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

Unexampled Courage: The Blinding of Sgt. Isaac Woodard and the Awakening of President Harry S. Truman and Judge J. Waites Waring

Judge Gergel’s book spotlights the work of distinguished Fordham Law alumnus Franklin Williams ’45 who represented Isaac Woodward while working with the NAACP Legal Defense Fund.https://ir.lawnet.fordham.edu/bt/1000/thumbnail.jp

Unexampled Courage: The Blinding of Sgt. Isaac Woodard and the Awakening of President Harry S. Truman and Judge J. Waites Waring

Judge Gergel’s book spotlights the work of distinguished Fordham Law alumnus Franklin Williams ’45 who represented Isaac Woodward while working with the NAACP Legal Defense Fund.https://ir.lawnet.fordham.edu/bt/1000/thumbnail.jp

Characteristic heterotopic ossification of the proximal humerus after total shoulder arthroplasty

OBJECTIVE: A bony spur in a characteristic location involving the proximal humerus is identified on post-operative radiographs in some patients with history of total shoulder arthroplasty. The spur is theorized to represent heterotopic ossification near the attachment site of the pectoralis major tendon on the proximal humerus which is partially detached and then reattached during total shoulder arthroplasty. In this study, we determine the morphology, incidence, demographic associations, and clinical impact of this finding. MATERIALS AND METHODS: This is a single-center, retrospective study of 500 patients who underwent total shoulder arthroplasty (250 standard and 250 reverse technique) between 2012 and 2017. Pre- and post-operative shoulder radiographs were reviewed to identify and measure the characteristic spur; inter-observer agreement was evaluated between the two reviewers. Incidence, demographic associations, and clinical significance were then determined. RESULTS: The study group included 268 men and 234 women with a mean age of 70 (42-89) years, and clinical follow-up of 25 (1-84) months. Characteristic heterotopic ossification was seen in 88 patients (17.6%) and was first noted radiographically at a mean (interquartile range) of 12.1 (11.5-12.8) months after surgery. Male sex (adjusted odds ratio (95% confidence interval), 3.00 (0.68-5.34), p \u3c 0.001) was independently associated with heterotopic ossification. No significant relationships between heterotopic ossification and adverse clinical outcomes were observed. CONCLUSION: Characteristic heterotopic ossification of the proximal humerus in patients status post total shoulder arthroplasty is a common imaging finding that is not associated with adverse clinical outcomes

Characteristic heterotopic ossification of the proximal humerus after total shoulder arthroplasty.

OBJECTIVE: A bony spur in a characteristic location involving the proximal humerus is identified on post-operative radiographs in some patients with history of total shoulder arthroplasty. The spur is theorized to represent heterotopic ossification near the attachment site of the pectoralis major tendon on the proximal humerus which is partially detached and then reattached during total shoulder arthroplasty. In this study, we determine the morphology, incidence, demographic associations, and clinical impact of this finding. MATERIALS AND METHODS: This is a single-center, retrospective study of 500 patients who underwent total shoulder arthroplasty (250 standard and 250 reverse technique) between 2012 and 2017. Pre- and post-operative shoulder radiographs were reviewed to identify and measure the characteristic spur; inter-observer agreement was evaluated between the two reviewers. Incidence, demographic associations, and clinical significance were then determined. RESULTS: The study group included 268 men and 234 women with a mean age of 70 (42-89) years, and clinical follow-up of 25 (1-84) months. Characteristic heterotopic ossification was seen in 88 patients (17.6%) and was first noted radiographically at a mean (interquartile range) of 12.1 (11.5-12.8) months after surgery. Male sex (adjusted odds ratio (95% confidence interval), 3.00 (0.68-5.34), p \u3c 0.001) was independently associated with heterotopic ossification. No significant relationships between heterotopic ossification and adverse clinical outcomes were observed. CONCLUSION: Characteristic heterotopic ossification of the proximal humerus in patients status post total shoulder arthroplasty is a common imaging finding that is not associated with adverse clinical outcomes

Critical shoulder angle is associated with full-thickness rotator cuff tears in patients with glenohumeral osteoarthritis.

BACKGROUND: Higher critical shoulder angle (CSA) is correlated with rotator cuff tears (RCTs), whereas lower CSA is associated with glenohumeral osteoarthritis (OA). Our goal was to investigate whether patients with concurrent glenohumeral OA and full-thickness RCTs demonstrate a higher CSA than patients with OA alone. METHODS: Using a 2-surgeon shoulder arthroplasty registry, we identified 31 patients with glenohumeral OA and full-thickness RCTs confirmed by plain radiography and magnetic resonance imaging, respectively. Sixty-two age- and gender-matched controls (1:2 ratio) with glenohumeral OA and an intact rotator cuff were identified from the same registry. Two independent observers evaluated the radiographs for CSA and acromiohumeral index. RESULTS: The average CSA was 30° in the OA control group and 35° in the concurrent RCT and OA group (P \u3c .0001). Acromiohumeral index was comparable between the groups (P = .13). Interobserver reliability of the independent reviewers was excellent (κ = 0.89; Ρ = 0.95). The receiver operating characteristic curve for CSA demonstrated that a value \u3e35° was 90% specific and 52% sensitive for a full-thickness RCT in the setting of OA (area under curve = 0.84). CONCLUSION: Concurrent glenohumeral OA and full-thickness RCT are associated with greater CSA values compared with patients with glenohumeral OA alone. The CSA measurement may be useful in determining the need for magnetic resonance imaging to assess rotator cuff integrity in the arthritic population

Human CTP synthase filament structure reveals the active enzyme conformation.

The universally conserved enzyme CTP synthase (CTPS) forms filaments in bacteria and eukaryotes. In bacteria, polymerization inhibits CTPS activity and is required for nucleotide homeostasis. Here we show that for human CTPS, polymerization increases catalytic activity. The cryo-EM structures of bacterial and human CTPS filaments differ considerably in overall architecture and in the conformation of the CTPS protomer, explaining the divergent consequences of polymerization on activity. The structure of human CTPS filament, the first structure of the full-length human enzyme, reveals a novel active conformation. The filament structures elucidate allosteric mechanisms of assembly and regulation that rely on a conserved conformational equilibrium. The findings may provide a mechanism for increasing human CTPS activity in response to metabolic state and challenge the assumption that metabolic filaments are generally storage forms of inactive enzymes. Allosteric regulation of CTPS polymerization by ligands likely represents a fundamental mechanism underlying assembly of other metabolic filaments

Human CTP synthase filament structure reveals the active enzyme conformation.

The universally conserved enzyme CTP synthase (CTPS) forms filaments in bacteria and eukaryotes. In bacteria, polymerization inhibits CTPS activity and is required for nucleotide homeostasis. Here we show that for human CTPS, polymerization increases catalytic activity. The cryo-EM structures of bacterial and human CTPS filaments differ considerably in overall architecture and in the conformation of the CTPS protomer, explaining the divergent consequences of polymerization on activity. The structure of human CTPS filament, the first structure of the full-length human enzyme, reveals a novel active conformation. The filament structures elucidate allosteric mechanisms of assembly and regulation that rely on a conserved conformational equilibrium. The findings may provide a mechanism for increasing human CTPS activity in response to metabolic state and challenge the assumption that metabolic filaments are generally storage forms of inactive enzymes. Allosteric regulation of CTPS polymerization by ligands likely represents a fundamental mechanism underlying assembly of other metabolic filaments