Campus & alumni news

Boston University Medicine was published by the Boston University Medical Campus, and presented stories on events and topics of interest to members of the BU Medical Campus community. It followed the discontinued publication Centerscope as Boston University Medicine from 1991-2005, and was continued as Campus & Alumni News from 2006-2013 before returning to the title Boston University Medicine from 2014-present

Left ventricular assist device implantation augments nitric oxide dependent control of mitochondrial respiration in failing human hearts

AbstractOBJECTIVESThe objective of the study was to evaluate nitric oxide (NO) mediated regulation of mitochondrial respiration after implantation of a mechanical assist device in end-stage heart failure.BACKGROUNDVentricular unloading using a left ventricular assist device (LVAD) can improve mitochondrial function in end-stage heart failure. Nitric oxide modulates the activity of the mitochondrial electron transport chain to regulate myocardial oxygen consumption (MVO2).METHODSMyocardial oxygen consumption was measured polarographically using a Clark-type oxygen electrode in isolated left ventricular myocardium from 26 explanted failing human hearts obtained at the time of heart transplantation.RESULTSThe rate of decrease in oxygen concentration was expressed as a percentage of baseline. Results of the highest dose of drug are shown. Decrease in MVO2 was greater in LVAD hearts (n = 8) compared with heart failure controls (n = 18) in response to the following drugs: bradykinin (−34 ± 3% vs. −24 ± 5%), enalaprilat (−37 ± 5% vs. −23 ± 5%) and amlodipine (−43 ± 13% vs. −16 ± 5%; p < 0.05 from controls). The decrease in MVO2 in LVAD hearts was not significantly different from controls in response to diltiazem (−22 ± 5% in both groups) and exogenous NO donor, nitroglycerin (−33 ± 7% vs. −30 ± 3%). Nw-nitro-L-arginine methyl ester, inhibitor of NO synthase, attenuated the response to bradykinin, enalaprilat and amlodipine. Reductions in MVO2 in response to diltiazem and nitroglycerin were not altered by inhibiting NO.CONCLUSIONSChronic LVAD support potentiates endogenous NO-mediated regulation of mitochondrial respiration. Use of medical or surgical interventions that augment NO bioavailability may promote myocardial recovery in end-stage heart failure

Noncoding deletions reveal a gene that is critical for intestinal function.

Large-scale genome sequencing is poised to provide a substantial increase in the rate of discovery of disease-associated mutations, but the functional interpretation of such mutations remains challenging. Here we show that deletions of a sequence on human chromosome 16 that we term the intestine-critical region (ICR) cause intractable congenital diarrhoea in infants1,2. Reporter assays in transgenic mice show that the ICR contains a regulatory sequence that activates transcription during the development of the gastrointestinal system. Targeted deletion of the ICR in mice caused symptoms that recapitulated the human condition. Transcriptome analysis revealed that an unannotated open reading frame (Percc1) flanks the regulatory sequence, and the expression of this gene was lost in the developing gut of mice that lacked the ICR. Percc1-knockout mice displayed phenotypes similar to those observed upon ICR deletion in mice and patients, whereas an ICR-driven Percc1 transgene was sufficient to rescue the phenotypes found in mice that lacked the ICR. Together, our results identify a gene that is critical for intestinal function and underscore the need for targeted in vivo studies to interpret the growing number of clinical genetic findings that do not affect known protein-coding genes

Development and validation of HERWIG 7 tunes from CMS underlying-event measurements

This paper presents new sets of parameters (“tunes”) for the underlying-event model of the HERWIG7 event generator. These parameters control the description of multiple-parton interactions (MPI) and colour reconnection in HERWIG7, and are obtained from a fit to minimum-bias data collected by the CMS experiment at s=0.9, 7, and 13Te. The tunes are based on the NNPDF 3.1 next-to-next-to-leading-order parton distribution function (PDF) set for the parton shower, and either a leading-order or next-to-next-to-leading-order PDF set for the simulation of MPI and the beam remnants. Predictions utilizing the tunes are produced for event shape observables in electron-positron collisions, and for minimum-bias, inclusive jet, top quark pair, and Z and W boson events in proton-proton collisions, and are compared with data. Each of the new tunes describes the data at a reasonable level, and the tunes using a leading-order PDF for the simulation of MPI provide the best description of the dat

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe