Wave ripples formed in ancient, ice-free lakes in Gale crater, Mars.

Symmetrical wave ripples identified with NASA's Curiosity rover in ancient lake deposits at Gale crater provide a key paleoclimate constraint for early Mars: At the time of ripple formation, climate conditions must have supported ice-free liquid water on the surface of Mars. These features are the most definitive examples of wave ripples on another planet. The ripples occur in two stratigraphic intervals within the orbitally defined Layered Sulfate Unit: a thin but laterally extensive unit at the base of the Amapari member of the Mirador formation, and a sandstone lens within the Contigo member of the Mirador formation.

Coping with extreme heat: current exposure and implications for the future.

A preview of how effective behavioral, biological and technological responses might be in the future, when outdoor conditions will be at least 2°C hotter than current levels, is available today from studies of individuals already living in extreme heat. In areas where high temperatures are common-particularly those in the hot and humid tropics-several studies report that indoor temperatures in low-income housing can be significantly hotter than those outdoors. A case study indicates that daily indoor heat indexes in almost all the 123 slum dwellings monitored in Kolkata during the summer were above 41°C (106°F) for at least an hour.

A NPAS4-NuA4 complex couples synaptic activity to DNA repair.

Neuronal activity is crucial for adaptive circuit remodelling but poses an inherent risk to the stability of the genome across the long lifespan of postmitotic neurons. Whether neurons have acquired specialized genome protection mechanisms that enable them to withstand decades of potentially damaging stimuli during periods of heightened activity is unknown. Here we identify an activity-dependent DNA repair mechanism in which a new form of the NuA4-TIP60 chromatin modifier assembles in activated neurons around the inducible, neuronal-specific transcription factor NPAS4.

Heat Exposure, Heat-Related Symptoms and Coping Strategies among Elderly Residents of Urban Slums and Rural Vilages in West Bengal, India.

The impact of heat stress among the elderly in India-particularly the elderly poor-has received little or no attention. Consequently, their susceptibility to heat-related illnesses is virtually unknown, as are the strategies they use to avoid, or deal with, the heat. This study examined perceptions of comfort, heat-related symptoms, and coping behaviors of 130 elderly residents of Kolkata slums and 180 elderly residents of rural villages south of Kolkata during a 90-day period when the average 24-h heat indexes were between 38.

Formation of thyroid hormone revealed by a cryo-EM structure of native bovine thyroglobulin.

Thyroid hormones are essential regulators of metabolism, development, and growth. They are formed from pairs of iodinated tyrosine residues within the precursor thyroglobulin (TG), a 660-kDa homodimer of the thyroid gland, by an oxidative coupling reaction. Tyrosine pairs that give rise to thyroid hormones have been assigned within the structure of human TG, but the process of hormone formation is poorly understood.

Individually experienced heat stress among elderly residents of an urban slum and rural village in India.

The elderly are one of the most vulnerable groups to heat-related illnesses and mortality. In tropical countries like India, where heat waves have increased in frequency and severity, few studies have focused on the level of stress experienced by the elderly. The study presented here included 130 elderly residents of Kolkata slums and 180 elderly residents of rural villages about 75 km south of Kolkata.

Circadian hepatocyte clocks keep synchrony in the absence of a master pacemaker in the suprachiasmatic nucleus or other extrahepatic clocks.

It has been assumed that the suprachiasmatic nucleus (SCN) synchronizes peripheral circadian oscillators. However, this has never been convincingly shown, since biochemical time series experiments are not feasible in behaviorally arrhythmic animals. By using long-term bioluminescence recording in freely moving mice, we show that the SCN is indeed required for maintaining synchrony between organs.

Cardiac MR Imaging of Muscular Dystrophies.

Muscular dystrophies (MDs) are a group of inherited disorders caused by mutations that interfere with muscular structure, contraction, or relaxation. As the cardiac sarcomeric unit shares multiple proteins with the skeletal muscle unit, the heart is affected in several MDs, sometimes without apparent musculoskeletal involvement. Early detection of MD-related cardiomyopathy is crucial as timely initiation of cardioprotective therapy can slow adverse cardiac remodeling.

Geology of the InSight landing site on Mars.

The Interior Exploration using Seismic Investigations, Geodesy and Heat Transport (InSight) spacecraft landed successfully on Mars and imaged the surface to characterize the surficial geology. Here we report on the geology and subsurface structure of the landing site to aid in situ geophysical investigations. InSight landed in a degraded impact crater in Elysium Planitia on a smooth sandy, granule- and pebble-rich surface with few rocks.

Using multiple correspondence analysis to identify behaviour patterns associated with overweight and obesity in Vanuatu adults.

