

Eutrophication, global warming, and rising carbon dioxide (CO2) levels are the three most prevalent pressures impacting the biosphere. Despite their individual effects are well-known, it remains untested how oligotrophication (i.e. nutrients reduction) can alter the planktonic community responses to warming and elevated CO2 levels. Here, we performed an indoor mesocosm experiment to investigate the warming × CO2 interaction under a nutrient reduction scenario (40%) mediated by an in-lake management strategy (i.e. addition of a commercial solid-phase phosphorus sorbent -Phoslock®) on a natural freshwater plankton community. Biomass production increased under warming × CO2 relative to present-day conditions; however, a Phoslock®-mediated oligotrophication reduced such values by 30-70%. Conversely, the warming × CO2 × oligotrophication interaction stimulated the photosynthesis by 20% compared to ambient nutrient conditions, and matched with higher resource use efficiency (RUE) and nutrient demand. Surprisingly, at a group level, we found that the multi-stressors scenario increased the photosynthesis in eukaryotes by 25%, but greatly impaired in cyanobacteria (ca. -25%). This higher cyanobacterial sensitivity was coupled with a reduced light harvesting efficiency and compensation point. Since Phoslock®-induced oligotrophication unmasked a strong negative warming × CO2 effect on cyanobacteria, it becomes crucial to understand how the interplay between climate change and nutrient abatement actions may alter the, ecosystems functioning. With an integrative understanding of these processes, policy makers will design more appropriate management strategies to improve the ecological status of aquatic ecosystems without compromising their ecological attributes and functioning.

Cutaneous Manifestations of Zika in Peru.

This article aims to describe the cutaneous manifestations observed in the Zika epidemic in Peru during 2016 and 2017, as well as discuss the potential differential diagnoses. During the outbreak, the main reason for seeking medical advice was the development of a pruriginous maculopapular rash with a marked papular component, which started on the chest and later generalized to the rest of the body. Similar manifestations were noted in adults, children, and pregnant women. Other manifestations such as conjunctivitis, edema, or petechiae on the palate were rare. We suggest that in areas that are endemic for arboviral infections, in the differential diagnosis of a rash one must consider infections such as dengue, Zika, or chikungunya viruses. In nonendemic areas, the diagnosis is more difficult, as the rash may result from other viral infections not transmitted by arthropods and/or reactive or inflammatory diseases (urticaria, atopic dermatitis, systemic lupus erythematosus). We recommend that primary care health personnel are trained in the recognition of the mucocutaneous lesions caused by Zika virus infection, which could contribute to the identification of suspicious cases, particularly pregnant women.

Brachionus paranguensis sp. nov. (Rotifera, Monogononta), a member of the L group of the Brachionus plicatilis complex.

The Brachionus plicatilis complex represents the most studied group of rotifers, although the systematics of the species complex has not been completely clarified. Many studies have been conducted trying to explore the diversity within the complex, leading to the recognition of three major morphotypes: large (L), small-medium (SM), and small (SS). Currently six species have been described and classified under these types and another nine taxa have been identified but not formally described. Within the L group, three species have been officially described [B. plicatilis s.s. (L1), B. manjavacas (L2), and B. asplanchnoidis (L3)], while a formal description of L4, unofficially known as B. 'Nevada', is still lacking. In the present study, a new species, Brachionus paranguensis sp. nov., is formally described and presented as a representative of the L4 clade. The species has been named after a high altitude saline crater lake from Central Mexico, where the specimens were collected. An integrated approach using DNA taxonomy through COI and ITS1 markers, morphology, and ecology was used to confirm the identity of the new species.

[Asociación del estado hormonal con el riesgo cardiovascular evaluado por Globorisk en mujeres mexicanas].

