Opening Roads to Angola’s Future

Angola’s Road Threat Reduction Project, funded by the Humpty Dumpty Institute, cleared heavily mined roads in the country’s Planalto region. The project made safe travel possible among the over 200 small communities and other bordering nations. With help from the U.S. Department of Agriculture and HALO Trust, HDI opened several roads for the Angolan people, creating new possibilities for the developing government

Clearing Mined Roads for Agricultural Development in Angola: HDI\u27s Unique Public-Private Partnership

The Humpty Dumpty Institute (HDI) is putting the pieces together again—again! This time, HDI is putting together landmines, agriculture, milk and the U.S. government to create and implement an innovative partnership project for mine clearance in Angola

The Humpty Dumpty Institute Forges Innovative Public-Private Partnerships for Landmine Clearance in the Caucasus

The Humpty Dumpty Institute (HDI) is a New York-based, non-profit organization dedicated to establishing effective and innovative public-private partnerships to ameliorate the global landmine crisis. The Institute has ongoing partnerships with a variety of public and private organizations. Together, these partnerships have raised over $1.5 million (U.S.) for landmine detection and clearance operations in Armenia, Azerbaijan, Mozambique, Lebanon, Sri Lanka and Eritrea. To date, HDI’s programs have focused on clearance and subsequent economic re-development in partnership with the U.S. State Department (DOS), the International Trust Fund (ITF), the Children of Armenia Fund (COAF), the Marshall Legacy Institute (MLI), the New York Wine and Grape Foundation (NYWGF), SkyLink Aviation, the One Sri Lanka Foundation, HALO Trust, the Armenian National Mine Action Center, and the Azerbaijan National Agency for Mine Action (ANAMA)

Adrenergic Signaling-Induced Ultrastructural Strengthening of Intercalated Discs via Plakoglobin Is Crucial for Positive Adhesiotropy in Murine Cardiomyocytes

Intercalated discs (ICDs), which connect adjacent cardiomyocytes, are composed of desmosomes, adherens junctions (AJs) and gap junctions (GJs). Previous data demonstrated that adrenergic signaling enhances cardiac myocyte cohesion, referred to as positive adhesiotropy, via PKA-mediated phosphorylation of plakoglobin (PG). However, it was unclear whether positive adhesiotropy caused ultrastructural modifications of ICDs. Therefore, we further investigated the role of PG in adrenergic signaling-mediated ultrastructural changes in the ICD of cardiomyocytes. Quantitative transmission electron microscopy (TEM) analysis of ICD demonstrated that cAMP elevation caused significant elongation of area composita and thickening of the ICD plaque, paralleled by enhanced cardiomyocyte cohesion, in WT but not PG-deficient cardiomyocytes. STED microscopy analysis supported that cAMP elevation ex vivo enhanced overlap of desmoglein-2 (Dsg2) and N-cadherin (N-cad) staining in ICDs of WT but not PG-deficient cardiomyocytes. For dynamic analyses, we utilized HL-1 cardiomyocytes, in which cAMP elevation induced translocation of Dsg2 and PG but not of N-cad to cell junctions. Nevertheless, depletion of N-cad but not of Dsg2 resulted in a decrease in basal cell cohesion whereas positive adhesiotropy was abrogated in monolayers depleted for either Dsg2 or N-cad. In the WT mice, ultrastrutural changes observed after cAMP elevation were paralleled by phosphorylation of PG at serine 665. Our data demonstrate that in murine hearts adrenergic signaling enhanced N-cad and Dsg2 in the ICD paralleled by ultrastrutural strengthening of ICDs and that effects induced by positive adhesiotropy were strictly dependent on Pg

Radar sounding evidence for buried glaciers in the southern mid-latitudes of Mars

Lobate features abutting massifs and escarpments in the middle latitudes of Mars have been recognized in images for decades, but their true nature has been controversial, with hypotheses of origin such as ice-lubricated debris flows or glaciers covered by a layer of surface debris. These models imply an ice content ranging from minor and interstitial to massive and relatively pure. Soundings of these deposits in the eastern Hellas region by the Shallow Radar on the Mars Reconnaissance Orbiter reveal radar properties entirely consistent with massive water ice, supporting the debris-covered glacier hypothesis. The results imply that these glaciers formed in a previous climate conducive to glaciation at middle latitudes. Such features may collectively represent the most extensive nonpolar ice yet recognized on Mars

Clinical, histopathological and molecular features of dedifferentiated melanomas:An EORTC Melanoma Group Retrospective Analysis

PURPOSE: Dedifferentiated melanoma (DedM) poses significant diagnostic challenges. We aimed to investigate the clinical, histopathological and molecular features of DedM. Methylation signature (MS) and copy number profiling (CNP) were carried out in a subgroup of cases.PATIENTS AND METHODS: A retrospective series of 78 DedM tissue samples from 61 patients retrieved from EORTC (European Organisation for Research and Treatment of Cancer) Melanoma Group centres were centrally reviewed. Clinical and histopathological features were retrieved. In a subgroup of patients, genotyping through Infinium Methylation microarray and CNP analysis was carried out.RESULTS: Most patients (60/61) had a metastatic DedM showing most frequently an unclassified pleomorphic, spindle cell, or small round cell morphology akin to undifferentiated soft tissue sarcoma, rarely associated with heterologous elements. Overall, among 20 successfully analysed tissue samples from 16 patients, we found retained melanoma-like MS in only 7 tissue samples while a non-melanoma-like MS was observed in 13 tissue samples. In two patients from whom multiple specimens were analysed, some of the samples had a preserved cutaneous melanoma MS while other specimens exhibited an epigenetic shift towards a mesenchymal/sarcoma-like profile, matching the histological features. In these two patients, CNP was largely identical across all analysed specimens, in line with their common clonal origin, despite significant modification of their epigenome.CONCLUSIONS: Our study further highlights that DedM represents a real diagnostic challenge. While MS and genomic CNP may help pathologists to diagnose DedM, we provide proof-of-concept that dedifferentiation in melanoma is frequently associated with epigenetic modifications.</p

Overexpression of Inosine 5′-Monophosphate Dehydrogenase Type II Mediates Chemoresistance to Human Osteosarcoma Cells

overexpression in osteosarcoma patients with poor response to chemotherapy. The aim of this study was to provide evidence for direct involvement of IMPDH2 in the development of chemoresistance..IMPDH2 is directly involved in the development of chemoresistance in osteosarcoma cells, suggesting that targeting of IMPDH2 by RNAi or more effective pharmacological inhibitors in combination with chemotherapy might be a promising means of overcoming chemoresistance in osteosarcomas with high IMPDH2 expression

Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet

The physicochemical deposition of calcium-phosphate in the arterial wall is prevented by calcification inhibitors. Studies in cohorts of patients with rare genetic diseases have shed light on the consequences of loss-of-function mutations for different calcification inhibitors, and genetic targeting of these pathways in mice have generated a clearer picture on the mechanisms involved. For example, generalized arterial calcification of infancy (GACI) is caused by mutations in the enzyme ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (eNPP1), preventing the hydrolysis of ATP into pyrophosphate (PPi). The importance of PPi for inhibiting arterial calcification has been reinforced by the protective effects of PPi in various mouse models displaying ectopic calcifications. Besides PPi, Matrix Gla Protein (MGP) has been shown to be another potent calcification inhibitor as Keutel patients carrying a mutation in the encoding gene or Mgp-deficient mice develop spontaneous calcification of the arterial media. Whereas PPi and MGP represent locally produced calcification inhibitors, also systemic factors contribute to protection against arterial calcification. One such example is Fetuin-A, which is mainly produced in the liver and which forms calciprotein particles (CPPs), inhibiting growth of calcium-phosphate crystals in the blood and thereby preventing their soft tissue deposition. Other calcification inhibitors with potential importance for arterial calcification include osteoprotegerin, osteopontin, and klotho. The aim of the present review is to outline the latest insights into how different calcification inhibitors prevent arterial calcification both under physiological conditions and in the case of disturbed calcium-phosphate balance, and to provide a consensus statement on their potential therapeutic role for arterial calcification

A Validated Preclinical Animal Model for Primary Bone Tumor Research

Funding for this study was provided by the German Research Foundation (Grant DFG WA 3606/1-1 to F. Wagner and Grant HO 5056/1-1 to B.M. Holzapfel), the Australian Research Council (Future Fellowship Program) and the Technical University Munich Hans Fischer Senior Fellowship (D.W. Hutmacher), and a Research Fellowship from the National Health and Medical Research Council (#1044091 to J.-P. Lévesque

Evaluation of fluorescence in situ hybridisation (FISH) for the detection of fungi directly from blood cultures and cerebrospinal fluid from patients with suspected invasive mycoses

The aim of this study was to evaluate the diagnostic performance of in-house FISH (fluorescence in situ hybridisation) procedures for the direct identification of invasive fungal infections in blood cultures and cerebrospinal fluid (CSF) samples and to compare these FISH results with those obtained using traditional microbiological techniques and PCR targeting of the ITS1 region of the rRNA gene. In total, 112 CSF samples and 30 positive blood cultures were investigated by microscopic examination, culture, PCR-RFLP and FISH. The sensitivity of FISH for fungal infections in CSF proved to be slightly better than that of conventional microscopy (India ink) under the experimental conditions, detecting 48 (instead of 46) infections in 112 samples. The discriminatory powers of traditional microbiology, PCR-RFLP and FISH for fungal bloodstream infections were equivalent, with the detection of 14 fungal infections in 30 samples. However, the mean times to diagnosis after the detection of microbial growth by automated blood culture systems were 5 hours, 20 hours and 6 days for FISH, PCR-RFLP and traditional microbiology, respectively. The results demonstrate that FISH is a valuable tool for the identification of invasive mycoses that can be implemented in the diagnostic routine of hospital laboratories. © 2015 Da Silva et al