Objective: The present study evaluates the use of multiple correspondence analysis (MCA), a type of exploratory factor analysis designed to reduce the dimensionality of large categorical data sets, in identifying behaviours associated with measures of overweight/obesity in Vanuatu, a rapidly modernizing Pacific Island country.

Design: Starting with seventy-three true/false questions regarding a variety of behaviours, MCA identified twelve most significantly associated with modernization status and transformed the aggregate binary responses of participants to these twelve questions into a linear scale. Using this scale, individuals were separated into three modernization groups (tertiles) among which measures of body fat were compared and OR for overweight/obesity were computed.

Coming to grips with economic development: Variation in adult hand grip strength during health transition in Vanuatu.

Objectives: To determine whether (1) maximal handgrip strength (HGS) is associated with inter-island level of economic development in Vanuatu, (2) how associations between island of residence and HGS are mediated by age, sex, body size/composition, and individual sociodeomographic variation, and (3) whether HGS is predictive of hypertension.

Material And Methods: HGS was collected from 833 adult (aged 18 and older) men and women on five islands representing a continuum of economic development in Vanuatu. HGS was measured using a handheld dynamometer.

Guidelines for Genome-Scale Analysis of Biological Rhythms.

Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs of the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout the day. These methods hold significant promise for future discovery, particularly when combined with computational modeling. However, genome-scale experiments are costly and laborious, yielding "big data" that are conceptually and statistically difficult to analyze.

Macromolecular Assemblies of the Mammalian Circadian Clock.

The mammalian circadian clock is built on a feedback loop in which PER and CRY proteins repress their own transcription. We found that in mouse liver nuclei all three PERs, both CRYs, and Casein Kinase-1δ (CK1δ) are present together in an ∼1.9-MDa repressor assembly that quantitatively incorporates its CLOCK-BMAL1 transcription factor target.

Rolling Tobacco in Banana Leaves, Newspaper, or Copybook Paper Associated With Significant Reduction in Lung Function in Vanuatu.

In addition to the widespread availability of packaged cigarettes, the inhabitants of island nations of the Southwest Pacific frequently smoke commercially available loose tobacco using manufactured rolling papers, as well as locally grown tobacco rolled in manufactured rolling paper or wrapped in leaves, copybook paper, and newspaper. In this study, Vanuatu men who smoked local tobacco rolled in leaves, copybook paper, or newspaper showed significantly lower forced vital capacity (FVC), forced expiratory volume in 1 second (FEV), and FEV/FVC ratios than men who smoked packaged cigarettes, store-bought tobacco rolled in manufactured rolling paper, or who smoked locally grown tobacco rolled in manufactured rolling papers. The addition of toxins from these unusual tobacco-wrapping media produces lung function deficits similar to the pattern noted among tobacco smokers who also inhale smoke from burning biomass.

Secular change in adult stature associated with modernization in Vanuatu.

Objective: To determine whether: (1) there is a secular increase in adult stature in Vanuatu, and (2) whether adult stature is positively associated with modernization in Vanuatu.

Methods: This study reports on stature measurements collected on 650 adult (age > 17 years) men and women from four islands of varying economic development in Vanuatu. Measurements were collected as part of the Vanuatu Health Transitions Research Project in 2007 and 2011.

Ownership of consumer electronics is associated with measures of adiposity during health transition in Vanuatu.

Objective: The Republic of Vanuatu, like many developing nations, is undergoing a rapid health transition. Our previous study identified several behavioral risk factors for the rising prevalence of obesity. Unexpectedly, daily time spent using television and radio was revealed as a protective factor for obesity in 2007.

Pain sensitivity in patients with haemophilia following moderate aerobic exercise intervention.

Background: Physical activity is influenced by pain and vice versa. Although studies recommend exercise therapy for patients with haemophilia (PwH), the influence of physical activity on the pain condition in PwH has not been investigated so far.

Aim: Aim of this study was to examine the effect of a treadmill intervention with self-chosen velocity on the acute pain sensitivity in PwH.

Larger FVC and FEV1 among Tibetans compared to Han born and raised at high altitude.

Objectives: This study compares forced vital capacity (FVC) and Forced Expiratory Volume at 1 Second (FEV1 ) of Tibetans with those of Han who were born and raised at high altitude.

Materials And Methods: FVC and FEV1 tests were conducted among 1,063 children and adolescents between the ages of 6 and 20 years, and 184 adults between the ages of 21 and 39 years who had lived their entire lives at 3200 m, 3800 m and 4300 m in Qinghai Provence, Peoples Republic of China.

