Functional chromatin features are associated with structural mutations in cancer.

BACKGROUND: Structural mutations (SMs) play a major role in cancer development. In some cancers, such as breast and ovarian, DNA double-strand breaks (DSBs) occur more frequently in transcribed regions, while in other cancer types such as prostate, there is a consistent depletion of breakpoints in transcribed regions. Despite such regularity, little is understood about the mechanisms driving these effects. A few works have suggested that protein binding may be relevant, e.g. in studies of androgen receptor binding and active chromatin in specific cell types. We hypothesized that this behavior might be general, i.e. that correlation between protein-DNA binding (and open chromatin) and breakpoint locations is common across divergent cancers. RESULTS: We investigated this hypothesis by comprehensively analyzing the relationship among 457 ENCODE protein binding ChIP-seq experiments, 125 DnaseI and 24 FAIRE experiments, and 14,600 SMs from 8 diverse cancer datasets covering 147 samples. In most cancers, including breast and ovarian, we found enrichment of protein binding and open chromatin in the vicinity of SM breakpoints at distances up to 200 kb. Furthermore, for all cancer types we observed an enhanced enrichment in regions distant from genes when compared to regions proximal to genes, suggesting that the SM-induction mechanism is independent from the bias of DSBs to occur near transcribed regions. We also observed a stronger effect for sites with more than one protein bound. CONCLUSIONS: Protein binding and open chromatin state are associated with nearby SM breakpoints in many cancer datasets. These observations suggest a consistent mechanism underlying SM locations across different cancers.

Thyroid carcinoma with papillary and squamous features: report of a case with histogenetic considerations.

We present a case of an 82-year-old female with a painless left latero-cervical swelling, which increased in size over the course of 6 months, compressing adjacent organs. The histopathological examination, following dissection of the left thyroid lobe and ipsilateral cervical lymph nodes, yielded two intermingled morphologically distinct histotypes that included conventional papillary thyroid carcinoma (PTC) and poorly differentiated squamous cell carcinoma (SCC) with cystic features. The clinical presentation, the immunophenotype, and the genotype, especially of the malignant squamous component with partial expression of TTF1, marked expression of p63 and mutation of BRAF, were consistent with the diagnosis of a papillary thyroid carcinoma with squamous component. The possibility of a squamous cell carcinoma of unknown origin metastasizing to a primary papillary thyroid carcinoma cannot be completely ruled out. This particular presentation of thyroid carcinoma carries a poor prognosis in 20% of cases, with high recurrence rates and distant metastasis.

Late bloomer or language impaired? Screening the speech of a Spanish-English bilingual toddler for early signs of language impairment

This case study presents corpus data gathered from a Spanish-English bilingual child with expressive language delay. Longitudinal data on the child’s linguistic development was collected from the onset of productive speech at age 1;1 until age 4 over the course of 28 video-taped sessions with the child’s principal caregivers. A literature review focused on the relationship between language delay and persisting disorders—including a discussion of the frequent difficulty in distinguishing between the two at early stages of bilingual development—is followed by an analysis of the child’s productive development in 2 distinct phases. An attempt is made to assess the child’s speech at age 4 for preliminary signs of SLI and to consider techniques for identifying ‘at risk’ bilingual children (that is, those with productive language delay, poor oral fluency, and family history of language problems) based on samples of recorded and transcribed speech.

Regulation of the immune response by macrophage migration inhibitory factor: biological and structural features.

The classical T cell cytokine macrophage migration inhibitory factor (MIF) has reemerged recently as a critical mediator of the host immune and stress response. MIF has been found to be a mediator of several diseases including gram-negative septic shock and delayed-type hypersensitivity reactions. Its immunological functions include the modulation of the host macrophage and T and B cell response. In contrast to other known cytokines, MIF production is induced rather than suppressed by glucocorticoids, and MIF has been found to override the immunosuppressive effects of glucocorticoids. Recently, elucidation of the three-dimensional structure of MIF revealed that MIF has a novel, unique cytokine structure. Here the biological role of MIF is reviewed in view of its distinct immunological and structural properties.

Clinical features of myocardial infarction and myocarditis in young adults: a retrospective study.

OBJECTIVES: To evaluate the prevalence and clinical presentation of myocardial infarction (MI) and myocarditis in young adults presenting with chest pain (CP) and an elevated serum troponin I (TnI) to the emergency department (ED). DESIGN: Retrospective, observational, single-centre study. PARTICIPANTS: All consecutive patients 18-40 years old admitted to the ED for CP with an elevated TnI concentration. PRIMARY OUTCOME MEASURES: Prevalence of MI, myocarditis and the characterisation of clinical presentation. RESULTS: 1588 patients between 18 and 40 years old were admitted to the ED with CP during 30 consecutive months. 49 (3.1%) patients with an elevated TnI (>0.09 μg/l) were included. 32.7% (16/49) were diagnosed with MI (11 ST-elevation myocardial infarction (STEMI) and 5 non-ST-elevation myocardial infarction (NSTEMI)) and 59.2% (29/49) with myocarditis. Compared with patients with myocarditis, MI patients were older (34.1±3.8 vs 26.9±6.4, p=0.0002) with more cardiovascular risk factors (mean 2.06 vs 0.69). Diabetes (18.8% vs 0%, p=0.0039), dyslipidaemia (56.2% vs 3.4%, p<0.0001) and family history of coronary artery disease (CAD) (37.5% vs 10.3% p=0.050) were associated with MI. Fever or recent viral illness were present in 75.9% (22/29) of patients with myocarditis, and in 0% of MI patients (p<0.0001). During follow-up, two patients with myocarditis were re-admitted for CP. CONCLUSIONS: In this study, 32.7% of patients <40-year-old admitted to an ED with CP and elevated TnI had a diagnosis of MI. Key distinctive clinical factors include diabetes, dyslipidaemia, family history of CAD and fever or recent viral illness.

The Origins of old Prtuguese features in Papiamentu

This paper is concerned with both the linguistic and historical relationships between papiamentu, spoken on the ABC-Island.