Loss of Fgfr1 and Fgfr2 in Scleraxis-lineage cells leads to enlarged bone eminences and attachment cell death

BACKGROUND Tendons and ligaments attach to bone are essential for joint mobility and stability in vertebrates. Tendon and ligament attachments (ie, entheses) are found at bony protrusions (ie, eminences), and the shape and size of these protrusions depend on both mechanical forces and cellular cues during growth. Tendon eminences also contribute to mechanical leverage for skeletal muscle. Fibroblast growth factor receptor (FGFR) signaling plays a critical role in bone development, and Fgfr1 and Fgfr2 are highly expressed in the perichondrium and periosteum of bone where entheses can be found. RESULTS AND CONCLUSIONS We used transgenic mice for combinatorial knockout of Fgfr1 and/or Fgfr2 in tendon/attachment progenitors (ScxCre) and measured eminence size and shape. Conditional deletion of both, but not individual, Fgfr1 and Fgfr2 in Scx progenitors led to enlarged eminences in the postnatal skeleton and shortening of long bones. In addition, Fgfr1/Fgfr2 double conditional knockout mice had more variation collagen fibril size in tendon, decreased tibial slope, and increased cell death at ligament attachments. These findings identify a role for FGFR signaling in regulating growth and maintenance of tendon/ligament attachments and the size and shape of bony eminences

Volunteering in the care of people with severe mental illness: a systematic review

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

The Impacts of U.S. Economic and Military Aid on Human Rights Violations in Cold War Latin America

What are the impacts and legacies of the United States in Latin America? There is a long history and tumultuous relationship between the two. Especially in the Cold War period, there is much evidence of extensive U.S. intervention in the region. While much of this involvement has been documented by the press and activists, this paper strives to further our understanding as a society of the consequences of our actions and assistance. The question that this work posits is: what impacts did economic and military aid given by the United States have on Latin American regimes\u27 human rights violations during the Cold War? Due to availability of data, the period to be studied is 1976-1996, which follows the end of the Cold War. Other variables studied for their possible impacts on human rights violations include democracy, involvement in international or civil wars, international law, economic development and growth, poverty, population and population growth. While the findings of the quantitative analysis show mixed significance of these variables, there are some clear, significant relationships that have important ramifications for our understanding of history and policy. ¿Qué son los impactos y las legacías de los Estados Unidos para con Latinoamérica? Hay una historia larga y una relación tumultuosa entre los dos. Particularmente durante la Guerra Fría, existe mucha evidencia extensa de intervención por parte de los EEUU en la región. Mientras que muchas de las implicaciones han sido documentadas por la prensa y los activistas, el presente trabajo se esfuerza por profundizar nuestra comprensión como una sociedad de las consecuencias de nuestras acciones y asistencia. La cuestión que asienta este trabajo propone es, ¿qué impactos ha tenido la ayuda económica y militar estadounidense en cuanto a las violaciones de los derechos humanos durante la Guerra Fría? Por la falta de datos disponibles, el período que va a ser estudiado es 1976-1996, que coincide con el fin de la Guerra Fría. Otras variables estudiadas por sus impactos posibles respecto a las violaciones de los derechos humanos incluyen la democracia, la participación en guerras internacionales y domésticas, la ley internacional, el desarrollo económico, el crecimiento económico, la pobreza, la población y el crecimiento de la población. Mientras que los resultados del análisis cuantitativo muestran niveles diferentes de significancia para las variables, existen algunas relaciones claras y significantes que tienen ramificaciones importantes para nuestro entendimiento de la historia y la política

The influence of direct cylinder injection of ethyl alcohol and water on detonation

This thesis document was issued under the authority of another institution, not NPS. At the time it was written, a copy was added to the NPS Library collection for reasons not now known. It has been included in the digital archive for its historical value to NPS. Not believed to be a CIVINS (Civilian Institutions) title.Tests were run at the Sloane Laboratory, Massachusetts Institute of Technology, to compare the relative effect of injecting ethyl alcohol and distilled water directly into the cylinder of an internal combustion engine for the purpose of suppressing detonation.http://archive.org/details/theinfluenceofdi109456431Lieutenant, United States NavyCivilia

Intraocular Lens Unfurling Time Exponentially Decays with Increased Solution Temperature

Erick E Rocher,1 Rishima Mukherjee,1 James Pitingolo,1 Eli Levenshus,1 Gwyneth Alexander,1 Minyoung Park,1 Rupsa Acharya,1 Sarah Khan,1 Jordan Shuff,1 Andres Aguirre,1 Shababa Matin,2 Keith Walter,3 Allen O Eghrari4 1Center for Bioengineering Innovation and Design, Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA; 2Rice 360 Institute for Global Health Technologies, Rice University, Houston, TX, USA; 3Department of Ophthalmology, Wake Forest Baptist Health, Winston-Salem, NC, USA; 4Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USACorrespondence: Allen O Eghrari, Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Smith 5013, Baltimore, MD, 21231, USA, Email [email protected]: Intraocular lens (IOL) unfurling can be a rate-limiting step in cataract surgery, limiting operative efficiency. Furthermore, inefficient unfurling has important implications for clinical outcomes. We examine the effects of solution temperature on IOL unfurling time using three in vitro models of the ocular environment.Methods: IOLs were injected into a 6-well plate filled with balanced salt solution (BSS), dispersive ophthalmic viscoelastic device (OVD), or cohesive OVD. Experiments were also performed in a plastic eye filled with dispersive or cohesive OVD. IOL unfurling time was recorded against the temperature of the respective solution.Results: IOL unfurling time decayed exponentially as solution temperature increased in all experiments, including the BSS-filled 6-well plate, the OVD-filled 6-well plate, and the OVD-filled plastic eye. IOLs failed to unfurl within 10 min at 10°C, below the glass transition temperature of the tested IOLs. Increasing solution temperature from 20°C to 30°C decreases IOL unfurling by greater than 2 min. Further heating to 40°C did not significantly decrease IOL unfurling time.Conclusion: Increased solution temperature rapidly decreases IOL unfurling time in vitro. IOLs do not unfurl within a clinically acceptable timeframe at or below their glass transition temperature. Increased BSS and/or OVD temperature may be a potential method to decrease IOL unfurling time in cataract surgery. However, future research is needed to elucidate potential consequences of warmed BSS and/or OVD on post-operative outcomes. This study demonstrates the potential for temperature regulation to decrease cataract surgery operative time and provides preliminary evidence to justify future clinical validation of this relationship.Plain Language Summary: During cataract surgery, a prosthetic intraocular lens (IOL) is inserted into the eye once the clouded lens is removed. The IOL must then unfurl before the procedure can proceed. When IOLs fail to unfurl or unfurl slowly, this can delay the operation and may even cause post-operative complications. Thus, we studied the effect temperature may have on IOL unfurling time to optimize this segment of the operation.We injected IOLs into solutions of saline (balanced salt solution) or ophthalmic viscoelastic device (OVD), two fluids injected into the eye during surgery. In both a well plate and a plastic eye, we found that increasing the temperature of the solution significantly affected IOL unfurling time. Specifically, heating the solution from refrigeration to room temperature decreased unfurling time from over 10 min to less than four. Heating to physiological temperature further decreased unfurling time to less than a minute.Our results show promise for potentially utilizing heated BSS and/or OVD to accelerate IOL unfurling and decrease cataract surgery operative time.Keywords: cataract surgery, balanced salt solution, ophthalmic viscoelastic devic

Linoleate-Enrichment of Mitochondrial Cardiolipin Molecular Species Is Developmentally Regulated and a Determinant of Metabolic Phenotype

Cardiolipin (CL), the major mitochondrial phospholipid, regulates the activity of many mitochondrial membrane proteins. CL composition is shifted in heart failure with decreases in linoleate and increases in oleate side chains, but whether cardiolipin composition directly regulates metabolism is unknown. This study defines cardiolipin composition in rat heart and liver at three distinct ages to determine the influence of CL composition on beta-oxidation (ß-OX). CL species, expression of ß-OX and glycolytic genes, and carnitine palmitoyltransferase (CPT) activity were characterized in heart and liver from neonatal, juvenile, and adult rats. Ventricular myocytes were cultured from neonatal, juvenile, and adult rats and cardiolipin composition and CPT activity were measured. Cardiolipin composition in neonatal rat ventricular cardiomyocytes (NRVMs) was experimentally altered and mitochondrial respiration was assessed. Linoleate-enrichment of CL was observed in rat heart, but not liver, with increasing age. ß-OX genes and CPT activity were generally higher in adult heart and glycolytic genes lower, as a function of age, in contrast to liver. Palmitate oxidation increased in NRVMs when CL was enriched with linoleate. Our results indicate (1) CL is developmentally regulated, (2) linoleate-enrichment is associated with increased ß-OX and a more oxidative mitochondrial phenotype, and (3) experimentally induced linoleate-enriched CL in ventricular myocytes promotes a shift from pyruvate metabolism to fatty acid ß-OX

Identifying vulnerable brain networks in mouse models of genetic risk factors for late onset Alzheimer's disease

The major genetic risk for late onset Alzheimer’s disease has been associated with the presence of APOE4 alleles. However, the impact of different APOE alleles on the brain aging trajectory, and how they interact with the brain local environment in a sex specific manner is not entirely clear. We sought to identify vulnerable brain circuits in novel mouse models with homozygous targeted replacement of the mouse ApoE gene with either human APOE3 or APOE4 gene alleles. These genes are expressed in mice that also model the human immune response to age and disease-associated challenges by expressing the human NOS2 gene in place of the mouse mNos2 gene. These mice had impaired learning and memory when assessed with the Morris water maze (MWM) and novel object recognition (NOR) tests. Ex vivo MRI-DTI analyses revealed global and local atrophy, and areas of reduced fractional anisotropy (FA). Using tensor network principal component analyses for structural connectomes, we inferred the pairwise connections which best separate APOE4 from APOE3 carriers. These involved primarily interhemispheric connections among regions of olfactory areas, the hippocampus, and the cerebellum. Our results also suggest that pairwise connections may be subdivided and clustered spatially to reveal local changes on a finer scale. These analyses revealed not just genotype, but also sex specific differences. Identifying vulnerable networks may provide targets for interventions, and a means to stratify patients