The interaction between nesprins and sun proteins at the nuclear envelope is critical for force transmission between the nucleus and cytoskeleton

Maintaining physical connections between the nucleus and the cytoskeleton is important for many cellular processes that require coordinated movement and positioning of the nucleus. Nucleo-cytoskeletal coupling is also necessary to transmit extracellular mechanical stimuli across the cytoskeleton to the nucleus, where they may initiate mechanotransduction events. The LINC (Linker of Nucleoskeleton and Cytoskeleton) complex, formed by the interaction of nesprins and SUN proteins at the nuclear envelope, can bind to nuclear and cytoskeletal elements; however, its functional importance in transmitting intracellular forces has never been directly tested. This question is particularly relevant since recent findings have linked nesprin mutations to muscular dystrophy and dilated cardiomyopathy. Using biophysical assays to assess intracellular force transmission and associated cellular functions, we identified the LINC complex as a critical component for nucleo-cytoskeletal force transmission. Disruption of the LINC complex caused impaired propagation of intracellular forces and disturbed organization of the perinuclear actin and intermediate filament networks. Although mechanically induced activation of mechanosensitive genes was normal (suggesting that nuclear deformation is not required for mechanotransduction signaling) cells exhibited other severe functional defects after LINC complex disruption; nuclear positioning and cell polarization were impaired in migrating cells and in cells plated on micropatterned substrates, and cell migration speed and persistence time were significantly reduced. Taken together, our findings suggest that the LINC complex is critical for nucleo-cytoskeletal force transmission and that LINC complex disruption can result in defects in cellular structure and function that may contribute to the development of muscular dystrophies and cardiomyopathies.     

Inference of population structure and patterns of gene flow in canine heartworm (Dirofilaria immitis)

Understanding the genetic variation within a parasitic species is crucial to implementing successful control programs and preventing the dispersal of drug resistance alleles. We examined the population genetics and structure of canine heartworm (Dirofilaria immitis) by developing a panel of 11 polymorphic microsatellite loci for this abundant parasite. In total, 192 individual nematodes were opportunistically sampled from 9 geographic regions in the United States and Mexico and genotyped. Population genetic analyses indicate the presence of 4 genetic clusters. The canine heartworm samples used in this study were characterized by low heterozygosity, with eastern and central North America experiencing high levels of reciprocal gene flow. Geographic barriers impede the movement of vectors and infected hosts west of the Rocky Mountains and south of the Central Mexican Plateau. This, combined with corridors of contiguous habitat, could influence the spread of drug resistance alleles.     

Denture-related stomatitis managed with tissue conditioner and hard autopolymerising reline material

doi: 10.1111/j.1741–2358.2010.00398.x
Denture related stomatitis managed with tissue conditioner and hard autopolymerising reline material. Objective: To compare the response of denture‐related stomatitis (DS) under management with a tissue conditioner (TC) and autopolymerising hard reline material (AHRM). Background data: Denture‐related stomatitis affects up to 75% of denture wearers; not wearing the denture at night, using TC or prescribing topical or systemic antifungal agents could reduce its incidence. Materials and methods: This was a double‐blind study consisting of 44 participants with DS who wear denture; they were randomly divided into two unmatched groups according to the material used for the management of DS. The TC was replaced weekly, and the AHRM was placed at the beginning of the study and was not changed for 4 weeks. A dentist performed an initial and a weekly clinical diagnosis for DS; the clinical situation was recorded by means of photographs for each week. Results: Both TC and AHRM were effective in the management of DS. Significant differences were found in the DS resolution time (p < 0.001), taking longer for the TC. Conclusions: Both the tissue conditioner and AHRM are effective for the management of DS, but AHRM requires less time for recovery and as a result fewer appointments are required for the patient.     

Analysis of Wuchereria bancrofti infections in a village community in northern Nigeria: increased prevalence in individuals infected with Onchocerca volvulus

Infections with Wuchereria bancrofti causing lymphatic filariasis still represent one of the major health problems in the tropics, with 120 million people infected and over 750 million exposed to this filarial parasite. We have studied lymphatic filariasis infections as part of a multi-parasite survey in a village community in the savannah of northern Nigeria. We analysed serum samples from 341 individuals aged 5-70 years, detecting a W. bancrofti circulating antigen using the commercially available ICT Filariasis card test. The prevalence of infections was 10% and clearly age-dependent, increasing from below 2% in children to over 20% in subjects older than 40 years. Measuring IgG4 antibodies against the recombinant W. bancrofti antigen SXP1 showed that 36% of all tested individuals had been at least exposed to the parasite. Antibody levels also increased very significantly with age. A further analysis measuring Onchocerca volvulus-specific IgG4 antibodies showed a very significant association between infections with O. volvulus and those with W. bancrofti. Our data show that infections with W. bancrofti in Nigeria are still a frequently occurring health problem, since they are more prevalent than previously reported, and that individuals with an O. volvulus infection are more often infected with W. bancrofti than expected statistically.     

