Frontotemporal lobar degeneration targets brain regions linked to expression of recently evolved genes

In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional and language functions. In most patients, disease protein aggregates contain either TDP-43 (FTLD-TDP) or tau (FTLD-tau). Here, we explored whether FTLD-associated regional degeneration patterns relate to regional gene expression of human accelerated regions (HARs), conserved sequences that have undergone positive selection during recent human evolution. To this end, we used structural neuroimaging from patients with FTLD and human brain regional transcriptomic data from controls to identify genes expressed in FTLD-targeted brain regions. We then integrated primate comparative genomic data to test our hypothesis that FTLD targets brain regions linked to expression levels of recently evolved genes. In addition, we asked whether genes whose expression correlates with FTLD atrophy are enriched for genes that undergo cryptic splicing when TDP-43 function is impaired. We found that FTLD-TDP and FTLD-tau subtypes target brain regions with overlapping and distinct gene expression correlates, highlighting many genes linked to neuromodulatory functions. FTLD atrophy-correlated genes were strongly enriched for HARs. Atrophy-correlated genes in FTLD-TDP showed greater overlap with TDP-43 cryptic splicing genes and genes with more numerous TDP-43 binding sites compared with atrophy-correlated genes in FTLD-tau. Cryptic splicing genes were enriched for HAR genes, and vice versa, but this effect was due to the confounding influence of gene length. Analyses performed at the individual-patient level revealed that the expression of HAR genes and cryptically spliced genes within putative regions of disease onset differed across FTLD-TDP subtypes. Overall, our findings suggest that FTLD targets brain regions that have undergone recent evolutionary specialization and provide intriguing potential leads regarding the transcriptomic basis for selective vulnerability in distinct FTLD molecular-anatomical subtypes

Security Policies of India, Brazil and South Africa – Regional Security Contexts as Constraints for a Common Agenda

In the course of the last decade, the IBSA states (India, Brazil, South Africa) have increased their weight in the shifting global order, particularly in economic affairs. Can the same be said about the IBSA states' position in the international security hierarchy? After locating the IBSA coalition in the shifting world order, we analyze its member states' willingness and capacity to coordinate their security policies and build a common global security agenda. In addition, we explore the state of and perspectives on bi- and trilateral collaboration initiatives on defense and armaments between India, Brazil and South Africa. A key reason for the mostly modest results of global security agenda coordination and cross-regional defense collaboration is that the prevailing security concerns of each country are located at the regional level. Therefore, the starting point of an assessment of the prospects of IBSA's security cooperation and its potential impact on the strategic global landscape has to be a comparative evaluation of the regional security environments, focusing on overlaps and potential synergies between the national security policies of the three state actors.Im Verlauf der letzten Dekade konnten die IBSA-Staaten (Indien, Brasilien, Südafrika) ihre Position in der sich verschiebenden Weltordnung erheblich verbessern; das gilt insbesondere für ihren Einfluss auf globale Handelsfragen. Lässt sich ein ähnlicher Aufstieg der IBSA-Staaten in der internationalen Sicherheitsordnung konstatieren? Die Autoren verorten die IBSA-Koalition in der sich verschiebenden Weltordnung und analysieren die Bereitschaft und Fähigkeit der drei Staaten, ihre Sicherheitsstrategien zu koordinieren und eine gemeinsame Sicherheitsagenda zu entwerfen. Ferner werden die Bedingungen und Perspektiven biund trilateraler Verteidigungs- und Rüstungszusammenarbeit untersucht. Im Ergebnis zeichnen sich bisher allenfalls anfängliche Bemühungen bei der Zusammenarbeit im Verteidigungssektor und bei der Entwicklung einer globalen Sicherheitsagenda ab. Ausschlaggebend dafür sind die primär auf der regionalen Ebene liegenden Sicherheitsprioritäten der IBSA-Staaten. Die perspektivische Bewertung des potenziellen Einflusses der Staatenkoalition auf globale Sicherheitsfragen erfolgt demnach vor dem Hintergrund der regionalen Sicherheitsstrategien Indiens, Brasiliens und Südafrikas. Dabei stehen mögliche Überschneidungen und Synergien zwischen den regionalen Sicherheitsstrategien im Zentrum des Interesses

Application of ecological momentary assessment in stress-related diseases

Many physical diseases have been reported to be associated with psychosocial factors. In these diseases, assessment relies mainly on subjective symptoms in natural settings. Therefore, it is important to assess symptoms and/or relationships between psychosocial factors and symptoms in natural settings. Symptoms are usually assessed by self-report when patients visit their doctors. However, self-report by recall has an intrinsic problem; "recall bias". Recently, ecological momentary assessment (EMA) has been proposed as a reliable method to assess and record events and subjective symptoms as well as physiological and behavioral variables in natural settings. Although EMA is a useful method to assess stress-related diseases, it has not been fully acknowledged, especially by clinicians. Therefore, the present brief review introduces the application and future direction of EMA for the assessment and intervention for stress-related diseases

The COMBREX Project: Design, Methodology, and Initial Results

© 2013 Brian P. et al.Prior to the “genomic era,” when the acquisition of DNA sequence involved significant labor and expense, the sequencing of genes was strongly linked to the experimental characterization of their products. Sequencing at that time directly resulted from the need to understand an experimentally determined phenotype or biochemical activity. Now that DNA sequencing has become orders of magnitude faster and less expensive, focus has shifted to sequencing entire genomes. Since biochemistry and genetics have not, by and large, enjoyed the same improvement of scale, public sequence repositories now predominantly contain putative protein sequences for which there is no direct experimental evidence of function. Computational approaches attempt to leverage evidence associated with the ever-smaller fraction of experimentally analyzed proteins to predict function for these putative proteins. Maximizing our understanding of function over the universe of proteins in toto requires not only robust computational methods of inference but also a judicious allocation of experimental resources, focusing on proteins whose experimental characterization will maximize the number and accuracy of follow-on predictions.COMBREX is funded by a GO grant from the National Institute of General Medical Sciences (NIGMS) (1RC2GM092602-01).Peer Reviewe

The Growing Rivalry Between America and China and the Future of Globalization (Winter 2021/2022)

In this article, Aaron Friedberg considers the ways in which the intensifying rivalry between the United States and China may influence, and be influenced by, the evolving structure of the international economy. After reviewing the evolution of the international economy over the last two centuries, he looks at five possible scenarios for the how the global economy might continue to evolve.LBJ School of Public Affair