ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Prompt K_short production in pp collisions at sqrt(s)=0.9 TeV

The production of K_short mesons in pp collisions at a centre-of-mass energy of 0.9 TeV is studied with the LHCb detector at the Large Hadron Collider. The luminosity of the analysed sample is determined using a novel technique, involving measurements of the beam currents, sizes and positions, and is found to be 6.8 +/- 1.0 microbarn^-1. The differential prompt K_short production cross-section is measured as a function of the K_short transverse momentum and rapidity in the region 0 < pT < 1.6 GeV/c and 2.5 < y < 4.0. The data are found to be in reasonable agreement with previous measurements and generator expectations.Comment: 6+18 pages, 6 figures, updated author lis

Prevalence of computed tomographic subchondral bone lesions in the scapulohumeral joint of 32 immature dogs with thoracic limb lameness

Osteochondrosis is a common developmental abnormality affecting the subchondral bone of immature, large breed dogs. The purpose of this retrospective study was to describe CT lesions detected in scapulohumeral joints of 32 immature dogs undergoing CT for thoracic limb lameness. Eight dogs (14 scapulohumeral joints) had arthroscopy following imaging. Thirteen dogs (19 scapulohumeral joints) were found to have CT lesions, including 10 dogs (16 scapulohumeral joints) with subchondral bone lesions and 3 dogs with enthesopathy of the supraspinatus tendon. In one dog, subchondral bone lesions appeared as large oval defects within the mid-aspect of the glenoid cavities, bilaterally. These lesions resembled osseous cyst-like lesions commonly identified in the horse. This is the first report of such a presentation of a subchondral bone lesion in the glenoid cavity of a dog. In all dogs, small, focal, round or linear lucent defects were visible within the cortical bone at the junction of the greater tubercle and intertubercular groove. These structures were thought to represent vascular channels. Findings from this study support the use of CT as an adjunct modality for the identification and characterization of scapulohumeral subchondral bone lesions in immature dogs with thoracic limb lameness

Hematological and immunological development from birth to six months of age in Holstein calves

ABSTRACT The hematological and immunological development of calves from birth to 6 months of age was performed by hemogram and cellular phenotype. Ten male Holstein calves were assessed in 13 moments: before colostrum intake (D0), every 2 days until the 10th day of life (D2 to D10), at the 15th day after birth (D15), and then monthly up to 6 months (D180). Calves presented hemoconcentration on day (D) 0 and showed a gradual decrease in hematimetric rates until D180. The inversion of the neutrophilic for lymphocytic profile was observed on D4. The percentage of CD3+ cells on D10 was higher than D30 up to D180. The number of CD4+ and CD8+ cells did not change between time points. The number of CD21+ lymphocytes was significantly higher at early time points of D0 up to D15, compared on D30 until D150. In conclusion, the neonatal period was marked by stress leukogram in the first 4 days, and low number of B lymphocytes. These might be risk factors for bacterial infections responsible for navel inflammation and diarrhea. The increase in the number of B cells from 30 days of age demonstrated that the calves were functional and able to generate an immune response

Disruption of the integrin-linked kinase (ILK) pseudokinase domain affects kidney development in mice.

Integrin-linked kinase (ILK), a central component of the intracellular ILK–pinch–parvin complex, localizes together with paxillin to focal adhesions and regulates integrin-mediated cell functions. ILK was initially misclassified as a kinase based on phenotypical characterization of cells expressing ILK mutated in the “kinase” domain, such as the E359K and K220M mutants and a V386G/T387G mutation in the paxillin-binding site (PBS). ILK is now known to be a pseudokinase, and mechanisms of action of these mutants are not clear. We selectively induced expression of only the E359K, PBS, and K220M ILK mutations in the developing kidney collecting system and kidney collecting duct (CD) cells and analyzed their impact on structural integrity using molecular dynamics (MD) simulations. Mice or CD cells carrying the E359K mutation had a severe phenotype that is indistinguishable from ILK-null mice or ILK-null CD cells. The K220M mutant mice developed normally, and K220M-CD cells had a mild adhesion, migration, and tubulogenesis defect. The PBS mutant mice had a subtle developmental defect, and PBS-CD cells had moderate functional abnormalities. Consistent with these observed phenotypes, MD studies suggest that the E359K mutant produces the most structurally perturbed, and K220M the most WT-like ILK molecules. Although all three mutations disrupted ILK binding to parvin and paxillin in vitro, only the E359K mutation decreased ILK binding to pinch suggesting that it increases ILK misfolding. Thus, point mutations in the ILK pseudokinase domain cause functional abnormalities by altering the ILK structure, leading to increased turnover and destabilization of ILK–parvin and (sometimes) ILK–pinch interactions. The integrin-linked kinase (ILK)–pinch–parvin (IPP) complex is a critical component of focal adhesions that binds to the cytoplasmic tail of the integrin β subunits. Integrins, composed of an α and a β subunit, are the principal receptors that mediate cell–extracellular matrix interactions and regulate many cell functions, including adhesion, spreading, migration, polarization, and tubulogenesis. ILK is a 450 amino acid multidomain

Enhanced third-order nonlinear effects in optical AlGaAs nanowires

We report the first observation of enhanced third-order nonlinear effects in AlGaAs nanowires. AlGaAs nanowaveguides with widths varying from 100 to 600nm were fabricated and characterized. Nonlinear phase shifts of ∼π were experimentally observed at 1.55μm with peak powers of 30-40W in 600μm long, 550nm wide guides