Rates of asymptomatic respiratory virus infection across age groups.

Respiratory viral infections are a leading cause of disease worldwide. A variety of respiratory viruses produce infections in humans with effects ranging from asymptomatic to life-treathening. Standard surveillance systems typically only target severe infections (ED outpatients, hospitalisations, deaths) and fail to track asymptomatic or mild infections. Here we performed a large-scale community study across multiple age groups to assess the pathogenicity of 18 respiratory viruses. We enrolled 214 individuals at multiple New York City locations and tested weekly for respiratory viral pathogens, irrespective of symptom status, from fall 2016 to spring 2018. We combined these test results with participant-provided daily records of cold and flu symptoms and used this information to characterise symptom severity by virus and age category. Asymptomatic infection rates exceeded 70% for most viruses, excepting influenza and human metapneumovirus, which produced significantly more severe outcomes. Symptoms were negatively associated with infection frequency, with children displaying the lowest score among age groups. Upper respiratory manifestations were most common for all viruses, whereas systemic effects were less typical. These findings indicate a high burden of asymptomatic respiratory virus infection exists in the general population.

Predictors of summertime heat index levels in New York City apartments.

During heat waves, fatal overexposure to heat most often occurs at home. It is not known how factors such as building size, floor level, and different types of air conditioning (AC) contribute to excess indoor heat. We monitored indoor temperature and humidity in 36 apartments in New York City during summers 2014 and 2015 and used these values to calculate the indoor heat index (HI). We investigated the role of AC type and building-level factors on indoor HI using multilevel regression models. Thirty-four of 36 homes had AC. Central and ductless AC types were associated with the coolest indoor conditions; homes with window and portable AC were significantly warmer. Apartments on the top floor of a building were significantly hotter during heat advisory periods than other apartments regardless of the presence of AC. High indoor HI levels persisted in some homes for approximately 1 day following the end of the two heat advisory periods. We provide concrete evidence of higher heat levels in top floor apartments and in homes with certain types of AC. High heat levels that persist indoors after outdoor heat has subsided may present an underappreciated public health risk.

Socioeconomic and Outdoor Meteorological Determinants of Indoor Temperature and Humidity in New York City Dwellings.

BACKGROUND: Numerous mechanisms link outdoor weather and climate conditions to human health. It is likely that many health conditions are more directly affected by indoor rather than outdoor conditions. Yet, the relationship between indoor temperature and humidity conditions to outdoor variability, and the heterogeneity of the relationship among different indoor environments are largely unknown. METHODS: We use 5-14 day measures of indoor temperature and relative humidity from 327 dwellings in New York City for the years 2008-2011 to investigate the relationship between indoor climate, outdoor meteorological conditions, socioeconomic conditions, and building descriptors. Study households were primarily middle-income and located across the boroughs of Brooklyn, Queens, Bronx, and Manhattan. RESULTS: Indoor temperatures are positively associated with outdoor temperature during the warm season and study dwellings in higher socioeconomic status neighborhoods are significantly cooler. During the cool season, outdoor temperatures have little effect on indoor temperatures; however, indoor temperatures can range more than 10 °C between dwellings despite similar outdoor temperatures. Apartment buildings tend to be significantly warmer than houses and dwellings on higher floors are also significantly warmer than dwellings on lower floors. Outdoor specific humidity is positively associated with indoor specific and relative humidity, but there is no consistent relationship between outdoor and indoor relative humidity. CONCLUSIONS: In New York City, the relationship between indoor and outdoor temperature and humidity conditions vary significantly between dwellings. These results can be used to inform studies of health outcomes for which temperature or humidity is an established factor affecting human health and highlights the need for more research on the determinants of indoor climate.

Sperm DNA fragmentation: awakening the sleeping genome.

We have recently demonstrated that mammalian spermatozoa have the ability to degrade their DNA by a mechanism that is similar to apoptosis in somatic cells. When this mechanism is activated, the DNA is first degraded into loop-sized fragments by TOP2B (topoisomerase IIB). This degradation, termed sperm chromatin fragmentation, can be reversed by EDTA, which causes TOP2B to religate the double-stranded breaks it originally produced. Under certain conditions, a nuclease then degrades the sperm DNA further, digesting the entire sperm genome. When mouse spermatozoa which have been treated to induce TOP2B-mediated DNA breaks are injected into oocytes, the paternal DNA is specifically and completely degraded. This total digestion of paternal DNA occurs at the time of DNA synthesis initiation. In the present study, we explore the significance of an active TOP2B in the nucleus for mouse sperm function.

Role for nucleolin/Nsr1 in the cellular localization of topoisomerase I.

Nucleolin functions in ribosome biogenesis and contains an acidic N terminus that binds nuclear localization sequences. In previous work we showed that human nucleolin associates with the N-terminal region of human topoisomerase I (Top1). We have now mapped the topoisomerase I interaction domain of nucleolin to the N-terminal 225 amino acids. We also show that the Saccharomyces cerevisiae nucleolin ortholog, Nsr1p, physically interacts with yeast topoisomerase I, yTop1p. Studies of isogenic NSR1(+) and Deltansr1 strains indicate that NSR1 is important in determining the cellular localization of yTop1p. Moreover, deletion of NSR1 reduces sensitivity to camptothecin, an antineoplastic topoisomerase I inhibitor. By contrast, Deltansr1 cells are hypersensitive to the topoisomerase II-targeting drug amsacrine. These findings indicate that nucleolin/Nsr1 is involved in the cellular localization of Top1 and that this localization may be important in determining sensitivity to drugs that target topoisomerases.

Analysis of HLA-DMB mutants and -DMB genomic structure.

The HLA-DM locus encodes class II-like A and B chains and apparently regulates the antigen presentation function of conventional major histocompatibility complex (MHC) class II molecules. Here we describe the HLA-DMB mutations in three presentation defective B lymphoblastoid cells lines (B-LCL), 7.19.6, 10.6.6, and 10.78.6, which express DMB transcripts of abnormal length. Mutant 7.19.6 has a C-->T point mutation that introduces a 5' splice site into exon 3 of DMB. The independently derived mutants, 10.6.6 and 10.78.6, each harbor a G-->A mutation in exon 3 and also lack an identical downstream segment of RNA. Mapping of DMB intron/exon borders, using a genomic clone, revealed that the segment missing in mutants 10.6.6 and 10.78.6 represents the fourth exon of DMB; no mutations were found within exon 4 in either 10.6.6 or 10.78.6, however. In addition, the DMB gene was found to have a six exon genomic structure, typical of MHC class II B genes.

An essential role for HLA-DM in antigen presentation by class II major histocompatibility molecules.

In antigen-presenting cells, class II molecules of the major histocompatibility complex (MHC) bind peptides derived from endocytosed proteins. In certain B-lymphoblastoid cell mutants, MHC class II molecule-peptide complex formation is impaired, resulting in deficient antigen-presenting function. MHC deletion mutants with this defect map the responsible gene(s) to the class II region of the MHC. Here we report that multiple independent mutants with the class II presentation defect harbour lesions in HLA-DMB, an MHC-linked gene encoding a class II-like beta-chain. Expression of DMB complementary DNA in mutants lacking DMB messenger RNA restores the wild-type phenotype. These results establish HLA-DM as a critical regulatory molecule in class II-restricted antigen presentation and suggest that it functions at an intracellular site to promote class II molecule-peptide association.