bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen withdrawal alters cytoskeletal and primary ciliary dynamics resulting in increased Hedgehog and osteoclastogenic paracrine signalling in osteocytes
Authors: Geoghegan Ivor P. , McNamara Laoise M. , Hoey David A. 
Published: April 2021

AbstractEstrogen deficiency during post-menopausal osteoporosis leads to osteoclastogenesis and bone loss. Increased pro-osteoclastogenic signalling (RANKL/OPG) by osteocytes occurs following estrogen withdrawal (EW) and is associated with impaired focal adhesions (FAs) and a disrupted actin cytoskeleton. RANKL production is mediated by Hedgehog signalling in osteocytes, a signalling pathway associated with the primary cilium, and the ciliary structure is tightly coupled to the cytoskeleton. Therefore, the objective of this study was to investigate the role of the cilium and associated signalling in EW-mediated osteoclastogenic signalling in osteocytes. We report that EW leads to an elongation of the cilium and increase in Hedgehog and osteoclastogenic signalling. Significant trends were identified linking cilia elongation with reductions in cell area and % FA area/cell area, indicating that cilia elongation is associated with disruption of FAs and actin contractility. To verify this, we inhibited FA assembly via αvβ3 antagonism and inhibited actin contractility and demonstrated an elongated cilia and increased expression of Hh markers and Rankl expression. Therefore, our results suggest that the EW conditions associated with osteoporosis lead to a disorganisation of αvβ3 integrins and reduced actin contractility, which were associated with an elongation of the cilium, activation of the Hh pathway and osteoclastogenic paracrine signalling.
Impact of metformin treatment during pregnancy on maternal outcomes: a systematic review/meta-analysis
Authors: Tarry-Adkins Jane L. , Ozanne Susan E. , Aiken Catherine E. 
Published: April 2021

AbstractWe systematically assessed the impact of metformin treatment on maternal pregnancy outcomes. PubMed, Ovid Embase, Medline, Web of Science, ClinicalTrials.gov and Cochrane databases were systematically searched (inception-1st February 2021). Randomised controlled trials reporting pregnancy outcomes in women randomised to metformin versus any other treatment for any indication were included. Outcomes included gestational weight gain (GWG), pre-eclampsia, gestational hypertension, preterm birth, gestational age at delivery, caesarean section, gestational diabetes, glycaemic control, and gastrointestinal side-effects. Two independent reviewers conducted screening, with a third available to evaluate disagreements. Risk-of-bias and GRADE assessments were conducted using Cochrane Risk-of-Bias and GRADE-pro software. Thirty-five studies (n = 8033 pregnancies) met eligibility criteria. GWG was lower in pregnancies randomised to metformin versus other treatments (1.57 kg ± 0.60 kg; I2 = 86%, p < 0.0001), as was likelihood of pre-eclampsia (OR 0.69, 95% CI 0.50–0.95; I2 = 55%, p = 0.02). The risk of gastrointestinal side-effects was greater in metformin-exposed versus other treatment groups (OR 2.43, 95% CI 1.53–3.84; I2 = 76%, p = 0.0002). The risk of other maternal outcomes assessed was not significantly different between metformin-exposed versus other treatment groups. Metformin for any indication during pregnancy is associated with lower GWG and a modest reduced risk of pre-eclampsia, but increased gastrointestinal side-effects compared to other treatments.
Modeling and live imaging of mechanical instabilities in the zebrafish aorta during hematopoiesis
Authors: Chalin Dmitrii , Bureau Charlotte , Parmeggiani Andrea , Rochal Sergei , Kissa Karima , Golushko Ivan 
Published: April 2021

