Intentional Innovation: How Getting More Systematic About Innovation Could Improve Philanthropy and Increase Social Impact

Based on a review of case studies and current innovation theory and practice, proposes a framework integrating best practices, processes, and tools for making innovation a more consistent and integral element of philanthropy. Lists models and resources

Abiotic and Biotic Limitations to Nodulation by Leguminous Cover Crops in South Texas

Many farms use leguminous cover crops as a nutrient management strategy to reduce their need for nitrogen fertilizer. When they are effective, leguminous cover crops are a valuable tool for sustainable nutrient management. However, the symbiotic partnership between legumes and nitrogen fixing rhizobia is vulnerable to several abiotic and biotic stressors that reduce nitrogen fixation efficiency in real world contexts. Sometimes, despite inoculation with rhizobial strains, this symbiosis fails to form. Such failure was observed in a 14-acre winter cover crop trial in the Rio Grande Valley (RGV) of Texas when three legume species produced no signs of nodulation or nitrogen fixation. This study examined the role of nitrogen, phosphorus, moisture, micronutrients, and native microbial communities in the nodulation of cowpea (Vigna unguiculata L. Walp) and assessed arbuscular mycorrhizal fungi as an intervention to improve nodulation. Results from two controlled studies confirm moisture and native microbial communities as major factors in nodulation success. Micronutrients showed mixed impacts on nodulation depending on plant stress conditions. Nitrogen and phosphorus deficiencies, however, were not likely causes, nor was mycorrhizal inoculation an effective intervention to improve nodulation. Inoculation method also had a major impact on nodulation rates. Continued research on improved inoculation practices and other ways to maximize nitrogen fixation efficiency will be required to increase successful on-farm implementation

Cover crops may exacerbate moisture limitations on South Texas dryland farms

Cover crops are a sustainable management tool for mediating weed pressure, reducing soil erosion, and enhancing soil organic carbon (C) and nitrogen (N) levels. Yet, adoption rates across water-limited farms in Texas remain low, especially among producers without irrigation access, due to concerns that cover crop use of soil moisture will negatively impact subsequent cash crop yields. This three-year cover crop trial in a rain-fed sorghum (Sorghum bicolor L.) farm in Lyford, Texas, trialed different cover crop mixes and seeding rates and confirmed that cover cropping leads to significant soil moisture deficits and cash crop failure when rainfall is low between cover crop termination and cash crop planting (\u3c30 \u3emm). In seasons one and three, moisture deficits contributed to significantly lower germination of post-cover crop sorghum compared to fallow control plots. In season two, increased precipitation during a longer moisture recharge period between cover crop termination and cash crop planting helped avoid sorghum yield drops. Length of recharge period, amount of rainfall, species selection, planting density, and termination method are major determinants of subsequent cash crop outcomes. Careful management can minimize some of the risks cover cropping poses to soil moisture, but without reliable rainfall at key points in the cropping cycle, cover cropping remains risky for farmers without irrigation access

Mesenchymal stem cell and gelatin microparticle encapsulation in thermally and chemically gelling injectable hydrogels for tissue engineering

In this work, we investigated the viability and osteogenic differentiation of mesenchymal stem cells encapsulated with gelatin microparticles (GMPs) in an injectable, chemically and thermally gelling hydrogel system combining poly(N-isopropylacrylamide)-based thermogelling macromers containing pendant epoxy rings with polyamidoamine-based hydrophilic and degradable diamine crosslinking macromers. Specifically, we studied how the parameters of GMP size and loading ratio affected the viability and differentiation of cells encapsulated within the hydrogel. We also examined the effects of cell and GMP co-encapsulation on hydrogel mineralization. Cells demonstrated long-term viability within the hydrogels, which was shown to depend on GMP size and loading ratio. In particular, increased interaction of cells and GMPs through greater available GMP surface area, use of an epoxy-based chemical gelation mechanism, and the tunable high water content of the thermogelled hydrogels led to favorable long-term cell viability. Compared with cellular hydrogels without GMPs, hydrogels co-encapsulating cells and GMPs demonstrated greater production of alkaline phosphatase by cells at all time-points and a transient early enhancement of hydrogel mineralization for larger GMPs at higher loading ratios. Such injectable, in situ forming hydrogels capable of delivering and maintaining populations of encapsulated mesenchymal stem cells and promoting mineralization in vitro offer promise as novel therapies for applications in tissue engineering and regenerative medicine

