Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis>studies

Background  

Human insulin-like growth factor-I (hIGF-I) is a growth factor which is highly resemble to insulin. It is essential for cell proliferation and has been proposed for treatment of various endocrine-associated diseases including growth hormone insensitivity syndrome and diabetes mellitus. In the present study, an efficient plant expression system was developed to produce biologically active recombinant hIGF-I (rhIGF-I) in transgenic rice grains.     

Naturally Occurring Disseminated Group B Streptococcus Infections in Postnatal Rats

Group B Streptococcus (Streptococcus agalactiae, GBS) is a gram-positive commensal and occasional opportunistic pathogen of the human vaginal, respiratory, and intestinal tracts that can cause sepsis, pneumonia, or meningitis in human neonates, infants, and immunosuppressed persons. We report here on a spontaneous outbreak of postnatal GBS-associated disease in rats. Ten of 26 (38.5%) 21- to 24-d-old rat pups died or were euthanized due to a moribund state in a colony of rats transgenic for the human diphtheria toxin receptor on a Munich–Wistar–Frömter genetic background. Four pups had intralesional coccoid bacteria in various organs without accompanying inflammation. GBS was isolated from the liver of 2 of these pups and from skin abscesses in 3 littermates. A connection with the transgene could not be established. A treatment protocol was evaluated in the remaining breeding female rats. GBS is a potentially clinically significant spontaneous infection in various populations of research rats, with some features that resemble late-onset postnatal GBS infection in human infants.Abbreviations: GBS, Group B Streptococcus; MWF, Munich Wistar Frömter; hDTR, human diphtheria toxin receptorStreptococci are gram-positive, coccoid bacteria that typically are classified according to their hemolytic capacity. α-hemolytic streptococci produce a zone of partial hemolysis that appears greenish on blood agar, whereas β-hemolytic streptococci produce a zone of complete hemolysis, and γ-hemolytic organisms produce no hemolysis on blood agar.²⁴ The β-hemolytic streptococci are further subdivided into Lancefield groups (A through G), according to cell-wall carbohydrate antigens.^24,29,39 The group B β-hemolytic Streptococcus (GBS) have been speciated as Streptococcus agalactiae.^28,39 It was first isolated as a causative agent of mastitis in cattle.²⁹ This organism has since been recognized as a cause of severe infection in human neonates.^28,39 In humans, GBS is harbored asymptomatically in the maternal genitourinary tract.^24,28 Infants can be infected and present with serious systemic disease in the first week of life (early-onset GBS) or from 1 wk to 3 mo of age (late-onset GBS).³⁹ In laboratory animals, rats have been used experimentally as models for neonatal^{1,6,7,20,37,38,43,44,47,50,51} or adult⁴⁵ GBS infection, but to our knowledge, GBS has not been associated with spontaneous disease in rats.     

Prothrombotic Effects of Thrombolytic Therapy in a Rat (Rattus norvegicus) Model of Venous Thrombolysis

