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Aneuploidy, the unbalanced segregation of chromosomes during cell division, is recurrent in many tumors and the cause of birth defects and genetic diseases. Centromeric chromatin represents the chromosome attachment site to the mitotic spindle, marked by specialized nucleosomes containing a specific histone variant, CEN-H3/Cse4, in yeast. Mislocalization of Cse4 outside the centromere is deleterious and may cause aberrant chromosome behavior and mitotic loss. For this reason, ubiquitylation by the E3-ubiquitin ligase Psh1 and subsequent proteolysis tightly regulates its restricted localization. Among multiproteic machineries, the SAGA complex is not merely engaged in acetylation but also directly involved in deubiquitylation. In this study, we investigated the role of SAGA-DUB’s Ubp8-driven deubiquitylation of the centromeric histone variant Cse4 in budding yeast. We found that Ubp8 works in concert with the E3-ubiquitin ligase Psh1, and that its loss causes defective deubiquitylation and the accumulation of a short ubiquitin oligomer on Cse4. We also show that lack of Ubp8 and defective deubiquitylation increase mitotic instability, cause faster Cse4 proteolysis and induce mislocalization of the centromeric histone outside the centromere. Our data provide evidence for a fundamental role of DUB-Ubp8 in deubiquitylation and the stability of the centromeric histone in budding yeast.

Blue light, a key abiotic signal, regulates a wide variety of physiological processes in many organisms. One of these phenomena is the circadian rhythm presents in organisms sensitive to the phase-setting effects of blue light and under control of the daily alternation of light and dark. Circadian clocks consist of autoregulatory alternating negative and positive feedback loops intimately connected with the cellular metabolism and biochemical processes. Neurospora crassa provides an excellent model for studying the molecular mechanisms involved in these phenomena. The White Collar Complex (WCC), a blue-light receptor and transcription factor of the circadian oscillator, and Frequency (FRQ), the circadian clock pacemaker, are at the core of the Neurospora circadian system. The eukaryotic circadian clock relies on transcriptional/translational feedback loops: some proteins rhythmically repress their own synthesis by inhibiting the activity of their transcriptional factors, generating self-sustained oscillations over a period of about 24 h. One of the basic mechanisms that perpetuate self-sustained oscillations is post translation modification (PTM). The acronym PTM generically indicates the addition of acetyl, methyl, sumoyl, or phosphoric groups to various types of proteins. The protein can be regulatory or enzymatic or a component of the chromatin. PTMs influence protein stability, interaction, localization, activity, and chromatin packaging. Chromatin modification and PTMs have been implicated in regulating circadian clock function in Neurospora. Research into the epigenetic control of transcription factors such as WCC has yielded new insights into the temporal modulation of light-dependent gene transcription. Here we report on epigenetic and protein PTMs in the regulation of the Neurospora crassa circadian clock. We also present a model that illustrates the molecular mechanisms at the basis of the blue light control of the circadian clock.

La paniculitis mesentérica es una rara entidad de caracte - rísticas benignas que afecta al tejido adiposo del mesenterio intestinal y que puede progresar de distintas formas, desde la resolución espontánea hasta la fibrosis. La etiología aún es incierta, siendo causas probables el trauma, infecciones o cirugía. Presentamos el caso de un paciente de sexo masculino de 64 años de edad que comenzó de forma súbita con dolor abdominal y leucocitosis. Se realizó diagnóstico de paniculi - tis mesentérica mediante una tomografía computada y el pa - ciente evolucionó con resolución espontánea a los dos meses.

El páncreas heterotópico es la presencia de tejido pancreático fuera de la localización anatómica del páncreas. Es una entidad rara que puede presentarse en cualquier parte del tracto gastrointestinal, siendo el estómago y el intestino delgado los sitios más comunes. Usualmente es asintomático, pero puede hacerse clínicamente evidente cuando se complica con cambios patológicos como inflamación, sangrado, obstrucción y transformación maligna. Presentamos un paciente de 49 años de edad de sexo masculino que consultó por presentar dolor epigástrico recurrente. La endoscopía digestiva alta reveló un tumor submucoso en el antro. El estudio histopatológico posterior a la cirugía demostró tejido pancreático heterotópico. El páncreas ectópico debe considerarse en el diagnóstico diferencial de los tumores gástricos submucosos.

