Influence of Water Quality on Cholesterol-Induced Tau Pathology: Preliminary Data

The studies employed the cholesterol-fed rabbit model of Alzheimer's disease (AD) to investigate the relationship between AD-like neurofibrillary tangle (NFT) neuropathology and tau protein levels as the main component of NFT. We measured brain and plasma tau levels and semiquantified NFT-like neuropathology in cholesterol-fed rabbits administered drinking water of varying quality (distilled, tap, and distilled+copper) compared to animals receiving normal chow and local tap water. Total tau levels in plasma were increased in all cholesterol-fed rabbits compared to animals on normal chow, regardless of quality of water. In contrast, increased tau in brain and increased AT8 immunoreactive NFT-like lesions were greatest in cholesterol-fed rabbits administered distilled water. A substantial decrease in brain tau and incidence and density of AT8 immunoreactive NFT-like lesions occurred in cholesterol-fed rabbits administered copper water, and an even greater decrease was observed in cholesterol-fed animals on local tap water. These studies suggest the possibility that circulating tau could be the source of the tau accumulating in the brain

Effects of Moderate Sleep Restriction During 8-week Calorie Restriction on Lipoprotein Particles and Glucose Metabolism

Study Objectives This study examined how glucose, glucose regulatory hormones, insulin sensitivity, and lipoprotein subclass particle concentrations and sizes change with sleep restriction during weight loss elicited by calorie restriction. Methods Overweight or obese adults were randomized into an 8-week calorie restriction intervention alone (CR, n = 12; 75% female; body mass index = 31.4 ± 2.9 kg/m2) or combined with sleep restriction (CR+SR, n = 16; 75% female; body mass index = 34.5 ± 3.1 kg/m2). Participants in both groups were given the same instructions to reduce calorie intake. Those in the CR+SR group were instructed to reduce their habitual time-in-bed by 30–90 minutes 5 days each week with 2 ad libitum sleep days. Fasting venous blood samples were collected at pre- and post-intervention. Results Differential changes were found between the two groups (p = 0.028 for group × time interaction) in glucagon concentration, which decreased in the CR group (p = 0.016) but did not change in CR+SR group. Although changes in mean HDL particle (HDL-P) size and visfatin concentration were not statistically different between groups (p = 0.066 and 0.066 for group×time interaction, respectively), mean HDL-P size decreased only in the CR+SR group (Cohen’s d = 0.50, p = 0.022); visfatin concentrations did not change significantly in either group but appeared to decrease in the CR group (Cohen’s d = 0.67, p = 0.170) but not in the CR+SR group (Cohen’s d = 0.43, p = 0.225). Conclusion These results suggest that moderate sleep restriction, despite the presence of periodic ad libitum sleep, influences lipoprotein subclass particles and glucose regulation in individuals undergoing calorie restriction. Clinical trial registration: ClinicalTrials.gov (NCT02413866, Weight Outlooks by Restriction of Diet and Sleep

The Fading Optical Counterpart of GRB~970228, Six Months and One Year Later

We report on observations of the fading optical counterpart of the gamma-ray burst GRB 970228, made with the Hubble Space Telescope STIS CCD approximately six months after outburst and with the HST/NICMOS and Keck/NIRC approximately one year after outburst. The unresolved counterpart is detected by STIS at V=28.0 +/- 0.25, consistent with a continued power-law decline with exponent -1.14 +/- 0.05. The counterpart is located within, but near the edge of, a faint extended source with diameter ~0."8 and integrated magnitude V=25.8 +/- 0.25. A reanalysis of HST and NTT observations performed shortly after the burst shows no evidence of proper motion of the point source or fading of the extended emission. Only the extended source is visible in the NICMOS images with a magnitude of H=23.3 +/- 0.1. The Keck observations find K = 22.8 +/- 0.3. Several distinct and independent means of deriving the foreground extinction in the direction of GRB 970228 all agree with A_V = 0.75 +/- 0.2. After adjusting for Galactic extinction, we find that the size of the observed extended emission is consistent with that of galaxies of comparable magnitude found in the Hubble Deep Field (HDF) and other deep HST images. Only 2% of the sky is covered by galaxies of similar or greater surface brightness; therefore the extended source is almost certainly the host galaxy. Additionally, we find that the extinction-corrected V - H and V - K colors of the host are as blue as any galaxy of comparable or brighter magnitude in the HDF. Taken in concert with recent observations of GRB 970508, GRB 971214, and GRB 980703 our work suggests that all four GRBs with spectroscopic identification or deep multicolor broad-band imaging of the host lie in rapidly star-forming galaxies.Comment: 24 pages, Latex, 4 PostScript figures, to appear in the May 10 issue of The Astrophysical Journal (Note: displayed abstract is abridged