The use of thrombolytic agents has greatly improved patient outcomes, but the prothrombotic response to these drugs in vivo is unknown. Approximately 24 h after we induced thrombosis in male Sprague–Dawley rats, we placed an infusion line in the inferior vena cava and administered either saline or a thrombolytic agent (tissue plasminogen activator [tPA] or plasmin) for 30 min. Blood was drawn immediately after infusion; rats were euthanized 24 h after infusion for collection of blood and tissue (inferior vena cava and thrombus). Thrombus size was decreased in the tPA-treated rats but not in those that received saline or plasmin; this change correlated with the significant rise in D-dimer levels noted immediately after infusion in the tPA-treated rats. Plasma soluble P-selectin, a prothrombotic marker, was elevated at 24 h in the plasmin group compared with the other treatment groups. There were no significant differences in plasma C3a, C5a, or C5b9 levels or in thrombus C3 levels between groups. According to ultrastructural analysis, thrombus structure and vein wall effects did not differ between groups. Local tPA did not induce a prothrombotic state during acute DVT or after thrombolytic therapy in a rodent model of venous thrombolysis. Conversely, levels of the prothrombotic marker plasma soluble P-selectin increased when plasmin was administered.Abbreviations: DVT, deep vein thrombosis; IVC, inferior vena cava; tPA, tissue plasminogen activatorDeep vein thrombosis (DVT) is part of a disease condition known as venous thromboembolism. Approximately 360,000 new cases of DVT occur annually^7,36 in the United States, and this number has not changed appreciably over the years.³³ DVT can lead to serious sequelae such as chronic venous insufficiency and postthrombotic syndrome,^4,13 and recurrence of thrombosis is a significant risk.¹² To prevent these complications, the goals of treatment are to restore vessel patency and prevent valvular damage.²⁴ Standard-of-care anticoagulants do not always meet both of these goals, and catheter-directed thrombolysis has arisen as an alternative treatment method.²⁴ This technique uses placement of a multiport catheter at the site of the thrombus, with subsequent infusion of a thrombolytic agent.²⁴ The thrombolytic agents most commonly used are plasminogen activators, such as tissue-plasminogen activator (tPA), urokinase plasminogen activator (uPA), and streptokinase. These agents work on the fibrinolytic system and catalyze the conversion of plasminogen to plasmin.⁶ Plasmin then binds to fibrin, which leads to breakdown of fibrin and initiates the formation of fibrin degradation products, such as D-dimer.^6,10 Recently, there has been increased interest in the use of plasmin,²⁰ due to its direct thrombolytic ability (already in the active form to break down fibrin) and enhanced safety profile when compared with plasminogen activators.²¹Inflammation plays an important role in the development and progression of DVT²⁷ and therefore has become a target for treatment of this disease. Soluble plasma P-selectin has been documented to be a biomarker of thrombosis, and increased concentrations are associated with a prothrombotic state.^2,25 Several components of the innate immune system, specifically the complement system, are upregulated in the presence of thrombolytics.^1,3 In addition, the presence of certain complement components (for example, C3) within the thrombus may lead to states of hypofibrinolysis.^14,16 Taken together, these factors may impede successful therapy via catheter-directed thrombolysis and lead to a poorer patient outcome.Therefore, we set out to determine whether thrombolytic agents create a prothrombotic environment during acute DVT, especially at the site of treatment with catheter-directed thrombolysis. Our hypothesis was that local and systemic prothrombotic indicators would be activated after therapy with thrombolytic agents with different mechanisms of action (indirect, recombinant tPA; direct thrombolytic, plasmin) in a rat model of venous thrombolysis.     

Sex-specific risk of cardiovascular disease and cognitive decline: pregnancy and menopause

Understanding the biology of sex differences is integral to personalized medicine. Cardiovascular disease and cognitive decline are two related conditions, with distinct sex differences in morbidity and clinical manifestations, response to treatments, and mortality. Although mortality from all-cause cardiovascular diseases has declined in women over the past five years, due in part to increased educational campaigns regarding the recognition of symptoms and application of treatment guidelines, the mortality in women still exceeds that of men. The physiological basis for these differences requires further research, with particular attention to two physiological conditions which are unique to women and associated with hormonal changes: pregnancy and menopause. Both conditions have the potential to impact life-long cardiovascular risk, including cerebrovascular function and cognition in women. This review draws on epidemiological, translational, clinical, and basic science studies to assess the impact of hypertensive pregnancy disorders on cardiovascular disease and cognitive function later in life, and examines the effects of post-menopausal hormone treatments on cardiovascular risk and cognition in midlife women. We suggest that hypertensive pregnancy disorders and menopause activate vascular components, i.e., vascular endothelium and blood elements, including platelets and leukocytes, to release cell-membrane derived microvesicles that are potential mediators of changes in cerebral blood flow, and may ultimately affect cognition in women as they age. Research into specific sex differences for these disease processes with attention to an individual’s sex chromosomal complement and hormonal status is important and timely.     

Waveguide evanescent field scattering microscopy: bacterial biofilms and their sterilization response via UV irradiation

Waveguide Evanescent Field Scattering (WEFS) microscopy is introduced as a new and simple tool for label‐free, high contrast imaging of bacteria and bacteria sensors. Bacterial microcolonies and single bacteria were discriminated both by their bright field images and by their evanescent scattering intensity. By comparing bright field images with WEFS images, the proportion of planktonic: sessile (i.e., “floating”: attached) bacteria were measured. Bacteria were irradiated with UV light, which limited their biofilm forming capability. A quantitative decrease in attachment of individual, sessile bacteria and in attached, microcolony occupied areas was easily determined within the apparent biofilms with increasing UV dose. WEFS microscopy is an ideal tool for providing rapid quantitative data on biofilm formation. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Incorporating Climate Change and Exotic Species into Forecasts of Riparian Forest Distribution

