Cytoskeletal control of B cell responses to antigens.

The actin cytoskeleton is essential for cell mechanics and has increasingly been implicated in the regulation of cell signalling. In B cells, the actin cytoskeleton is extensively coupled to B cell receptor (BCR) signalling pathways, and defects of the actin cytoskeleton can either promote or suppress B cell activation. Recent insights from studies using single-cell imaging and biophysical techniques suggest that actin orchestrates BCR signalling at the plasma membrane through effects on protein diffusion and that it regulates antigen discrimination through the biomechanics of immune synapses. These mechanical functions also have a role in the adaptation of B cell subsets to specialized tasks during antibody responses

A syndrome of severe idiopathic pulmonary parenchymal disease with pulmonary hypertension in Pekingese

Liza S Köster,1 Robert M Kirberger2 1Section of Medicine, Department of Clinical Sciences, Integrative Mammalian Research (IMR) Center, Ross University School of Veterinary Medicine (RUSVM), Basseterre, St Kitts, West Indies; 2Diagnostic Imaging Section, Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa Abstract: This paper describes 35 Pekingese dogs with a syndrome characterized by dyspnea, cyanosis, episodic syncope, soft pulmonary “Velcro” crackles, pulmonary hypertension (PH), and computed tomography and radiographic changes consistent with pulmonary parenchymal disease. The medical data base was searched with the criteria “Pekingese” and “syncope” or “dyspnea” or “tachypnea” or “pulmonary hypertension”, over a 36-month period. Inclusion criteria were echocardiographic changes consistent with noninvasive diagnosis of PH, either subjectively by B-mode or objectively by Doppler. Dogs were excluded (n=106) if there were insufficient or poor-quality radiographic or echocardiographic records or if diseases other than chronic pulmonary disease were found to be the etiology. The records of 35 dogs met these criteria and presented with a respiratory crises preceded by a history of chronic exercise intolerance and episodic syncope. The average age was 14.5 years (range: 7–19 years), with 21 males and 14 females. Most of the dogs had an interstitial lung pattern with radiographic evidence of right heart enlargement. There was a 77% (n=27) mortality and a median survival of 60 days (interquartile range: 9–210 days). This study highlights a cor pulmonale syndrome from PH due to chronic pulmonary parenchymal disease, with a grave prognosis, in middle-aged to geriatric population of Hong Kong Pekingese. Keywords: computed tomography, interstitial lung disease, dog, syncop

Canine babesiosis: a perspective on clinical complications, biomarkers, and treatment

Liza S Köster,1 Remo G Lobetti,2 Patrick Kelly1 1Department of Clinical Sciences, One Health Center for Zoonoses and Tropical Veterinary Medicine, Ross University School of Veterinary Medicine, St Kitts, West Indies; 2Bryanston Veterinary Hospital, Bryanston, South Africa Abstract: Canine babesiosis is a common tick transmitted disease of dogs worldwide. A number of Babesia sp. can infect dogs and the spectrum is increasing as molecular methods are developed to differentiate organisms. Clinical signs are generally attributed to hemolysis caused by the organisms in the erythrocytes but in some animals with some Babesia spp. there can be an immune mediated component to the anemia and/or a severe inflammatory reaction associated. This complicated form of canine babesiosis is associated with high morbidity and mortality. A variety of clinical markers has been investigated to enable clinicians to provide more accurate prognoses and adapt their treatments which vary according to the infecting species. In this review, we discuss the taxonomy, clinical signs, diagnostic imaging, clinical biomarkers, treatment, and prophylaxis of one of the most common and important diseases of dogs worldwide. Keywords: babesiosis, vector-borne disease, do

Myosin II filament dynamics in actin networks revealed with interferometric scattering microscopy

The plasma membrane and the underlying cytoskeletal cortex constitute active platforms for a variety of cellular processes. Recent work has shown that the remodeling acto-myosin network modifies local membrane organization, but the molecular details are only partly understood because of difficulties with experimentally accessing the relevant time and length scales. Here, we use interferometric scattering microscopy to investigate a minimal acto-myosin network linked to a supported lipid bilayer membrane. Using the magnitude of the interferometric contrast, which is proportional to molecular mass, and fast acquisition rates, we detect and image individual membrane-attached actin filaments diffusing within the acto-myosin network and follow individual myosin II filament dynamics. We quantify myosin II filament dwell times and processivity as functions of ATP concentration, providing experimental evidence for the predicted ensemble behavior of myosin head domains. Our results show how decreasing ATP concentrations lead to both increasing dwell times of individual myosin II filaments and a global change from a remodeling to a contractile state of the acto-myosin network

Growth Hormone-Releasing Hormone Receptor Splice Variant 1 is Frequently Expressed in Oral Squamous Cell Carcinomas

The expression of growth hormone-releasing hormone (GHRH) splice variant 1 (SV1) receptor in neoplastic lesions of the oral cavity was assessed. The sensitivity of HaCaT keratinocytes to GHRH analogs was also evaluated. Thirty-three benign precancerous oral lesions and 27 squamous cell carcinomas of the oral cavity were evaluated by immunohistochemistry for SV1 expression. SV1 expression in HaCaT keratinocytes was assessed by western blot. HaCaT proliferation was evaluated by cell counting. Anti-SV1 immunoreactivity was detected in only 9  % (three of 33) precancerous lesions (one hyperplasia and two dysplasias), while 44 % (12 of 27) carcinomas were positive for SV1 (p < 0.002). GHRH(1–29)NH2 and GHRH agonist JI-38 stimulated HaCaT proliferation in vitro, and this effect was blocked by GHRH antagonists. These results indicate that SV1 expression may be associated with the transition of precancerous lesions to carcinomas of the oral epithelium. GHRH antagonists may be useful for the management of the disease