المؤلفون: Yongtao Zhang, Di Wu, Xia Zhao, Mikhail Pakvasa, Andrew Blake Tucker, Huaxiu Luo, Kevin H. Qin, Daniel A. Hu, Eric J. Wang, Alexander J. Li, Meng Zhang, Yukun Mao, Maya Sabharwal, Fang He, Changchun Niu, Hao Wang, Linjuan Huang, Deyao Shi, Qing Liu, Na Ni, Kai Fu, Connie Chen, William Wagstaff, Russell R. Reid, Aravind Athiviraham, Sherwin Ho, Michael J. Lee, Kelly Hynes, Jason Strelzow, Tong-Chuan He, Mostafa El Dafrawy

المصدر: Frontiers in Bioengineering and Biotechnology, Vol 8 (2020)

مصطلحات موضوعية: bone tissue engineering, biomaterials—cells, decellularizate ECM, polymer, stem cells—cartilage—bone marrow stem cells clinical application, mesenchymal stem cell, Biotechnology, TP248.13-248.65

الوصف: Bone is a dynamic organ with high regenerative potential and provides essential biological functions in the body, such as providing body mobility and protection of internal organs, regulating hematopoietic cell homeostasis, and serving as important mineral reservoir. Bone defects, which can be caused by trauma, cancer and bone disorders, pose formidable public health burdens. Even though autologous bone grafts, allografts, or xenografts have been used clinically, repairing large bone defects remains as a significant clinical challenge. Bone tissue engineering (BTE) emerged as a promising solution to overcome the limitations of autografts and allografts. Ideal bone tissue engineering is to induce bone regeneration through the synergistic integration of biomaterial scaffolds, bone progenitor cells, and bone-forming factors. Successful stem cell-based BTE requires a combination of abundant mesenchymal progenitors with osteogenic potential, suitable biofactors to drive osteogenic differentiation, and cell-friendly scaffold biomaterials. Thus, the crux of BTE lies within the use of cell-friendly biomaterials as scaffolds to overcome extensive bone defects. In this review, we focus on the biocompatibility and cell-friendly features of commonly used scaffold materials, including inorganic compound-based ceramics, natural polymers, synthetic polymers, decellularized extracellular matrix, and in many cases, composite scaffolds using the above existing biomaterials. It is conceivable that combinations of bioactive materials, progenitor cells, growth factors, functionalization techniques, and biomimetic scaffold designs, along with 3D bioprinting technology, will unleash a new era of complex BTE scaffolds tailored to patient-specific applications.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fbioe.2020.598607/fullTest; https://doaj.org/toc/2296-4185Test

الوصول الحر: https://doaj.org/article/e7fdcfbfffb049cd928640e111c8a4d7Test

المؤلفون: Keizo Misumi, David S. Wheeler, Yoshiro Aoki, Michael P. Combs, Russell R. Braeuer, Ryuji Higashikubo, Wenjun Li, Daniel Kreisel, Ragini Vittal, Jeffrey Myers, Amir Lagstein, Natalie M. Walker, Carol F. Farver, Vibha N. Lama

المصدر: JCI Insight, Vol 5, Iss 23 (2020)

مصطلحات موضوعية: Pulmonology, Transplantation, Medicine

الوصف: Understanding the distinct pathogenic mechanisms that culminate in allograft fibrosis and chronic graft failure is key in improving outcomes after solid organ transplantation. Here, we describe an F1 → parent orthotopic lung transplant model of restrictive allograft syndrome (RAS), a particularly fulminant form of chronic lung allograft dysfunction (CLAD), and identify a requisite pathogenic role for humoral immune responses in development of RAS. B6D2F1/J (H2-b/d) donor lungs transplanted into the parent C57BL/6J (H2-b) recipients demonstrated a spectrum of histopathologic changes, ranging from lymphocytic infiltration, fibrinous exudates, and endothelialitis to peribronchial and pleuroparenchymal fibrosis, similar to those noted in the human RAS lungs. Gene expression profiling revealed differential humoral immune cell activation as a key feature of the RAS murine model, with significant B cell and plasma cell infiltration noted in the RAS lung allografts. B6D2F1/J lung allografts transplanted into μMt–/– (mature B cell deficient) or activation-induced cytidine deaminase (AID)/secretory μ-chain (μs) double-KO (AID−/−μs−/−) C57BL/6J mice demonstrated significantly decreased allograft fibrosis, indicating a key role for antibody secretion by B cells in mediating RAS pathology. Our study suggests that skewing of immune responses determines the diverse allograft remodeling patterns and highlights the need to develop targeted therapies for specific CLAD phenotypes.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2379-3708Test