La neumatosis intestinal es una entidad muy infrecuente asociada a varias patologías, como el infarto intestino-mesentérico, la enterocolitis necrotizante y la enfermedad pulmonar obstructiva crónica. Se caracteriza por la presencia de gas en la subserosa o submucosa a través del tracto gastrointestinal. Presentamos el caso de un paciente de sexo masculino de 63 años de edad que consultó por dolor en abdomen superior, vómitos y fiebre elevada (39º) nueve días después de una gastrectomía total por cáncer. La radiografía directa de abdomen constató distensión intestinal y la tomografía computada (TC) demostró distensión intestinal, edema mesentérico, neumatosis intestinal a través del intestino delgado y neumatosis portal, preferentemente en el lóbulo hepático izquierdo. Se realizó una laparotomía de urgencia que reveló únicamente distensión intestinal por adherencias, sin evidenciar necrosis intestinal. El paciente evolucionó desfavorablemente, falleciendo posteriormente. Reportamos un nuevo caso y revisamos la literatura de la neumatosis intestinal asociada con neumatosis portal.The pneumatosis intestinalis is a very infrequent condition associated with a number of diseases, such as mesenteric infarction, necrotizing enterocolitis, and obstructive pulmonary disease characterized by the presence of subserosal or submucosal gas cyst throughout the gastrointestinal tract. A 63- year- old man complained of upper abdominal pain, vomiting and high fever (39º C) on the nine day after total gastrectomy for cancer. Abdominal X-ray revealed intestinal distension. The abdominal Computed Tomography (CT) showed intestinal dilatation, mesenteric oedema, diffuse pneumatosis throughout the small intestine and gas in the portal venous system predominantly in the left hepatic lobe. It was performed emergency activity that revealed intestinal distension secondary to adhesion without intestinal necrosis. The patient had a downhill course and died thereafter. We report a new case and reviewed the literature of pneumatosis intestinalis associated with hepatic portal venous gas.

We conducted a clinical and electromyographical study in patients with Chagas' disease in the indeterminate or chronic stages of the illness. Altogether 841 patients were examined. Only 511 were admitted within the protocol; the remainder patients were rejected because they showed other causes able to damage the nervous system. Fifty two (10.17%) out of the 511 patients showed signs and symptoms of peripheral nervous system involvement in the form of sensory impairment and diminished tendon jerks suggesting the presence of neuropathy. Forty five of them were submitted to a conventional electromyographical examination. Fifteen of mem showed normal results, while the remainder 30 disclosed a reduced interference pattern, being most of the remaining motor unit potentials fragmented or poliphasic, reduced sensory and motor conduction velocities and diminished amplitude of the sensory action potential. The findings suggest that some chagasic patients in the indeterminate or chronic stages of the disease may develop a clinical mild sensory-motor peripheral neuropathy.El estúdio presente fue diseftado con ei objeto de pesquizar Ia existência de manifestaciones clinicas en pacientes afectados por enfermedad de Chagas, en estádio indeterminado o crônico, que tuviesen, ai menos, 2 reacciones serologicas positivas. En total fueron examinados 841 enfermos. De ellos solo 511 fueron admitidos en ei protocolo; los restantes fueron rechazados por mostrar Ia presencia de otras causas que hubiesen podido danar su sistema nervioso. Dentro de los 511 pacientes admitidos, 52 (10.17%) evidenciaron alteraciones objetivas y subjetivas de Ia sensibilidad y disminucion de los reflejos osteotendinosos. Estos signos y sintomas, que sugieren la presencia de neuropatia, podian combinarse de diferente manera. Como complemento dei examen clinico, se efectuo estúdio electromiografico convencional en 45 de estos pacientes. En 15 los hallazgos fueron normales, en tanto que en los restantes 30 pudo demostrarse reduccion de la capacidad de reclutamiento voluntário de unidad motora, presencia de potenciales de unidad motora fragmentados o polifasicos, reduccion de la velocidad de conduccion motora y sensitiva y disminucion de la amplitud dei potencial sensitivo. Los resultados obtenidos sefialan que una proporcion de los pacientes en el estádio indeterminado o crônico de la infeccion pueden desarrollar una moderada neuropatia sensitivo-motora con expresion clinica.

Abstract Background We describe a patient who underwent transurethral resection of the prostate for urinary obstructive symptoms and had histological findings of adenocarcinoma of the prostate with prostatic localization of chronic lymphocitic leukemia (CLL).The contemporary presence of CLL, adenocarcinoma of the prostate and residual prostatic gland after transurethral resection has never been reported before and the authors illustrate how they managed this unusual patient. Case presentation A 79-years-old white man, presented with acute urinary retention, had a peripheral blood count with an elevated lymphocytosis (21.250/mL) with a differential of 65.3% lymphocytes and the prostate-specific antigen (PSA) value was 3.38 ng/mL with a percent free PSA of 8.28%. The transrectal ultrasound (TRUS) indicated an isoechonic and homogenic enlarged prostate of 42 cm3 and the abdomen ultrasound found a modest splenomegaly and no peripheral lymphadenophaty. The patient underwent transurethral resection of the prostate and had a pathological finding of adenocarcinoma in the prostate with a Gleason Score 4 (2+2) of less than 5% of the material (clinical stage T1a), associated with a diffused infiltration of chronic lymphocitic leukemia elements. Conclusions The incidental finding of a prostatic localization of a low-grade non-Hodgkin's lymphoma does not modify eventually further treatments for neither prostate cancer nor lymphoma. The presence of a low-grade and low-stage lymphoma, confirmed by a hematological evaluation, and the simultaneous evidence of an adenocarcinoma after transurethral resection of the prostate for acute urinary retention do not require any immediate treatment due to its long-term survival rate and the follow-up remains based on periodical PSA evaluation and complete blood count.