Genetic basis of total colourblindness among the Pingelapese islanders

Complete achromatopsia is a rare, autosomal recessive disorder characterized by photophobia, low visual acuity, nystagmus and a total inability to distinguish colours. In this disease, cone photoreceptors, the retinal sensory neurons mediating colour vision, seem viable but fail to generate an electrical response to light. Achromatopsia, or rod monochromatism, was first mapped to 2p11-2q12 (MIM 216900; ref. 3), where it is associated with missense mutations in CNGA3 (ref. 4). CNGA3 encodes the alpha-subunit of the cone cyclic nucleotide-gated cation channel, which generates the light-evoked electrical responses of cone photoreceptors. A second locus at 8q21-q22 has been identified among the Pingelapese islanders of Micronesia, who have a high incidence of recessive achromatopsia (MIM 262300). Here we narrow the achromatopsia locus to 1.4 cM and show that Pingelapese achromatopsia segregates with a missense mutation at a highly conserved site in CNGB3, a new gene that encodes the beta-subunit of the cone cyclic nucleotide-gated cation channel. Two independent frameshift deletions establish that achromatopsia is the null phenotype of CNGB3. Combined with earlier findings, our results demonstrate that both alpha- and beta-subunits of the cGMP-gated channel are essential for phototransduction in all three classes of cones.     

Tree species impoverishment and the future flora of the Atlantic forest of northeast Brazil

Estimates of species extinction due to human impact on tropical forests have previously been based on the relationship between species number and area. Here we use a different approach to estimate loss of tree species in the Atlantic forest of northeast Brazil. We evaluate the characteristics of plant species, their avian dispersers and the distribution of the forest remnants on the landscape to estimate that about 33.9% of tree species in this region will become extinct on a regional scale. Because northeast Brazil is the most threatened sector of South American Atlantic forest, our results highlight the need to change the current conservation paradigm for this region. Rather than focus on the creation of isolated reserves in any medium-to-large forest remnant, a bioregional planning approach is urgently required to rescue this unique biota from extinction.     

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.     

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.     

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.