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

Photolytic, radical-mediated hydrophosphination: a convenient post-polymerisation modification route to P-di(organosubstituted) polyphosphinoboranes [RR’0PBH2]n

Polymers with a phosphorus-boron main chain have attracted interest as novel inorganic materials with potentially useful properties since the 1950s. Although examples have recently been shown to be accessible via several routes, the materials reported so far have been limited to P-mono(organosubstituted) materials, [RHPBH2]n, containing P–H groups. Here we report a general route for the post-polymerisation modification of such polyphosphinoboranes giving access to a large range of previously unknown examples featuring P-disubstituted units. Insertion of alkenes, R′CH[double bond, length as m-dash]CH2 into the P–H bonds of poly(phenylphosphinoborane), [PhHPBH2]n was facilitated by irradiation under UV light in the presence of the photoinitiator 2,2-dimethoxy-2-phenylacetophenone (DMPAP) and (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) under benchtop conditions giving high molar mass, air-stable polymers [PhR′PBH2]n with controlled functionalisation and tunable material properties. The mechanistic explanation for the favourable effect of the addition of TEMPO was also investigated and was proposed to be a consequence of reversible binding to radical species formed from the photolysis of DMPAP. This new methodology was also extended to the formation of crosslinked gels and to water-soluble bottlebrush copolymers showcasing applicability to form a wide range of polyphosphinoborane-based soft materials with tunable properties.A. W. K thanks the Bristol Chemical Synthesis Centre for Doctoral Training, funded by EPSRC (EP/L015366/1) and the University of Bristol for a PhD studentship. S. S. C. acknowledges the Government of Canada (201409BAF-344343-257775) for the award of a Banting Postdoctoral Fellowship. I. M. thanks the Government of Canada for a Canada 150 Research Chair and the University of Bristol for support.FacultyReviewe

Photolytic, radical-mediated hydrophosphination: a convenient post-polymerisation modification route to P-di(organosubstituted) polyphosphinoboranes [RR′PBH₂]_n

New, air-stable inorganic soft materials are accessible under mild conditions via TEMPO-mediated radical hydrophosphination of alkenes using polyphosphinoboranes.</p

Synthetic, structural and reaction chemistry of N-heterocyclic germylene and stannylene compounds featuring<i>N</i>-boryl substituents

N-Heterocyclic germylenes/stannylenes featuring diazaborolyl groups as the N-substituents have been investigated.</p

Tirzepatide on ingestive behavior in adults with overweight or obesity: a randomized 6-week phase 1 trial

Tirzepatide induces weight reduction but the underlying mechanisms are unknown. This 6-week phase 1 study investigated early effects of tirzepatide on energy intake. Male and female adults without diabetes (n = 114) and a body mass index from 27 to 50 kg per m2 were randomized 1:1:1 to blinded once-weekly tirzepatide or placebo, or open-label once-daily liraglutide. The primary outcome was change from baseline to week 3 in energy intake during an ad libitum lunch with tirzepatide versus placebo. Secondary outcomes assessed self-reported ingestive behavior and blood-oxygenation-level-dependent functional magnetic resonance imaging with food photos. Tirzepatide reduced energy intake versus placebo at week 3 (estimated treatment difference -524.6 kcal (95% confidence interval -648.1 to -401.0), P < 0.0001). With regard to secondary outcomes versus placebo, tirzepatide decreased overall appetite, food cravings, tendency to overeat, perceived hunger and reactivity to foods in the environment but did not impact volitional restriction of dietary intake. At week 3 versus placebo, tirzepatide did not statistically significantly impact blood-oxygenation-level-dependent activation to highly palatable food photos (aggregated category of high-fat, high-sugar foods and high-fat, high-carbohydrate foods) but decreased activation to high-fat, high-sugar food photos in the medial frontal and cingulate gyri, orbitofrontal cortex and hippocampus. Our results suggest tirzepatide reduces food intake, potentially by impacting ingestive behavior