bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diastereomer recognition of three pairs of tetracyclines by electrospray ionization mass spectrometry
Authors: Zhu Peixi , Zhou Luxi , Jiang Kezhi , Su Weike , Van Schepdael Ann , Adams Erwin 
Published: November 2021

RationaleStereoisomer profiling is always a difficult issue. Based on the difference between diastereomers, usually because of steric hindrance, isomers can be differentiated by mass spectrometry (MS), although it is often not an easy task. In the current study, tetracycline, chlortetracycline and doxycycline could be distinguished from their respective 4‐epimers by MS.MethodsThe electrospray ionization tandem mass spectrometry (ESI‐MSn) analyses were carried out on a Bruker 3000plus ion trap mass spectrometer. For MS/MS experiments, the collision energy was set between 0.18 and 0.45 V to perform energy‐resolved mass spectrometry (ERMS). Test solutions were prepared in methanol/water (90:10, v/v) at a concentration of 10 μg/mL.ResultsCompared with the collision‐induced dissociation (CID) spectrum of protonated tetracycline, the most abundant peak changed from m/z 427 to m/z 410 for 4‐epitetracycline. For chlortetracycline and its 4‐epimer, differences in relative abundance were observed too. In the CID spectrum of a fragment ion of doxycycline, the abundance of m/z 154 was relatively higher than for the 4‐epimer, showing the same trend as in the CID spectra of the other two pairs of tetracyclines.ConclusionsThe CID spectra of tetracycline and chlortetracycline were different from those of their 4‐epimers. The CID spectra of protonated doxycycline and its 4‐epimer showed only a subtle difference, but the m/z 154 fragment ion in the CID spectra of the fragment ion at m/z 428 offers the possibility to differentiate both epimers.
Unraveling the Influence of Thermal Drawing Parameters on the Microstructure and Thermo–Mechanical Properties of Multimaterial Fibers
Authors: Richard Inès , Maurya Anjani K. , Shadman Shahrzad , Masquelier Eloïse , Marthey Lison S. , Neels Antonia , Sorin Fabien 
Published: November 2021

AbstractMultimaterial thermally drawn fibers are becoming important building blocks in several foreseen applications in surgical probes, protective gears, or medical textiles. Here, the influence of the thermal drawing parameters on the degree of polymer chain orientation, the related thermal shrinkage behavior, and the mechanical properties of the final fibers is investigated via thermo–mechanical testing and small‐ and wide‐angle X‐ray scattering (SAXS and WAXS) analyses. This study on polyetherimide fibers reveals that the drawing stress, which depends on the drawing speed and temperature, controls the thermal shrinkage behavior and mechanical properties. Furthermore, SAXS and WAXS analyses show that the degree of chain orientation increases with drawing stresses below 8 MPa and then saturates, which correlates with the amount of observed shrinkage. The use of this process‐dependent polymer chain alignment to tune the mechanical and shrinkage properties of the fibers is highlighted and controlled bending multimaterial fibers made of two polymethyl methacrylates having different molecular weights are developed. Finally, a heat treatment procedure is proposed to relax the chain alignment and increase the dimensional stability of devices such as temperature sensors. This deeper understanding can serve as a guide for the processing of complex fibers requiring specific mechanical properties or enhanced thermal stability.
Revealing Size Dependent Structural Transitions in Supported Gold Nanoparticles in Hydrogen at Atmospheric Pressure
Authors: Nassereddine Abdallah , Wang Qing , Loffreda David , Ricolleau Christian , Alloyeau Damien , Louis Catherine , Delannoy Laurent , Nelayah Jaysen , Guesmi Hazar 
Published: November 2021

AbstractThe enhancement of the catalytic activity of gold nanoparticles with their decreasing size is often attributed to the increasing proportion of low‐coordinated surface sites. This correlation is based on the paradigmatic picture of working gold nanoparticles as perfect crystal forms having complete and static outer surface layers whatever their size. This picture is incomplete as catalysts can dynamically change their structure according to the reaction conditions and as such changes can be eventually size‐dependent. In this work, using aberration‐corrected environmental electron microscopy, size‐dependent crystal structure and morphological evolution in gold nanoparticles exposed to hydrogen at atmospheric pressure, with loss of the face‐centered cubic crystal structure of gold for particle size below 4 nm, are revealed for the first time. Theoretical calculations highlight the role of mobile gold atoms in the observed symmetry changes and particle reshaping in the critical size regime. An unprecedented stable surface molecular structure of hydrogenated gold decorating a highly distorted core is identified. By combining atomic scale in situ observations and modeling of nanoparticle structure under relevant reaction conditions, this work provides a fundamental understanding of the size‐dependent reactivity of gold nanoparticles with a precise picture of their surface at working conditions.
LncRNA, PLXDC2-OT Promoted the Osteogenesis Potentials of MSCs by Inhibiting the Deacetylation Function of RBM6/SIRT7 Complex and OSX Specific Isoform
Authors: Liu Huina , Hu Lei , Yu Guoxia , Yang Haoqing , Cao Yangyang , Wang Songlin , Fan Zhipeng 
Published: November 2021

Abstract
Bone regeneration and remodeling are complex physiological processes that are regulated by key transcription factors. Understanding the regulatory mechanism of key transcription factors on the osteogenic differentiation of mesenchymal stem cells (MSCs) is a key issue for successful bone regeneration and remodeling. In the present study, we investigated the regulatory mechanism of the histone deacetylase Sirtuin 7 (SIRT7) on the key transcription factor OSX and osteogenesis of MSCs. In this study, we found that SIRT7 knockdown increased ALP activity and in vitro mineralization and promoted the expression of the osteogenic differentiation markers DSPP, DMP1, BSP, OCN, and the key transcription factor OSX in MSCs. In addition, SIRT7 could associate with RNA binding motif protein 6 (RBM6) to form a protein complex. Moreover, RBM6 inhibited ALP activity, the expression of DSPP, DMP1, BSP, OCN, and OSX in MSCs, and the osteogenesis of MSCs in vivo. Then, the SIRT7/RBM6 protein complex was shown to downregulate the level of H3K18Ac in the OSX promoter by recruiting SIRT7 to the OSX promoter and inhibiting the expression of OSX isoforms 1 and 2. Furthermore, lncRNA PLXDC2-OT could associate with the SIRT7/RBM6 protein complex to diminish its binding and deacetylation function in the OSX promoter and its inhibitory function on OSX isoforms 1 and 2 and to promote the osteogenic potential of MSCs.
Characterization of Highly Proliferative Decidual Precursor Cells During the Window of Implantation in Human Endometrium
Authors: Diniz-da-Costa Maria , Kong Chow-Seng , Fishwick Katherine J. , Rawlings Thomas , Brighton Paul J. , Hawkes Amelia , Odendaal Joshua , Quenby Siobhan , Ott Sascha , Lucas Emma S. , Vrljicak Pavle , Brosens Jan J. 
Published: November 2021

Abstract
Pregnancy depends on the wholesale transformation of the endometrium, a process driven by differentiation of endometrial stromal cells (EnSC) into specialist decidual cells. Upon embryo implantation, decidual cells impart the tissue plasticity needed to accommodate a rapidly growing conceptus and invading placenta, although the underlying mechanisms are unclear. Here we characterize a discrete population of highly proliferative mesenchymal cells (hPMC) in midluteal human endometrium, coinciding with the window of embryo implantation. Single-cell transcriptomics demonstrated that hPMC express genes involved in chemotaxis and vascular transmigration. Although distinct from resident EnSC, hPMC also express genes encoding pivotal decidual transcription factors and markers, most prominently prolactin. We further show that hPMC are enriched around spiral arterioles, scattered throughout the stroma, and occasionally present in glandular and luminal epithelium. The abundance of hPMC correlated with the in vitro colony-forming unit activity of midluteal endometrium and, conversely, clonogenic cells in culture express a gene signature partially conserved in hPMC. Cross-referencing of single-cell RNA-sequencing data sets indicated that hPMC differentiate into a recently discovered decidual subpopulation in early pregnancy. Finally, we demonstrate that recurrent pregnancy loss is associated with hPMC depletion. Collectively, our findings characterize midluteal hPMC as novel decidual precursors that are likely derived from circulating bone marrow-derived mesenchymal stem/stromal cells and integral to decidual plasticity in pregnancy.
Vascularization of Human Brain Organoids
Authors: Matsui Takeshi K. , Tsuru Yuichiro , Hasegawa Koichi , Kuwako Ken-ichiro 
Published: November 2021

