Distance tuneable integral membrane protein containing floating bilayers via in situ directed self-assembly

Model membranes allow for structural and biophysical studies on membrane biochemistry at the molecular level, albeit on systems of reduced complexity which can limit biological accuracy. Floating supported bilayers offer a means of producing planar lipid membrane models not adhered to a surface, which allows for improved accuracy compared to other model membranes. Here we communicate the incorporation of an integral membrane protein complex, the multidomain β-barrel assembly machinery (Bam), into our recently developed in situ self-assembled floating supported bilayers. Using neutron reflectometry and quartz crystal microbalance measurements we show this sample system can be fabricated using a two-step self-assembly process. We then demonstrate the complexity of the model membrane and tuneability of the membrane-to-surface distance using changes in the salt concentration of the bulk solution. Results demonstrate an easily fabricated, biologically accurate and tuneable membrane assay system which can be utilized for studies on integral membrane proteins within their native lipid matrix

Distance tuneable integral membrane protein containing floating bilayers via in situ directed self-assembly

Model membranes allow for structural and biophysical studies on membrane biochemistry at the molecular level, albeit on systems of reduced complexity which can limit biological accuracy. Floating supported bilayers offer a means of producing planar lipid membrane models not adhered to a surface, which allows for improved accuracy compared to other model membranes. Here we communicate the incorporation of an integral membrane protein complex, the multidomain β-barrel assembly machinery (Bam), into our recently developed in situ self-assembled floating supported bilayers. Using neutron reflectometry and quartz crystal microbalance measurements we show this sample system can be fabricated using a two-step self-assembly process. We then demonstrate the complexity of the model membrane and tuneability of the membrane-to-surface distance using changes in the salt concentration of the bulk solution. Results demonstrate an easily fabricated, biologically accurate and tuneable membrane assay system which can be utilized for studies on integral membrane proteins within their native lipid matrix

2020-04-15 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: Daily NM recap. NM Hospital financial challenges. NM absentee voting. NM dairy farmers impact. 19-20 states open May 1? USA halts WHO funding. More NYC deaths. 250K tests AZ first responders. Global pandemic updates. Imported cases China. Masked South Korea elections. Danish children school return. PPE angiography. NYC cancels healthcare workers. GI shedding endoscopes. Blockade reduces transmission. Fever screening. Viral shedding post seroconversion. Radiology mitigations. Endoscopy units. Tracheostomy reduced transmission. Survivors plasma. Medical Imaging. Useful CTs. Electrophysiology procedures. Renin angiotensin blockers. Hemostasis. Dermatologic surgery. Pediatric gastroenterology. Autoimmune liver disease. Orthopedic surgical care. Updated treatment evidence. Asymptomatic detection. CVD pharmacology. Bleach disinfection. Arbidol beats lopinavir/ritonavir. IV immunoglobulin therapy. No HCQ clinical efficacy. Cepharantine inhibition pangolins. Machine learning antivirals. Eat bitter substances. 59 new trials. Combining RNA and antibody tests. No SARS-CoV-2 in patient ward air. Influenza impact prevention. Encephalitis. Low CD4+ and CD8+ severe. G6PD-deficient issues. Cytokine storm. Biosensor detection. Immunopathogenesis

Supervised learning with word embeddings derived from PubMed captures latent knowledge about protein kinases and cancer.

Inhibiting protein kinases (PKs) that cause cancers has been an important topic in cancer therapy for years. So far, almost 8% of \u3e530 PKs have been targeted by FDA-approved medications, and around 150 protein kinase inhibitors (PKIs) have been tested in clinical trials. We present an approach based on natural language processing and machine learning to investigate the relations between PKs and cancers, predicting PKs whose inhibition would be efficacious to treat a certain cancer. Our approach represents PKs and cancers as semantically meaningful 100-dimensional vectors based on word and concept neighborhoods in PubMed abstracts. We use information about phase I-IV trials in ClinicalTrials.gov to construct a training set for random forest classification. Our results with historical data show that associations between PKs and specific cancers can be predicted years in advance with good accuracy. Our tool can be used to predict the relevance of inhibiting PKs for specific cancers and to support the design of well-focused clinical trials to discover novel PKIs for cancer therapy

