The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Longitudinal clinical and biomarker characteristics of non-manifesting LRRK2 G2019S carriers in the PPMI cohort

We examined 2-year longitudinal change in clinical features and biomarkers in LRRK2 non-manifesting carriers (NMCs) versus healthy controls (HCs) enrolled in the Parkinson’s Progression Markers Initiative (PPMI). We analyzed 2-year longitudinal data from 176 LRRK2 G2019S NMCs and 185 HCs. All participants were assessed annually with comprehensive motor and non-motor scales, dopamine transporter (DAT) imaging, and biofluid biomarkers. The latter included cerebrospinal fluid (CSF) Abeta, total tau and phospho-tau; serum urate and neurofilament light chain (NfL); and urine bis(monoacylglycerol) phosphate (BMP). At baseline, LRRK2 G2019S NMCs had a mean (SD) age of 62 (7.7) years and were 56% female. 13% had DAT deficit (defined as <65% of age/sex-expected lowest putamen SBR) and 11% had hyposmia (defined as ≤15th percentile for age and sex). Only 5 of 176 LRRK2 NMCs developed PD during follow-up. Although NMCs scored significantly worse on numerous clinical scales at baseline than HCs, there was no longitudinal change in any clinical measures over 2 years or in DAT binding. There were no longitudinal differences in CSF and serum biomarkers between NMCs and HCs. Urinary BMP was significantly elevated in NMCs at all time points but did not change longitudinally. Neither baseline biofluid biomarkers nor the presence of DAT deficit correlated with 2-year change in clinical outcomes. We observed no significant 2-year longitudinal change in clinical or biomarker measures in LRRK2 G2019S NMCs in this large, well-characterized cohort even in the participants with baseline DAT deficit. These findings highlight the essential need for further enrichment biomarker discovery in addition to DAT deficit and longer follow-up to enable the selection of NMCs at the highest risk for conversion to enable future prevention clinical trials

Training system choice as relate to genotype, site vigour and grape quality targets.

Duo to its long flexible canes, the grapevine is especiaiiy suitabie to be trained to a multitude of canopy forms and more than 40 of them are named in viticulture textbooks (Eynard and Daimasso, 1990). Vet, grapevine training systems can be more simply categorized according to canopy division (singie versus spht canopies), growth habil (vertically shoot-positioned or 1 ree growing) and growth orientation (upward versus sloped or horizontal). The aim of the next paragraphs is to anaiyze which factors are more tightly bound te the treliis system choice in wine grape growing.Série Documentos, 5

Inventories and the concentration of suppliers and customers: Evidence from the Chinese manufacturing sector

This study investigates the links between supplier- and customer-base concentrations, and inventory holdings in the Chinese manufacturing sector. Using financial data from a cohort of 516 companies, we find that firms that face higher supplier density - benefiting from better co-ordination with suppliers - hold fewer inventories, whereas firms with higher customer density retain larger inventories, as a result of the bargaining power exercised by customers. We then extend the analysis by investigating the impact of account payables, receivables and bad debt reserves, finding that inventory holdings are positively associated with the two forms of financing, and negatively associated with bad debts. This last relationship, however, becomes less severe when firms have access to large volumes of payables. Finally, we show that the above results hold – with varying degrees of similarity - also when we partition the dataset into six homogenous industrial segments. Overall, this study contributes to the growing literature on inventories and the structure of the supply chain by shedding new light on the importance of both supplier and customer densities, as well as the volume of payables and receivables, for inventory management