We examined the impact climate change (CC) will have on the availability of climatically suitable habitat for three native and one exotic riparian species. Due to its increasing prevalence in arid regions throughout the western US, we predicted that an exotic species, Tamarix, would have the greatest increase in suitable habitat relative to native counterparts under CC. We used an ecological niche model to predict range shifts of Populus fremontii, Salix gooddingii, Salix exigua and Tamarix, from present day to 2080s, under five general circulation models and one climate change scenario (A1B). Four major findings emerged. 1) Contrary to our original hypothesis, P. fremontii is projected to have the greatest increase in suitable habitat under CC, followed closely by Tamarix. 2) Of the native species, S. gooddingii and S. exigua showed the greatest loss in predicted suitable habitat due to CC. 3) Nearly 80 percent of future P. fremontii and Salix habitat is predicted to be affected by either CC or Tamarix by the 2080s. 4) By the 2080s, 20 percent of S. gooddingii habitat is projected to be affected by both Tamarix and CC concurrently, followed by S. exigua (19 percent) and P. fremontii (13 percent). In summary, while climate change alone will negatively impact both native willow species, Tamarix is likely to affect a larger portion of all three native species'' distributions. We discuss these and other results in the context of prioritizing restoration and conservation efforts to optimize future productivity and biodiversity. As we are accounting for only direct effects of CC and Tamarix on native habitat, we present a possible hierarchy of effects- from the direct to the indirect- and discuss the potential for the indirect to outweigh the direct effects. Our results highlight the need to account for simultaneous challenges in the face of CC.     

Cannibalism as an interacting phenotype: precannibalistic aggression is influenced by social partners in the endangered Socorro Isopod (Thermosphaeroma thermophilum)

Models for the evolution of cannibalism highlight the importance of asymmetries between individuals in initiating cannibalistic attacks. Studies may include measures of body size but typically group individuals into size/age classes or compare populations. Such broad comparisons may obscure the details of interactions that ultimately determine how socially contingent characteristics evolve. We propose that understanding cannibalism is facilitated by using an interacting phenotypes perspective that includes the influences of the phenotype of a social partner on the behaviour of a focal individual and focuses on variation in individual pairwise interactions. We investigated how relative body size, a composite trait between a focal individual and its social partner, and the sex of the partners influenced precannibalistic aggression in the endangered Socorro isopod, Thermosphaeroma thermophilum. We also investigated whether differences in mating interest among males and females influenced cannibalism in mixed sex pairs. We studied these questions in three populations that differ markedly in range of body size and opportunities for interactions among individuals. We found that relative body size influences the probability of and latency to attack. We observed differences in the likelihood of and latency to attack based on both an individual's sex and the sex of its partner but found no evidence of sexual conflict. The instigation of precannibalistic aggression in these isopods is therefore a property of both an individual and its social partner. Our results suggest that interacting phenotype models would be improved by incorporating a new conditional ψ, which describes the strength of a social partner's influence on focal behaviour.     

Symmetric cyanine dyes for detecting nucleic acids

A novel approach to the design of sensitive fluorescent probes for nucleic acids detection is proposed. Suitable modifications of tri- and pentamethine cyanine dyes in the polymethine chain and/or in the heterocyclic residues can result in a significant decrease in unbound dye fluorescence intensity and an increase in dye emission intensity in the presence of DNA compared to the unsubstituted dye. The sharp enhancement in the fluorescence intensity upon dye interaction with double-stranded DNA permits the application of the modified tri- and pentamethine dyes as fluorescent probes in double-stranded DNA detection in homogeneous assays.     

Diabetogenic diet-induced insulin resistance associates with lipid droplet proteins and adipose tissue secretome,but not with sexual dimorphic adipose tissue fat accumulation in Wistar rats

The role of sexual dimorphic adipose tissue fat accumulation in the development of insulin resistance is well known. However, whether vitamin A status and/or its metabolic pathway display any sex- or depot (visceral/subcutaneous)-specific pattern and have a role in sexual dimorphic adipose tissue development and insulin resistance are not completely understood. Therefore, to assess this, 5 weeks old Wistar male and female rats of eight from each sex were provided either control or diabetogenic (high fat, high sucrose) diet for 26 weeks. At the end, consumption of diabetogenic diet increased the visceral fat depots (p < 0.001) in the males and subcutaneous depot (p < 0.05) in the female rats, compared to their sex-matched controls. On the other hand, it caused adipocyte hypertrophy (p < 0.05) of visceral depot (retroperitoneal) in the females and subcutaneous depot of the male rats. Although vitamin A levels displayed sex- and depot-specific increase due to the consumption of diabetogenic diet, the expression of most of its metabolic pathway genes in adipose depots remained unaltered. However, the mRNA levels of some of lipid droplet proteins (perilipins) and adipose tissue secretory proteins (interleukins, lipocalin-2) did display sexual dimorphism. Nonetheless, the long-term feeding of diabetogenic diet impaired the insulin sensitivity, thus affected glucose clearance rate and muscle glucose-uptake in both the sexes of rats. In conclusion, the chronic consumption of diabetogenic diet caused insulin resistance in the male and female rats, but did not corroborate with sexual dimorphic adipose tissue fat accumulation or its vitamin A status.