Vascular rarefaction in peripheral skeletal muscle after experimental heart failure

A decrease in vascular density in peripheral skeletal muscle has been associated with exercise intolerance in humans with congestive heart failure (CHF). The purpose of this study was to determine whether CHF results in a reduction in vascular density in peripheral skeletal muscle. In this established model, CHF was induced by coronary artery ligation in New Zealand White rabbits and sham rabbits that underwent an identical surgical procedure without ligation of the coronary artery. At study termination, rabbits underwent hemodynamic testing and skeletal muscle analysis. The first series of rabbits was divided into sham (n = 6) and CHF (n = 6) 21 days postoperatively. Ten CHF rabbits were then examined 3 (n = 3), 7 (n = 3), and 14 days (n = 4) postoperatively. Vascular density in sham tibialis anterior muscle was 347 +/- 41 capillaries/mm2 or 1.20 +/- 0.11 capillaries/muscle fiber. In 21-day CHF rabbits, the capillary density was significantly lower, 236 +/- 14 capillaries/mm2 or 0.84 +/- 0.04 capillaries/muscle fiber (both P < 0.00001 vs. sham); PECAM protein was 2-fold lower (P < 0.0001) in muscle protein lysates; the fraction of apoptotic cells was greater, 3.8 +/- 2.2 vs. 0.69 +/- 0.56 (P < 0.02 vs. sham) with many TdT-mediated dUTP-biotin nick-end labeling-positive endothelial cells; and Bax protein was 2.8-fold greater (P < 0.0001). By regression analysis, vascular density tended to decrease over time (r2 = 0.572, P < 0.0001). Vascular rarefaction and endothelial apoptosis develop after experimental CHF and may contribute to the skeletal muscle abnormalities in this disease. Modulating vascular density may provide new approaches to treat exercise intolerance in CHF.     

The relationship between otolith size and estimated age of tigertooth croaker (Otolithes ruber Bloch and Schneider, 1801) in Oman Sea,Iran

The relationships between somatic growth and otolith dimensions, otolith size to estimated age and growth parameters of the tigertooth croaker (Otolithes ruber) were investigated in 100 specimens (size range: 19.1–52.0 cm, total length) from the Oman Sea area, September 2014. All 100 otoliths were sectioned and determined by age. The oldest specimen was a 4.5‐year‐old female with a total length of 40.6 cm; the youngest specimen was also a female estimated at 1 year of age with a total length of 19.1 cm. The von Bertalanffy growth equation was estimated as L_t = 54.70 (1 ? exp (?0.37 (t + 0.21))). Concluded was that there is a significant relationship between body size, otolith dimensions and estimated age of Otolithes ruber.     

Functional Anatomy of the Forelimb Muscles of the Ocelot (Leopardus pardalis)

The myology of most members of the cat family (Felidae) is poorly documented. This study describes the forelimb myology of the ocelot (Leopardus pardalis) and compares the forelimb anatomy of the ocelot to that of other well-documented felids (Felis catus, Panthera leo). A substantial number of myological features vary among the three species and are distributed in a manner consistent with major ecomorphological variables (prey size preference and locomotor repertoire). The origin of m. triceps brachii caput longum is most extensive in Panthera leo, consistent with the fact that this species pursues prey over greater distances compared to F. catus or L. pardalis. In addition, the origins and insertions of the pronator and supinator musculature are reduced in Felis catus, which has little need to supinate during locomotion or prey capture. Furthermore, muscles serving the digits are best developed in the lion and ocelot, both of which make greater use of the forelimb for grasping and manipulation than does the domestic cat. However, while the lion probably retains the primitive morphology for the family, the ocelot shows evidence of secondary adaptation to increased mobility of the digits. Overall, results indicate that additional studies of felid forelimb myology are warranted, as they are likely to provide valuable functional insights.     