الوصول الحر: https://doaj.org/article/23cc3c55a9cf486dad2c4230b7195d23Test

المؤلفون: Bodil A. Bluhm, Markus A. Janout, Seth L. Danielson, Ingrid Ellingsen, Maria Gavrilo, Jacqueline M. Grebmeier, Russell R. Hopcroft, Katrin B. Iken, Randi B. Ingvaldsen, Lis L. Jørgensen, Ksenia N. Kosobokova, Ron Kwok, Igor V. Polyakov, Paul E. Renaud, Eddy C. Carmack

المصدر: Frontiers in Marine Science, Vol 7 (2020)

مصطلحات موضوعية: biological communities, boundary current, climate change, connectivity, continental slopes, pan-Arctic, Science, General. Including nature conservation, geographical distribution, QH1-199.5

الوصف: Continental slopes – steep regions between the shelf break and abyssal ocean – play key roles in the climatology and ecology of the Arctic Ocean. Here, through review and synthesis, we find that the narrow slope regions contribute to ecosystem functioning disproportionately to the size of the habitat area (∼6% of total Arctic Ocean area). Driven by inflows of sub-Arctic waters and steered by topography, boundary currents transport boreal properties and particle loads from the Atlantic and Pacific Oceans along-slope, thus creating both along and cross-slope connectivity gradients in water mass properties and biomass. Drainage of dense, saline shelf water and material within these, and contributions of river and meltwater also shape the characteristics of the slope domain. These and other properties led us to distinguish upper and lower slope domains; the upper slope (shelf break to ∼800 m) is characterized by stronger currents, warmer sub-surface temperatures, and higher biomass across several trophic levels (especially near inflow areas). In contrast, the lower slope has slower-moving currents, is cooler, and exhibits lower vertical carbon flux and biomass. Distinct zonation of zooplankton, benthic and fish communities result from these differences. Slopes display varying levels of system connectivity: (1) along-slope through property and material transport in boundary currents, (2) cross-slope through upwelling of warm and nutrient rich water and down-welling of dense water and organic rich matter, and (3) vertically through shear and mixing. Slope dynamics also generate separating functions through (1) along-slope and across-slope fronts concentrating biological activity, and (2) vertical gradients in the water column and at the seafloor that maintain distinct physical structure and community turnover. At the upper slope, climatic change is manifested in sea-ice retreat, increased heat and mass transport by sub-Arctic inflows, surface warming, and altered vertical stratification, while the lower slope has yet to display evidence of change. Model projections suggest that ongoing physical changes will enhance primary production at the upper slope, with suspected enhancing effects for consumers. We recommend Pan-Arctic monitoring efforts of slopes given that many signals of climate change appear there first and are then transmitted along the slope domain.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmars.2020.544386/fullTest; https://doaj.org/toc/2296-7745Test

الوصول الحر: https://doaj.org/article/1040dbbc96d3470aaebc7ed427e6e678Test

المؤلفون: Stephanie H. O’Daly, Seth L. Danielson, Sarah M. Hardy, Russell R. Hopcroft, Catherine Lalande, Dean A. Stockwell, Andrew M. P. McDonnell

المصدر: Frontiers in Marine Science, Vol 7 (2020)

مصطلحات موضوعية: carbon cycling, particulate organic carbon, Bering and Chukchi Sea Shelves, marine particles, marine snow, Arctic, Science, General. Including nature conservation, geographical distribution, QH1-199.5

الوصف: The shallow Pacific Arctic shelf has historically acted as an effective carbon sink, characterized by tight benthic pelagic coupling. However, the strength of the biological carbon pump in the Arctic has been predicted to weaken with climate change due to increased duration of the open-water period for primary production, enhanced nutrient limitation, and increased pelagic heterotrophy. In order to gain insights into how the biological carbon pump is functioning under the recent conditions of extreme warming and sea ice loss on the Pacific Arctic shelf, we measured sinking particulate organic carbon (POC) fluxes with drifting and moored sediment traps, as well as rates of primary production and particle-associated microbial respiration during June 2018. In Bering Shelf/Anadyr Water masses, sinking POC fluxes ranged from 0.8 to 2.3 g C m–2 day–1, making them among the highest fluxes ever documented in the global oceans. Furthermore, high export ratios averaging 82% and low rates of particle-associated microbial respiration also indicated negligible recycling of sinking POC in the water column. These results highlight the extraordinary strength of the biological carbon pump on the Pacific Arctic shelf during an unusually warm and low-sea ice year. While additional measurements and time are needed to confirm the ultimate trajectory of these fluxes in response to ongoing climate change, these results do not support the prevailing hypothesis that the strength of the biological carbon pump in the Pacific Arctic will weaken under these conditions.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmars.2020.548931/fullTest; https://doaj.org/toc/2296-7745Test

