Mutations in NMNAT1 cause Leber congenital amaurosis with early-onset severe macular and optic atrophy

In addition to its activity in nicotinamide adenine dinucleotide (NAD(+)) synthesis, the nuclear nicotinamide mononucleotide adenyltransferase NMNAT1 acts as a chaperone that protects against neuronal activity-induced degeneration. Here we report that compound heterozygous and homozygous NMNAT1 mutations cause severe neonatal neurodegeneration of the central retina and early-onset optic atrophy in 22 unrelated individuals. Their clinical presentation is consistent with Leber congenital amaurosis and suggests that the mutations affect neuroprotection of photoreceptor cells.     

Genome-wide association analysis identifies three new breast cancer susceptibility loci

Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ～8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ～70,000 cases and ～68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 × 10(-35)), 12q24 (rs1292011; P = 4.3 × 10(-19)) and 21q21 (rs2823093; P = 1.1 × 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.     

Building Scenarios of Multiple Time Series that Take into Account the Effects of an Expected Intervention

We consider a forecasting problem that arises when an intervention is expected to occur on an economic system during the forecast horizon. The time series model employed is seen as a statistical device that serves to capture the empirical regularities of the observed data on the variables of the system without relying on a particular theoretical structure. Either the deterministic or the stochastic structure of a vector autoregressive error correction model of the system is assumed to be affected by the intervention. The information about the intervention effect is just provided by some linear restrictions imposed on the future values of the variables involved. Formulas for restricted forecasts with intervention effects and their mean squared errors are derived as a particular case of Catlin's static updating theorem. An empirical illustration uses Mexican macroeconomic data on five variables and the restricted forecasts consider targets for years 2011–2014. Copyright © 2013 John Wiley & Sons, Ltd.     

BBS10 encodes a vertebrate-specific chaperonin-like protein and is a major BBS locus

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous ciliopathy. Although nine BBS genes have been cloned, they explain only 40-50% of the total mutational load. Here we report a major new BBS locus, BBS10, that encodes a previously unknown, rapidly evolving vertebrate-specific chaperonin-like protein. We found BBS10 to be mutated in about 20% of an unselected cohort of families of various ethnic origins, including some families with mutations in other BBS genes, consistent with oligogenic inheritance. In zebrafish, mild suppression of bbs10 exacerbated the phenotypes of other bbs morphants.     

Forecasting models in the manufacturing processes and operations management: Systematic literature review

The purpose of this paper is to present the result of a systematic literature review regarding the application and development of forecasting models in the industrial context, especially the context of manufacturing processes and operations management. The study was conducted considering the preparation of an established research protocol to know, discuss, and analyze the main approaches adopted by researchers in the field. To achieve this objective, we analyzed 354 recent papers published in periodicals between 2008 and 2018. This paper makes three main contributions to the field: (i) it presents an updated portfolio of prediction models in the industrial context, providing a reference point for researchers and industrial managers; (ii) it presents a characterization of the field of study through the identification of publication vehicles, frequency, and the principal authors and countries related to the development of research on the theme; (iii) it proposes a unified framework, listing the characteristics of the prediction models with their respective application contexts, identifying the current research directions to provide theoretical aids for the development of new approaches to forecasting in industry. The results of this study provide an empirical base for further discussions on studies that focus on forecasting in the industrial context.     

Carapace ontogeny of the bromeliad dwelling ostracod Elpidium bromeliarum Müller, 1880 (Crustacea: Ostracoda)

Ostracods have discontinuous development, marked by ecdyses, and determinate growth. Ontogenetic studies have suggested a pattern of nine postembryonic stages (eight juvenile phases and the adult) for the main freshwater ostracod superfamilies Cypridoidea, Cytheroidea and Darwinuloidea. However, cases of a supposed extra moult in the adult stage have been proposed for some ostracod species, which would amount to 10 postembryonic growth stages. One such example is Elpidium bromeliarum Müller, 1880, a cytheroidean that inhabits tank-bromeliads. The present study is aimed at investigating the ontogenetic development of E. bromeliarum using width and length measurements, as well as carapace and appendage morphology in order to test the existing hypothesis of an additional growth stage in adults of this species. Our results revealed nine postembryonic growth stages (eight juvenile and the adult), with sexual dimorphism beginning its expression in the last juvenile stage. Thus, the ontogenetic development of E. bromeliarum agrees with the overall pattern observed for podocopid ostracods and the hypothesis of 10 postembryonic growth stages was not corroborated. We argue that the inability to differentiate juveniles from adults, or different species from one another, may have misled to the assumption of an additional moult in E. bromeliarum.