Measuring Gaussian rigidity using curved substrates

The Gaussian (saddle splay) rigidity of fluid membranes controls their equilibrium topology but is notoriously difficult to measure. In lipid mixtures, typical of living cells, linear interfaces separate liquid ordered (LO) from liquid disordered (LD) bilayer phases at subcritical temperatures. Here we consider such membranes supported by curved supports that thereby control the membrane curvatures. We show how spectral analysis of the fluctuations of the LO-LD interface provides a novel way of measuring the difference in Gaussian rigidity between the two phases. We provide a number of conditions for such interface fluctuations to be both experimentally measurable and sufficiently sensitive to the value of the Gaussian rigidity, whilst remaining in the perturbative regime of our analysis.Comment: 5 pages, 3 figures. v2: version accepted for publicatio

Hydro-osmotic instabilities in active membrane tubes

We study a membrane tube with unidirectional ion pumps driving an osmotic pressure difference. A pressure driven peristaltic instability is identified, qualitatively distinct from similar tension-driven Rayleigh type instabilities on membrane tubes. We discuss how this instability could be related to the function and biogenesis of membrane bound organelles, in particular the contractile vacuole complex. The unusually long natural wavelength of this instability is in agreement with that observed in cells

Dynamics of passive and active membrane tubes

Utilising Onsager's variational formulation, we derive dynamical equations for the relaxation of a fluid membrane tube in the limit of small deformation, allowing for a contrast of solvent viscosity across the membrane and variations in surface tension due to membrane incompressibility. We compute the relaxation rates, recovering known results in the case of purely axis-symmetric perturbations and making new predictions for higher order (azimuthal) $m$-modes. We analyse the long and short wavelength limits of these modes by making use of various asymptotic arguments. We incorporate stochastic terms to our dynamical equations suitable to describe both passive thermal forces and non-equilibrium active forces. We derive expressions for the fluctuation amplitudes, an effective temperature associated with active fluctuations, and the power spectral density for both the thermal and active fluctuations. We discuss an experimental assay that might enable measurement of these fluctuations to infer the properties of the active noise. Finally we discuss our results in the context of active membranes more generally and give an overview of some open questions in the field.Comment: 14 pages, 9 figure

Enhancing your ‘webside’ manner: communication during COVID‐19

Virtual communication and interacting with patients while partially hidden behind a mask are now part of everyday clinical practice as a result of COVID‐19. Healthcare professionals need to develop new strategies to ensure that non‐verbal cues and the reassurance that subtle body language can provide are not compromised

Mutations in DSTYK and dominant urinary tract malformations.

ABSTRACT Introduction Congenital abnormalities of the kidney of the urinary tract are the most common cause of pediatric kidney failure. These disorders are highly heterogeneous, and their etiology is poorly understood. Methods We performed genome-wide linkage analysis and whole-exome sequencing in a family with autosomal dominant congenital abnormalities of the kidney of the urinary tract (7 affected family members). We also performed sequence analysis in 311 unrelated patients, as well as histologic and functional studies. Results Linkage analysis identified five regions of the genome that were shared among all affected family members. Exome sequencing identified a single rare deleterious variant within these linkage intervals, a heterozygous splice-site mutation in dual serine/threonine and tyrosine protein kinase (DSTYK). This variant, which resulted in aberrant gene product splicing, was present in all affected family members. Additional independent DSTYK mutations, including nonsense and splice-site mutations, were detected among 7/311 unrelated patients. DSTYK is highly expressed in the maturing epithelia of all major organs, localizing to cell membranes. Knockdown in zebrafish resulted in multi-organ developmental defects, resembling loss of fibroblast growth factor (FGF) signaling. Consistent with this finding, DSTYK colocalizes with FGF receptors in the ureteric bud and metanephric mesenchyme. Finally, DSTYK knockdown in human embryonic kidney cells inhibited FGF-stimulated ERK-phosphorylation, the principal signal downstream of receptor tyrosine kinases. Conclusions We detected DSTYK mutations in 2.2% of patients with congenital abnormalities of the kidney and urinary tract whom we studied, suggesting that DSTYK is a major determinant of human urinary tract development, downstream of FGF signaling

Does co-infection with vector-borne pathogens play a role in clinical canine leishmaniosis?

The severity of canine leishmaniosis (CanL) due to Leishmania infantum might be affected by other vector-borne organisms that mimic its clinical signs and clinicopathological abnormalities. The aim of this study was to determine co-infections with other vector-borne pathogens based on serological and molecular techniques in dogs with clinical leishmaniosis living in Spain and to associate them with clinical signs and clinicopathological abnormalities as well as disease severity. Sixty-one dogs with clinical leishmaniosis and 16 apparently healthy dogs were tested for Rickettsia conorii, Ehrlichia canis, Anaplasma phagocytophilum and Bartonella henselae antigens by the immunofluorescence antibody test (IFAT) and for E. canis, Anaplasma spp., Hepatozoon spp., Babesia spp. and filarioid DNA by polymerase chain reaction (PCR). Among the dogs examined by IFAT, the seroprevalences were: 69% for R. conorii, 57% for E. canis, 44% for A. phagocytophilum and 37% for B. henselae ; while the prevalences found by PCR were: 8% for Ehrlichia / Anaplasma, 3% for Anaplasma platys and 1% for H. canis. No other pathogen DNA was detected. Statistical association was found between dogs with clinical leishmaniosis and seroreactivity to R. conorii antigen (Fisher's exact test: P = 0.025, OR = 4.1, 95% CI = 1-17) and A. phagocytophilum antigen (Fisher's exact test: P = 0.002, OR = 14.3, 95% CI = 2-626) and being positive to more than one serological or molecular tests (co-infections) (Mann-Whitney test: U = 243, Z = -2.6, n = 14, n = 61, P = 0.01) when compared with healthy dogs. Interestingly, a statistical association was found between the presence of R. conorii, E. canis, A. phagocytophilum and B. henselae antibodies in sick dogs and some clinicopathological abnormalities such as albumin and albumin/globulin ratio decrease and increase in serum globulins. Furthermore, seroreactivity with A. phagocytophilum antigens was statistically associated with CanL clinical stages III and IV. This study demonstrates that dogs with clinical leishmaniosis from Catalonia (Spain) have a higher rate of co-infections with other vector-borne pathogens when compared with healthy controls. Furthermore, positivity to some vector-borne pathogens was associated with more marked clinicopathological abnormalities as well as disease severity with CanL