الوصول الحر: https://doaj.org/article/2e6d73c1f32d48edb8cf879d53efedafTest

المؤلفون: Russell R. Fling, Timothy R. Zacharewski

المصدر: International Journal of Molecular Sciences, Vol 22, Iss 22, p 12431 (2021)

مصطلحات موضوعية: 2,3,7,8-tetrachlorodibenzo-p-dioxin, dioxin, aryl hydrocarbon receptor, non-alcoholic fatty liver disease, gut microbiome, fibrosis, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Gut dysbiosis with disrupted enterohepatic bile acid metabolism is commonly associated with non-alcoholic fatty liver disease (NAFLD) and recapitulated in a NAFLD-phenotype elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice. TCDD induces hepatic fat accumulation and increases levels of secondary bile acids, including taurolithocholic acid and deoxycholic acid (microbial modified bile acids involved in host bile acid regulation signaling pathways). To investigate the effects of TCDD on the gut microbiota, the cecum contents of male C57BL/6 mice orally gavaged with sesame oil vehicle or 0.3, 3, or 30 µg/kg TCDD were examined using shotgun metagenomic sequencing. Taxonomic analysis identified dose-dependent increases in Lactobacillus species (i.e., Lactobacillus reuteri). Increased species were also associated with dose-dependent increases in bile salt hydrolase sequences, responsible for deconjugation reactions in secondary bile acid metabolism. Increased L. reuteri levels were further associated with mevalonate-dependent isopentenyl diphosphate (IPP) biosynthesis and o-succinylbenzoate synthase, a menaquinone biosynthesis associated gene. Analysis of the gut microbiomes from cirrhosis patients identified an increased abundance of genes from the mevalonate-dependent IPP biosynthesis as well as several other menaquinone biosynthesis genes, including o-succinylbenzoate synthase. These results extend the association of lactobacilli with the AhR/intestinal axis in NAFLD progression and highlight the similarities between TCDD-elicited phenotypes in mice to human NAFLD.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/22/22/12431Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/41119752f628489ea5a9b3ddd7de6fcbTest

المؤلفون: Alison G.C.S. Smith, Russell R. Kempker, Liya Wassie, Kidist Bobosha, Azhar Nizam, Neel Gandhi, Matthew J. Magee, Henry M. Blumberg

المصدر: Journal of Clinical and Translational Science, Vol 5, Pp 30-31 (2021)