Molecular evidence for the monophyly of tenrecidae (mammalia) and the timing of the colonization of Madagascar by Malagasy Tenrecs

Tenrecs are a diverse family of insectivores, with an Afro-Malagasian biogeographic distribution. Three subfamilies (Geogalinae, Oryzorictinae, Tenrecinae) are restricted to Madagascar and one subfamily, the otter shrews (Potamogalinae), occurs on the mainland. Morphological studies have generated conflicting hypotheses according to which both tenrecids and Malagassy tenrecs are either monophyletic or paraphyletic. Competing hypotheses have different implications for the biogeographic history of Tenrecidae. At present, there are no molecular studies that address these hypotheses. The present study provides sequences of a nuclear protein-coding gene (vWF) and the mitochondrial 12S rRNA, tRNA valine, and 16S rRNA genes from a potamogaline (Micropotamogale). New sequences of these genes are also reported for the tenrecine, Tenrec ecaudatus. The 12S sequences from these taxa were combined with data already available for this locus from two other tenrecids (Echinops telfairi, subfamily Tenrecinae and Oryzorictes talpoides, subfamily Oryzorictinae). Phylogenetic analyses provided strong bootstrap support for the monophyly of Tenrecidae and Malagasy tenrecs. The majority of statistical tests rejected morphological claims for both a Tenrecinae--Chrysochloridae clade and an Oryzorictinae--Potamogalinae clade. Molecular clock estimates suggest a split of otter shrews and Malagasy tenrecs at approximately 53 MYA. We estimate that the ancestor of Malagasy tenrecs dispersed to Madagascar subsequent to this split but prior to about 37 MYA.     

Functional and structural impact of pirfenidone on the alterations of cardiac disease and diabetes mellitus

A synthetic compound, termed pirfenidone (PFD), is considered promising for the treatment of cardiac disease. It leads to beneficial effects in animal models of diabetes mellitus (DM); as well as in heart attack, atrial fibrillation, muscular dystrophy, and diabetic cardiomyopathy (DC). The latter is a result of alterations linked to metabolic syndrome as they promote cardiac hypertrophy, fibrosis and contractile dysfunction. Although reduced level of fibrosis and stiffness represent an essential step in the mechanism of PFD action, a wide range of functional effects might also contribute to the therapeutic benefits. For example, PFD stimulates L-type voltage-gated Ca²⁺ channels (LTCCs), which are pivotal for a process known as excitation–contraction coupling (ECC). Recent evidence suggests that these two types of actions – namely structural and functional – aid in treating both cardiac disease and DM. This view is supported by the fact that in DC, for example, systolic dysfunction arises from both cardiac stiffness linked to fibrosis and down-regulation of ECC. Thus, not surprisingly, clinical trials have been conducted with PFD in the settings of DM, for treating not only cardiac but also renal disease. This review presents all these concepts, along with the possible mechanisms and pathophysiological consequences.     

Fission‐fusion dynamics of Guiana dolphin (Sotalia guianensis) groups at Pipa Bay,Rio Grande do Norte,Brazil

Fission‐fusion dynamics seem to reflect individual decisions as well as temporal and spatial variations in the organization of groups of the same species. To understand the group dynamics of the Guiana dolphin, Sotalia guianensis, at Pipa Bay, Brazil, we investigated the three dimensions of a fission‐fusion social system: (1) variation in spatial cohesion, (2) variation in party size, and (3) variation in party composition. Sampling took place from December 2007 to February 2009 over 176 d and we analyzed the behavioral patterns of 658 groups. Within subgroups, animals remained cohesive, particularly in groups of adults and calves. Greater cohesion was also observed during resting and fission‐fusion rates were higher during milling and feeding. Groups composed of adults and juveniles showed a higher dynamics index (group size variation as a function of time) than groups composed only of adults and the fission‐fusion rate was higher during dry periods. Guiana dolphin groups frequently changed their group size and composition every 20 min on average. Taking these factors into consideration, we suggest that the Guiana dolphin demonstrates fission‐fusion dynamics, a pattern of behavior similar to what has been observed in other coastal odontocete species, such as Tursiops spp. and Lagenorhynchus obscurus.