Multidimensional relationships between sensory perception and cognitive aging

A growing literature suggests that declines in sensory/perceptual systems predate cognitive declines in aging, and furthermore, they are highly predictive for developing Alzheimer’s disease and Alzheimer’s related dementias (ADRD). While vision, hearing, olfaction, and vestibular function have each been shown to be related to ADRD, their causal relations to cognitive declines, how they interact with each other remains to be clarified. Currently, there is substantial debate whether sensory/perceptual systems that fail early in disease progression are causal in their contributions to cognitive load and/or social isolation or are simply coincident declines due to aging. At the same time, substantial declines in any of these senses requires compensation, can strain other neural processes and impact activities of daily living, including social engagement, quality of life, and the risk of falls. In this perspective piece, we review literature that illustrates the different relationships between sensory/perceptual systems, cognitive aging and ADRD. We suggest that broadly administered and precise assessment of sensory/perceptual functions could facilitate early detection of ADRD and pave the way for intervention strategies that could help reduce the multifaceted risk of developing ADRD and to improve everyday functioning as people age

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Science on the March

Structures of Civilization The various civilizations of mankind known to us are characterized both by remarkable similarities, stemming from the common problems of humanity in all environments, and by quite remarkable differences, related to differences in culture and environment. The differences may be of secondary importance, or they may be so important that they determine the fate of a given civilization in a major way. Except for a brief period of expansionism at the time of the Han Dynasty, coincident with the Roman era, Chinese civilization has been characterized by an introspective or isolationist character. It is true that the Chinese "discovered" Persia and the Mediterranean world, and probably even Australia, and that they entered into extensive trade with foreign regions. It is also true that China was conquered by outsiders several times and, hence, was subject to outside stimulus. Nevertheless, the indigenous culture remained essentially isolationist until the very recent past. This trait of Chinese civilization has done much to help the people preserve unity and continuity for nearly 5, 000 years. On the other hand, it has prevented them from being colonizers on any major scale. One can well imagine what the status of North and South America would be at present if the Chinese civilization had been more extroverted in the past.published or submitted for publicatio