Characterization of muscle in OI Model mice

Abstract only availableOsteogenesis imperfecta (OI) is a congenital connective tissue disorder characterized by decreased bone mineral density and increased bone fragility and susceptibility to fracture. In addition to skeletal fragility, patients with OI reportedly have muscle weakness although currently no systematic evaluation of muscle function or morphology in humans or animal models of the disease has been performed. Normal type I collagen is coded for two genes located on different chromosomes: COL1A1 and COL1A2. The oim/oim mouse is homozygous for a null mutation in the COL1A2 gene and is a phenocopy of human type III OI (severe disease phenotype). Heterozygous mice (oim/+) harbor the null mutation in only one allele of the COL1A2 gene and model human patients with type I OI (mild disease phenotype). We wanted to determine whether the reported muscle weakness in OI patients is due to a muscle pathology. We analyzed the muscle mass, fiber morphology, and cross-sectional area of muscles fibers of the hind limb muscles (quadriceps, gastrocnemius, plantaris, tibialis anterior and soleus), as well as the fiber type composition of the soleus muscle of wildtype (wt), heterozygous (oim/+), and homozygous (oim/oim) mice. Our results demonstrate that the muscle mass/body mass, fiber morphology, cross-sectional area of hindlimb muscles, as well as fiber type composition of the soleus muscle of oim, oim/+ relative to wt (+/+) mouse muscles were not significantly different between the genotypes. We correlated our morphologic findings with a functional contractile assay and determined that muscle tension-force generation and nerve conduction are not impaired in oim/oim or oim/+ mice. These findings suggest that oim and oim/+ mice do not have inherent muscle pathology. This knowledge is important in our ultimate understanding of skeletal muscle in OI model mice and ultimately, humans with this disease.Life Sciences Undergraduate Research Opportunity Progra

Do type I collagen defects that cause Osteogenesis Imperfecta result in an inherent muscle pathology? [abstract]

Abstract only availableOsteogenesis imperfecta (OI) is a congenital connective tissue disorder characterized by decreased bone mineral density and increased bone fragility and susceptibility to fracture. In addition to skeletal fragility, patients with OI reportedly have muscle weakness, although currently no systematic evaluation of muscle function or morphology in humans or animal models of the disease has been performed. Normal type I collagen is coded for by two genes located on different chromosomes: COL1A1 and COL1A2. The oim/oim mouse is homozygous for a null mutation in the COL1A2 gene and is a phenocopy of a human type III OI (severe disease phenotype). Heterozygous mice (oim/+) harbor the null mutation in only one allele of the COL1A2 gene and model human patients with type I OI (mild disease phenotype). One of our aims is to characterize and determine muscle mass and cross-sectional area of hind limb muscle fibers in wild type (+/+), heterozygous (oim/+), and homozygous (oim/oim) mice. We analyzed muscle mass, fiber morphology, cross-sectional area of hindlimb muscles, as well as fiber type composition of the soleus muscle of oim, oim/+ relative to +/+ mouse muscles and determined that significant differences do not exist between genotypes. We also determined that there is no evidence of necrosis, degeneration, regeneration, hypertrophy or atrophy in hindlimb muscles of oim/oim and oim/+ mice. We correlated our morphologic findings with a functional contractile assay and determined that muscle tension-force generation and nerve conduction are not impaired in oim mice. These findings suggest that oim and oim/+ mice do not have inherent muscle pathology. This knowledge is important in our ultimate understanding of skeletal muscle in OI model mice and ultimately, humans with this disease.Biochemistry Departmen

Ticks produce highly selective chemokine binding proteins with antiinflammatory activity

Bloodsucking parasites such as ticks have evolved a wide variety of immunomodulatory proteins that are secreted in their saliva, allowing them to feed for long periods of time without being detected by the host immune system. One possible strategy used by ticks to evade the host immune response is to produce proteins that selectively bind and neutralize the chemokines that normally recruit cells of the innate immune system that protect the host from parasites. We have identified distinct cDNAs encoding novel chemokine binding proteins (CHPBs), which we have termed Evasins, using an expression cloning approach. These CHBPs have unusually stringent chemokine selectivity, differentiating them from broader spectrum viral CHBPs. Evasin-1 binds to CCL3, CCL4, and CCL18; Evasin-3 binds to CXCL8 and CXCL1; and Evasin-4 binds to CCL5 and CCL11. We report the characterization of Evasin-1 and -3, which are unrelated in primary sequence and tertiary structure, and reveal novel folds. Administration of recombinant Evasin-1 and -3 in animal models of disease demonstrates that they have potent antiinflammatory properties. These novel CHBPs designed by nature are even smaller than the recently described single-domain antibodies (Hollinger, P., and P.J. Hudson. 2005. Nat. Biotechnol. 23:1126–1136), and may be therapeutically useful as novel antiinflammatory agents in the future

Postharvest conservation of strawberry fruits at different storage conditions

O morango ? um produto muito apreciado pelos consumidores devido ?s caracter?sticas organol?pticas. Por?m, os frutos do morangueiro s?o altamente perec?veis depois de colhidos, sendo necess?rio adotar medidas alternativas para prolongar o per?odo de conserva??o dos frutos. O trabalho foi realizado com o objetivo de avaliar a conserva??o p?s-colheita de frutos de cultivares de morangueiro em diferentes condi??es de armazenamento. Os frutos de morangueiro utilizados no experimento foram cultivados na fazenda da empresa Mape Frutas, localizada no munic?pio de Datas-MG. Foram avaliados os frutos de oito cultivares (Festival, Campinas, Toyonoka, Dover, Oso Grande, Camarosa Diamante e Aromas). As condi??es de armazenamento e as an?lises foram realizadas no Laborat?rio de Tecnologia Biomassa do Cerrado da UFVJM. As condi??es de armazenamento foram em c?mara fria (temperatura m?dia 2,34?0,78?C e umidade relativa 89,93?4,14%) e condi??es ambiente (temperatura m?dia 17,43?2,68?C e umidade relativa 74,11?10,44%). As caracter?sticas foram analisadas por 12 dias, com avalia??es a cada 3 dias: apar?ncia, incid?ncia de doen?as, teores de s?lidos sol?veis totais, acidez titul?vel total, vitamina C e firmeza. O delineamento experimental utilizado foi em blocos casualizados, em esquema fatorial com oito cultivares de morangueiro e cinco tempos de armazenamento, com tr?s repeti??es, avaliados separadamente nas duas condi??es de armazenamento. Em condi??es ambiente os frutos de morangueiro podem ser armazenados por no m?ximo tr?s dias. O armazenamento em c?mara fria proporciona maior conserva??o p?s-colheita de frutos de morangueiro, podendo os frutos ser armazenados at? doze dias. A cv. Festival apresentou melhor conserva??o p?s-colheita nas duas condi??es de armazenamento, enquanto que as cvs. Toyonoka e Campinas apresentaram maior incid?ncia de doen?as e menor firmeza de frutos quando comparadas com as outras cultivares.Strawberry is a product appreciated by consumers due to the organoleptic characteristics. However, strawberry fruits are highly perishable after harvest, so alternative measures to prolong the shelf life of fruits are necessary. The objective of this experiment was to evaluate the fruit postharvest conservation of strawberry cultivars under different storage conditions. Strawberry fruits of eight cultivars (Festival, Campinas, Toyonoka, Dover, Oso Grande, Camarosa, Diamante and Aromas) were grown at ?Mape Frutas? farm, in Datas municipality, Minas Gerais State, Brazil. Strawberry fruits were stored at cold storage (2.34?0.78?C; 89.93?4.14% RH) and environmental conditions (17.43?2.68?C; 74.11?10.44%). The experimental design was randomized blocks in a factorial arrangement with eight strawberry cultivars and five storage times, with three replications. Fruits appearance, disease incidence, total soluble solids, titratable acidity, vitamin C and firmness were evaluated every 3 days, until 12 days. At room condition, strawberry fruit could be stored for only three days. Fruits kept in cold chamber kept quality until 12 days. Cv. Festival had the best postharvest shelf life in both storage conditions and cvs. Toyonoka and Campinas showed higher incidence of diseases and less fruit firmness when compared to the other cultivars

The cellular and synaptic architecture of the mechanosensory dorsal horn

The deep dorsal horn is a poorly characterized spinal cord region implicated in processing low-threshold mechanoreceptor (LTMR) information. We report an array of mouse genetic tools for defining neuronal components and functions of the dorsal horn LTMR-recipient zone (LTMR-RZ), a role for LTMR-RZ processing in tactile perception, and the basic logic of LTMR-RZ organization. We found an unexpectedly high degree of neuronal diversity in the LTMR-RZ: seven excitatory and four inhibitory subtypes of interneurons exhibiting unique morphological, physiological, and synaptic properties. Remarkably, LTMRs form synapses on between four and 11 LTMR-RZ interneuron subtypes, while each LTMR-RZ interneuron subtype samples inputs from at least one to three LTMR classes, as well as spinal cord interneurons and corticospinal neurons. Thus, the LTMR-RZ is a somatosensory processing region endowed with a neuronal complexity that rivals the retina and functions to pattern the activity of ascending touch pathways that underlie tactile perception

Integrated ecosystem assessment around islands of the tropical South Mid-Atlantic Ridge

The South Mid Atlantic Ridge comprises three main oceanic islands in the equatorial and tropical portions of the Atlantic Ocean. These islands are isolated from each other and equidistant from both the continental margins of South America and Africa, sharing common patterns but with different types of human use and pressures. Moreover, the areas beyond national jurisdiction between those islands are visited and exploited by distant fishing fleets and include large areas of shipping activity for commodities. Here, a pioneering integrated ecosystem assessment (IEA) process is constructed for the region among Saint Peter and Saint Paul’s Archipelago (Brazil), Saint Helena Island and Ascension Island (UK overseas territories). For that, we used a qualitative assessment of risks arising from anthropogenic activities, representing a novel contribution to the field. The Options for Delivering Ecosystem-Based Marine Management (ODEMM) approach was applied to trace sector–pressure–component pathways. A ‘linkage framework’ was outlined including pressures affecting each ecosystem component, and supported a process of knowledge attributions that scored the impact risks. All results were validated with regional stakeholders through workshops, including local and international management bodies, non-governmental organizations (NGOs) and scientists. The approach focused on a significant area among encompassing the open ocean, shallow and deep-sea biomes, analyzing the main sectors and pressures affecting the ecological components. Our results identified 14 sectors and 16 key pressures associated with 23 ecosystem components, totaling 780 impact chains. Fishing, shipping, wastewater, and tourism/recreation appeared as the top impacting sectors. Fishing and shipping were the most connected with ecosystem components links. Litter, species extraction, contaminants, and bycatch were the pressures that had the highest risk of impact values. Lastly, demersal and pelagic fish and pelagic and demersal elasmobranchs were the groups with the highest risk related to overall impacts, which were supported by local and regional evidence from long term monitoring programs and local studies. Our study demonstrated that these seemingly pristine islands and oceanic waters are already experiencing human impacts that should be addressed by local both conservation measures and international agreements. We also highlight the pressures that should be prioritized for better monitoring and policy, as well as those linkage components that have been less investigated

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression