Cyt c (cytochrome c) has been traditionally envisioned as rapidly diffusing in two dimensions at the surface of the mitochondrial inner membrane when not engaged in redox reactions with physiological partners. However, the discovery of the extended lipid anchorage (insertion of an acyl chain of a bilayer phospholipid into the protein interior) suggests that this may not be exclusively the case. The physical and structural factors underlying the conformational changes that occur upon interaction of ferrous cyt c with phospholipid membrane models have been investigated by monitoring the extent of the spin state change that result from this interaction. Once transiently linked by electrostatic forces between basic side chains and phosphate groups, the acyl chain entry may occur between two parallel hydrophobic polypeptide stretches that are surrounded by positively charged residues. Alteration of these charges, as in the case of non-trimethylated (TML72K) yeast cyt c and Arg91Nle horse cyt c (where Nle is norleucine), led to a decline in the binding affinity for the phospholipid liposomes. The electrostatic association was sensitive to ionic strength, polyanions and pH, whereas the hydrophobic interactions were enhanced by conformational changes that contributed to the loosening of the tertiary structure of cyt c. In addition to proposing a mechanistic model for the extended lipid anchorage of cyt c, we consider what, if any, might be the physiological relevance of the phenomenon.

In high-risk rectal cancer, oxaliplatin-containing neoadjuvant therapy may promote an immune response that favours survival without metastatic progression.

Background The coronavirus disease (COVID-19) pandemic is an emerging threat across the African continent where national critical care capacity is underdeveloped or unknown. In this paper, we compile data on critical care capacity -- including number of ICU beds, number of ventilators, and number of physician and non-physician anesthesia providers -- for 54 African countries. Methods Data was compiled from a variety of resources including World Bank databases, local and international news media, government reports, local healthcare workers, and published scientific literature. Results Overall, data on number of ICU beds were available for 49 (91%) countries and on number of ventilators for 46 (85%) countries, respectively. Data on physician anesthesia providers and non-physician providers was available for 47 (87%) and 37 (69%) of the 54 African countries. Conclusion Most low and lower middle-income African countries have limited critical care capacity available to cope with potential surges in critical care demand due to COVID-19 outbreaks. Keywords: COVID-19, SARS-CoV-2, critical care capacity, ICU, ventilators, Africa

ObjectivesAs of 13 January 2021, there have been 3 113 963 confirmed cases of SARS-CoV-2 and 74 619 deaths across the African continent. Despite relatively lower numbers of cases initially, many African countries are now experiencing an exponential increase in case numbers. Estimates of the progression of disease and potential impact of different interventions are needed to inform policymaking decisions. Herein, we model the possible trajectory of SARS-CoV-2 in 52 African countries under different intervention scenarios.DesignWe developed a compartmental model of SARS-CoV-2 transmission to estimate the COVID-19 case burden for all African countries while considering four scenarios: no intervention, moderate lockdown, hard lockdown and hard lockdown with continued restrictions once lockdown is lifted. We further analysed the potential impact of COVID-19 on vulnerable populations affected by HIV/AIDS and tuberculosis (TB).ResultsIn the absence of an intervention, the most populous countries had the highest peaks in active projected number of infections with Nigeria having an estimated 645 081 severe infections. The scenario with a hard lockdown and continued post-lockdown interventions to reduce transmission was the most efficacious strategy for delaying the time to the peak and reducing the number of cases. In South Africa, projected peak severe infections increase from 162 977 to 2 03 261, when vulnerable populations with HIV/AIDS and TB are included in the analysis.ConclusionThe COVID-19 pandemic is rapidly spreading across the African continent. Estimates of the potential impact of interventions and burden of disease are essential for policymakers to make evidence-based decisions on the distribution of limited resources and to balance the economic costs of interventions with the potential for saving lives.

As many as 30% to 40% of locally advanced rectal cancer (LARC) patients experience metastatic progression of the disease. Recognizing the potential of the genetic cargo in tumor-derived exosomes, we hypothesized that plasma exosomal microRNA (miRNA) may reflect biological aggressiveness in LARC and provide new markers for rectal cancer aggressiveness and risk stratification. In a prospective LARC cohort ( NCT01816607 ), plasma samples were collected from 29 patients at the time of diagnosis, before neoadjuvant therapy and surgery. Exosomes, precipitated from plasma using a commercial kit, were verified by cryo-electron microscopy, nanoparticle tracking analysis, and western blotting. Expression of exosomal miRNAs was profiled using a miRCURY LNA miRNA microarray and validation of six miRNAs associated with pathological and clinical end-points was undertaken in plasma collected at the time of diagnosis from 64 patients in an independent prospective LARC cohort ( NCT00278694 ). In both cohorts, exosomal miR-141-3p and miR-375 were higher in patients with synchronous liver metastasis than in those without ( P = .010 and P = .017 respectively in the investigative cohort, and P < .001 for both in the validation cohort). Further , high exosomal miR-141-3p was associated with post-operative metastatic liver progression in the investigative cohort ( P = .034). Because both miRNAs are associated with tumor angiogenesis and immune modulation, we propose that these miRNAs in circulating exosomes may reflect rectal cancer aggressiveness and accordingly be candidate biomarkers for further investigations.