مصطلحات موضوعية: Medicine

الوصف: ABSTRACT IMPACT: This work examines the association between diabetes mellitus and latent tuberculosis infection among a cohort of household contacts exposed to active tuberculosis in Ethiopia, focusing attention on the need for further translational research to determine the mechanisms of susceptibility to Mycobacterium tuberculosis infection among individuals with diabetes and pre-diabetes. OBJECTIVES/GOALS: Diabetes mellitus (DM) is an established risk factor for active TB disease, but there is limited understanding of the relationship of DM and latent tuberculosis (LTBI). We sought to determine the relationship between DM or pre-DM with LTBI among household or close contacts (HHCs) of active TB cases in Ethiopia. METHODS/STUDY POPULATION: We conducted a cross-sectional study of the HHCs of index active TB cases enrolled in an ongoing TB Research Unit (TBRU) study in Addis Ababa, Ethiopia. HHCs of individuals with laboratory-confirmed TB had QuantiFERON ®-TB Gold Plus (QFT) and glycated hemoglobin (HbA1c) tests performed. LTBI was defined as a positive QFT and lack of symptoms. HbA1C results were used to define no DM (HbA1c 6.5% or prior history of diabetes). Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) after adjustment for age, sex and HIV status as potential confounders. RESULTS/ANTICIPATED RESULTS: Among 466 HHCs, the median age was 29 years (IQR 23-38), 58.8% were female, 3.4% were HIV-positive, and median BMI was 20.9 kg/m^2 (IQR 18.9-23.8). Overall, 329 HHCs (70.6%) had LTBI, 26 (5.6%) had DM and 73 (15.7%) had pre-DM. Compared to HHC without DM, the prevalence of LTBI was higher in those with pre-DM (68.9% vs. 72.6%; OR 1.19, 95% CI 0.69-2.13) and those with DM (88.5%; OR 3.45, 95% CI 1.17-14.77). In multivariable analysis, there was a trend towards increased LTBI risk among HHCs with DM vs. without DM (OR 2.16, 95% CI 0.67-9.70) but the difference was not statistically significant. Among HHCs with LTBI, the median IFN-? response to TB1 antigen was modestly greater in those with DM (5.3 IU/mL; IQR 3.0-7.8) and pre-DM (5.4 IU/mL; IQR 2.0-8.4) compared to HHCs without DM (4.3 IU/mL; IQR 1.4-7.7). DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results suggest that DM may increase the risk of LTBI among HHCs recently exposed to active TB. Among those with LTBI, increased IFN-? antigen response in the presence of DM and pre-DM may indicate an exaggerated but ineffectual response to TB. Further investigation is needed to assess how dysglycemia impacts susceptibility to M. tuberculosis.

وصف الملف: electronic resource

العلاقة: https://www.cambridge.org/core/product/identifier/S2059866121004830/type/journal_articleTest; https://doaj.org/toc/2059-8661Test

الوصول الحر: https://doaj.org/article/65422d9ab42d4a1b9617b42a49004547Test

المؤلفون: Vittoria Roncalli, Matthew C. Cieslak, Russell R. Hopcroft, Petra H. Lenz

المصدر: Frontiers in Marine Science, Vol 7 (2020)

مصطلحات موضوعية: Neocalanus flemingeri, gene expression, RNA-Seq, oogenesis, energy resources, Science, General. Including nature conservation, geographical distribution, QH1-199.5

الوصف: Capital breeders must balance the energetic requirements of cellular function and the cost of reproduction. The subarctic copepod Neocalanus flemingeri, a small planktonic crustacean, depends on a short annual phytoplankton bloom to acquire the energy needed to support a non-feeding adult female that enters a period of diapause prior to spawning 5 to 7 months later. After emergence from diapause, the reproductive program takes 2 months starting with germline development. In this study, the regulation of genes involved in energy utilization and cellular maintenance were investigated using RNA-Seq as females progressed from diapause to end-of-life. Hierarchical clustering of expression profiles from 61 individual females identified four major transitions in transcriptional profiles along a timeline spanning from diapause to spawning and post-reproduction. The clusters were analyzed statistically for differential gene expression followed by functional analyses. The transition from diapause to post-diapause (early to mid-oogenesis) was characterized by the up-regulation of genes involved in cellular homeostasis, glycolysis and lipid catabolism. As females approached spawning genes involved in cellular homeostasis, like innate immunity became down-regulated. Genes involved in protein ubiquitination and programmed cell death became up-regulated as females started to spawn. Gene expression patterns suggest that energy allocation and utilization is highly dynamic in N. flemingeri during the progression of the reproductive period. Major changes in the expression of genes involved in cellular homeostasis, metabolic processes and autophagy were linked to stages of egg maturation. Changes in gene expression that marked the transition from diapause to post-diapause were similar to those reported in other arthropods that resume feeding after emergence from diapause. As egg maturation progressed, gene expression patterns indicate that resources became concentrated on provisioning eggs, while being diverted away from cellular homeostasis. The data suggest that in N. flemingeri genes are regulated such that organismal function and sources of energy are synchronized with stages of egg maturation to optimize the exploitation of finite resources. The existence of mechanisms that regulate fecundity to match the availability of stored resources could reduce reproductive failure in this species.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fmars.2020.00056/fullTest; https://doaj.org/toc/2296-7745Test

الوصول الحر: https://doaj.org/article/408c26cabb8d41bc8b973b881fef28e6Test

المؤلفون: Kerry L. McIver, Russell R. Pate, Marsha Dowda, Suzanne Bennett Johnson, Jimin Yang, Martha Butterworth, Xiang Liu

المصدر: International Journal of Pediatrics, Vol 2020 (2020)

مصطلحات موضوعية: Pediatrics, RJ1-570

الوصف: Purpose. Previous studies have observed that physical activity (PA) levels tend to be lower in the U.S. population than in many other countries. Within the U.S., PA levels in children are lower in the South than in other regions. Cross-country and interregional differences in PA have not been studied in young children. Methods. In an ongoing study of children at genetic risk for Type 1 diabetes, PA was measured by accelerometry in samples of 5-year-old children (n=2008) from Finland (n=370), Germany (n=85), Sweden (n=706), and the U.S. (n=847). The U.S. sample was drawn from centers in Washington State, Colorado, and Georgia/Florida. Children wore accelerometers for 7 days, and the data were reduced to daily minutes of light-, moderate- (MPA), vigorous- (VPA), and moderate-to-vigorous- (MVPA) intensity PA and sedentary behavior. Multiple regression was used to compare children across countries and across regions in the U.S, adjusting for wear time, body mass index, and demographic characteristics. Results. After adjusting for previously mentioned factors, MVPA and MPA were lower in U.S. children than those in Finland and Sweden. Estimates of physical activity were higher in Finland than in other countries, although not all comparisons were significantly different. U.S children spent significantly more time in sedentary behavior than children in Finland (p

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1687-9740Test; https://doaj.org/toc/1687-9759Test

الوصول الحر: https://doaj.org/article/e30aeb29160b4438876cd2a4e49b3da3Test

المؤلفون: R. Tyler Hillman, Joseph Celestino, Christopher Terranova, Hannah C. Beird, Curtis Gumbs, Latasha Little, Tri Nguyen, Rebecca Thornton, Samantha Tippen, Jianhua Zhang, Karen H. Lu, David M. Gershenson, Kunal Rai, Russell R. Broaddus, P. Andrew Futreal

المصدر: Nature Communications, Vol 9, Iss 1, Pp 1-7 (2018)

مصطلحات موضوعية: Science

الوصف: Adult-type granulosa cell tumors of the ovary (aGCTs) are rare and recurrence is difficult to treat. Here, the authors observe in aGCT a novel recurrent somatic truncating mutation of KMT2D, more frequent in recurrent aGCT, and also non-genetic loss of KMT2D expression.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/aaaf9455dfe54c3aac5bc54116b1802bTest

المؤلفون: Shujuan Yan, Ruyi Zhang, Ke Wu, Jing Cui, Shifeng Huang, Xiaojuan Ji, Liping An, Chengfu Yuan, Cheng Gong, Linghuan Zhang, Wei Liu, Yixiao Feng, Bo Zhang, Zhengyu Dai, Yi Shen, Xi Wang, Wenping Luo, Bo Liu, Rex C. Haydon, Michael J. Lee, Russell R. Reid, Jennifer Moriatis Wolf, Qiong Shi, Hue H. Luu, Tong-Chuan He, Yaguang Weng

المصدر: Genes and Diseases, Vol 5, Iss 2, Pp 172-184 (2018)

مصطلحات موضوعية: Medicine (General), R5-920, Genetics, QH426-470

الوصف: Mesenchymal stem cells (MSCs) are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic, chondrogenic and adipogenic lineages. We previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully understood. Here, we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of MSCs. Using two different siRNA bioinformatic prediction programs, we design five siRNAs targeting mouse BMP9 (or simB9), which are expressed under the control of the converging H1 and U6 promoters in recombinant adenovirus vectors. We demonstrate that two of the five siRNAs, simB9-4 and simB9-7, exhibit the highest efficiency on silencing exogenous mouse BMP9 in MSCs. Furthermore, simB9-4 and simB9-7 act synergistically in inhibiting BMP9-induced expression of osteogenic markers, matrix mineralization and ectopic bone formation from MSCs. Thus, our findings demonstrate the important role of BMP9 in osteogenic differentiation of MSCs. The characterized simB9 siRNAs may be used as an important tool to investigate the molecular mechanism behind BMP9 osteogenic signaling. Our results also indicate that recombinant adenovirus-mediated expression of siRNAs is efficient and sustained, and thus may be used as an effective delivery vehicle of siRNA therapeutics. Keywords: BMP9, Bone formation, Mesenchymal stem cells, Osteogenic differentiation, RNA interference, Recombinant adenovirus, siRNA

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2352304218300576Test; https://doaj.org/toc/2352-3042Test

الوصول الحر: https://doaj.org/article/9c10001a2700478488cc85ac656f4c48Test