INTRODUCTION: Cardiovascular disease is the main cause of mortality worldwide. In women, its incidence increases at the sixth decade of life, coinciding with postmenopause. Whether this effect is due to menopause-related hormonal changes is not known. OBJECTIVE: To evaluate the differences in cardiovascular risk in pre- and postmenopausal women by means of the Globorisk risk scale, the triglyceride/high-density lipoproteins cholesterol (Tg/HDL-C) ratio and metabolic syndrome (MS) criteria. METHOD: Cross-sectional study that included 408 women from 40 to 60 years of age; anthropometric measurements and biochemical determinations were performed. The participants were classified as premenopausal and postmenopausal. Cardiovascular risk was assessed using the MS criteria, the Globorisk risk calculator and the Tg/HDL-C ratio. RESULTS: Postmenopausal women showed a significant increase in waist circumference, total cholesterol and triglycerides in comparison with premenopausal women. Significant associations were found between hormonal state and Globorisk measured cardiovascular risk (OR = 2.50; 95 % CI = 1.67-3.74) and the Tg/HDL-C ratio (OR = 1.66; 95 % CI = 1.09-2.52). CONCLUSION: Cardiovascular risk factors have a higher prevalence in postmenopause. The Globorisk scale and Tg/HDL-C ratio identify cardiovascular risk in postmenopausal women.

INTRODUCCIÓN: La enfermedad cardiovascular es la principal causa de mortalidad en el mundo. En la mujer se incrementa en la sexta década de la vida, coincidiendo con la posmenopausia. Se desconoce si este efecto se debe a cambios hormonales relacionados con la menopausia. OBJETIVO: Evaluar diferencias del riesgo cardiovascular en mujeres pre y posmenopáusicas mediante la escala de riesgo Globorisk, el índice triglicéridos/c-HDL (Tg/c-HDL) y los criterios de síndrome metabólico (SM). MÉTODOS: Estudio transversal que incluyó a 408 mujeres de 40 a 60 años; se realizaron mediciones antropométricas y bioquímicas. Las participantes se clasificaron en premenopáusicas y posmenopáusicas. El riesgo cardiovascular se evaluó utilizando los criterios de SM, calculadora de riesgo Globorisk y el índice Tg/c-HDL. RESULTADOS: Las mujeres en etapa posmenopáusica presentaron incremento significativo en la circunferencia de cintura, de colesterol total y triglicéridos, en comparación con las mujeres premenopáusicas. Se encontraron asociaciones significativas del estado hormonal con el riesgo cardiovascular evaluado por Globorisk (RM = 2.50, IC 95 % = 1.67-3.74) y con el índice Tg/c-HDL (RM = 1.66, IC 95 % = 1.09-2.52). CONCLUSIÓN: Los factores de riesgo cardiovascular tienen mayor prevalencia en la posmenopausia. La escala Globorisk y el índice Tg/c-HDL identifican el riesgo cardiovascular en la mujer posmenopáusica.

The Capicua tumor suppressor: a gatekeeper of Ras signaling in development and cancer.

The transcriptional repressor Capicua (CIC) has emerged as an important rheostat of cell growth regulated by RAS/MAPK signaling. Cic was originally discovered in Drosophila, where it was shown to be inactivated by MAPK signaling downstream of the RTKs Torso and EGFR, which results in signal-dependent responses that are required for normal cell fate specification, proliferation and survival of developing and adult tissues. CIC is highly conserved in mammals, where it is also negatively regulated by MAPK signaling. Here, we review the roles of CIC during mammalian development, tissue homeostasis, tumor formation and therapy resistance. Available data indicate that CIC is involved in multiple biological processes, including lung development, liver homeostasis, autoimmunity and neurobehavioral processes. Moreover, CIC has been shown to be involved in tumor development as a tumor suppressor, both in human as well as in mouse models. Finally, several lines of evidence implicate CIC as a determinant of sensitivity to EGFR and MAPK pathway inhibitors, suggesting that CIC may play a broader role in human cancer than originally anticipated.

Capicua controls Toll/IL-1 signaling targets independently of RTK regulation.