Akt/Protein kinase B modulates macrophage inflammatory response to Francisella infection and confers a survival advantage in mice

The Gram-negative bacterium Francisella novicida infects primarily monocytes/macrophages and is highly virulent in mice. Macrophages respond by producing inflammatory cytokines that confer immunity against the infection. However, the molecular details of host cell response to Francisella infection are poorly understood. In this study, we demonstrate that F. novicida infection of murine macrophages induces the activation of Akt. Inhibition of Akt significantly decreases proinflammatory cytokine production in infected macrophages, whereas production of the anti-inflammatory cytokine IL-10 is enhanced. Analysis of the mechanism of Akt influence on cytokine response demonstrated that Akt promotes NF-kappaB activation. We have extended these findings to show that Akt activation may be regulated by bacterial genes associated with phagosomal escape. Infection with mglA mutants of F. novicida elicited sustained activation of Akt in comparison to cells infected with wild-type F. novicida. Concomitantly, there was significantly higher proinflammatory cytokine production and lower IL-10 production in cells infected with the mglA mutant. Finally, transgenic animals expressing constitutively active Akt displayed a survival advantage over their wild-type littermates when challenged with lethal doses of F. novicida. Together, these observations indicate that Akt promotes proinflammatory cytokine production by F. novicida-infected macrophages through its influence on NF-kappaB, thereby contributing to immunity against F. novicida infection.     

Localization of the proto-oncogene MOS to 8q11-q12 by in situ chromosomal hybridization

The human MOS proto-oncogene has been mapped previously to two different sites on chromosome 8 (8q22 and 8q11). Here we report in situ hybridization data from two different laboratories which confirm the localization of MOS to the proximal region of the long arm of chromosome 8, at 8q11-q12.     

A novel method to scale up fungal endophyte isolations

Studies involving fungal endophytes very often rely on surface-sterilisation of plant samples to enable endophyte isolations. However, surface-sterilisation can be very time-consuming, potentially limiting the number of samples processed. To overcome this limitation, a novel method was developed to bulk surface-sterilise multiple plant tissue samples simultaneously and separately. The method relies on 24 perforated Falcon? tubes, each containing a sample, sequentially transferred through a series of containers holding the sterilants. The samples that can be surface-sterilised using this method include roots, stems and leaves or entire seedlings. This method increased our throughput by a factor of 24 relative to conventional surface-sterilisation methods.     

Microprinted feeder cells guide embryonic stem cell fate

We introduce a non‐contact approach to microprint multiple types of feeder cells in a microarray format using immiscible aqueous solutions of two biopolymers. Droplets of cell suspension in the denser aqueous phase are printed on a substrate residing within a bath of the immersion aqueous phase. Due to their affinity to the denser phase, cells remain localized within the drops and adhere to regions of the substrate underneath the drops. We show the utility of this technology for creating duplex heterocellular stem cell niches by printing two different support cell types on a gel surface and overlaying them with mouse embryonic stem cells (mESCs). As desired, the type of printed support cell spatially direct the fate of overlaid mESCs. Interestingly, we found that interspaced mESCs colonies on differentiation‐inducing feeder cells show enhanced neuronal differentiation and give rise to dense networks of neurons. This cell printing technology provides unprecedented capabilities to efficiently identify the role of various feeder cells in guiding the fate of stem cells. Biotechnol. Bioeng. 2011;108: 2509–2516. © 2011 Wiley Periodicals, Inc.     

