bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone Marrow-Derived Mesenchymal Stem Cells Improve Rat Islet Graft Revascularization by Upregulating ISL1
Authors: Wang Ying , Wang Jing-Wen , Li Yang , Tian Xiao-Hui , Feng Xin-Shun , Zhang Shu-Cong , Liu Pei-Jun , Xue Wu-Jun , Zheng Jin , Ding Xiao-Ming 
Published: November 2021

Abstract
Revascularization of the islet transplant is a crucial step that defines the success rate of patient recovery. Bone marrow-derived mesenchymal stem cells (BMSCs) have been reported to promote revascularization; however, the underlying cellular mechanism remains unclear. Moreover, our liquid chromatography-tandem mass spectrometry results showed that BMSCs could promote the expression of insulin gene enhancer binding protein-1 (ISL1) in islets. ISL1 is involved in islets proliferation and plays a potential regulatory role in the revascularization of islets. This study identifies the ISL1 protein as a potential modulator in BMSCs-mediated revascularization of islet grafts. We demonstrated that the survival rate and insulin secretion of islets were increased in the presence of BMSCs, indicating that BMSCs promote islet revascularization in a coculture system and rat diabetes model. Interestingly, we also observed that the presence of BMSCs led to an increase in ISL1 and vascular endothelial growth factor A (VEGFA) expression in both islets and the INS-1 rat insulinoma cell line. In silico protein structure modeling indicated that ISL1 is a transcription factor that has four binding sites with VEGFA mRNA. Further results showed that overexpression of ISL1 increased both the abundance of VEGFA transcripts and protein accumulation, while inhibition of ISL1 decreased the abundance of VEGFA. Using a ChIP-qPCR assay, we demonstrated that direct molecular interactions between ISL1 and VEGFA occur in INS-1 cells. Together, these findings reveal that BMSCs promote the expression of ISL1 in islets and lead to an increase in VEGFA in islet grafts. Hence, ISL1 is a potential target to induce early revascularization in islet transplantation.
miR-351-3p Promotes Rat Amniotic Fluid-Derived Mesenchymal Stromal Cell Proliferation via Targeting the Coding Sequence of Abca4
Authors: Huang Jieting , Zhao Qi , Wei Xiaowei , Ma Wei , Luo Wenting , Gu Hui , Liu Dan , He Yiwen , Huang Tianchu , Liu Yusi , Wang Chenfei , Yuan Zhengwei 
Published: November 2021

Abstract
Amniotic fluid-derived mesenchymal stromal cells (AFMSCs) present different features, depending on the isolation timing and culture conditions. The lack of uniform experimental standards hinders the comparison of results from different studies on AFMSCs. Moreover, understanding the molecular mechanisms that underlie the features of AFMSCs isolated at different embryonic developmental stages might allow the obtention of more viable and highly proliferative AFMSCs through genetic modification. We isolated AFMSCs from pregnant rats at embryonic day (E)12, E15, E18, and E21 and compared their cell proliferation capacity and transcriptome. The cell counting kit-8 assay and RNA sequencing revealed that E12 and E15 AFMSCs showed different characteristics from E18 and E21 AFMSCs. Therefore, AFMSCs were divided into two groups: early (E12 and E15) and late (E18 and E21) pregnancy-stage groups. Next, we screened the gene/microRNA pair Abca4/miR-351-3p that was related to cell proliferation. Abca4 knockdown/overexpression suggested that this gene represses the proliferation of AFMSCs, which is a newly discovered function of this gene. Finally, dual luciferase reporter gene assays confirmed that miR-351-3p targeted the coding sequence of Abca4 and regulated AFMSC proliferation. miR-351-3p promotes AFMSC proliferation via targeting the coding sequence of Abca4. Our findings provide a molecular foundation for further research for obtaining AFMSCs with a higher proliferation capacity.
Directly Reprogrammed Huntington's Disease Neural Precursor Cells Generate Striatal Neurons Exhibiting Aggregates and Impaired Neuronal Maturation
Authors: Monk Ruth , Lee Kevin , Jones Kathryn S. , Connor Bronwen 
Published: November 2021

Abstract
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by the progressive loss of striatal medium spiny neurons. Using a highly efficient protocol for direct reprogramming of adult human fibroblasts with chemically modified mRNA, we report the first generation of HD induced neural precursor cells (iNPs) expressing striatal lineage markers that differentiated into DARPP32+ neurons from individuals with adult-onset HD (41-57 CAG). While no transcriptional differences between normal and HD reprogrammed neurons were detected by NanoString nCounter analysis, a subpopulation of HD reprogrammed neurons contained ubiquitinated polyglutamine aggregates. Importantly, reprogrammed HD neurons exhibited impaired neuronal maturation, displaying altered neurite morphology and more depolarized resting membrane potentials. Reduced BDNF protein expression in reprogrammed HD neurons correlated with increased CAG repeat lengths and earlier symptom onset. This model represents a platform for investigating impaired neuronal maturation and screening for neuronal maturation modifiers to treat HD.
Characterization in Mice of the Resident Mesenchymal Niche Maintaining At2 Stem Cell Proliferation in Homeostasis and Disease
Authors: Taghizadeh Sara , Heiner Monika , Vazquez-Armendariz Ana Ivonne , Wilhelm Jochen , Herold Susanne , Chen Chengshui , Zhang Jin San , Bellusci Saverio 
Published: November 2021

Abstract
Resident mesenchymal cells (rMCs defined as Cd31NegCd45NegEpcamNeg) control the proliferation and differentiation of alveolar epithelial type 2 (AT2) stem cells in vitro. The identity of these rMCs is still elusive. Among them, Axin2Pos mesenchymal alveolar niche cells (MANCs), which are expressing Fgf7, have been previously described. We propose that an additional population of rMCs, expressing Fgf10 (called rMC-Sca1PosFgf10Pos) are equally important to maintain AT2 stem cell proliferation. The alveolosphere model, based on the AT2-rMC co-culture in growth factor-reduced Matrigel, was used to test the efficiency of different rMC subpopulations isolated by FACS from adult murine lung to sustain the proliferation and differentiation of AT2 stem cells. We demonstrate that rMC-Sca1PosFgf10Pos cells are efficient to promote the proliferation and differentiation of AT2 stem cells. Co-staining of adult lung for Fgf10 mRNA and Sftpc protein respectively, indicate that 28% of Fgf10Pos cells are located close to AT2 cells. Co-ISH for Fgf7 and Fgf10 indicate that these two populations do not significantly overlap. Gene arrays comparing rMC-Sca1PosAxin2Pos and rMC-Sca1PosFgf10Pos support that these two cell subsets express differential markers. In addition, rMC function is decreased in obese ob/ob mutant compared to WT mice with a much stronger loss of function in males compared to females. In conclusion, rMC-Sca1PosFgf10Pos cells play important role in supporting AT2 stem cells proliferation and differentiation. This result sheds a new light on the subpopulations of rMCs contributing to the AT2 stem cell niche in homeostasis and in the context of pre-existing metabolic diseases.
Cytokine and Epigenetic Regulation of Programmed Death-Ligand 1 in Stem Cell Differentiation and Cancer Cell Plasticity
Authors: Kuo Ming-Han , Chen Pei-Yu , Yang Yi-Ping , Zheng Ming-Yi , Miao Chia-Cheng , Wen Kuo-Chang , Chang Kuo-Ming , Chou Shih-Jie , Wang Mong-Lien , Chiou Shih-Hwa , Chou Yu-Ting 
Published: November 2021

Abstract
Programmed death-ligand 1 (PD-L1), an immune checkpoint ligand, is recognized as a potential target for cancer immunotherapy as well as for the induction of transplantation tolerance. However, how the crosstalk between stem cell programming and cytokine signaling regulates PD-L1 expression during stem cell differentiation and cancer cell plasticity remains unclear. Herein, we reported that PD-L1 expression was regulated by SOX2 during embryonic stem cell (ESC) differentiation and lung cancer cell plasticity. PD-L1 was induced during ESC differentiation to fibroblasts and was downregulated during SOX2-mediated reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs). Furthermore, SOX2 activation affected cancer cell plasticity and inhibited PD-L1 expression in lung cancer cells. We discovered that the H3K27ac signal at the PD-L1 locus was enhanced during ESC differentiation to fibroblasts as well as during cancer plasticity of SOX2-positive lung cancer cells to SOX2-negative counterparts. Romidepsin, an epigenetic modifier, induced PD-L1 expression in lung cancer cells, whereas TGF-β stimulation downregulated SOX2 but upregulated PD-L1 expression in lung cancer cells. Furthermore, in addition to PD-L1, the expressions of EGFR and its ligand HBEGF were downregulated by activation of endogenous SOX2 expression during lung cancer cell plasticity and iPSC reprogramming, and the activation of EGFR signaling by HBEGF upregulated PD-L1 expression in lung cancer cells. Together, our results reveal the crosstalk between SOX2 programming and cytokine stimulation influences PD-L1 expression, and these findings may provide insights into PD-L1-mediated therapeutics.
Prostacyclin is an Endosteal Bone Marrow Niche Component and its Clinical Analog Iloprost Protects Hematopoietic Stem Cell Potential During Stress
Authors: Tay Joshua , Barbier Valerie , Helwani Falak M. , Price Gareth R. , Levesque Jean-Pierre , Winkler Ingrid G. 
Published: November 2021

Abstract
Hematopoietic stem cells (HSCs) with superior reconstitution potential are reported to be enriched in the endosteal compared to central bone marrow (BM) region. To investigate whether specific factors at the endosteum may contribute to HSC potency, we screened for candidate HSC niche factors enriched in the endosteal compared to central BM regions. Together with key known HSC supporting factors Kitl and Cxcl12, we report that prostacyclin/prostaglandin I2 (PGI2) synthase (Ptgis) was one of the most highly enriched mRNAs (&gt;10-fold) in endosteal compared to central BM. As PGI2 signals through receptors distinct from prostaglandin E2 (PGE2), we investigated functional roles for PGI2 at the endosteal niche using therapeutic PGI2 analogs, iloprost, and cicaprost. We found PGI2 analogs strongly reduced HSC differentiation in vitro. Ex vivo iloprost pulse treatment also significantly boosted long-term competitive repopulation (LT-CR) potential of HSCs upon transplantation. This was associated with increased tyrosine-phosphorylation of transducer and activator of transcription-3 (STAT3) signaling in HSCs but not altered cell cycling. In vivo, iloprost administration protected BM HSC potential from radiation or granulocyte colony-stimulating factor-induced exhaustion, and restored HSC homing potential with increased Kitl and Cxcl12 transcription in the BM. In conclusion, we propose that PGI2 is a novel HSC regulator enriched in the endosteum that promotes HSC regenerative potential following stress.
Aryl Hydrocarbon Receptor Controls Skin Homeostasis, Regeneration, and Hair Follicle Cycling by Adjusting Epidermal Stem Cell Function
Authors: Rico-Leo Eva María , Lorenzo-Martín Luis Francisco , Román Ángel Carlos , Bustelo Xosé Ramón , Merino Jaime María , Fernández-Salguero Pedro María 
Published: November 2021

AbstractSkin integrity requires constant maintenance of a quiescent, yet responsive, population of stem cells. While interfollicular epidermal progenitors control normal homeostasis, hair follicle stem cells residing within the bulge provide regenerative potential during hair cycle and in response to wounding. The aryl hydrocarbon receptor (AhR) modulates cell plasticity and differentiation and its overactivation results in severe skin lesions in humans. However, its physiological role in skin homeostasis and hair growth is unknown. Reconstitution assays grafting primary keratinocytes and dermal fibroblasts into nude mice and 3-D epidermal equivalents revealed a positive role for AhR in skin regeneration, epidermal differentiation, and stem cell maintenance. Furthermore, lack of receptor expression in AhR−/− mice delayed morphogenesis and impaired hair regrowth with a phenotype closely correlating with a reduction in suprabasal bulge stem cells (α6lowCD34+). Moreover, RNA-microarray and RT-qPCR analyses of fluorescence-activated cell sorting (FACS)-isolated bulge stem cells revealed that AhR depletion impaired transcriptional signatures typical of both epidermal progenitors and bulge stem cells but upregulated differentiation markers likely compromising their undifferentiated phenotype. Altogether, our findings support that AhR controls skin regeneration and homeostasis by ensuring epidermal stem cell identity and highlights this receptor as potential target for the treatment of cutaneous pathologies.
Increased Lipogenesis is Critical for Self-Renewal and Growth of Breast Cancer Stem Cells: Impact of Omega-3 Fatty Acids
Authors: Luo Haiqing , Chen Chih-Yu , Li Xiangyong , Zhang Xin , Su Chien-Wen , Liu Yinghua , Cao Tinglan , Hao Lei , Wang Meng , Kang Jing X. 
Published: November 2021

Abstract
Aberrant lipid metabolism has recently been recognized as a new hallmark of malignancy, but the characteristics of fatty acid metabolism in breast cancer stem cells (BCSC) and potential interventions targeting this pathway remain to be addressed. Here, by using the in vitro BCSC models, mammosphere-derived MCF-7 cells and HMLE-Twist-ER cells, we found that the cells with stem cell-like properties exhibited a very distinct profile of fatty acid metabolism compared with that of their parental cancer cells, characterized by increased lipogenesis, especially the activity of stearoyl-CoA desaturase 1 (SCD1) responsible for the production of monounsaturated fatty acids, and augmented synthesis and utilization of the omega-6 arachidonic acid (AA). Suppression of SCD1 activity by either enzyme inhibitors or small interfering RNA (siRNA) knockdown strikingly limited self-renewal and growth of the BCSC, suggesting a key role for SCD1 in BCSC proliferation. Furthermore, elevated levels of SCD1 and other lipogenic enzymes were observed in human breast cancer tissues relative to the noncancer tissues from the same patients and correlated with the pathological grades. Interestingly, treatment of BCSC with omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, effectively downregulated the expression of the lipogenic enzymes and markedly suppressed BCSC self-renewal and growth. Dietary supplementation of nude mice bearing BCSC-derived tumors with omega-3 fatty acids also significantly reduced their tumor load. These findings have demonstrated that increased lipogenesis is critical for self-renewal and growth of BCSC, and that omega-3 fatty acids are effective in targeting this pathway to exert their anticancer effect.
Bilateral ectopic ureteroceles complicated by a large calculus within the left ureterocele in a dog
Authors: Agut Amalia , Sánchez‐Porlan Sandra , Soler Marta , Laredo Francisco G. , Carrillo Juana D. 
Published: November 2021

AbstractA 4‐year‐old, entire female Siberian husky was presented with a history of urinary incontinence since she was a puppy and intermittent haematuria. A diagnosis of bilateral ectopic ureteroceles, calculus in the left ureterocele and bilateral pyelectasia was made by ultrasonography and CT excretory urography. The ureters were visualized communicating with opacified oblong structures, both located in the bladder neck, and the left one extended into the urethra. Resection of ureteroceles, neoureterostomy and calculus removal was performed. The dog made an uneventful recovery and was discharged from the hospital after 36 hours. A 2‐week course of antibiotic treatment was followed (marbofloxacin). Chemical analysis of the calculus revealed that it was composed of struvite. Treatment is mandatory at the time of diagnosis to prevent chronic kidney injury and urolithiasis secondary to obstructive uropathy. To the best of our knowledge, this is the first description of bilateral ectopic ureteroceles associated with calculus in a dog.
The anti‐inflammatory effects of equine bone marrow stem cell‐derived extracellular vesicles on autologous chondrocytes
Authors: Hotham William Edward , Thompson Charlotte , Szu‐Ting Lin , Henson Frances Margaret Daphne 
Published: November 2021

AbstractBackgroundOsteoarthritis (OA) in the horse is an economic and welfare issue and there are no current disease modifying drugs available. Stem cells have been suggested as a therapeutic intervention for OA, originally on the basis of their regenerative capacity. However, it is hypothesised that mesenchymal stem cells (MSC) exert their effects via paracrine factors including the production of extracellular vesicles that can themselves recapitulate the MSC effects in the joint.ObjectivesTo isolate extracellular vesicles from bone marrow MSC and investigate their anti‐inflammatory effects on chondrocytes.Study designAn in vitro assessment of the effect of direct culturing extracellular vesicles on artificially inflamed chondrocytes.MethodsExtracellular vesicles were isolated from bone marrow MSC using differential sequential ultracentrifugation. Vesicles were characterised using electron microscopy, nanoparticle tracing analysis and protein analysis. Vesicle internalisation was carried out via vesicles being pre‐stained and co‐cultured with equine chondrocytes before analysis using confocal microscopy. The effects of vesicles on artificially inflamed chondrocytes was examined using quantitative PCR.ResultsTo the best of the authors' knowledge, this is the first study to isolate and characterise extracellular vesicles from equine bone MSC. Vesicles were taken up by autologous chondrocytes and had anti‐inflammatory effects on gene expression following chondrocyte exposure to tumour necrosis factor α and Interleukin 1β.Main limitationsOnly three independent biological repeats were performed and the work was done in vitro.ConclusionExtracellular vesicles can be isolated from equine bone marrow MSC; they may be taken up by chondrocytes and have an anti‐inflammatory action.
Chapter 1: Russia’s Foreign Food Trade: An Historical Survey
Authors: Wegren Stephen K. 
Published: November 2021