Abstract
Human brain organoids are three-dimensional tissues that are generated in vitro from pluripotent stem cells and recapitulate the early development of the human brain. Brain organoids consist mainly of neural lineage cells, such as neural stem/precursor cells, neurons, astrocytes, and oligodendrocytes. However, all human brain organoids lack vasculature, which plays indispensable roles not only in brain homeostasis but also in brain development. In addition to the delivery of oxygen and nutrition, accumulating evidence suggests that the vascular system of the brain regulates neural differentiation, migration, and circuit formation during development. Therefore, vascularization of human brain organoids is of great importance. Current trials to vascularize various organoids include the adjustment of cultivation protocols, the introduction of microfluidic devices, and the transplantation of organoids into immunodeficient mice. In this review, we summarize the efforts to accomplish vascularization and perfusion of brain organoids, and we discuss these attempts from a forward-looking perspective.
An Aged Bone Marrow Niche Restrains Rejuvenated Hematopoietic Stem Cells
Authors: Guidi Novella , Marka Gina , Sakk Vadim , Zheng Yi , Florian Maria Carolina , Geiger Hartmut 
Published: November 2021

Abstract
Aging-associated leukemia and aging-associated immune remodeling are in part caused by aging of hematopoietic stem cells (HSCs). An increase in the activity of the small RhoGTPase cell division control protein 42 (Cdc42) within HSCs causes aging of HSCs. Old HSCs, treated ex vivo with a specific inhibitor of Cdc42 activity termed CASIN, stay rejuvenated upon transplantation into young recipients. We determined in this study the influence of an aged niche on the function of ex vivo rejuvenated old HSCs, as the relative contribution of HSCs intrinsic mechanisms vs extrinsic mechanisms (niche) for aging of HSCs still remain unknown. Our results show that an aged niche restrains the function of ex vivo rejuvenated HSCs, which is at least in part linked to a low level of the cytokine osteopontin found in aged niches. The data imply that sustainable rejuvenation of the function of aged HSCs in vivo will need to address the influence of an aged niche on rejuvenated HSCs.
Fluid Shear Stress Promotes Embryonic Stem Cell Pluripotency via Interplay Between β-Catenin and Vinculin in Bioreactor Culture
Authors: Nath Suman C. , Day Bradley , Harper Lane , Yee Jeffrey , Hsu Charlie Yu-Ming , Larijani Leila , Rohani Leili , Duan Nicholas , Kallos Michael S. , Rancourt Derrick E. 
Published: November 2021

Abstract
The expansion of pluripotent stem cells (PSCs) as aggregates in stirred suspension bioreactors is garnering attention as an alternative to adherent culture. However, the hydrodynamic environment in the bioreactor can modulate PSC behavior, pluripotency and differentiation potential in ways that need to be well understood. In this study, we investigated how murine embryonic stem cells (mESCs) sense fluid shear stress and modulate a noncanonical Wnt signaling response to promote pluripotency. mESCs showed higher expression of pluripotency marker genes, Oct4, Sox2, and Nanog in the absence of leukemia inhibitory factor (LIF) in stirred suspension bioreactors compared to adherent culture, a phenomenon we have termed mechanopluripotency. In bioreactor culture, fluid shear promoted the nuclear translocation of the less well-known pluripotency regulator β-catenin and concomitant increase of c-Myc expression, an upstream regulator of Oct4, Sox2, and Nanog. We also observed similar β-catenin nuclear translocation in LIF-free mESCs cultured on E-cadherin substrate under defined fluid shear stress conditions in flow chamber plates. mESCs showed lower shear-induced expression of pluripotency marker genes when β-catenin was inhibited, suggesting that β-catenin signaling is crucial to mESC mechanopluripotency. Key to this process is vinculin, which is known to rearrange and associate more strongly with adherens junctions in response to fluid shear. When the vinculin gene is disrupted, we observe that nuclear β-catenin translocation and mechanopluripotency are abrogated. Our results indicate that mechanotransduction through the adherens junction complex is important for mESC pluripotency maintenance.
Acute myeloid leukemia-induced functional inhibition of healthy CD34+ hematopoietic stem and progenitor cells
Authors: Jäger Paul , Geyh Stefanie , Twarock Sören , Cadeddu Ron-Patrick , Rabes Pablo , Koch Annemarie , Maus Uwe , Hesper Tobias , Zilkens Christoph , Rautenberg Christina , Bormann Felix , Köhrer Karl , Petzsch Patrick , Wieczorek Dagmar , Betz Beate , Surowy Harald , Hildebrandt Barbara , Germing Ulrich , Kobbe Guido , Haas Rainer , Schroeder Thomas 
Published: November 2021

