Humboldt University of Berlin

About: Humboldt University of Berlin is a education organization based out in Berlin, Germany. It is known for research contribution in the topics: Population & Medicine. The organization has 33671 authors who have published 61781 publications receiving 1908102 citations. The organization is also known as: Humboldt-Universität zu Berlin & Universitas Humboldtiana Berolinensis.

A C4887A polymorphism in exon 7 of human CYP1A1: population frequency, mutation linkages, and impact on lung cancer susceptibility.

Abstract: This study reports a C-->A transversion at position 4887 in exon 7 of cytochrome P4501A1 (CYP1A1), resulting in a threonine-asparagine exchange in codon 461. The polymorphism is located directly beside the known codon 462-Ile/Val mutation (m2) near the heme binding region. The C4887A mutation leads to the loss of a BsaI cleavage site, which allows analysis. No linkage of this mutation, termed m4, with other mutations such as m1 (MspI polymorphism in the 3'-flanking region) or m2 was observed on the same DNA strand. Systematic molecular genetic analyses of mutation linkages revealed that mutation m2 is in strict linkage disequilibrium with m1. To distinguish the different CYP1A1 alleles and genotypes, mutation linkages were considered. Frequency of the m4-containing allele, termed CYP1A1*4, among 880 unrelated Caucasian individuals was 2.95% (95% confidence limits, 2.21%, 3.86%). m1 was found in 7.73%, and m2 in 2.67% of alleles. No case of African black-specific mutation m3 was detected. The allele frequency of CYP1A1*4 among 157 lung cancer patients was 2.87% (95% confidence limits, 1.32%, 5.37%); it was 2.87% (95% confidence limits, 1.71%, 4.49%) in 314 controls matched by age and sex. Thus, the novel m4-mutation may not represent a susceptibility factor for lung cancer.

Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2.

Abstract: The coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with more than 780,000 deaths worldwide (as of 20 August 2020). To develop antiviral interventions quickly, drugs used for the treatment of unrelated diseases are currently being repurposed to treat COVID-19. Chloroquine is an anti-malaria drug that is used for the treatment of COVID-19 as it inhibits the spread of SARS-CoV-2 in the African green monkey kidney-derived cell line Vero1-3. Here we show that engineered expression of TMPRSS2, a cellular protease that activates SARS-CoV-2 for entry into lung cells4, renders SARS-CoV-2 infection of Vero cells insensitive to chloroquine. Moreover, we report that chloroquine does not block infection with SARS-CoV-2 in the TMPRSS2-expressing human lung cell line Calu-3. These results indicate that chloroquine targets a pathway for viral activation that is not active in lung cells and is unlikely to protect against the spread of SARS-CoV-2 in and between patients.

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

Abstract: 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.

Fluorinated copolymer PCPDTBT with enhanced open-circuit voltage and reduced recombination for highly efficient polymer solar cells.

Abstract: A novel fluorinated copolymer (F-PCPDTBT) is introduced and shown to exhibit significantly higher power conversion efficiency in bulk heterojunction solar cells with PC(70)BM compared to the well-known low-band-gap polymer PCPDTBT. Fluorination lowers the polymer HOMO level, resulting in high open-circuit voltages well exceeding 0.7 V. Optical spectroscopy and morphological studies with energy-resolved transmission electron microscopy reveal that the fluorinated polymer aggregates more strongly in pristine and blended layers, with a smaller amount of additives needed to achieve optimum device performance. Time-delayed collection field and charge extraction by linearly increasing voltage are used to gain insight into the effect of fluorination on the field dependence of free charge-carrier generation and recombination. F-PCPDTBT is shown to exhibit a significantly weaker field dependence of free charge-carrier generation combined with an overall larger amount of free charges, meaning that geminate recombination is greatly reduced. Additionally, a 3-fold reduction in non-geminate recombination is measured compared to optimized PCPDTBT blends. As a consequence of reduced non-geminate recombination, the performance of optimized blends of fluorinated PCPDTBT with PC(70)BM is largely determined by the field dependence of free-carrier generation, and this field dependence is considerably weaker compared to that of blends comprising the non-fluorinated polymer. For these optimized blends, a short-circuit current of 14 mA/cm(2), an open-circuit voltage of 0.74 V, and a fill factor of 58% are achieved, giving a highest energy conversion efficiency of 6.16%. The superior device performance and the low band-gap render this new polymer highly promising for the construction of efficient polymer-based tandem solar cells.

Impairment of Ventilatory Efficiency in Heart Failure Prognostic Impact

Abstract: Background—Impairment of ventilatory efficiency in congestive heart failure (CHF) correlates well with symptomatology and contributes importantly to dyspnea. Methods and Results—We investigated 142 CHF patients (mean NYHA class, 2.6; mean maximum oxygen consumption [Vo2max], 15.3 mL O2 · kg−1 · min−1; mean left ventricular ejection fraction [LVEF], 27%). Patients were compared with 101 healthy control subjects. Cardiopulmonary exercise testing was performed, and ventilatory efficiency was defined as the slope of the linear relationship of Vco2 and ventilation (VE). Results are presented in percent of age- and sex-adjusted mean values. Forty-four events (37 deaths and 7 instances of heart transplantation, cardiomyoplasty, or left ventricular assist device implantation) occurred. Among Vo2max, NYHA class, LVEF, total lung capacity, and age, the most powerful predictor of event-free survival was the VE versus Vco2 slope; patients with a slope ≤130% of age- and sex-adjusted normal values had a significant...