The HMG-box protein Capicua (Cic) is a conserved transcriptional repressor that functions downstream of receptor tyrosine kinase (RTK) signaling pathways in a relatively simple switch: In the absence of signaling, Cic represses RTK-responsive genes by binding to nearly invariant sites in DNA, whereas activation of RTK signaling down-regulates Cic activity, leading to derepression of its targets. This mechanism controls gene expression in both Drosophila and mammals, but whether Cic can also function via other regulatory mechanisms remains unknown. Here, we characterize an RTK-independent role of Cic in regulating spatially restricted expression of Toll/IL-1 signaling targets in Drosophila embryogenesis. We show that Cic represses those targets by binding to suboptimal DNA sites of lower affinity than its known consensus sites. This binding depends on Dorsal/NF-κB, which translocates into the nucleus upon Toll activation and binds next to the Cic sites. As a result, Cic binds to and represses Toll targets only in regions with nuclear Dorsal. These results reveal a mode of Cic regulation unrelated to the well-established RTK/Cic depression axis and implicate cooperative binding in conjunction with low-affinity binding sites as an important mechanism of enhancer regulation. Given that Cic plays a role in many developmental and pathological processes in mammals, our results raise the possibility that some of these Cic functions are independent of RTK regulation and may depend on cofactor-assisted DNA binding.

Lesiones cutáneas como manifestación de una histoplasmosis diseminada en un hospital del Perú / Skin lesions of a disseminated histoplasmosis in Peru

The dermatological manifestations of disseminated histoplasmosis present in about 17% of the cases, is a challenge for its diagnosis. We report the case of a patient from the northern coast of Peru, who presented diffuse dermal lesions, erythema-violaceous nodules, and ulcers histopathologically compatible with the infection of the genus Histoplasma var. capsulatum

Inactivation of Capicua in adult mice causes T-cell lymphoblastic lymphoma.

CIC (also known as Capicua) is a transcriptional repressor negatively regulated by RAS/MAPK signaling. Whereas the functions of Cic have been well characterized in Drosophila, little is known about its role in mammals. CIC is inactivated in a variety of human tumors and has been implicated recently in the promotion of lung metastases. Here, we describe a mouse model in which we inactivated Cic by selectively disabling its DNA-binding activity, a mutation that causes derepression of its target genes. Germline Cic inactivation causes perinatal lethality due to lung differentiation defects. However, its systemic inactivation in adult mice induces T-cell acute lymphoblastic lymphoma (T-ALL), a tumor type known to carry CIC mutations, albeit with low incidence. Cic inactivation in mice induces T-ALL by a mechanism involving derepression of its well-known target, Etv4 Importantly, human T-ALL also relies on ETV4 expression for maintaining its oncogenic phenotype. Moreover, Cic inactivation renders T-ALL insensitive to MEK inhibitors in both mouse and human cell lines. Finally, we show that Ras-induced mouse T-ALL as well as human T-ALL carrying mutations in the RAS/MAPK pathway display a genetic signature indicative of Cic inactivation. These observations illustrate that CIC inactivation plays a key role in this human malignancy.

A new mode of DNA binding distinguishes Capicua from other HMG-box factors and explains its mutation patterns in cancer.

HMG-box proteins, including Sox/SRY (Sox) and TCF/LEF1 (TCF) family members, bind DNA via their HMG-box. This binding, however, is relatively weak and both Sox and TCF factors employ distinct mechanisms for enhancing their affinity and specificity for DNA. Here we report that Capicua (CIC), an HMG-box transcriptional repressor involved in Ras/MAPK signaling and cancer progression, employs an additional distinct mode of DNA binding that enables selective recognition of its targets. We find that, contrary to previous assumptions, the HMG-box of CIC does not bind DNA alone but instead requires a distant motif (referred to as C1) present at the C-terminus of all CIC proteins. The HMG-box and C1 domains are both necessary for binding specific TGAATGAA-like sites, do not function via dimerization, and are active in the absence of cofactors, suggesting that they form a bipartite structure for sequence-specific binding to DNA. We demonstrate that this binding mechanism operates throughout Drosophila development and in human cells, ensuring specific regulation of multiple CIC targets. It thus appears that HMG-box proteins generally depend on auxiliary DNA binding mechanisms for regulating their appropriate genomic targets, but that each sub-family has evolved unique strategies for this purpose. Finally, the key role of C1 in DNA binding also explains the fact that this domain is a hotspot for inactivating mutations in oligodendroglioma and other tumors, while being preserved in oncogenic CIC-DUX4 fusion chimeras associated to Ewing-like sarcomas.