AbstractThe chapter utilises four variables to examine Russia’s food trade from the 1970s to the present. The four variables include: frequency of entrance into the global food market; degree of food trade protectionism; degree of integration with Western global trading institutions; and degree of involvement in the global food market. For the period since 2014, the chapter concludes that thefrequencyof Russia’s entrance into the global food market is likely to remain high as an annual importer and exporter. Agriculturalprotectionismis likely to remain selectively high. The degree ofintegrationwith Western trade institutions is likely to remain low. Russia’s degree ofinvolvementwith the global food market is likely to remain high.
Salvage of too slow gravitinos
Authors: Antoniadis I. , Benakli K. , Ke W. 
Published: November 2021

Abstract
Gravitinos can inherit a non-relativistic dispersion relation while propagating in a background breaking both supersymmetry and Lorentz symmetry spontaneously. This is because the longitudinal mode velocity is controlled by the sound speed in the background. It was pointed out recently by Kolb, Long and McDonough that the production of gravitinos might diverge when this sound speed vanishes. We argue that in the framework of cosmological models with linearly spontaneously broken realised supersymmetry, where the physical fermions are combinations of the vacuum goldstino and the inflatino, the gravitino longitudinal mode has a relativistic dispersion relation and therefore avoids the catastrophic production. We illustrate this in some explicit examples.
Non-perturbative heterotic duals of M-theory on G2 orbifolds
Authors: Acharya Bobby Samir , Kinsella Alex , Morrison David R. 
Published: November 2021

Abstract
By fibering the duality between the E8 × E8 heterotic string on T3 and M-theory on K3, we study heterotic duals of M-theory compactified on G2 orbifolds of the form T7/$$ {\mathbb{Z}}_2^3 $$

ℤ
2
3

. While the heterotic compactification space is straightforward, the description of the gauge bundle is subtle, involving the physics of point-like instantons on orbifold singularities. By comparing the gauge groups of the dual theories, we deduce behavior of a “half-G2” limit, which is the M-theory analog of the stable degeneration limit of F-theory. The heterotic backgrounds exhibit point-like instantons that are localized on pairs of orbifold loci, similar to the “gauge-locking” phenomenon seen in Hořava-Witten compactifications. In this way, the geometry of the G2 orbifold is translated to bundle data in the heterotic background. While the instanton configuration looks surprising from the perspective of the E8 × E8 heterotic string, it may be understood as T-dual Spin(32)/ℤ2 instantons along with winding shifts originating in a dual Type I compactification.
Islands in the stream of Hawking radiation
Authors: Hollowood Timothy J. , Kumar S. Prem , Legramandi Andrea , Talwar Neil 
Published: November 2021

Abstract
We consider the island formula for the entropy of subsets of the Hawking radiation in the adiabatic limit where the black hole evaporation is very slow. We find a simple concrete ‘on-shell’ formula for the generalized entropy which involves the image of the island out in the stream of radiation, the ‘island in the stream’. The resulting recipe for the entropy allows us to calculate the quantum information properties of the radiation and verify various constraints including the Araki-Lieb inequality and strong subadditivity.
Correlated gravitational wave and microlensing signals of macroscopic dark matter
Authors: Marfatia Danny , Tseng Po-Yan 
Published: November 2021

Abstract
Fermion dark matter particles can aggregate to form extended dark matter structures via a first-order phase transition in which the particles get trapped in the false vacuum. We study Fermi balls created in a phase transition induced by a generic quartic thermal effective potential. We show that for Fermi balls of mass, 3 × 10−12M⊙ ≲ MFB ≲ 10−5M⊙, correlated observations of gravitational waves produced during the phase transition (at SKA/THEIA/μAres), and gravitational microlensing caused by Fermi balls (at Subaru-HSC), can be made.