Improving the provision of ecosystem services from urban forest by integrating the species’ potential environmental functions in tree selecting process

Due to the fact that urban environments and population demands are evolving rapidly and species selection is inevitable, it is possible to gain substantial environmental benefit by implementing more effective urban tree planting programs, especially with the aim of increasing the upcoming provision of multiple ecosystem services (ES) through proper species selection. In this paper, we used a new approach to improve the potential of urban trees in optimizing more desirable environmental benefits. This was done by selecting the most appropriate tree species among a vast range of species based on their potential environmental function (both services and disservices) in Tabriz city, Iran. Also, three main planting scenarios (divided to six sub-scenarios) were developed so as to understand the long-term effectiveness of introducing the selected tree species in improving the environmental benefits (both urban forest structure and ES) in comparison with planting the existing tree species. The results indicate that regardless of the quantity of planting, the benefits of introducing the selected trees will be more than planting the existing species. Moreover, as the amount of the annual planting of the recommended species increases, so does the improvement in the projected tree characteristics and ES. This approach creates more opportunities which enable urban forest managers and policymakers to understand the importance of selecting the proper urban tree species when looking for a nature-based solution to promote the wellbeing of the urban population, to create more livable and ecologically sustainable cities and to mitigate urban environmental problems.

     

Transient Inhibition of FGFR2b-Ligands Signaling Leads to Irreversible Loss of Cellular β-Catenin Organization and Signaling in AER during Mouse Limb Development

The vertebrate limbs develop through coordinated series of inductive, growth and patterning events. Fibroblast Growth Factor receptor 2b (FGFR2b) signaling controls the induction of the Apical Ectodermal Ridge (AER) but its putative roles in limb outgrowth and patterning, as well as in AER morphology and cell behavior have remained unclear. We have investigated these roles through graded and reversible expression of soluble dominant-negative FGFR2b molecules at various times during mouse limb development, using a doxycycline/transactivator/tet(O)-responsive system. Transient attenuation (≤24 hours) of FGFR2b-ligands signaling at E8.5, prior to limb bud induction, leads mostly to the loss or truncation of proximal skeletal elements with less severe impact on distal elements. Attenuation from E9.5 onwards, however, has an irreversible effect on the stability of the AER, resulting in a progressive loss of distal limb skeletal elements. The primary consequences of FGFR2b-ligands attenuation is a transient loss of cell adhesion and down-regulation of P63, β1-integrin and E-cadherin, and a permanent loss of cellular β-catenin organization and WNT signaling within the AER. Combined, these effects lead to the progressive transformation of the AER cells from pluristratified to squamous epithelial-like cells within 24 hours of doxycycline administration. These findings show that FGFR2b-ligands signaling has critical stage-specific roles in maintaining the AER during limb development.     

Mannose-Binding Lectin 2 Gene and Risk of Adult Glioma

Background and Aims

The immune system is likely to play a key role in the etiology of gliomas. Genetic polymorphisms in the mannose-binding lectin gene, a key activator in the lectin complement pathway, have been associated with risk of several cancers.

Methods

To examine the role of the lectin complement pathway, we combined data from prospectively collected cohorts with available DNA specimens. Using a nested case-control design, we genotyped 85 single nucleotide polymorphisms (SNPs) in 9 genes in the lectin complement pathway and 3 additional SNPs in MBL2 were tested post hoc). Initial SNPs were selected using tagging SNPs for haplotypes; the second group of SNPs for MBL2 was selected based on functional SNPs related to phenotype. Associations were examined using logistic regression analysis. All statistical tests were two-sided. Nominal p-values are presented and are not corrected for multiple comparisons.

Results

A total of 143 glioma cases and 419 controls were available for this analysis. Statistically significant associations were observed for two SNPs in the mannose-binding lectin 2 (ML2) gene and risk of glioma (rs1982266 and rs1800450, test for trend p = 0.003 and p = 0.04, respectively, using the additive model). One of these SNPs, rs1800450, was associated with a 58% increase in glioma risk among those carrying one or two mutated alleles (odds ratio = 1.58, 95% confidence interval = 0.99–2.54), compared to those homozygous for the wild type allele.

Conclusions

Overall, our findings suggest that MBL may play a role in the etiology of glioma. Future studies are needed to confirm these findings which may be due to chance, and if reproduced, to determine mechanisms that link glioma pathogenesis with the MBL complement pathway.