Do dietary patterns in older men influence change in homocysteine through folate fortification? The Normative Aging Study

Objective We aimed to describe the difference in B-vitamin intake and in plasma B-vitamin and homocysteine concentrations before and after folic acid fortification, in relation to dietary patterns. Design The Normative Aging Study (NAS) is a longitudinal study on ageing. Between 1961 and 1970, 2280 male volunteers aged 21¿80 years (mean 42 years) were recruited. Dietary intake data have been collected since 1987 and assessment of plasma B vitamins and homocysteine was added in 1993. Setting Boston, Massachusetts, USA. Subjects In the present study, 354 men who had completed at least one FFQ and one measurement of homocysteine, both before and after the fortification period, were included. Results Three dietary patterns were identified by cluster analysis: (i) a prudent pattern, with relatively high intakes of fruit, vegetables, low-fat milk and breakfast cereals; (ii) an unhealthy pattern, with high intakes of baked products, sweets and added fats; and (iii) a low fruit and vegetable but relatively high alcohol intake pattern. Dietary intake and plasma concentrations of folate increased significantly (P <0·05) among all dietary patterns after the fortification period. Homocysteine tended to decrease in supplement non-users and in subjects in the high alcohol, low fruit and vegetable dietary pattern (both P = 0·08). Conclusions After fortification with folic acid, folate intake and plasma folate concentration increased significantly in all dietary patterns. There was a trend towards greatest homocysteine lowering in the high alcohol, low fruit and vegetable grou

Residual Cajal bodies in coilin knockout mice fail to recruit Sm snRNPs and SMN, the spinal muscular atrophy gene product

Cajal bodies (CBs) are nuclear suborganelles involved in the biogenesis of small nuclear ribonucleoproteins (snRNPs). In addition to snRNPs, they are highly enriched in basal transcription and cell cycle factors, the nucleolar proteins fibrillarin (Fb) and Nopp140 (Nopp), the survival motor neuron (SMN) protein complex, and the CB marker protein, p80 coilin. We report the generation of knockout mice lacking the COOH-terminal 487 amino acids of coilin. Northern and Western blot analyses demonstrate that we have successfully removed the full-length coilin protein from the knockout animals. Some homozygous mutant animals are viable, but their numbers are reduced significantly when crossed to inbred backgrounds. Analysis of tissues and cell lines from mutant animals reveals the presence of extranucleolar foci that contain Fb and Nopp but not other typical nucleolar markers. These so-called “residual” CBs neither condense Sm proteins nor recruit members of the SMN protein complex. Transient expression of wild-type mouse coilin in knockout cells results in formation of CBs and restores these missing epitopes. Our data demonstrate that full-length coilin is essential for proper formation and/or maintenance of CBs and that recruitment of snRNP and SMN complex proteins to these nuclear subdomains requires sequences within the coilin COOH terminus

Defects and rescue of the minor salivary glands in Eda pathway mutants

AbstractDespite their importance to oral health, the mechanisms of minor salivary gland (SG) development are largely unexplored. Here we present in vivo and in vitro analyses of developing minor SGs in wild type and mutant mice. Eda, Shh and Fgf signalling pathway genes are expressed in these glands from an early stage of development. Developing minor SGs are absent in Eda pathway mutant embryos, and these mice exhibit a dysplastic circumvallate papilla with disrupted Shh expression. Supplementation of Eda pathway mutant minor SG explants with recombinant EDA rescues minor SG induction. Supplementation with Fgf8 or Shh, previously reported targets of Eda signalling, leads to induction of gland like structures in a few cases, but these fail to develop into minor SGs

Terrestrial habitat requirements of nesting freshwater turtles

Because particular life history traits affect species vulnerability to development pressures, cross-species summaries of life history traits are useful for generating management guidelines. Conservation of aquatic turtles, many members of which are regionally or globally imperiled, requires knowing the extent of upland habitat used for nesting. Therefore, we compiled distances that nests and gravid females had been observed from wetlands. Based on records of \u3e 8000 nests and gravid female records compiled for 31 species in the United States and Canada, the distances that encompass 95% of nests vary dramatically among genera and populations, from just 8 m for Malaclemys to nearly 1400 m for Trachemys. Widths of core areas to encompass varying fractions of nesting populations (based on mean maxima across all genera) were estimated as: 50% coverage = 93 m, 75% = 154 m, 90% = 198 m, 95% = 232 m, 100% = 942 m. Approximately 6–98 m is required to encompass each consecutive 10% segment of a nesting population up to 90% coverage; thereafter, ca. 424 m is required to encompass the remaining 10%. Many genera require modest terrestrial areas (\u3c200 m zones) for 95% nest coverage (Actinemys, Apalone, Chelydra, Chrysemys, Clemmys, Glyptemys, Graptemys, Macrochelys, Malaclemys, Pseudemys, Sternotherus), whereas other genera require larger zones (Deirochelys, Emydoidea, Kinosternon, Trachemys). Our results represent planning targets for conserving sufficient areas of uplands around wetlands to ensure protection of turtle nesting sites, migrating adult female turtles, and dispersing turtle hatchlings

2022 Upgrade and Improved Low Frequency Camera Sensitivity for CMB Observation at the South Pole

Constraining the Galactic foregrounds with multi-frequency Cosmic Microwave Background (CMB) observations is an essential step towards ultimately reaching the sensitivity to measure primordial gravitational waves (PGWs), the sign of inflation after the Big-Bang that would be imprinted on the CMB. The BICEP Array telescope is a set of multi-frequency cameras designed to constrain the energy scale of inflation through CMB B-mode searches while also controlling the polarized galactic foregrounds. The lowest frequency BICEP Array receiver (BA1) has been observing from the South Pole since 2020 and provides 30 GHz and 40 GHz data to characterize the Galactic synchrotron in our CMB maps. In this paper, we present the design of the BA1 detectors and the full optical characterization of the camera including the on-sky performance at the South Pole. The paper also introduces the design challenges during the first observing season including the effect of out-of-band photons on detectors performance. It also describes the tests done to diagnose that effect and the new upgrade to minimize these photons, as well as installing more dichroic detectors during the 2022 deployment season to improve the BA1 sensitivity. We finally report background noise measurements of the detectors with the goal of having photon noise dominated detectors in both optical channels. BA1 achieves an improvement in mapping speed compared to the previous deployment season.Comment: Proceedings of SPIE Astronomical Telescopes + Instrumentation 2022 (AS22

Polarization Calibration of the QUaD Experiment

We describe the polarization calibration of the QUaD experiment, including determination of the polarization efficiency of the detectors and their orientation angles. QUaD is a millimeter-wavelength polarimeter that observed the Cosmic Microwave Background (CMB) from a site at the South Pole. The experiment comprises a 2.64 m Cassegrain telescope equipped with a cryogenically cooled receiver containing an array of 62 polarization-sensitive bolometers. The focal plane contains pixels at two different frequency bands, 100 GHz and 150 GHz, with angular resolutions of 5prime and 3farcm5, respectively. The high angular resolution allows observation of CMB temperature and polarization anisotropies over a wide range of scales. The instrument commenced operation in early 2005 and collected science data during three successive Austral winter seasons of observation

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele