Increased Stability of Nucleolar PinX1 in the Presence of TERT

PinX1, a nucleolar protein of 328 amino acids, inhibits telomerase activity, which leads to the shortening of telomeres. The C-terminal region of PinX1 is responsible for its nucleolar localization and binding with TERT, a catalytic component of telomerase. A fraction of TERT localizes to the nucleolus, but the role of TERT in the nucleolus is largely unknown. Here, we report a functional connection between PinX1 and TERT regarding PinX1 stability. The C-terminal of PinX1^205–328, a nucleolar fragment, was much more stable than the N-terminal of PinX1^1–204, a nuclear fragment. Interestingly, PinX1 was less stable in TERT-depleted cells and more stable in TERT-myc expressing cells. Stability assays for PinX1 truncation forms showed that both PinX1^1–328 and PinX1^205–328, nucleolar forms, were more rapidly degraded in TERT-depleted cells, while they were more stably maintained in TERT-overexpressing cells, compared to each of the controls. However, PinX1^1–204 was degraded regardless of the TERT status. These results reveal that the stability of PinX1 is maintained in nucleolus in the presence of TERT and suggest a role of TERT in the regulation of PinX1 steady-state levels.     

Oxidized low density lipoprotein impairs endothelial progenitor cell function by downregulation of E-selectin and integrin alpha(v)beta5

Background

Oxidized low density lipoprotein (oxLDL) has been shown to induce apoptosis and senescence of endothelial progenitor cells (EPC). In the present study, we hypothesized that even sub-apoptotic concentrations of oxLDL impair the angiogenic potential of EPC and investigated if this effect is mediated by affecting adhesion and incorporation.

Methods

A co-culture system of human microvascular endothelial cells and EPC was used to study the effect of sub-apoptotic concentrations of native (nLDL) and oxLDL on cell-cell interaction. The expression and the functional role of angiogenic adhesion molecules and integrins was monitored by FACS and neutralizing assay, respectively.

Results

We observed an inhibition of tube formation and impairment of EPC integration into the vascular network of mature endothelial cells by oxLDL. In contrast, nLDL did not affect angiogenic properties of EPC. Incubation of EPC with sub-apoptotic oxLDL concentrations significantly decreased E-selectin and integrin α_vβ₅ expression (37.6% positive events vs. 71.5% and 24.3% vs. 49.9% compared to control culture media without oxLDL). Interestingly, expression of α_vβ₃, VE-cadherin and CD31 remained unchanged. Blocking of E-selectin and integrin α_vβ₅ by neutralizing antibody effectively inhibited adhesion of EPC to differentiated endothelial cells (56.5% and 41.9% of control; p < 0.001).

Conclusion

In conclusion, oxidative alteration of LDL impairs angiogenic properties of EPC at sub-apoptotic levels by downregulation of E-selectin and integrin α_vβ₅, both substantial mediators of EPC-endothelial cell interaction.     

A framework for assessing readiness for tiger <Emphasis Type="Italic">Panthera tigris</Emphasis> reintroduction: a case study from eastern Cambodia

Reintroduction is a viable conservation strategy for large carnivores however such reintroductions require robust feasibility assessments, considering ecological, management, and social factors, prior to implementation. Plans are being developed in a number of tiger range countries, including Cambodia, for tiger Panthera tigris reintroductions in response to local and national extinctions. We provide a framework for undertaking feasibility assessments for tiger, and other large carnivore, reintroductions and present a number of methodological tools, and appropriate indicators, for conducting such assessments. We apply the framework to plans by the Royal Government of Cambodia for tiger reintroduction into Srepok Wildlife Sanctuary (formally Mondulkiri Protected Forest), eastern Cambodia. Srepok Wildlife Sanctuary forms part of a large (>13,000-km²) trans-boundary conservation landscape with potential to support a tiger source population. Current ungulate prey densities, assessed through robust line-transect sampling, at approximately 5.0 individuals per km² may be sufficient to support a breeding tiger population. However levels of protected area management and law enforcement fall below global standards for tiger recovery. Local communities, though supportive of conservation efforts, also identified a number of concerns regarding reintroduction. Therefore current ecological, social, and management conditions within SWS are not currently suitable for tiger reintroduction. However with improved and more effective law enforcement, combined with robust monitoring of the indicators within our framework, such conditions could be met. We recommend that our framework for assessing landscape suitability for reintroductions offers an effective road map for reintroduction-based recovery of tiger populations across tiger range countries.     