Spectroscopic confirmation of an ultra-faint galaxy at the epoch of reionization

Within one billion years of the Big Bang, intergalactic hydrogen was ionized by sources emitting ultraviolet and higher energy photons. This was the final phenomenon to globally affect all the baryons (visible matter) in the Universe. It is referred to as cosmic reionization and is an integral component of cosmology. It is broadly expected that intrinsically faint galaxies were the primary ionizing sources due to their abundance in this epoch. However, at the highest redshifts ($z>7.5$; lookback time 13.1 Gyr), all galaxies with spectroscopic confirmations to date are intrinsically bright and, therefore, not necessarily representative of the general population. Here, we report the unequivocal spectroscopic detection of a low luminosity galaxy at $z>7.5$. We detected the Lyman-$\alpha$ emission line at $\sim 10504$ {\AA} in two separate observations with MOSFIRE on the Keck I Telescope and independently with the Hubble Space Telescope's slit-less grism spectrograph, implying a source redshift of $z = 7.640 \pm 0.001$. The galaxy is gravitationally magnified by the massive galaxy cluster MACS J1423.8+2404 ($z = 0.545$), with an estimated intrinsic luminosity of $M_{AB} = -19.6 \pm 0.2$ mag and a stellar mass of $M_{\star} = 3.0^{+1.5}_{-0.8} \times 10^8$ solar masses. Both are an order of magnitude lower than the four other Lyman-$\alpha$ emitters currently known at $z > 7.5$, making it probably the most distant representative source of reionization found to date

Inhibition of HDACs reduces Ewing sarcoma tumor growth through EWS-FLI1 protein destabilization

Oncogenic transcription factors lacking enzymatic activity or targetable binding pockets are typically considered "undruggable". An example is provided by the EWS-FLI1 oncoprotein, whose continuous expression and activity as transcription factor are critically required for Ewing sarcoma tumor formation, maintenance, and proliferation. Because neither upstream nor downstream targets have so far disabled its oncogenic potential, we performed a high-throughput drug screen (HTS), enriched for FDA-approved drugs, coupled to a Global Protein Stability (GPS) approach to identify novel compounds capable to destabilize EWS-FLI1 protein by enhancing its degradation through the ubiquitin-proteasome system. The protein stability screen revealed the dual histone deacetylase (HDAC) and phosphatidylinositol-3-kinase (PI3K) inhibitor called fimepinostat (CUDC-907) as top candidate to modulate EWS-FLI1 stability. Fimepinostat strongly reduced EWS-FLI1 protein abundance, reduced viability of several Ewing sarcoma cell lines and PDX-derived primary cells and delayed tumor growth in a xenograft mouse model, whereas it did not significantly affect healthy cells. Mechanistically, we demonstrated that EWS-FLI1 protein levels were mainly regulated by fimepinostat's HDAC activity. Our study demonstrates that HTS combined to GPS is a reliable approach to identify drug candidates able to modulate stability of EWS-FLI1 and lays new ground for the development of novel therapeutic strategies aimed to reduce Ewing sarcoma tumor progression. Keywords: EWS-FLI1; Ewing sarcoma; Fimepinostat; HDACi; Protein stabilit

Corrigendum to "Inhibition of HDACs reduces Ewing sarcoma tumor growth through EWS-FLI1 protein destabilization" [Neoplasia volume 27 (2022) pp. 100784/Number C]