Results: Even though FVC and FEV1 values of Han born and raised at high altitude are generally lower than those of Tibetans through age 15 in girls and age 16 in boys, differences are largely explained by variation in stature (height-squared) and chest circumference.

Stunting and the Prediction of Lung Volumes Among Tibetan Children and Adolescents at High Altitude.

This study examines the extent to which stunting (height-for-age Z-scores ≤ -2) compromises the use of low altitude prediction equations to gauge the general increase in lung volumes during growth among high altitude populations. The forced vital capacity (FVC) and forced expiratory volume (FEV1) of 208 stunted and 365 non-stunted high-altitude Tibetan children and adolescents between the ages of 6 and 20 years are predicted using the Third National Health and Nutrition Examination Survey (NHANESIII) and the Global Lung Function Initiative (GLF) equations, and compared to observed lung volumes. Stunted Tibetan children show smaller positive deviations from both NHANESIII and GLF prediction equations at most ages than non-stunted children.

Histone monoubiquitination by Clock-Bmal1 complex marks Per1 and Per2 genes for circadian feedback.

Circadian rhythms in mammals are driven by a feedback loop in which the transcription factor Clock-Bmal1 activates expression of Per and Cry proteins, which together form a large nuclear complex (Per complex) that represses Clock-Bmal1 activity. We found that mouse Clock-Bmal1 recruits the Ddb1-Cullin-4 ubiquitin ligase to Per (Per1 and Per2), Cry (Cry1 and Cry2) and other circadian target genes. Histone H2B monoubiquitination at Per genes was rhythmic and depended on Bmal1, Ddb1 and Cullin-4a.

Single-cell analysis of circadian dynamics in tissue explants.

Tracking molecular dynamics in single cells in vivo is instrumental to understanding how cells act and interact in tissues. Current tissue imaging approaches focus on short-term observation and typically nonendogenous or implanted samples. Here we develop an experimental and computational setup that allows for single-cell tracking of a transcriptional reporter over a period of >1 wk in the context of an intact tissue.

Impact of modernization on adult body composition on five islands of varying economic development in Vanuatu.

Objective: The Republic of Vanuatu, similar to other South Pacific island nations, is undergoing a rapid health transition as a consequence of modernization. The pace of modernization is uneven across Vanuatu's 63 inhabited islands, resulting in differential impacts on overall body composition and prevalence of obesity among islands, and between men and women. In this study, we investigated (1) how modernization impacts body composition between adult male and female Melanesians living on four islands of varying economic development in Vanuatu, and (2) how body composition differs between adult Melanesians and Polynesians living on rural islands in Vanuatu.

Purification and analysis of PERIOD protein complexes of the mammalian circadian clock.

In mammals, circadian rhythms are generated at least in part by a cell-autonomous transcriptional feedback loop in which the three PERIOD (PER) and two CRYPTOCHROME (CRY) proteins inhibit the activity of the dimeric transcription factor CLOCK-BMAL1, thereby repressing their own expression. Upon nuclear entry, the PER and CRY proteins form a large protein complex (PER complex) that carries out circadian negative feedback by means of at least two basic functions: (1) it brings together multiple effector proteins that repress transcription and (2) it delivers these repressive effectors directly to CLOCK-BMAL1 bound to E-box sequences of circadian target genes. At present, the composition, mechanisms of action, and dynamics of PER complexes in circadian clock negative feedback are incompletely understood.

Specificity in circadian clock feedback from targeted reconstitution of the NuRD corepressor.

Mammalian circadian rhythms are generated by a negative feedback loop in which PERIOD (PER) proteins accumulate, form a large nuclear complex (PER complex), and bind the transcription factor CLOCK-BMAL1, repressing their own expression. We found that mouse PER complexes include the Mi-2/nucleosome remodelling and deacetylase (NuRD) transcriptional corepressor. Unexpectedly, two NuRD subunits, CHD4 and MTA2, constitutively associate with CLOCK-BMAL1, with CHD4 functioning to promote CLOCK-BMAL1 transcriptional activity.

Temporal orchestration of repressive chromatin modifiers by circadian clock Period complexes.

The mammalian circadian clock is built on a molecular feedback loop in which the Period (PER) proteins, acting in a large, poorly understood complex, repress Clock-Bmal1, the transcription factor driving their expression. We found that mouse PER complexes include the histone methyltransferase HP1γ-Suv39h. PER proteins recruited HP1γ-Suv39h to the Per1 and Per2 promoters, and HP1γ-Suv39h proved important for circadian di- and trimethylation of histone H3 Lys9 (H3K9) at the Per1 promoter, feedback repression and clock function.