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

Multi-institutional Collaborative Surgery Education Didactics: Virtual Adaptations During a Global Pandemic.

ObjectiveThe COVID-19 pandemic has disrupted graduate medical education, impacting Accreditation Council for Graduate Medical Education (ACGME)-mandated didactics. We aimed to study the utility of 2 methods of virtual learning: the daily National Surgery Resident Lecture Series (NSRLS), and weekly "SCORE School" educational webinars designed around the Surgical Council on Resident Education (SCORE) curriculum.Design and settingNSRLS: The National Surgery Resident Lecture Series was a daily virtual educational session initially led by faculty at an individual surgical residency program. Thirty-eight lectures were assessed for number of live viewings (March 23, 2020-May 15, 2020).Score schoolAttendance at eleven weekly SCORE educational webinars was characterized into live and asynchronous viewings (May 13, 2020-August 5, 2020). Each 1-hour live webinar was produced by SCORE on a Wednesday evening and featured nationally recognized surgeon educators using an online platform that allowed for audience interaction.ResultsNSRLS: There were a mean of 71 live viewers per NSRLS session (range 19-118). Participation began to decline in the final 2 weeks as elective case volumes increased, but sessions remained well-attended.Score schoolThere were a range of 164-3889 live viewers per SCORE School session. Sessions have most commonly been viewed asynchronously (89.8% of viewings). Live viewership decreased as the academic year ended and then rebounded with the start of the new academic year (range 4.9%-27%). Overall, the eight webinars were viewed 11,135 times. Each webinar continues to be viewed a mean of 43 times a day (range 0-102). Overall, the eleven webinars have been viewed a total of 22,722 times.ConclusionsVirtual didactics aimed at surgical residents are feasible, well-attended (both live and recorded), and have high levels of viewer engagement. We have observed that careful coordination of timing and topics is ideal. The ability for asynchronous viewing is particularly important for attendance. As the COVID-19 pandemic continues to disrupt healthcare systems, training programs must continue to adapt to education via virtual platforms

Vertical Transmission of Babesia microti, United States

Babesiosis is usually acquired from a tick bite or through a blood transfusion. We report a case of babesiosis in an infant for whom vertical transmission was suggested by evidence of Babesia spp. antibodies in the heel-stick blood sample and confirmed by detection of Babesia spp. DNA in placenta tissue

Regulation of purine metabolism connects KCTD13 to a metabolic disorder with autistic features

Genetic variation of the 16p11.2 deletion locus containing the KCTD13 gene and of CUL3 is linked with autism. This genetic connection suggested that substrates of a CUL3-KCTD13 ubiquitin ligase may be involved in disease pathogenesis. Comparison of Kctd13 mutant (Kctd13(-/-)) and wild-type neuronal ubiquitylomes identified adenylosuccinate synthetase (ADSS), an enzyme that catalyzes the first step in adenosine monophosphate (AMP) synthesis, as a KCTD13 ligase substrate. In Kctd13(-/-) neurons, there were increased levels of succinyl-adenosine (S-Ado), a metabolite downstream of ADSS. Notably, S-Ado levels are elevated in adenylosuccinate lyase deficiency, a metabolic disorder with autism and epilepsy phenotypes. The increased S-Ado levels in Kctd13(-/-)neurons were decreased by treatment with an ADSS inhibitor. Lastly, functional analysis of human KCTD13 variants suggests that KCTD13 variationmay alter ubiquitination of ADSS. These data suggest that succinyl-AMP metabolites accumulate in Kctd13(-/-) neurons, and this observation may have implications for our understanding of 16p11.2 deletion syndrome.ISSN:2589-004