Technology transfer within the NASA Goddard Space Flight Center

Viewgraphs on technology transfer within the NASA Goddard Space Flight Center presented to Civil Space Technology Development workshop on technology transfer and effectiveness are provided. Topics covered include: obstacles to technology transfer; technology transfer improvement program at GSFC: communication between technology developers and users; and user feedback to technologists

Cx43 and mechanotransduction in bone

Bone adaptation to changes in mechanical stimuli occurs by adjusting bone formation and resorption by osteoblasts and osteoclasts, to maintain optimal bone mass. Osteocytes coordinate the actions of these cells on the bone surface by sensing mechanical forces and producing cytokines that increase or prevent osteoblast and osteoclast differentiation and function. Channels formed by connexins (Cxs) and, in particular, connexin 43 (Cx43) in osteoblasts and osteocytes are central part of this mechanism to control bone mass. Cx43 hemichannels are opened by fluid flow and mediate the anti-apoptotic effect of mechanical stimulation in vitro, suggesting that Cx43 participates in mechanotransduction. However, mice lacking Cx43 in osteoblasts and/or osteocytes show an increased anabolic response to loading and decreased catabolic response to unloading. This evidence suggests that Cx43 channels expressed in osteoblastic cells are not required for the response to mechanical stimulation, but mediate the consequence of lack thereof. The molecular basis of these unexpected responses to mechanical stimulation is currently under investigation

Improvements in newborn care and newborn resuscitation following a quality improvement program at scale: results from a before and after study in Tanzania

Background: Every year, more than a million of the world’s newborns die on their first day of life; as many as two-thirds of these deaths could be saved with essential care at birth and the early newborn period. Simple interventions to improve the quality of essential newborn care in health facilities – for example, improving steps to help newborns breathe at birth – have demonstrated up to 47% reduction in newborn mortality in health facilities in Tanzania. We conducted an evaluation of the effects of a large-scale maternal-newborn quality improvement intervention in Tanzania that assessed the quality of provision of essential newborn care and newborn resuscitation. Methods: Cross-sectional health facility surveys were conducted pre-intervention (2010) and post intervention (2012) in 52 health facilities in the program implementation area. Essential newborn care provided by health care providers immediately following birth was observed for 489 newborns in 2010 and 560 in 2012; actual management of newborns with trouble breathing were observed in 2010 (n = 18) and 2012 (n = 40). Assessments of health worker knowledge were conducted with case studies (2010, n = 206; 2012, n = 217) and a simulated resuscitation using a newborn mannequin (2010, n = 299; 2012, n = 213). Facility audits assessed facility readiness for essential newborn care. Results: Index scores for quality of observed essential newborn care showed significant overall improvement following the quality-of-care intervention, from 39% to 73% (p <0.0001). Health worker knowledge using a case study significantly improved as well, from 23% to 41% (p <0.0001) but skills in resuscitation using a newborn mannequin were persistently low. Availability of essential newborn care supplies, which was high at baseline in the regional hospitals, improved at the lower-level health facilities. Conclusions: Within two years, the quality improvement program was successful in raising the quality of essential newborn care services in the program facilities. Some gaps in newborn care were persistent, notably practical skills in newborn resuscitation. Continued investment in life-saving improvements to newborn care through the health services is a priority for reduction of newborn mortality in Tanzania

Inhibition of Toll-Like Receptor 4 Signaling Mitigates Microvascular Loss but Not Fibrosis in a Model of Ischemic Acute Kidney Injury

The development of chronic kidney disease (CKD) following an episode of acute kidney injury (AKI) is an increasingly recognized clinical problem. Inhibition of toll-like receptor 4 (TLR4) protects renal function in animal models of AKI and has become a viable therapeutic strategy in AKI. However, the impact of TLR4 inhibition on the chronic sequelae of AKI is unknown. Consequently, we examined the chronic effects of TLR4 inhibition in a model of ischemic AKI. Mice with a TLR4-deletion on a C57BL/6 background and wild-type (WT) background control mice (C57BL/6) were subjected to bilateral renal artery clamping for 19 min and reperfusion for up to 6 weeks. Despite the acute protective effect of TLR4 inhibition on renal function (serum creatinine 1.6 ± 0.4 mg/dL TLR4-deletion vs. 2.8 ± 0.3 mg/dL·WT) and rates of tubular apoptosis following ischemic AKI, we found no difference in neutrophil or macrophage infiltration. Furthermore, we observed significant protection from microvascular rarefaction at six weeks following injury with TLR4-deletion, but this did not alter development of fibrosis. In conclusion, we validate the acute protective effect of TLR4 signal inhibition in AKI but demonstrate that this protective effect does not mitigate the sequential fibrogenic response in this model of ischemic AKI

TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions

Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here, we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n = 14), with the major allele correlated with later age at death (p = 0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n = 75), again finding that the major allele associates with later age at death (p = 0.016), as well as later age at onset (p = 0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease

Precis of Vaulting Ambition: Sociobiology and the Quest for Human Nature

The debate about the credentials of sociobiology has persisted because scholars have failed to distinguish the varieties of sociobiology and because too little attention has been paid to the details of the arguments that are supposed to support the provocative claims about human social behavior. I seek to remedy both dcfieieneies. After analysis of the relationships among different kinds of sociobiology and contemporary evolutionary theory, I attempt to show how some of the studies of the behavior of nonhuman animals meet the methodological standards appropriate to evolutionary research. I contend that the efforts of E. O. Wilson, Richard Alexander, Charles Lumsden, and others to generate conclusions about human nature are flawed, both because they apply evolutionary ideas in an unrigorous fashion and because they use dubious assumptions to connect their evolutionary analyses with their conclusions. This contention rests on analyses of many of the major sociobiological proposals about human social behavior, including: differences in sex roles, racial hostility, homosexuality, conflict between parents and adolescent offspring, incest avoidance, the avunculate, alliances in combat, female infanticide, and gene-culture coevolution. Vaulting Ambition thus seeks to identify what is good in sociobiology, to expose the errors of premature speculations about human nature, and to prepare the way for serious study of the evolution of human social behavior

Relationship between amino acid composition and gene expression in the mouse genome

<p>Abstract</p> <p>Background</p> <p>Codon bias is a phenomenon that refers to the differences in the frequencies of synonymous codons among different genes. In many organisms, natural selection is considered to be a cause of codon bias because codon usage in highly expressed genes is biased toward optimal codons. Methods have previously been developed to predict the expression level of genes from their nucleotide sequences, which is based on the observation that synonymous codon usage shows an overall bias toward a few codons called major codons. However, the relationship between codon bias and gene expression level, as proposed by the translation-selection model, is less evident in mammals.</p> <p>Findings</p> <p>We investigated the correlations between the expression levels of 1,182 mouse genes and amino acid composition, as well as between gene expression and codon preference. We found that a weak but significant correlation exists between gene expression levels and amino acid composition in mouse. In total, less than 10% of variation of expression levels is explained by amino acid components. We found the effect of codon preference on gene expression was weaker than the effect of amino acid composition, because no significant correlations were observed with respect to codon preference.</p> <p>Conclusion</p> <p>These results suggest that it is difficult to predict expression level from amino acid components or from codon bias in mouse.</p

Radiological progression of cerebral metastases after radiosurgery: assessment of perfusion MRI for differentiating between necrosis and recurrence

To assess the capability of perfusion MRI to differentiate between necrosis and tumor recurrence in patients showing radiological progression of cerebral metastases treated with stereotactic radiosurgery (SRS). From 2004 to 2006 dynamic susceptibility-weighted contrast-enhanced perfusion MRI scans were performed on patients with cerebral metastasis showing radiological progression after SRS during follow-up. Several perfusion MRI characteristics were examined: a subjective visual score of the relative cerebral blood volume (rCBV) map and quantitative rCBV measurements of the contrast-enhanced areas of maximal perfusion. For a total of 34 lesions in 31 patients a perfusion MRI was performed. Diagnoses were based on histology, definite radiological decrease or a combination of radiological and clinical follow-up. The diagnosis of tumor recurrence was obtained in 20 of 34 lesions, and tumor necrosis in 14 of 34. Regression analyses for all measures proved statistically significant (χ2 = 11.6–21.6, P < 0.001–0.0001). Visual inspection of the rCBV map yielded a sensitivity and specificity of 70.0 respectively 92.9%. The optimal cutoff point for maximal tumor rCBV relative to white matter was 2.00 (improving the sensibility to 85.0%) and 1.85 relative to grey matter (GM), improving the specificity to 100%, with a corresponding sensitivity of 70.0%. Perfusion MRI seems to be a useful tool in the differentiation of necrosis and tumor recurrence after SRS. For the patients displaying a rCBV-GM greater than 1.85, the diagnosis of necrosis was excluded. Salvage treatment can be initiated for these patients in an attempt to prolong survival