Structural stability of SARS-CoV-2 virus like particles degrades with temperature.

SARS-CoV-2 is a novel coronavirus which has caused the COVID-19 pandemic. Other known coronaviruses show a strong pattern of seasonality, with the infection cases in humans being more prominent in winter. Although several plausible origins of such seasonal variability have been proposed, its mechanism is unclear. SARS-CoV-2 is transmitted via airborne droplets ejected from the upper respiratory tract of the infected individuals. It has been reported that SARS-CoV-2 can remain infectious for hours on surfaces. As such, the stability of viral particles both in liquid droplets as well as dried on surfaces is essential for infectivity. Here we have used atomic force microscopy to examine the structural stability of individual SARS-CoV-2 virus like particles at different temperatures. We demonstrate that even a mild temperature increase, commensurate with what is common for summer warming, leads to dramatic disruption of viral structural stability, especially when the heat is applied in the dry state. This is consistent with other existing non-mechanistic studies of viral infectivity, provides a single particle perspective on viral seasonality, and strengthens the case for a resurgence of COVID-19 in winter.

Structural stability of SARS-CoV-2 degrades with temperature.

SARS-CoV-2 is a novel coronavirus which has caused the COVID-19 pandemic. Other known coronaviruses show a strong pattern of seasonality, with the infection cases in humans being more prominent in winter. Although several plausible origins of such seasonal variability have been proposed, its mechanism is unclear. SARS-CoV-2 is transmitted via airborne droplets ejected from the upper respiratory tract of the infected individuals. It has been reported that SARS-CoV-2 can remain infectious for hours on surfaces. As such, the stability of viral particles both in liquid droplets as well as dried on surfaces is essential for infectivity. Here we have used atomic force microscopy to examine the structural stability of individual SARS-CoV-2 virus like particles at different temperatures. We demonstrate that even a mild temperature increase, commensurate with what is common for summer warming, leads to dramatic disruption of viral structural stability, especially when the heat is applied in the dry state. This is consistent with other existing non-mechanistic studies of viral infectivity, provides a single particle perspective on viral seasonality, and strengthens the case for a resurgence of COVID-19 in winter. STATEMENT OF SCIENTIFIC SIGNIFICANCE: The economic and public health impact of the COVID-19 pandemic are very significant. However scientific information needed to underpin policy decisions are limited partly due to novelty of the SARS-CoV-2 pathogen. There is therefore an urgent need for mechanistic studies of both COVID-19 disease and the SARS-CoV-2 virus. We show that individual virus particles suffer structural destabilization at relatively mild but elevated temperatures. Our nanoscale results are consistent with recent observations at larger scales. Our work strengthens the case for COVID-19 resurgence in winter.

Temperature-dependent activity of kinesins is regulable.

Cytoskeletal transport in cells is driven by enzymes whose activity shows sensitive, typically Arrhenius, dependence on temperature. Often, the duration and outcome of cargo transport is determined by the relative success of kinesin vs. dynein motors, which can simultaneously bind to individual cargos and move in opposite direction on microtubules. The question of how kinesin and dynein activity remain coupled over the large temperature ranges experienced by some cells is one of clear biological relevance. We report a break in the Arrhenius behavior of both kinesin-1 and kinesin-3 enzymatic activity at 4.7 °C and 10.5 °C, respectively. Further, we report that this transition temperature significantly changes as a function of chemical background: addition of 200 mM TMAO increases transition temperatures by ∼6 °C in all cases. Our results show that Arrhenius trend breaks are common to all cytoskeletal motors and open a broad question of how such activity transitions are regulated in vivo. STATEMENT OF SIGNIFICANCE: Many cytoskeletal motors studied to date follow Arrhenius kinetics, at least from room temperature up to mammalian body temperature. However the thermal dynamic range is typically finite, and breaks in Arrhenius trends are commonly observed at biologically relevant temperatures. Here we report that the thermal dynamic range of kinesins is also limited and moreover that the location of the Arrhenius break for kinesins can shift significantly based on chemical backgrounds. This implies that the balance of multiple motor cargo transport along the cytoskeleton is far more tunable as a function of temperature than previously appreciated.

Brachmann-de Lange syndrome: autosomal dominant inheritance and male-to-male transmission.

We report on familial occurrence of the Brachmann-de Lange syndrome (BDLS): a mildly affected father and his severely affected son and daughter who have different mothers. Both children are severely affected while the father has a much milder but definite BDLS phenotype. Our report documents the third example of male-to-male transmission and adds to the argument against exclusively maternal transmission in familial cases. In addition, our findings illustrate the occurrence of severe manifestations in cases of familial BDLS.

Reform: a test of management fundamentals.

The structure of the country's healthcare system is obviously far from being an easy one to understand. The challenge is upon the healthcare industry to carefully and systematically assess what works and what should be enhanced.

The role of the contralateral limb in below-knee amputee gait.

Very little quantitative biomechanical research has been carried out evaluating issues relevant to prosthetic management. The literature available suggests that amputees may demonstrate an asymmetrical gait pattern. Furthermore, studies suggest that the forces occurring during amputee gait may be unequally distributed between the contralateral and prosthetic lower limbs. This study investigates the role of the contralateral limb in amputee gait by determining lower limb joint reaction forces and symmetry of motion in an amputee and non-amputee population. Seven adult below-knee amputees and four non-amputees participated in the study. Testing involved collection of kinematic coordinate data employing a WATSMART video system and ground reaction force data using a Kistler force plate. The degree of lower limb symmetry was determined using bilateral angle-angle diagrams and a chain encoding technique. Ankle, knee and hip joint reaction forces were estimated in order to evaluate the forces acting across the joints of the amputee's contralateral limb. The amputees demonstrated a lesser degree of lower limb symmetry than the non-amputees. This asymmetrical movement was attributed to the inherent variability of the actions of the prosthetic lower limb. The forces acting across the joints of the contralateral limb were not significantly higher than that of the non-amputee. This suggests that, providing the adult amputee has a good prosthetic fit, there will not be increased forces across the joints of the contralateral limb and consequently no predisposition for the long-term wearer to develop premature degenerative arthritis.

Successful surgical repair in a patient with mitral stenosis, calcified left atrium and severe tricuspid regurgitation with a giant right atrium.

Successful mitral valve replacement and tricuspid annuloplasty were performed on a 66-year-old woman who had a calcified left atrium, giant right atrium, calcified mural thrombus and normal pulmonary pressures. Successful repair in such cases depends on an adequate preoperative investigation and a surgical approach tailored to the individual.