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

Dīpaṅkara Buddha and the Patan Samyak Mahādāna in Nepal: Performing the Sacred in Newar Buddhist Art

Every four years, in the middle of a cold winter night, devotees bearing images of 126 Buddhas, Bodhisattvas, and other important deities assemble in the Nepalese city of Patan for an elaborate gift giving festival known as Samyak Mahādāna (“The Perfect Great Gift”). Celebrated by Nepal’s Newar Buddhist community, Samyak honors one of the Buddhas of the historical past called Dīpaṅkara. Dīpaṅkara’s importance in Buddhism is rooted in ancient textual and visual narratives that promote the cultivation of generosity through religious acts of giving (Skt. dāna). During Samyak, large images of Dīpaṅkara Buddha ceremoniously walk in procession to the event site, aided by a man who climbs inside the wooden body to assume the legs of the Buddha. Once arranged at the event, Dīpaṅkara is honored with an array of offerings until dusk the following day. This dissertation investigates how Newar Buddhists utilize art and ritual at Samyak to reenact and reinforce ancient Buddhist narratives in their contemporary lives. The study combines art historical methods of iconographic analysis with a contextual study of the ritual components of the Samyak Mahādāna to analyze the ways religious spectacle embeds core Buddhist values within in the multilayered components of art, ritual, and communal performance. Principally, Samyak reaffirms the foundational Buddhist belief in the cultivation of generosity (Skt. dāna pāramitā) through meritorious acts of giving (Skt. dāna). However, the synergy of image and ritual performance at Samyak provides a critical framework to examine the artistic, religious, and ritual continuities of past and present in the Newar Buddhist community of the Kathmandu Valley. An analysis of the underlying meta-narrative and conceptualization of Samyak suggests the construction of a dynamic visual narrative associated with sacred space, ritual cosmology, and religious authority. Moreover, this dissertation demonstrates the role of Samyak Mahādāna in constructing Buddhist identity in Nepal, as the festival provides an opportunity to examine how Newar Buddhists utilize art, ritual, and performance to reaffirm their ancient Buddhist heritage

Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: A 2-y randomized controlled trial of calorie restriction in nonobese humans

Background: Calorie restriction (CR) retards aging and increases longevity in many animal models. However, it is unclear whether CR can be implemented in humans without adverse effects on body composition.Objective: We evaluated the effect of a 2-y CR regimen on body composition including the influence of sex and body mass index (BMI; in kg/m2) among participants enrolled in CALERIE-2 (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), a multicenter, randomized controlled trial.Design: Participants were 218 nonobese (BMI: 21.9-28.0) adults aged 21-51 y who were randomly assigned to 25% CR (CR, n = 143) or ad libitum control (AL, n = 75) in a 2:1 ratio. Measures at baseline and 12 and 24 mo included body weight, waist circumference, fat mass (FM), fat-free mass (FFM), and appendicular mass by dual-energy X-ray absorptiometry; activity-related energy expenditure (AREE) by doubly labeled water; and dietary protein intake by self-report. Values are expressed as means ± SDs.Results: The CR group achieved 11.9% ± 0.7% CR over 2-y and had significant decreases in weight (-7.6 ± 0.3 compared with 0.4 ± 0.5 kg), waist circumference (-6.2 ± 0.4 compared with 0.9 ± 0.5 cm), FM (-5.4 ± 0.3 compared with 0.5 ± 0.4 kg), and FFM (-2.0 ± 0.2 compared with -0.0 ± 0.2 kg) at 24 mo relative to the AL group (all between-group P < 0.001). Moreover, FFM as a percentage of body weight at 24 mo was higher, and percentage of FM was lower in the CR group than in the AL. AREE, but not protein intake, predicted preservation of FFM during CR (P < 0.01). Men in the CR group lost significantly more trunk fat (P = 0.03) and FFM expressed as a percentage of weight loss (P < 0.001) than women in the CR group.Conclusions: Two years of CR had broadly favorable effects on both whole-body and regional adiposity that could facilitate health span in humans. The decrements in FFM were commensurate with the reduced body mass; although men in the CR group lost more FFM than the women did, the percentage of FFM in the men in the CR group was higher than at baseline. CALERIE was registered at clinicaltrials.gov as NCT00427193