[Skin lesions of a disseminated histoplasmosis in Peru]. / Lesiones cutáneas como manifestación de una histoplasmosis diseminada en un hospital del Perú.

The dermatological manifestations of disseminated histoplasmosis present in about 17% of the cases, is a challenge for its diagnosis. We report the case of a patient from the northern coast of Peru, who presented diffuse dermal lesions, erythema-violaceous nodules, and ulcers histopathologically compatible with the infection of the genus Histoplasma var. capsulatum.

Manejo de la enfermedad aneurismática múltiple. Experiencia en un Hospital de Especialidades.

Objective: To establish the frequency and results in patients carriers with multiple aneurysms (MA) treated by microsurgery and/or neurological endovascular therapy (NET) in the Hospital of Specialties on The National Medical Center La Raza. Method: It is an ambispective, descriptive and longitudinal study that includes patients carriers of MA treated in the National Medical Center La Raza from March the 1st of 2009 to April the 30th of 2014. Results: 62 patients carriers of 151 aneurysms were treated. According to the type of treatment, 30 patients (49%) were included in the surgical group (GQ), 25 (40%) in the endovascular group (GE) and 7 (11%) in the combinated group (GC). The number of aneurysms was distributed this way: 69 (46%) in the GQ, 61 (40%) in the GE and 21 (14%) in the GC. At GQ, it was not possible to exclude all their aneurysms on 21% of the patients, while it was feasible in only 27%. In all GE patients (40%) the exclusion of all aneurysms was achieved. The GC, meaning surgical cases that were not completed by NET, formed 11% of the cases. At GQ there was a rate of 6% of complications, meanwhile at GE it was 0.5%.

Using CRISPR-Cas9 to Study ERK Signaling in Drosophila.

Genome engineering using the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated nuclease 9 (Cas9) technology is revolutionizing biomedical research. CRISPR-Cas9 enables precise editing of genes in a wide variety of cells and organisms, thereby accelerating molecular studies via targeted mutagenesis, epitope tagging, and other custom genetic modifications. Here, we illustrate the CRISPR-Cas9 methodology by focusing on Capicua (Cic), a nuclear transcriptional repressor directly phosphorylated and inactivated by ERK/MAPK. Specifically, we use CRISPR-Cas9 for targeting an ERK docking site of Drosophila Cic, thus generating ERK-insensitive mutants of this important signaling sensor.

Minibrain and Wings apart control organ growth and tissue patterning through down-regulation of Capicua.

The transcriptional repressor Capicua (Cic) controls tissue patterning and restricts organ growth, and has been recently implicated in several cancers. Cic has emerged as a primary sensor of signaling downstream of the receptor tyrosine kinase (RTK)/extracellular signal-regulated kinase (ERK) pathway, but how Cic activity is regulated in different cellular contexts remains poorly understood. We found that the kinase Minibrain (Mnb, ortholog of mammalian DYRK1A), acting through the adaptor protein Wings apart (Wap), physically interacts with and phosphorylates the Cic protein. Mnb and Wap inhibit Cic function by limiting its transcriptional repressor activity. Down-regulation of Cic by Mnb/Wap is necessary for promoting the growth of multiple organs, including the wings, eyes, and the brain, and for proper tissue patterning in the wing. We have thus uncovered a previously unknown mechanism of down-regulation of Cic activity by Mnb and Wap, which operates independently from the ERK-mediated control of Cic. Therefore, Cic functions as an integrator of upstream signals that are essential for tissue patterning and organ growth. Finally, because DYRK1A and CIC exhibit, respectively, prooncogenic vs. tumor suppressor activities in human oligodendroglioma, our results raise the possibility that DYRK1A may also down-regulate CIC in human cells.