Frequency of TERT promoter mutations in human cancers

Reactivation of telomerase has been implicated in human tumorigenesis, but the underlying mechanisms remain poorly understood. Here we report the presence of recurrent somatic mutations in the TERT promoter in cancers of the central nervous system (43%), bladder (59%), thyroid (follicular cell-derived, 10%) and skin (melanoma, 29%). In thyroid cancers, the presence of TERT promoter mutations (when occurring together with BRAF mutations) is significantly associated with higher TERT mRNA expression, and in glioblastoma we find a trend for increased telomerase expression in cases harbouring TERT promoter mutations. Both in thyroid cancers and glioblastoma, TERT promoter mutations are significantly associated with older age of the patients. Our results show that TERT promoter mutations are relatively frequent in specific types of human cancers, where they lead to enhanced expression of telomerase.

Mismatch negativity in childhood temporal lobe epilepsy: a proposed paradigm for testing central auditory processing

Background: Temporal lobe epilepsy (TLE) is a neurological disorder that directly affects cortical areas responsible for auditory processing. The resulting abnormalities can be assessed using event-related potentials (ERP), which have high temporal resolution. However, little is known about TLE in terms of dysfunction of early sensory memory encoding or possible correlations between EEGs, linguistic deficits, and seizures. Mismatch negativity (MMN) is an ERP component – elicited by introducing a deviant stimulus while the subject is attending to a repetitive behavioural task – which reflects pre-attentive sensory memory function and reflects neuronal auditory discrimination and perceptional accuracy. Hypothesis: We propose an MMN protocol for future clinical application and research based on the hypothesis that children with TLE may have abnormal MMN for speech and non-speech stimuli. The MMN can be elicited with a passive auditory oddball paradigm, and the abnormalities might be associated with the location and frequency of epileptic seizures. Significance: The suggested protocol might contribute to a better understanding of the neuropsychophysiological basis of MMN. We suggest that in TLE central sound representation may be decreased for speech and non-speech stimuli. Discussion: MMN arises from a difference to speech and non-speech stimuli across electrode sites. TLE in childhood might be a good model for studying topographic and functional auditory processing and its neurodevelopment, pointing to MMN as a possible clinical tool for prognosis, evaluation, follow-up, and rehabilitation for TLE.

Differences in Mismatch Negativity (MMN) response to Pure-tone and Speech sounds in normal subjects: an additional explanation

The relation of automatic auditory discrimination, measured with MMN, with the type of stimuli has not been well established in the literature, despite its importance as an electrophysiological measure of central sound representation. In this study, MMN response was elicited by pure-tone and speech binaurally passive auditory oddball paradigm in a group of 8 normal young adult subjects at the same intensity level (75 dB SPL). The frequency difference in pure-tone oddball was 100 Hz (standard = 1 000 Hz; deviant = 1 100 Hz; same duration = 100 ms), in speech oddball (standard /ba/; deviant /pa/; same duration = 175 ms) the Portuguese phonemes are both plosive bi-labial in order to maintain a narrow frequency band. Differences were found across electrode location between speech and pure-tone stimuli. Larger MMN amplitude, duration and higher latency to speech were verified compared to pure-tone in Cz and Fz as well as significance differences in latency and amplitude between mastoids. Results suggest that speech may be processed differently than non-speech; also it may occur in a later stage due to overlapping processes since more neural resources are required to speech processing.

Fractional derivatives: probability interpretation and frequency response of rational approximations

The theory of fractional calculus (FC) is a useful mathematical tool in many applied sciences. Nevertheless, only in the last decades researchers were motivated for the adoption of the FC concepts. There are several reasons for this state of affairs, namely the co-existence of different definitions and interpretations, and the necessity of approximation methods for the real time calculation of fractional derivatives (FDs). In a first part, this paper introduces a probabilistic interpretation of the fractional derivative based on the Grünwald-Letnikov definition. In a second part, the calculation of fractional derivatives through Padé fraction approximations is analyzed. It is observed that the probabilistic interpretation and the frequency response of fraction approximations of FDs reveal a clear correlation between both concepts.

Commercial squids: Characterization, assessment of potential health benefits/risks and discrimination based on mineral, lipid and vitamin E concentrations

The most consumed squid species worldwide were characterized regarding their concentrations of minerals, fatty acids, cholesterol and vitamin E. Interspecific comparisons were assessed among species and geographical origin. The health benefits derived from squid consumption were assessed based on daily minerals intake and on nutritional lipid quality indexes. Squids contribute significantly to daily intake of several macro (Na, K, Mg and P) and micronutrients (Cu, Zn and Ni). Despite their low fat concentration, they are rich in long-chain omega-3 fatty acids, particularly docosahexaenoic (DHA) and eicosapentanoic (EPA) acids, with highly favorable ω-3/ω-6 ratios (from 5.7 to 17.7), reducing the significance of their high cholesterol concentration (140–549 mg/100 g ww). Assessment of potential health risks based on minerals intake, non-carcinogenic and carcinogenic risks indicated that Loligo gahi (from Atlantic Ocean), Loligo opalescens (from Pacific Ocean) and Loligo duvaucelii (from Indic Ocean) should be eaten with moderation due to the high concentrations of Cu and/or Cd. Canonical discriminant analysis identified the major fatty acids (C14:0, C18:0, C18:1, C18:3ω-3, C20:4ω-6 and C22:5ω-6), P, K, Cu and vitamin E as chemical discriminators for the selected species. These elements and compounds exhibited the potential to prove authenticity of the commercially relevant squid species.

Low frequency of TERT promoter mutations in gastrointestinal stromal tumors (GISTs)

Somatic mutations in the promoter region of telomerase reverse transcriptase (TERT) gene, mainly at positions c.-124 and c.-146 bp, are frequent in several human cancers; yet its presence in gastrointestinal stromal tumor (GIST) has not been reported to date. Herein, we searched for the presence and clinicopathological association of TERT promoter mutations in genomic DNA from 130 bona fide GISTs. We found TERT promoter mutations in 3.8% (5/130) of GISTs. The c.-124C>T mutation was the most common event, present in 2.3% (3/130), and the c.-146C>T mutation in 1.5% (2/130) of GISTs. No significant association was observed between TERT promoter mutation and patient's clinicopathological features. The present study establishes the low frequency (4%) of TERT promoter mutations in GISTs. Further studies are required to confirm our findings and to elucidate the hypothetical biological and clinical impact of TERT promoter mutation in GIST pathogenesis.

Espresso beverages of pure origin coffee: Mineral characterization, contribution for mineral intake and geographical discrimination

Espresso coffee beverages prepared from pure origin roasted ground coffees from the major world growing regions (Brazil, Ethiopia, Colombia, India, Mexico, Honduras, Guatemala, Papua New Guinea, Kenya, Cuba, Timor, Mussulo and China) were characterized and compared in terms of their mineral content. Regular consumption of one cup of espresso contributes to a daily mineral intake varying from 0.002% (sodium; Central America) to 8.73% (potassium; Asia). The mineral profiles of the espresso beverages revealed significant inter- and intra-continental differences. South American pure origin coffees are on average richer in the analyzed elements except for calcium, while samples from Central America have generally lower mineral amounts (except for manganese). Manganese displayed significant differences (p < 0.05) among the countries of each characterized continent. Intercontinental and inter-country discrimination between the major world coffee producers were achieved by applying canonical discriminant analysis. Manganese and calcium were found to be the best chemical descriptors for origin.