Abstract
Acute myeloid leukemia (AML) is characterized by an expansion of leukemic cells and a simultaneous reduction of normal hematopoietic precursors in the bone marrow (BM) resulting in hematopoietic insufficiency, but the underlying mechanisms are poorly understood in humans. Assuming that leukemic cells functionally inhibit healthy CD34+ hematopoietic stem and progenitor cells (HSPC) via humoral factors, we exposed healthy BM-derived CD34+ HSPC to cell-free supernatants derived from AML cell lines as well as from 24 newly diagnosed AML patients. Exposure to AML-derived supernatants significantly inhibited proliferation, cell cycling, colony formation, and differentiation of healthy CD34+ HSPC. RNA sequencing of healthy CD34+ HSPC after exposure to leukemic conditions revealed a specific signature of genes related to proliferation, cell-cycle regulation, and differentiation, thereby reflecting their functional inhibition on a molecular level. Experiments with paired patient samples showed that these inhibitory effects are markedly related to the immunomagnetically enriched CD34+ leukemic cell population. Using PCR, ELISA, and RNA sequencing, we detected overexpression of TGFβ1 in leukemic cells on the transcriptional and protein level and, correspondingly, a molecular signature related to TGFβ1 signaling in healthy CD34+ HSPC. This inhibitory effect of TGFβ1 on healthy hematopoiesis was functionally corrobated and could be pharmacologically reverted by SD208, an inhibitor of TGFβ receptor 1 signaling. Overall, these data indicate that leukemic cells induce functional inhibition of healthy CD34+ HSPC, at least in part, through TGFβ1, suggesting that blockage of this pathway may improve hematopoiesis in AML.
Bone Marrow-Derived Progenitor Cells Contribute to Remodeling of the Postpartum Uterus
Authors: Tal Reshef , Kisa Jacqueline , Abuwala Nafeesa , Kliman Harvey J. , Shaikh Shafiq , Chen Alice Y. , Lyu Fang , Taylor Hugh S. 
Published: November 2021

Abstract
Endometrial stem/progenitor cells play a role in postpartum uterine tissue regeneration, but the underlying mechanisms are poorly understood. While circulating bone marrow (BM)-derived cells (BMDCs) contribute to nonhematopoietic endometrial cells, the contribution of BMDCs to postpartum uterus remodeling is unknown. We investigated the contribution of BMDCs to the postpartum uterus using 5-fluorouracil-based nongonadotoxic BM transplant from green fluorescent protein (GFP) donors into wild-type C57BL/6J female mice. Flow cytometry showed an influx of GFP+ cells to the uterus immediately postpartum accounting for 28.7% of total uterine cells, followed by a rapid decrease to prepregnancy levels. The majority of uterine GFP+ cells were CD45+ leukocytes, and the proportion of nonhematopoietic CD45−GFP+ cells peaked on postpartum day (PPD) 1 (17.5%). Immunofluorescence colocalization of GFP with CD45 pan-leukocyte and F4/80 macrophage markers corroborated these findings. GFP+ cells were found mostly in subepithelial stromal location. Importantly, GFP+ cytokeratin-positive epithelial cells were found within the luminal epithelium exclusively on PPD1, demonstrating direct contribution to postpartum re-epithelialization. A subset (3.2%) of GFP+ cells were CD31+CD45− endothelial cells, and found integrated within blood vessel endothelium. Notably, BM-derived GFP+ cells demonstrated preferential proliferation (PCNA+) and apoptosis (TUNEL+) on PPD1 vs resident GFP− cells, suggesting an active role for BMDCs in rapid tissue turnover. Moreover, GFP+ cells gradually acquired cell senescence together with decreased proliferation throughout the postpartum. In conclusion, BM-derived progenitors were found to have a novel nonhematopoietic cellular contribution to postpartum uterus remodeling. This contribution may have an important functional role in physiological as well as pathological postpartum endometrial regeneration.
Bone-Forming Perivascular Cells: Cellular Heterogeneity and Use for Tissue Repair
Authors: Xu Jiajia , Wang Yiyun , Gomez-Salazar Mario A. , Hsu Ginny Ching-Yun , Negri Stefano , Li Zhao , Hardy Winters , Ding Lijun , Peault Bruno , James Aaron W. 
Published: November 2021

