Curvature correction to the mobility of fluid membrane inclusions

For the first time, using rigorous low-Reynolds-number hydrodynamic theory on curved surfaces via a Stokeslet-type approach, we provide a general and concise expression for the leading-order curvature correction to the canonical, planar, Saffman-Delbrück value of the diffusion constant for a small inclusion embedded in an arbitrarily (albeit weakly) curved fluid membrane. In order to demonstrate the efficacy and utility of this wholly general result, we apply our theory to the specific case of calculating the diffusion coefficient of a locally curvature inducing membrane inclusion. By including both the effects of inclusion and membrane elasticity, as well as their respective thermal shape fluctuations, excellent agreement is found with recently published experimental data on the surface tension dependent mobility of membrane bound inclusions

Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy: A Review for the Otolaryngologist

Background: Cystic fibrosis (CF) is a genetic disease that may result in multiple systemic disorders and potentially fatal severe respiratory compromise. However, the advent of CF transmembrane conductance regulator (CFTR) modulators has changed the management of CF for patients with select mutations. Although clinical trials have highlighted increased pulmonary function and decreased exacerbations as a result of these novel therapies, their effect on the sinuses has not been well-described. Objective: Our objective is to review the CFTR modulators to provide otolaryngologists, physicians who frequently care for patients with CF, a basic understanding of these drugs and their effects on chronic rhinosinusitis (CRS) in patients with CF. Methods: The clinically approved and available CFTR modulators and specific indications for their use are reviewed. Additionally, a systematic review of these therapies and effects on CRS in CF was performed. Results: Four Food and Drug Administration approved CFTR modulators are available for patients with CF. Current drugs are approved for gating, residual function, or F508del mutations. Multiple reports describe CFTR modulators’ increase in transepithelial ion transport in nasal epithelial cultures; however, clinical studies regarding effects of these modulators on sinonasal health are limited to 5 studies that present new data of the effects of CFTR modulators in CRS. Conclusions: CFTR modulators have changed management of CF. Initial studies of these medications demonstrate promising results in CF; however, there is a paucity of literature describing the effect of CFTR modulators on CF-associated CRS, although initial results are encouraging

Observation of hard scattering in photoproduction events with a large rapidity gap at HERA

Events with a large rapidity gap and total transverse energy greater than 5 GeV have been observed in quasi-real photoproduction at HERA with the ZEUS detector. The distribution of these events as a function of the $\gamma p$ centre of mass energy is consistent with diffractive scattering. For total transverse energies above 12 GeV, the hadronic final states show predominantly a two-jet structure with each jet having a transverse energy greater than 4 GeV. For the two-jet events, little energy flow is found outside the jets. This observation is consistent with the hard scattering of a quasi-real photon with a colourless object in the proton.Comment: 19 pages, latex, 4 figures appended as uuencoded fil

Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review.

The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer. Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts. The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Cryptic species within the freshwater isopod Mesamphisopus capensis (Phreatoicidea: Amphisopodidae) in the Western Cape, South Africa: allozyme and 12S rRNA sequence data and morphometric evidence

The freshwater phreatoicidean isopod Mesamphisopus capensis has been regarded as the most widespread of the four Mesamphisopus species occurring in the Western Cape, South Africa. To determine whether this species was monotypic across its distribution over two mountainous regions, separated by a low-lying coastal plain remnant, genetic differentiation among populations from 11 localities was studied through allozyme electrophoresis of 12 loci and sequencing of a 338-bp 12S rRNA mtDNA fragment from representative individuals. Populations of the two regions were separated by a mean identity value of 0.477. Fixed allele differences at two loci distinguished these regions. Estimates of θ indicated substantial differentiation among populations across the entire sample, as well as within each of the regions. Topologies derived through parsimony and neighbour joining supported the monophyly of the two regions. On the basis of these topologies, allele frequencies and an allozyme dendrogram, five groups were identified. Discriminant function analyses, performed on body and pereopod variables independently, revealed these groups to be well differentiated with a high rate of correct a posteriori reclassification. Using genetic distance criteria these five distinct forms may be considered to be putative species. From a conservation perspective, the two regions can be seen to represent two evolutionarily significant units, while the five groups should be regarded as management units. © 2004 The Linnean Society of London.Articl

Genetic structure among populations of Potamonautes perlatus (Decapoda: Potamonautidae) from the Olifants River system in the Western Cape, South Africa

Populations of Potamonautes perlatus were sampled at various points along the Olifants Rivers (220 km), in the Western Cape to examine the degree of genetic variation. Allozyme electrophoresis revealed a near fixed allelic difference at one locus and extensive differentiation at another locus between populations from the upper and lower reaches of the Olifants River system. Limited hybridization in the region of population sympatry was observed. The narrow hybrid zone and the low occurrence of hybrids suggest selection against hybrids. These results provide evidence for two genetically distinct freshwater crab populations. We concluded that the genetic divergence between the two population groups represents a species boundary between the two populations.Articl