Oncogenic transcription factors lacking enzymatic activity or targetable binding pockets are typically considered “undruggable”. An example is provided by the EWS-FLI1 oncoprotein, whose continuous expression and activity as transcription factor are critically required for Ewing sarcoma tumor formation, maintenance, and proliferation. Because neither upstream nor downstream targets have so far disabled its oncogenic potential, we performed a high-throughput drug screen (HTS), enriched for FDA-approved drugs, coupled to a Global Protein Stability (GPS) approach to identify novel compounds capable to destabilize EWS-FLI1 protein by enhancing its degradation through the ubiquitin-proteasome system. The protein stability screen revealed the dual histone deacetylase (HDAC) and phosphatidylinositol-3-kinase (PI3K) inhibitor called fimepinostat (CUDC-907) as top candidate to modulate EWS-FLI1 stability. Fimepinostat strongly reduced EWS-FLI1 protein abundance, reduced viability of several Ewing sarcoma cell lines and PDX-derived primary cells and delayed tumor growth in a xenograft mouse model, whereas it did not significantly affect healthy cells. Mechanistically, we demonstrated that EWS-FLI1 protein levels were mainly regulated by fimepinostat's HDAC activity. Our study demonstrates that HTS combined to GPS is a reliable approach to identify drug candidates able to modulate stability of EWS-FLI1 and lays new ground for the development of novel therapeutic strategies aimed to reduce Ewing sarcoma tumor progression

Tetraphenyl­arsonium cis-bis­[1,2-bis­(tri­fluoro­meth­yl)ethene-1,2-dithiol­ato]platinate(II)

In the title compound, (C24H20As)[Pt(C4F6S2)2], the cation lies on a twofold rotation axis while the anion has crystallographic inversion symmetry. The PtII ion is in a slightly distorted square-planar coordination environment. The F atoms of both unique –CF3 groups are disordered over two sets of sites, the ratios of refined occupancies being 0.677 (15):0.323 (15) and 0.640 (16):0.360 (16). The crystal structure is the first to date of a monoanionic [Pt(tfd)2]− species [tfd is 1,2-bis­(trifluoro­meth­yl)ethene-1,2-dithiol­ate] with a non-redox-active cation

Cellular Aspects of Muscle Specialization Demonstrate Genotype – Phenotype Interaction Effects in Athletes

IntroductionGene polymorphisms are associated with athletic phenotypes relying on maximal or continued power production and affect the specialization of skeletal muscle composition with endurance or strength training of untrained subjects. We tested whether prominent polymorphisms in genes for angiotensin converting enzyme (ACE), tenascin-C (TNC), and actinin-3 (ACTN3) are associated with the differentiation of cellular hallmarks of muscle metabolism and contraction in high level athletes.MethodsMuscle biopsies were collected from m. vastus lateralis of three distinct phenotypes; endurance athletes (n = 29), power athletes (n = 17), and untrained non-athletes (n = 63). Metabolism-, and contraction-related cellular parameters (such as capillary-to-fiber ratio, capillary length density, volume densities of mitochondria and intramyocellular lipid, fiber mean cross sectional area (MCSA) and volume densities of myofibrils) and the volume densities of sarcoplasma were analyzed by quantitative electron microscopy of the biopsies. Gene polymorphisms of ACE (I/D (insertion/deletion), rs1799752), TNC (A/T, rs2104772), and ACTN3 (C/T, rs1815739) were determined using high-resolution melting polymerase chain reaction (HRM-PCR). Genotype distribution was assessed using Chi2 tests. Genotype and phenotype effects were analyzed by univariate or multivariate analysis of variance and post hoc test of Fisher. P-values below 0.05 were considered statistically significant.ResultsThe athletes demonstrated the specialization of metabolism- and contraction-related cellular parameters. Differences in cellular parameters could be identified for genotypes rs1799752 and rs2104772, and localized post hoc when taking the interaction with the phenotype into account. Between endurance and power athletes these concerned effects on capillary length density for rs1799752 and rs2104772, fiber type distribution and volume densities of myofibrils (rs1799752), and MSCA (rs2104772). Endurance athletes carrying the I-allele of rs1799752 demonstrated 50%-higher volume densities of mitochondria and sarcoplasma, when power athletes that carried only the D-allele showed the highest fiber MCSAs and a lower percentage of slow type muscle fibers.DiscussionACE and tenascin-C gene polymorphisms are associated with differences in cellular aspects of muscle metabolism and contraction in specifically-trained high level athletes. Quantitative differences in muscle fiber type distribution and composition, and capillarization in knee extensor muscle explain, in part, identified associations of the insertion/deletion genotypes of ACE (rs1799752) with endurance- and power-type Sports