A systems approach to model natural variation in reactive properties of bacterial ribosomes

<p>Abstract</p> <p>Background</p> <p>Natural variation in protein output from translation in bacteria and archaea may be an organism-specific property of the ribosome. This paper adopts a systems approach to model the protein output as a measure of specific ribosome reactive properties in a ribosome-mediated translation apparatus. We use the steady-state assumption to define a transition state complex for the ribosome, coupled with mRNA, tRNA, amino acids and reaction factors, as a subsystem that allows a focus on the completed translational output as a measure of specific properties of the ribosome.</p> <p>Results</p> <p>In analogy to the steady-state reaction of an enzyme complex, we propose a steady-state translation complex for mRNA from any gene, and derive a maximum specific translation activity, <it>T</it>_{<it>a</it>(max)}, as a property of the ribosomal reaction complex. <it>T</it>_{<it>a</it>(max)}has units of <it>a</it>-protein output per time per <it>a</it>-specific mRNA. A related property of the ribosome, <inline-formula><m:math name="1752-0509-2-62-i1" xmlns:m="http://www.w3.org/1998/Math/MathML"><m:semantics><m:mrow><m:msub><m:mover accent="true"><m:mi>T</m:mi><m:mo>˜</m:mo></m:mover><m:mrow><m:mi>a</m:mi><m:mo stretchy="false">(</m:mo><m:mi>max</m:mi><m:mo>⁡</m:mo><m:mo stretchy="false">)</m:mo></m:mrow></m:msub></m:mrow><m:annotation encoding="MathType-MTEF"> MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGafmivaqLbaGaadaWgaaWcbaGaemyyaeMaeiikaGIagiyBa0MaeiyyaeMaeiiEaGNaeiykaKcabeaaaaa@3464@</m:annotation></m:semantics></m:math></inline-formula>, has units of <it>a</it>-protein per time per total RNA with the relationship <inline-formula><m:math name="1752-0509-2-62-i1" xmlns:m="http://www.w3.org/1998/Math/MathML"><m:semantics><m:mrow><m:msub><m:mover accent="true"><m:mi>T</m:mi><m:mo>˜</m:mo></m:mover><m:mrow><m:mi>a</m:mi><m:mo stretchy="false">(</m:mo><m:mi>max</m:mi><m:mo>⁡</m:mo><m:mo stretchy="false">)</m:mo></m:mrow></m:msub></m:mrow><m:annotation encoding="MathType-MTEF"> MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGafmivaqLbaGaadaWgaaWcbaGaemyyaeMaeiikaGIagiyBa0MaeiyyaeMaeiiEaGNaeiykaKcabeaaaaa@3464@</m:annotation></m:semantics></m:math></inline-formula> = <it>ρ</it>_{<it>a </it>}<it>T</it>_{<it>a</it>(max)}, where <it>ρ</it>_{<it>a </it>}represents the fraction of total RNA committed to translation output of <it>P</it>_{<it>a </it>}from gene <it>a </it>message. <it>T</it>_{<it>a</it>(max)}as a ribosome property is analogous to <it>k</it>_catfor a purified enzyme, and <inline-formula><m:math name="1752-0509-2-62-i1" xmlns:m="http://www.w3.org/1998/Math/MathML"><m:semantics><m:mrow><m:msub><m:mover accent="true"><m:mi>T</m:mi><m:mo>˜</m:mo></m:mover><m:mrow><m:mi>a</m:mi><m:mo stretchy="false">(</m:mo><m:mi>max</m:mi><m:mo>⁡</m:mo><m:mo stretchy="false">)</m:mo></m:mrow></m:msub></m:mrow><m:annotation encoding="MathType-MTEF"> MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGafmivaqLbaGaadaWgaaWcbaGaemyyaeMaeiikaGIagiyBa0MaeiyyaeMaeiiEaGNaeiykaKcabeaaaaa@3464@</m:annotation></m:semantics></m:math></inline-formula> is analogous to enzyme specific activity in a crude extract.</p> <p>Conclusion</p> <p>Analogy to an enzyme reaction complex led us to a ribosome reaction model for measuring specific translation activity of a bacterial ribosome. We propose to use this model to design experimental tests of our hypothesis that specific translation activity is a ribosomal property that is subject to natural variation and natural selection much like <it>V</it>_maxand <it>K</it>_mfor any specific enzyme.</p

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Hydrogen bonds in Al2O3 as dissipative two-level systems in superconducting qubits

Dissipative two-level systems (TLS) have been a long-standing problem in glassy solids over the last fifty years, and have recently gained new relevance as sources of decoherence in quantum computing. Resonant absorption by TLSs in the dielectric poses a serious limitation to the performance of superconducting qubits; however, the microscopic nature of these systems has yet to be established. Based on first-principles calculations, we propose that hydrogen impurities in Al(2)O(3) are the main source of TLS resonant absorption. Hydrogen is an ubiquitous impurity and can easily incorporate in Al(2)O(3). We find that interstitial H in Al(2)O(3) forms a hydrogen bond (O-H…O). At specific O-O distances, consistent with bond lengths found in amorphous Al(2)O(3) or near Al(2)O(3) surfaces or interfaces, the H atom feels a double well. Tunneling between two symmetric positions gives rise to resonant absorption in the range of 10 GHz, explaining the experimental observations. We also calculate the expected qubit-TLS coupling and find it to lie between 16 and 20 MHz, consistent with experimental measurements