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

State of the climate in 2018

In 2018, the dominant greenhouse gases released into Earth’s atmosphere—carbon dioxide, methane, and nitrous oxide—continued their increase. The annual global average carbon dioxide concentration at Earth’s surface was 407.4 ± 0.1 ppm, the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contribute just over 3 W m−2 to radiative forcing and represent a nearly 43% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. With a weak La Niña in early 2018 transitioning to a weak El Niño by the year’s end, the global surface (land and ocean) temperature was the fourth highest on record, with only 2015 through 2017 being warmer. Several European countries reported record high annual temperatures. There were also more high, and fewer low, temperature extremes than in nearly all of the 68-year extremes record. Madagascar recorded a record daily temperature of 40.5°C in Morondava in March, while South Korea set its record high of 41.0°C in August in Hongcheon. Nawabshah, Pakistan, recorded its highest temperature of 50.2°C, which may be a new daily world record for April. Globally, the annual lower troposphere temperature was third to seventh highest, depending on the dataset analyzed. The lower stratospheric temperature was approximately fifth lowest. The 2018 Arctic land surface temperature was 1.2°C above the 1981–2010 average, tying for third highest in the 118-year record, following 2016 and 2017. June’s Arctic snow cover extent was almost half of what it was 35 years ago. Across Greenland, however, regional summer temperatures were generally below or near average. Additionally, a satellite survey of 47 glaciers in Greenland indicated a net increase in area for the first time since records began in 1999. Increasing permafrost temperatures were reported at most observation sites in the Arctic, with the overall increase of 0.1°–0.2°C between 2017 and 2018 being comparable to the highest rate of warming ever observed in the region. On 17 March, Arctic sea ice extent marked the second smallest annual maximum in the 38-year record, larger than only 2017. The minimum extent in 2018 was reached on 19 September and again on 23 September, tying 2008 and 2010 for the sixth lowest extent on record. The 23 September date tied 1997 as the latest sea ice minimum date on record. First-year ice now dominates the ice cover, comprising 77% of the March 2018 ice pack compared to 55% during the 1980s. Because thinner, younger ice is more vulnerable to melting out in summer, this shift in sea ice age has contributed to the decreasing trend in minimum ice extent. Regionally, Bering Sea ice extent was at record lows for almost the entire 2017/18 ice season. For the Antarctic continent as a whole, 2018 was warmer than average. On the highest points of the Antarctic Plateau, the automatic weather station Relay (74°S) broke or tied six monthly temperature records throughout the year, with August breaking its record by nearly 8°C. However, cool conditions in the western Bellingshausen Sea and Amundsen Sea sector contributed to a low melt season overall for 2017/18. High SSTs contributed to low summer sea ice extent in the Ross and Weddell Seas in 2018, underpinning the second lowest Antarctic summer minimum sea ice extent on record. Despite conducive conditions for its formation, the ozone hole at its maximum extent in September was near the 2000–18 mean, likely due to an ongoing slow decline in stratospheric chlorine monoxide concentration. Across the oceans, globally averaged SST decreased slightly since the record El Niño year of 2016 but was still far above the climatological mean. On average, SST is increasing at a rate of 0.10° ± 0.01°C decade−1 since 1950. The warming appeared largest in the tropical Indian Ocean and smallest in the North Pacific. The deeper ocean continues to warm year after year. For the seventh consecutive year, global annual mean sea level became the highest in the 26-year record, rising to 81 mm above the 1993 average. As anticipated in a warming climate, the hydrological cycle over the ocean is accelerating: dry regions are becoming drier and wet regions rainier. Closer to the equator, 95 named tropical storms were observed during 2018, well above the 1981–2010 average of 82. Eleven tropical cyclones reached Saffir–Simpson scale Category 5 intensity. North Atlantic Major Hurricane Michael’s landfall intensity of 140 kt was the fourth strongest for any continental U.S. hurricane landfall in the 168-year record. Michael caused more than 30 fatalities and $25 billion (U.S. dollars) in damages. In the western North Pacific, Super Typhoon Mangkhut led to 160 fatalities and$6 billion (U.S. dollars) in damages across the Philippines, Hong Kong, Macau, mainland China, Guam, and the Northern Mariana Islands. Tropical Storm Son-Tinh was responsible for 170 fatalities in Vietnam and Laos. Nearly all the islands of Micronesia experienced at least moderate impacts from various tropical cyclones. Across land, many areas around the globe received copious precipitation, notable at different time scales. Rodrigues and Réunion Island near southern Africa each reported their third wettest year on record. In Hawaii, 1262 mm precipitation at Waipā Gardens (Kauai) on 14–15 April set a new U.S. record for 24-h precipitation. In Brazil, the city of Belo Horizonte received nearly 75 mm of rain in just 20 minutes, nearly half its monthly average. Globally, fire activity during 2018 was the lowest since the start of the record in 1997, with a combined burned area of about 500 million hectares. This reinforced the long-term downward trend in fire emissions driven by changes in land use in frequently burning savannas. However, wildfires burned 3.5 million hectares across the United States, well above the 2000–10 average of 2.7 million hectares. Combined, U.S. wildfire damages for the 2017 and 2018 wildfire seasons exceeded $40 billion (U.S. dollars)

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

Statins to treat Alzheimer’s disease: An incomplete story

Evaluation of: Sano M, Bell KL, Galasko D et al. A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology 77(6), 556–563 (2011). The link between cholesterol and Alzheimer’s disease (AD) has been explored for almost two decades. The link stems from the observation that atherosclerotic heart disease increases the risk for AD and that people expiring from coronary artery disease had AD changes in their brains. Cholesterol is a cofactor of amyloid deposition, with substantial evidence showing that high cholesterol diets in animal models can accelerate amyloidogenesis. This link led investigators to posit the use of cholesterol-lowering agents as treatments for AD and cognitive decline. Indeed, the epidemiological data suggest that cholesterol-lowering agents may reduce the risk of developing AD. Early pilot studies suggested that statins may be useful as treatments for AD because of a reduction in the rates of decline. Recent reports of simvastatin and atorvastatin assessed in large randomized, double-blind, placebo-controlled multicenter trials have not confirmed a clinically demonstrable cognitive benefit for statins in the treatment of AD. This article will discuss the results of one of these trials and explore the reasons behind why the multicenter trials may not have been positive and the growing disparity between preclinical/epidemiological benefit and a lack of clinical efficacy. © 2012, Expert Reviews Ltd. All rights reserved