Dynamical Properties of Two Coupled Hubbard Chains at Half-filling

Using grand canonical Quantum Monte Carlo (QMC) simulations combined with Maximum Entropy analytic continuation, as well as analytical methods, we examine the one- and two-particle dynamical properties of the Hubbard model on two coupled chains at half-filling. The one-particle spectral weight function, $A({\bf k},\omega)$, undergoes a qualitative change with interchain hopping $t_\perp$ associated with a transition from a four-band insulator to a two-band insulator. A simple analytical model based on the propagation of exact rung singlet states gives a good description of the features at large $t_\perp$. For smaller $t_\perp$, $A({\bf k}, \omega)$ is similar to that of the one-dimensional model, with a coherent band of width the effective antiferromagnetic exchange $J$ reasonably well-described by renormalized spin-wave theory. The coherent band rides on a broad background of width several times the parallel hopping integral $t$, an incoherent structure similar to that found in calculations on both the one- and two-dimensional models. We also present QMC results for the two-particle spin and charge excitation spectra, and relate their behavior to the rung singlet picture for large $t_\perp$ and to the results of spin-wave theory for small $t_\perp$.Comment: 9 pages + 10 postscript figures, submitted to Phys.Rev.B, revised version with isotropic t_perp=t data include

Genetic mapping and evolutionary analysis of human-expanded cognitive networks

Cognitive brain networks such as the default-mode network (DMN), frontoparietal network, and salience network, are key functional networks of the human brain. Here we show that the rapid evolutionary cortical expansion of cognitive networks in the human brain, and most pronounced the DMN, runs parallel with high expression of human-accelerated genes (HAR genes). Using comparative transcriptomics analysis, we present that HAR genes are differentially more expressed in higher-order cognitive networks in humans compared to chimpanzees and macaques and that genes with high expression in the DMN are involved in synapse and dendrite formation. Moreover, HAR and DMN genes show significant associations with individual variations in DMN functional activity, intelligence, sociability, and mental conditions such as schizophrenia and autism. Our results suggest that the expansion of higher-order functional networks subserving increasing cognitive properties has been an important locus of genetic changes in recent human brain evolution

The Polygenic and Monogenic Basis of Blood Traits and Diseases

Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation. Analysis of blood cell traits in the UK Biobank and other cohorts illuminates the full genetic architecture of hematopoietic phenotypes, with evidence supporting the omnigenic model for complex traits and linking polygenic burden with monogenic blood diseases

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap

A comparative perspective on the human temporal lobe

Contains fulltext : 183756pub.pdf (publisher's version ) (Closed access)The temporal lobe is a morphological specialization of primates resulting from an expansion of higher-order visual cortex that is a hallmark of the primate brain. Among primates, humans possess a temporal lobe that has significantly expanded. Several uniquely human cognitive abilities, including language comprehension, semantic memory, and aspects of conceptual processing, are represented in the temporal lobe. Understanding how the temporal lobe has been modified and reorganized in the human lineage is crucial to understanding how it supports human cognitive specializations. Identifying these structural modifications requires a direct comparison with other primates, with special attention to our closest relatives, the chimpanzees. Comparative examination of data from architectonics, tract tracing, and newer imaging methodologies suggests modifications to external morphology (gyri and sulci), preferential expansion of association areas, and elaboration of white matter fasciculi, distinguishing the human temporal lobe from those of Old World monkeys. Chimpanzees and humans share some of these features of cortical expansion, although more research is needed in order to elucidate whether humans possess simply a large hominoid temporal lobe or whether important reorganization has happened since our divergence from chimpanzees

The relevance of brain evolution for the biomedical sciences

Most biomedical neuroscientists realize the importance of the study of brain evolution to help them understand the differences and similarities between their animal model of choice and the human brains in which they are ultimately interested. Many think of evolution as a linear process, going from simpler brains, as those of rats, to more complex ones, as those of humans. However, in reality, every extant species' brain has undergone as long a period of evolution as has the human brain, and each brain has its own species-specific adaptations. By understanding the variety of existing brain types, we can more accurately reconstruct the brains of common ancestors, and understand which brain traits (of humans as well as other species) are derived and which are ancestral. This understanding also allows us to identify convergently evolved traits, which are crucial in formulating hypotheses about structure–function relationships in the brain. A thorough understanding of the processes and patterns of brain evolution is essential to generalizing findings from ‘model species’ to humans, which is the backbone of modern biomedical science

A comparative perspective on the human temporal lobe

The temporal lobe is a morphological specialization of primates resulting from an expansion of higher-order visual cortex that is a hallmark of the primate brain. Among primates, humans possess a temporal lobe that has significantly expanded. Several uniquely human cognitive abilities, including language comprehension, semantic memory, and aspects of conceptual processing, are represented in the temporal lobe. Understanding how the temporal lobe has been modified and reorganized in the human lineage is crucial to understanding how it supports human cognitive specializations. Identifying these structural modifications requires a direct comparison with other primates, with special attention to our closest relatives, the chimpanzees. Comparative examination of data from architectonics, tract tracing, and newer imaging methodologies suggests modifications to external morphology (gyri and sulci), preferential expansion of association areas, and elaboration of white matter fasciculi, distinguishing the human temporal lobe from those of Old World monkeys. Chimpanzees and humans share some of these features of cortical expansion, although more research is needed in order to elucidate whether humans possess simply a large hominoid temporal lobe or whether important reorganization has happened since our divergence from chimpanzees

Scaling of inhibitory interneurons in areas V1 and V2 of anthropoid primates as revealed by calcium-binding protein immunohistochemistry

Inhibitory GABAergic interneurons are important for shaping patterns of activity in neocortical networks. We examined the distributions of inhibitory interneuron subtypes in layer II/III of areas V1 and V2 in 18 genera of anthropoid primates including New World monkeys, Old World monkeys, and hominoids (apes and humans). Interneuron subtypes were identified by immunohistochemical staining for calbindin, calretinin, and parvalbumin and densities were quantified using the optical disector method. In both V1 and V2, calbindin-immunoreactive neuron density decreased disproportionately with decreasing total neuronal density. Thus, V1 and V2 of hominoids were occupied by a smaller percentage of calbindin-immunoreactive interneurons compared to monkeys who have greater overall neuronal densities. At the transition from V1 to V2 across all individuals, we found a tendency for increased percentages of calbindin-immunoreactive multipolar cells and calretinin-immunoreactive interneurons. In addition, parvalbumin-immunoreactive cell soma volumes increased from V1 to V2. These findings suggest that modifications of specific aspects of inhibition might be critical to establishing the receptive field properties that distinguish visual areas. Furthermore, these results show that phylogenetic variation exists in the microcircuitry of visual cortex that could have general implications for sensory processing