51 research outputs found
A Homolog of Subtilisin-Like Proprotein Convertase 7 Is Essential to Anterior Neural Development in Xenopus
BACKGROUND: Subtilisin-like Proprotein Convertase 7 (SPC7) is a member of the subtilisin/kexin family of pro-protein convertases. It cleaves many pro-proteins to release their active proteins, including members of the bone morphogenetic protein (BMP) family of signaling molecules. Other SPCs are known to be required during embryonic development but corresponding data regarding SPC7 have not been reported previously. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that Xenopus SPC7 (SPC7) was expressed predominantly in the developing brain and eye, throughout the neural plate initially, then more specifically in the lens and retina primordia as development progressed. Since no prior functional information has been reported for SPC7, we used gain- and loss-of-function experiments to investigate the possibility that it may also convey patterning or tissue specification information similarly to Furin, SPC4, and SPC6. Overexpression of SPC7 was without effect. In contrast, injection of SPC7 antisense morpholino oligonucleotides (MO) into a single blastomere at the 2- or 4-cell stage produced marked disruption of head structures; anophthalmia was salient. Bilateral injections suppressed head and eye formation completely. In parallel with suppression of eye and brain development by SPC7 knockdown, expression of early anterior neural markers (Sox2, Otx2, Rx2, and Pax6) and late eye-specific markers (ÎČ-Crystallin and Opsin), and of BMP target genes such as Tbx2 and Tbx3, was reduced or eliminated. Taken together, these findings suggest a critical role for SPC7-perhaps, at least in part, due to activation of one or more BMPs-in early patterning of the anterior neural plate and its derivatives. CONCLUSION/SIGNIFICANCE: SPC7 is required for normal development of the eye and brain, possibly through processing BMPs, though other potential substrates cannot be excluded
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Current challenges and future directions for engineering extracellular vesicles for heart, lung, blood and sleep diseases.
Extracellular vesicles (EVs) carry diverse bioactive components including nucleic acids, proteins, lipids and metabolites that play versatile roles in intercellular and interorgan communication. The capability to modulate their stability, tissue-specific targeting and cargo render EVs as promising nanotherapeutics for treating heart, lung, blood and sleep (HLBS) diseases. However, current limitations in large-scale manufacturing of therapeutic-grade EVs, and knowledge gaps in EV biogenesis and heterogeneity pose significant challenges in their clinical application as diagnostics or therapeutics for HLBS diseases. To address these challenges, a strategic workshop with multidisciplinary experts in EV biology and U.S. Food and Drug Administration (USFDA) officials was convened by the National Heart, Lung and Blood Institute. The presentations and discussions were focused on summarizing the current state of science and technology for engineering therapeutic EVs for HLBS diseases, identifying critical knowledge gaps and regulatory challenges and suggesting potential solutions to promulgate translation of therapeutic EVs to the clinic. Benchmarks to meet the critical quality attributes set by the USFDA for other cell-based therapeutics were discussed. Development of novel strategies and approaches for scaling-up EV production and the quality control/quality analysis (QC/QA) of EV-based therapeutics were recognized as the necessary milestones for future investigations.Funding information:
National Heart, Lung, and Blood Institute,
Grant/Award Numbers: HL 122596, HL124021,
HL124074, HL128297, HL141080, HL155346-01,
R35HL150807, R56HL141206
Prithu Sundd was supported by NIH-NHLBI R01 grants (HL128297 and HL141080) and 18TPA34170588 from American Heart
Association. Stephen Y. Chan was supported by NIH grants R01 HL124021 and HL 122596 as well as AHA grant 18EIA33900027.
SuamyaDaswas supported by NIH grants R35HL150807, UH3 TR002878 andAHASFRN35120123. ZhenjiaWangwas supported
by NIH grant (R01EB027078). Pilar MartĂn was supported by MCIN-ISCIII-Fondo de InvestigaciĂłn Sanitaria grant PI22/01759.
KennethW.Witwer was supported in part by NIH grants R01AI144997, R01DA047807, R33MH118164 andUH3CA241694. Tianji
Chen was supported by AHA Career Development Award 18CDA34110301, Gilead Sciences Research Scholars Program in PAH,
NIH-NHLBI grant R56HL141206 and Chicago Biomedical ConsortiumCatalyst Award. EduardoMarbĂĄn was supported byNIH
R01 HL124074 and HL155346-01.S
Science Frontiers In Galaxy Evolution: Deep-Wide Surveys
Astro2010: The Astronomy and Astrophysics Decadal Survey : Science White Papers no 79. Available online : http://www8.nationalacademies.org/astro2010/DetailFileDisplay.aspx?id=24
Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers
https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd
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The Challenges of Afghanistan and Iraq Veterans' Transition from Military to Civilian Life and Approaches to Reconnection
Afghanistan and Iraq veterans experienced traumas during deployment, and disrupted connections with friends and family. In this context, it is critical to understand the nature of veteransâ transition to civilian life, the challenges navigated, and approaches to reconnection. We investigated these issues in a qualitative study, framed by homecoming theory, that comprised in-depth interviews with 24 veterans. Using an inductive thematic analysis approach, we developed three overarching themes. Military as family explored how many veterans experienced the military environment as a âfamilyâ that took care of them and provided structure. Normal is alien encompassed many veterans experiences of disconnection from people at home, lack of support from institutions, lack of structure, and loss of purpose upon return to civilian life. Searching for a new normal included strategies and supports veterans found to reconnect in the face of these challenges. A veteran who had successfully transitioned and provided support and advice as a peer navigator was frequently discussed as a key resource. A minority of respondentsâthose who were mistreated by the military system, women veterans, and veterans recovering from substance abuse problemsâwere less able to access peer support. Other reconnection strategies included becoming an ambassador to the military experience, and knowing transition challenges would ease with time. Results were consistent with and are discussed in the context of homecoming theory and social climate theory. Social support is known to be protective for veterans, but our findings add the nuance of substantial obstacles veterans face in locating and accessing support, due to disconnection and unsupportive institutions. Larger scale work is needed to better understand how to foster peer connection, build reconnection with family, and engage the broader community to understand and support veterans; interventions to support reconnection for veterans should be developed
The role of medical conditions and primary care services in 5-year substance use outcomes among chemical dependency treatment patients
Program characteristics and readmission among older substance abuse patients: Comparisons with middle-aged and younger patients
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