AbstractMesenchymal progenitor cells are broadly distributed across perivascular niches—an observation conserved between species. One common histologic zone with a high frequency of mesenchymal progenitor cells within mammalian tissues is the tunica adventitia, the outer layer of blood vessel walls populated by cells with a fibroblastic morphology. The diversity and functions of (re)generative cells present in this outermost perivascular niche are under intense investigation; we have reviewed herein our current knowledge of adventitial cell potential with a somewhat narrow focus on bone formation. Antigens of interest to functionally segregate adventicytes are discussed, including CD10, CD107a, aldehyde dehydrogenase isoforms, and CD140a, among others. Purified adventicytes (such as CD10+, CD107alow, and CD140a+ cells) have stronger osteogenic potential and promote bone formation in vivo. Recent bone tissue engineering applications of adventitial cells are also presented. A better understanding of perivascular progenitor cell subsets may represent a beneficial advance for future efforts in tissue repair and bioengineering.
A Protein-Centric View of in Vitro Biological Model Systems for Schizophrenia
Authors: Chandrasekaran Abinaya , Jensen Pia , Mohamed Fadumo A. , Lancaster Madeline , Benros Michael E. , Larsen Martin R. , Freude Kristine K. 
Published: November 2021

AbstractSchizophrenia (SCZ) is a severe brain disorder, characterized by psychotic, negative, and cognitive symptoms, affecting 1% of the population worldwide. The precise etiology of SCZ is still unknown; however, SCZ has a high heritability and is associated with genetic, environmental, and social risk factors. Even though the genetic contribution is indisputable, the discrepancies between transcriptomics and proteomics in brain tissues are consistently challenging the field to decipher the disease pathology. Here we provide an overview of the state of the art of neuronal two-dimensional and three-dimensional model systems that can be combined with proteomics analyses to decipher specific brain pathology and detection of alternative entry points for drug development.
Spatiotemporal Extracellular Matrix Modeling forin SituCell Niche Studies
Authors: Olesen Kim , Rodin Sergey , Mak Wing Cheung , Felldin Ulrika , Österholm Cecilia , Tilevik Andreas , Grinnemo Karl-Henrik 
Published: November 2021

AbstractExtracellular matrix (ECM) components govern a range of cell functions, such as migration, proliferation, maintenance of stemness, and differentiation. Cell niches that harbor stem-/progenitor cells, with matching ECM, have been shown in a range of organs, although their presence in the heart is still under debate. Determining niches depends on a range of in vitro and in vivo models and techniques, where animal models are powerful tools for studying cell-ECM dynamics; however, they are costly and time-consuming to use. In vitro models based on recombinant ECM proteins lack the complexity of the in vivo ECM. To address these issues, we present the spatiotemporal extracellular matrix model for studies of cell-ECM dynamics, such as cell niches. This model combines gentle decellularization and sectioning of cardiac tissue, allowing retention of a complex ECM, with recellularization and subsequent image processing using image stitching, segmentation, automatic binning, and generation of cluster maps. We have thereby developed an in situ representation of the cardiac ECM that is useful for assessment of repopulation dynamics and to study the effect of local ECM composition on phenotype preservation of reseeded mesenchymal progenitor cells. This model provides a platform for studies of organ-specific cell-ECM dynamics and identification of potential cell niches.
Intranasal Delivery of Mesenchymal Stem Cells-Derived Extracellular Vesicles for the Treatment of Neurological Diseases
Authors: Herman Shay , Fishel Idan , Offen Daniel 
Published: November 2021

Abstract
Neurological disorders are diseases of the central nervous system (CNS), characterized by a progressive degeneration of cells and deficiencies in neural functions. Mesenchymal stem cells (MSCs) are a promising therapy for diseases and disorders of the CNS. Increasing evidence suggests that their beneficial abilities can be attributed to their paracrine secretion of extracellular vesicles (EVs). Administration of EVs that contain a mixture of proteins, lipids, and nucleic acids, resembling the secretome of MSCs, has been shown to mimic most of the effects of the parental cells. Moreover, the small size and safety profile of EVs provide a number of advantages over cell transplantation. Intranasal (IN) administration of EVs has been established as an effective and reliable way to bypass the blood-brain barrier and deliver drugs to the CNS. In addition to pharmacological drugs, EVs can be loaded with a diverse range of cargo designed to modulate gene expression and protein functions in recipient cells, and lead to immunomodulation, neurogenesis, neuroprotection, and degradation of protein aggregates. In this review, we will explore the proposed physiological pathways by which EVs migrate through the nasal route to the CNS where they can actively target a region of injury or inflammation and exert their therapeutic effects. We will summarize the functional outcomes observed in animal models of neurological diseases following IN treatment with MSC-derived EVs. We will also examine key mechanisms that have been suggested to mediate the beneficial effects of EV-based therapy.