3,907 research outputs found
The prefusion structure of herpes simplex virus glycoprotein B.
Cell entry of enveloped viruses requires specialized viral proteins that mediate fusion with the host membrane by substantial structural rearrangements from a metastable pre- to a stable postfusion conformation. This metastability renders the herpes simplex virus 1 (HSV-1) fusion glycoprotein B (gB) highly unstable such that it readily converts into the postfusion form, thereby precluding structural elucidation of the pharmacologically relevant prefusion conformation. By identification of conserved sequence signatures and molecular dynamics simulations, we devised a mutation that stabilized this form. Functionally locking gB allowed the structural determination of its membrane-embedded prefusion conformation at sub-nanometer resolution and enabled the unambiguous fit of all ectodomains. The resulting pseudo-atomic model reveals a notable conservation of conformational domain rearrangements during fusion between HSV-1 gB and the vesicular stomatitis virus glycoprotein G, despite their very distant phylogeny. In combination with our comparative sequence-structure analysis, these findings suggest common fusogenic domain rearrangements in all class III viral fusion proteins
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Internet-enabled lab-on-a-chip technology for education
Despite many interventions, science education remains highly inequitable throughout the world. Internet-enabled experimental learning has the potential to reach underserved communities and increase the diversity of the scientific workforce. Here, we demonstrate the use of lab-on-a-chip (LoC) technologies to expose Latinx life science undergraduate students to introductory concepts of computer programming by taking advantage of open-loop cloud-integrated LoCs. We developed a context-aware curriculum to train students at over 8000 km from the experimental site. Through this curriculum, the students completed an assignment testing bacteria contamination in water using LoCs. We showed that this approach was sufficient to reduce the students' fear of programming and increase their interest in continuing careers with a computer science component. Altogether, we conclude that LoC-based internet-enabled learning can become a powerful tool to train Latinx students and increase the diversity in STEM
The Effectiveness of Fiscal Policy in Mexico
Using a VAR model with quarterly information for the 1980 to 2008 period, this paper studies the dynamic effects of fiscal policy on Gross Domestic Product in the Mexican economy. We find evidence of non–Keynesian effects of government expenditure on GDP in the short run. Also, we find evidence that government revenue has a significant impact on GDP only in the fourth quarter
The Effectiveness of Fiscal Policy in Mexico
Using a VAR model with quarterly information for the 1980 to 2008 period, this paper studies the dynamic effects of fiscal policy on Gross Domestic Product in the Mexican economy. We find evidence of non–Keynesian effects of government expenditure on GDP in the short run. Also, we find evidence that government revenue has a significant impact on GDP only in the fourth quarter
Trypsin/α-amylase inhibitors and thionins: possible defence proteins from barley
This chapter reviews recent work on the trypsin/α-amylase inhibitor and thionin protein families. The genomic distribution of protein genes in barley and related species, gene expression and in vitro activities are considered. Some of the evidence of a possible defence role against stored products pests for inhibitors and thionins is briefly discusse
Modelled agroforestry outputs at field and farm scale to support biophysical and environmental assessments
This report, comprising Deliverable 6.17, in the AGFORWARD project brings together examples of modelled outputs at field and farm scale to support the biophysical, social, and environmental assessment of the innovations selected from work-packages 2 to 5.N/
The pre-fusion structure of Herpes simplex virus glycoprotein B
Cell entry of enveloped viruses requires specialized viral proteins which mediate fusion with the
host membrane by substantial structural rearrangements from a metastable pre- to a stable postfusion
conformation. This metastability renders the Herpes simplex virus (HSV-1) fusion
glycoprotein B (gB) highly unstable such that it readily converts into the post-fusion form, thereby
precluding structural elucidation of the pharmacologically relevant pre-fusion conformation. By
identification of conserved sequence signatures and molecular dynamics simulations, we devised
a mutation that stabilized this form. Functionally locking gB, allowed the structural determination
of its membrane-embedded pre-fusion conformation at sub-nanometer resolution and enabled the
unambiguous fit of all ectodomains. The resulting pseudo-atomic model reveals a striking
conservation of conformational domain rearrangements during fusion between HSV-1 gB and the
Vesicular Stomatitis Virus glycoprotein G (VSV-G) despite their very distant phylogeny. In
combination with our comparative sequence-structure analysis, these findings suggest common
fusogenic domain rearrangements in all class III viral fusion proteins.
Rey, M. Topf, K
Response-adapted treatment with rituximab, bendamustine, mitoxantrone, and dexamethasone followed by rituximab maintenance in patients with relapsed or refractory follicular lymphoma after first-line immunochemotherapy: Results of the RBMDGELTAMO08 phase II trial
Background Consensus is lacking regarding the optimal salvage therapy for patients with follicular lymphoma who relapse after or are refractory to immunochemotherapy. Methods This phase II trial evaluated the efficacy and safety of response-adapted therapy with rituximab, bendamustine, mitoxantrone, and dexamethasone (RBMD) in follicular lymphoma patients who relapsed after or were refractory to first-line immunochemotherapy. Sixty patients received three treatment cycles, and depending on their response received an additional one (complete/unconfirmed complete response) or three (partial response) cycles. Patients who responded to induction received rituximab maintenance therapy for 2 years. Results Thirty-three (55%) and 42 (70%) patients achieved complete/unconfirmed complete response after three cycles and on completing induction therapy (4-6 cycles), respectively (final overall response rate, 88.3%). Median progression-free survival was 56.4 months (median follow-up, 28.3 months; 95% CI, 15.6-51.2). Overall survival was not reached. Progression-free survival did not differ between patients who received four vs six cycles (P = .6665), nor between patients who did/did not receive rituximab maintenance after first-line therapy (P = .5790). Median progression-free survival in the 10 refractory patients was 25.5 months (95% CI, 0.6-N/A) and was longer in patients who had shown progression of disease after 24 months of first-line therapy (median, 56.4 months; 95% CI, 19.8-56.4) than in those who showed early progression (median, 42.31 months; 95% CI, 24.41-NA) (P = .4258). Thirty-six (60%) patients had grade 3/4 neutropenia. Grade 3/4 febrile neutropenia and infection were recorded during induction (4/60 [6.7%] and 5/60 [8.3%] patients, respectively) and maintenance (2/43 [4.5%] and 4/43 [9.1%] patients, respectively). Conclusions This response-adapted treatment with RBMD followed by rituximab maintenance is an effective and well-tolerated salvage treatment for relapsed/refractory follicular lymphoma following first-line immunochemotherapy
Measurement of the cross-section and charge asymmetry of bosons produced in proton-proton collisions at TeV with the ATLAS detector
This paper presents measurements of the and cross-sections and the associated charge asymmetry as a
function of the absolute pseudorapidity of the decay muon. The data were
collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with
the ATLAS experiment at the LHC and correspond to a total integrated luminosity
of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements
varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the
1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured
with an uncertainty between 0.002 and 0.003. The results are compared with
predictions based on next-to-next-to-leading-order calculations with various
parton distribution functions and have the sensitivity to discriminate between
them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables,
submitted to EPJC. All figures including auxiliary figures are available at
https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13
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