2020-04-10 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: Extra NM HSD SNAP benefits. NM cases \u3e1000. Meds supply chain threatened. Mass graves in NY. Surgeon General screening app. Presidential briefing. Italian healthcare worker deaths. Taiwan tiered care model. Communicating risks to public. French public demand hydroxychloroquine. Vaccination pause dangers. Retesting needed after discharge. CDC report geography and incidence. UW clinical informatics response. UW preparedness guidelines. Wuhan outbreak control. CDC asymptomatic exposed worker guidelines. Mask innovation. Unemployment spikes. Workforce gaps. Workspace modifications reduce transmission. Guidelines and recommendations: ER physician, surgery, cardiopulmonary resuscitation, chest imaging, geriatrics, critically ill children, postpyloric tube placement, genitourinary malignancies, obstetrics, and home work health. Remdesivir clinically promising. Hydroxychloroquine safe but higher mortality with azithromycin. Lockdown health risks. Post-ICU syndrome. Tetracyline therapy potential. ACE2 review. Repurposing candidates. Patient self-triage tool. Video of aerosol spread and lingering. Modeling challenges. 34 new clinical trials registered today

2020-04-14 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: NMDOH county demographics online. NM emergency business loans. ABQ businesses violations. NM 5 new deaths 62 more cases. May 1 reopening too optimistic. MA contract tracing. Federal Ventilator Reserve. GM mass ventilator production. Ventilator-sharing device. $400M N-95 mask sterilization 60 sites. UNM PPE reprocessing online. Drug quality vulnerable. Managing urgent airway calls. Social distancing until 2022. SARS-Cov-2 blood supply. Contact tracing national blueprint. Mental health endangered. Successful surgical rapid response. Contact tracing medical ethics. Animal coronaviruses: human lessons. IDSA management guidelines. Ophthalmic practice. Pain management. Obstetrics management. Oncology practice. Forward triage. Scoring time-sensitive procedures. Outpatient structural heart disease. Thoracic surgery outcomes. Chest CT screening: epidemics. Sarcoma management. Endocrine diseases. Clinical pharmacists\u27 strategies. Non-invasive ventilation benefits. Essential laboratory testing. Psychiatric service. Hydroxychloroquine negative RCT. JAMA pharmacologic Tx review. Convalescent plasma. Promising antivirals. 55 clinical trials today. NYC hospitalization risk factors. Children milder disease. Blood morphology anomalies. No antimalarial consensus

2020-05-02/03 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: More NM cases. Free Shiprock testing. Prison release demands. 8 state parks reopen. Higher US deaths. NY PPE case dismissed. Orthopedic Tx down. European deaths down. UK mortality factors. People leaving large cities. Ending lockdown strategies. Public mask impact. Taiwan tracing. Homeless shelter prevalence. Homeless shelter outbreak. 50-state R0. COVID-19 decades later. US county tracking site. Hospital management model. COVID-19 behavioral transformation. Practice guidelines for: cardiology, IBD surgery, and rheumatic physical inactivity. Roche antibody test approved. Abbott antibody test EU-certified. Home anosmia assessment. CVD and ACE/ARBs. Tocilizumab early evidence. Tocilizumab systematic review. WHO vaccines trial. HCQ slower viral clearance. CBC predicts severity. Kidney disease meta-analysis. Innate/adaptive immunity timing. Combating misinformation. Mental health living reviews

2020-04-11/12 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: No NM church gatherings. NM a testing champ. Consolidation of elderly care. NM case update. 50-state disaster. Ventilator haggling. Economy reopening planning. PPE decontamination. Hospital ward contamination. Prolonged return to normal. FEMA projections. WHO tracking app. China SEIR model. Hubei epi. Mortality best measure. Covid-19 wave 2. Public should wear masks. Civil liberties. Safe grocery shopping. School closure impact. CDC caretaker guidelines. Psychiatric mobilization. Keep newborns with mom. C-section protocol. Italian obstetrics. Pediatric cardiac catherization. Chinese anesthesiology consensus. Cancer guidelines. Neuro-oncologic Tx. Radiology algorithm. Lung ultrasonography. ARF care. VTE common and predictable. Liver transplantation. Auto-immune treatments. Extracorporeal kidney involvement. Nutrition support. GI endoscopy. No stay-at-home for stroke. Intensive care collaboration. Supine swab collection. Lab tests for severity. Testing assay performance. False negative RT-PCR tests. IgM and IgG serum tests. FDA convalescent plasma. Blood purification device approval. Erythropoietin treatment. Tissue plasminogen activator. ECMO. Lopinavir/ritonavir study results. Immunotherapy review. Vaccine development. Hydroxychloroquine review. Candidates from in silico/virtual screening. Traditional Indian therapies. US trials update. Pathways and risk factors for death. ACE2 polymorphism. Severity in children. Lung tissue replication. Phylogenetic tracing. Text mining dataset. Risk by blood type