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

Direct Reversible Decarboxylation from Stable Organic Acids in Solution

Many classical and emerging methodologies in organic chemistry rely on carbon dioxide extrusion to generate reactive intermediates for subsequent bond-­forming events. Synthetic reactions that involve the microscopic reverse, the carboxylation of reactive intermediates such as organometallic nucleophiles, occur under vastly different reaction conditions. We found that under appropriate conditions chemically stable C(sp3) carboxylates undergo rapid, uncatalyzed reversible decarboxylation in solution. The decarboxylation/carboxylation process occurs through the generation and trapping of otherwise undetectable carbanion intermediates that are largely resistant to protodecarboxylation in the presence of Brønsted acids or to trapping by external electrophiles. Isotopically labelled carboxylic acids, including drug molecules and valuable synthetic intermediates, can be prepared in high chemical and isotopic yield by simply supplying an atmosphere of 13CO2 to carboxylate salts in polar aprotic solvents. Our results indicate that the reversibility of decarboxylation from organic acids should be taken into consideration when designing and executing decarboxylative functionalization processes

Regio- and Stereoselective Hydroamination of Alkynes Using an Ammonia Surrogate: Synthesis of <i>N</i>‑Silylenamines as Reactive Synthons

An anti-Markovnikov selective hydroamination of alkynes with <i>N</i>-silylamines to afford <i>N</i>-silylenamines is reported. The reaction is catalyzed by a bis­(amidate)­bis­(amido)­Ti­(IV) catalyst and is compatible with a variety of terminal and internal alkynes. Stoichiometric mechanistic studies were also performed. This method easily affords interesting <i>N</i>-silylenamine synthons in good to excellent yields and the easily removable silyl protecting group enables the catalytic synthesis of primary amines

Regio- and Stereoselective Hydroamination of Alkynes Using an Ammonia Surrogate: Synthesis of <i>N</i>‑Silylenamines as Reactive Synthons

An anti-Markovnikov selective hydroamination of alkynes with <i>N</i>-silylamines to afford <i>N</i>-silylenamines is reported. The reaction is catalyzed by a bis­(amidate)­bis­(amido)­Ti­(IV) catalyst and is compatible with a variety of terminal and internal alkynes. Stoichiometric mechanistic studies were also performed. This method easily affords interesting <i>N</i>-silylenamine synthons in good to excellent yields and the easily removable silyl protecting group enables the catalytic synthesis of primary amines

Regio- and Stereoselective Hydroamination of Alkynes Using an Ammonia Surrogate: Synthesis of <i>N</i>‑Silylenamines as Reactive Synthons

An anti-Markovnikov selective hydroamination of alkynes with <i>N</i>-silylamines to afford <i>N</i>-silylenamines is reported. The reaction is catalyzed by a bis­(amidate)­bis­(amido)­Ti­(IV) catalyst and is compatible with a variety of terminal and internal alkynes. Stoichiometric mechanistic studies were also performed. This method easily affords interesting <i>N</i>-silylenamine synthons in good to excellent yields and the easily removable silyl protecting group enables the catalytic synthesis of primary amines

Regio- and Stereoselective Hydroamination of Alkynes Using an Ammonia Surrogate: Synthesis of <i>N</i>‑Silylenamines as Reactive Synthons

An anti-Markovnikov selective hydroamination of alkynes with <i>N</i>-silylamines to afford <i>N</i>-silylenamines is reported. The reaction is catalyzed by a bis­(amidate)­bis­(amido)­Ti­(IV) catalyst and is compatible with a variety of terminal and internal alkynes. Stoichiometric mechanistic studies were also performed. This method easily affords interesting <i>N</i>-silylenamine synthons in good to excellent yields and the easily removable silyl protecting group enables the catalytic synthesis of primary amines

Mechanism Across Scales: A Holistic Modeling Framework Integrating Laboratory and Field Studies for Microbial Ecology.

Over the last century, leaps in technology for imaging, sampling, detection, high-throughput sequencing, and -omics analyses have revolutionized microbial ecology to enable rapid acquisition of extensive datasets for microbial communities across the ever-increasing temporal and spatial scales. The present challenge is capitalizing on our enhanced abilities of observation and integrating diverse data types from different scales, resolutions, and disciplines to reach a causal and mechanistic understanding of how microbial communities transform and respond to perturbations in the environment. This type of causal and mechanistic understanding will make predictions of microbial community behavior more robust and actionable in addressing microbially mediated global problems. To discern drivers of microbial community assembly and function, we recognize the need for a conceptual, quantitative framework that connects measurements of genomic potential, the environment, and ecological and physical forces to rates of microbial growth at specific locations. We describe the Framework for Integrated, Conceptual, and Systematic Microbial Ecology (FICSME), an experimental design framework for conducting process-focused microbial ecology studies that incorporates biological, chemical, and physical drivers of a microbial system into a conceptual model. Through iterative cycles that advance our understanding of the coupling across scales and processes, we can reliably predict how perturbations to microbial systems impact ecosystem-scale processes or vice versa. We describe an approach and potential applications for using the FICSME to elucidate the mechanisms of globally important ecological and physical processes, toward attaining the goal of predicting the structure and function of microbial communities in chemically complex natural environments

Mechanism Across Scales: A Holistic Modeling Framework Integrating Laboratory and Field Studies for Microbial Ecology.

Over the last century, leaps in technology for imaging, sampling, detection, high-throughput sequencing, and -omics analyses have revolutionized microbial ecology to enable rapid acquisition of extensive datasets for microbial communities across the ever-increasing temporal and spatial scales. The present challenge is capitalizing on our enhanced abilities of observation and integrating diverse data types from different scales, resolutions, and disciplines to reach a causal and mechanistic understanding of how microbial communities transform and respond to perturbations in the environment. This type of causal and mechanistic understanding will make predictions of microbial community behavior more robust and actionable in addressing microbially mediated global problems. To discern drivers of microbial community assembly and function, we recognize the need for a conceptual, quantitative framework that connects measurements of genomic potential, the environment, and ecological and physical forces to rates of microbial growth at specific locations. We describe the Framework for Integrated, Conceptual, and Systematic Microbial Ecology (FICSME), an experimental design framework for conducting process-focused microbial ecology studies that incorporates biological, chemical, and physical drivers of a microbial system into a conceptual model. Through iterative cycles that advance our understanding of the coupling across scales and processes, we can reliably predict how perturbations to microbial systems impact ecosystem-scale processes or vice versa. We describe an approach and potential applications for using the FICSME to elucidate the mechanisms of globally important ecological and physical processes, toward attaining the goal of predicting the structure and function of microbial communities in chemically complex natural environments