From biology to genes and back again: Gene discovery for monogenic forms of beta cell dysfunction in diabetes

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordThis review focusses on gene discovery strategies used to identify monogenic forms of diabetes caused by reduced pancreatic beta cell number (due to destruction or defective development) or impaired beta cell function. Gene discovery efforts in monogenic diabetes have identifi ed 36 genes so far. These genetic causes have been identified using four main approaches: linkage analysis, candidate gene sequencing and most recently, exome and genome sequencing. The advent of next-generation sequencing has allowed researchers to move away from linkage analysis (relying on large pedigrees and/or multiple families with the same genetic condition) and candidate gene (relying on previous knowledge on the gene’s role) strategies to use a gene agnostic approach, utilising genetic evidence (such as variant frequency, predicted variant effect on protein function, and predicted mode of inheritance) to identify the causative mutation. This approach led to the identification of 7 novel genetic causes of monogenic diabetes, 6 by exome sequencing and one by genome sequencing. In many of these cases, the disease-causing gene was not known to be important for beta cell function prior of the gene discovery study. These novel findings highlight a new role for gene discovery studies in furthering our understanding of beta cell function and dysfunction in diabetes. Whilst many gene discovery studies in the past were led by knowledge in the field (through the candidate gene strategy) now they often lead the scientific advances in the field by identifying new important biological players to be further characterised by in vitro and in vivo studies.EFSD Rising Star Fellowshi

The scientific and technological trajectories of four Latin American countries: Mexico, Costa Rica, Argentina, and Brazil

This paper introduces the differences and similarities of interactions between science and technology (S&T) among four Latin American countries: Argentina, Brazil, Costa Rica and Mexico. Through the analysis of articles and patents data as well as the elaboration of global matrices and national three-dimensional matrices, it was possible to observe the recent trajectory of the scientific and technological production of countries. The results indicate that the Latin American countries have a similar pattern regarding their scientific and technological structure and they are part of a regime characterized by immature National Systems of Innovation (NSI).Latin American countries, science and technology interaction, national systems of innovation

Selective darkening of degenerate transitions for implementing quantum controlled-NOT gates

We present a theoretical analysis of the selective darkening method for implementing quantum controlled-NOT (CNOT) gates. This method, which we recently proposed and demonstrated, consists of driving two transversely-coupled quantum bits (qubits) with a driving field that is resonant with one of the two qubits. For specific relative amplitudes and phases of the driving field felt by the two qubits, one of the two transitions in the degenerate pair is darkened, or in other words, becomes forbidden by effective selection rules. At these driving conditions, the evolution of the two-qubit state realizes a CNOT gate. The gate speed is found to be limited only by the coupling energy J, which is the fundamental speed limit for any entangling gate. Numerical simulations show that at gate speeds corresponding to 0.48J and 0.07J, the gate fidelity is 99% and 99.99%, respectively, and increases further for lower gate speeds. In addition, the effect of higher-lying energy levels and weak anharmonicity is studied, as well as the scalability of the method to systems of multiple qubits. We conclude that in all these respects this method is competitive with existing schemes for creating entanglement, with the added advantages of being applicable for qubits operating at fixed frequencies (either by design or for exploitation of coherence sweet-spots) and having the simplicity of microwave-only operation.Comment: 25 pages, 5 figure

A novel stepwise micro-TESE approach in non obstructive azoospermia

Background: The purpose of the study was to investigate whether micro-TESE can improve sperm retrieval rate (SRR) compared to conventional single TESE biopsy on the same testicle or to contralateral multiple TESE, by employing a novel stepwise micro-TESE approach in a population of poor prognosis patients with non-obstructive azoospermia (NOA). Methods: Sixty-four poor prognosis NOA men undergoing surgical testicular sperm retrieval for ICSI, from March 2007 to April 2013, were included in this study. Patients inclusion criteria were a) previous unsuccessful TESE, b) unfavorable histology (SCOS, MA, sclerahyalinosis), c) Klinefelter syndrome. We employed a stepwise micro-TESE consisting three-steps: 1) single conventional TESE biopsy; 2) micro-TESE on the same testis; 3) contralateral multiple TESE. Results: SRR was 28.1 % (18/64). Sperm was obtained in both the initial single conventional TESE and in the following micro-TESE. The positive or negative sperm retrieval was further confirmed by a contralateral multiple TESE, when performed. No significant pre-operative predictors of sperm retrieval, including patients’ age, previous negative TESE or serological markers (LH, FSH, inhibin B), were observed at univariate or multivariate analysis. Micro-TESE (step 2) did not improve sperm retrieval as compared to single TESE biopsy on the same testicle (step 1) or multiple contralateral TESE (step 3). Conclusions: Stepwise micro-TESE could represent an optimal approach for sperm retrieval in NOA men. In our view, it should be offered to NOA patients in order to gradually increase surgical invasiveness, when necessary. Stepwise micro-TESE might also reduce the costs, time and efforts involved in surgery

Comportamento agronômico de uvas de mesa no Vale do São Francisco.

O presente trabalho tem como objetivo avaliar 122 genótipos de uvas de mesa, visando selecionar aqueles com características superiores para serem recomendados para cultivo comercial ou para serem utilizados em programas de melhoramento genético