Adult and juvenile bearded capuchin monkeys handle stone hammers differently during nut-cracking

Wild bearded capuchin monkeys (Sapajus libidinosus) habitually use stone hammers to crack open palm nuts and seeds on anvils. This activity requires strength, balance, and precise movement of a large stone with respect to the item placed on an anvil. We explored how well young monkeys cope with these challenges by examining their behavior and the behavior of adults while they cracked palm nuts using a stone. Using video records, we compared actions of six juvenile (2–5 years) and six adult (7+ years) wild monkeys during their first 20 strikes with one unfamiliar ellipsoid, quartzite stone (540 g), and the outcomes of these strikes. Compared with adults, juveniles cracked fewer nuts, performed a more diverse set of exploratory actions, and less frequently placed one or both hands on top of the stone on the downward motion. Adults and juveniles displayed similar low frequencies of striking with a slanted trajectory, missing the nut, and losing control over the nut or stone after striking. These findings indicate that young monkeys control the trajectory of a stone adequately but that is not sufficient to crack nuts as effectively as adults do. Compared with juveniles, adults more quickly perceive how to grip the stone efficiently, and they are able to adjust their grip dynamically during the strike. Young monkeys develop expertise in the latter aspects of cracking nuts over the course of several years of regular practice, indicating that perceptual learning about these aspects of percussion occurs slowly. Juvenile and adult humans learning to use stones to crack nuts also master these features of cracking nuts very slowly.     

Role of the small Rho GTPases Rac1 and Cdc42 in host cell invasion of Campylobacter jejuni

Host cell invasion of the food-borne pathogen Campylobacter jejuni is one of the primary reasons of tissue damage in humans but molecular mechanisms are widely unclear. Here, we show that C. jejuni triggers membrane ruffling in the eukaryotic cell followed by invasion in a very specific manner first with its tip followed by the flagellar end. To pinpoint important signalling events involved in the C. jejuni invasion process, we examined the role of small Rho family GTPases. Using specific GTPase-modifying toxins, inhibitors and GTPase expression constructs we show that Rac1 and Cdc42, but not RhoA, are involved in C. jejuni invasion. In agreement with these observations, we found that internalization of C. jejuni is accompanied by a time-dependent activation of both Rac1 and Cdc42. Finally, we show that the activation of these GTPases involves different host cell kinases and the bacterial fibronectin-binding protein CadF. Thus, CadF is a bifunctional protein which triggers bacterial binding to host cells as well as signalling leading to GTPase activation. Collectively, our results suggest that C. jejuni invade host target cells by a unique mechanism and the activation of the Rho GTPase members Rac1 and Cdc42 plays a crucial role in this entry process.     

Stimulatory and inhibitory effects of EDTA on sugar transport by rat soleus muscle

The uptake of D-[¹⁴C]xylose by rat soleus muscle was stimulated rapidly and transiently by brief exposure to EDTA (0.1–20 mM). EDTA also stimulated xylose uptake in the presence of insulin (0.1 U/ml). Prolonged exposure to EDTA (60 min) inhibited insulin-stimulated xylose uptake and depressed ¹²⁵I-insulin binding; these effects were associated with the lowering of muscle ATP. The stimulatory effect was abolished by the substitution of Ca-EDTA (or Mg-EDTA) for EDTA; Ca-EDTA did not eliminate the inhibitory effect. There was no inhibitory effect when Ca²⁺ (5 mM) was added along with Ca-EDTA, or when Zn-EDTA was used instead. There was no effect of EGTA (5 mM) on xylose uptake measured in the presence or absence of insulin. It is concluded (1) that the stimulatory effect of EDTA is most likely due to the chelation of Mg²⁺, (2) that the inhibitory effects of EDTA are due to the chelation of some metal ion whith a higher affinity for the chelator than either Ca²⁺ or Mg²⁺.     

老挝北部宾夕法尼亚纪的一个新(筳)类动物群

作者报道了一个小型■类动物群,包括Eostaffella? sp., Pseudoendothyra sp., Staffella pseudosphae-roidea Dutkevich, Neostaffella ( N.)sp ., Profusulinella bona Grozdilova et Lebedeva以及P.cf .prisca (Depart) ,此动物群是在老挝北部琅勃拉邦省西南部的Thong Phiang Vilay村附近的石灰岩山中发现的。根据Profusulinella bona和P.cf. prisca的出现,该动物群的时代可归到晚石炭世宾夕法尼亚纪巴什基尔期或莫斯科期最早期。这是在老挝北部对该时代■类动物群的首次报道。当前■类动物群证明琅勃拉邦地区和泰国北部的黎地区在地质上有重要的关系,表明老挝北部地区从地质构造上属于印度支那板块的边缘。     

Discovery of a new open-air Hoabinhian site in Luang Prabang province (Lao PDR). Dating and technological study of the lithic assemblage

The Hoabinhian is a distinctive lithic techno-complex of mainland and Island Southeast Asia. Knowledge of its relationships with key patterns of technological change at a global scale has progressed over the last two decades. However, our understanding of the Hoabinhian as an indicator of evolution during Prehistory can be substantially enhanced by examining its regional and chronological variability. Here, we present the characteristics of original Hoabinhian artefacts found in a new open-air site at Houay Pano, near Lak Sip (Luang Prabang province, Laos). This technological study of such a classic assemblage, including sumatraliths dated to 5.5 ± 0.6 ka, is a major contribution to Laotian prehistory and our understanding of the tempo-spatial variability of the Hoabinhian techno-complex.