AbstractAll blood cells originate from hematopoietic stem/progenitor cells (HSPCs). HSPCs are formed from endothelial cells (ECs) of the dorsal aorta (DA), via endothelial-to-hematopoietic transition (EHT). The zebrafish is a primary model organism to study the process in vivo. While the role of mechanical stress in controlling gene expression promoting cell differentiation is actively investigated, mechanisms driving shape changes of the DA and individual ECs remain poorly understood. We address this problem by developing a new DA micromechanical model and applying it to experimental data on zebrafish morphogenesis. The model considers the DA as an isotropic tubular membrane subjected to hydrostatic blood pressure and axial stress. The DA evolution is described as a movement in the dimensionless controlling parameters space: normalized hydrostatic pressure and axial stress. We argue that HSPC production is accompanied by two mechanical instabilities arising in the system due to the plane stress in the DA walls and show how a complex interplay between mechanical forces in the system drives the emerging morphological changes.
N-Acetyl-l-leucine improves functional recovery and attenuates cortical cell death and neuroinflammation after traumatic brain injury in mice
Authors: Hegdekar Nivedita , Lipinski Marta M. , Sarkar Chinmoy 
Published: April 2021

AbstractTraumatic brain injury (TBI) is a major cause of mortality and long-term disability around the world. Even mild to moderate TBI can lead to lifelong neurological impairment due to acute and progressive neurodegeneration and neuroinflammation induced by the injury. Thus, the discovery of novel treatments which can be used as early therapeutic interventions following TBI is essential to restrict neuronal cell death and neuroinflammation. We demonstrate that orally administered N-acetyl-l-leucine (NALL) significantly improved motor and cognitive outcomes in the injured mice, led to the attenuation of cell death, and reduced the expression of neuroinflammatory markers after controlled cortical impact (CCI) induced experimental TBI in mice. Our data indicate that partial restoration of autophagy flux mediated by NALL may account for the positive effect of treatment in the injured mouse brain. Taken together, our study indicates that treatment with NALL would be expected to improve neurological function after injury by restricting cortical cell death and neuroinflammation. Therefore, NALL is a promising novel, neuroprotective drug candidate for the treatment of TBI.
Stimulus dependence of interocular suppression
Authors: Lew Wei Hau , Stevenson Scott B. , Coates Daniel R. 
Published: April 2021

AbstractInterocular suppression is the phenomenon in which the signal from one eye inhibits the other eye in the presence of dissimilar images. Various clinical and laboratory-based tests have been used to assess suppression, which vary in color, contrast, and stimulus size. These stimulus variations may yield different spatial extents of suppression, which makes it difficult to compare the outcomes. To evaluate the role of stimulus characteristics, we measured the suppression zone using a binocular rivalry paradigm in normally-sighted observers by systematically varying the stimulus parameters. The stimuli consist of a constantly visible horizontal reference seen by one eye while two vertical suppressors were presented to the other eye. With a keypress, the suppressors appeared for 1 s, to induce a transient suppression zone in the middle part of the reference. Subjects adjusted the width between the suppressors to determine the zone. The zone decreased significantly with increasing spatial frequency and lower contrast. The width was 1.4 times larger than the height. The zone was smaller with negative compared to positive contrast polarity but independent of eye dominance, luminance, and colored filters. A departure from scale invariance was captured with a model suggesting a stimulus-dependent and a small fixed non-stimulus-dependent portion.
Direct conversion of porcine primary fibroblasts into hepatocyte-like cells
Authors: Fráguas-Eggenschwiler Mariane , Eggenschwiler Reto , Söllner Jenny-Helena , Cortnumme Leon , Vondran Florian W. R. , Cantz Tobias , Ott Michael , Niemann Heiner 
Published: April 2021

AbstractThe pig is an important model organism for biomedical research, mainly due to its extensive genetic, physiological and anatomical similarities with humans. Until date, direct conversion of somatic cells into hepatocyte-like cells (iHeps) has only been achieved in rodents and human cells. Here, we employed lentiviral vectors to screen a panel of 12 hepatic transcription factors (TF) for their potential to convert porcine fibroblasts into hepatocyte-like cells. We demonstrate for the first time, hepatic conversion of porcine somatic cells by over-expression of CEBPα, FOXA1 and HNF4α2 (3TF-piHeps). Reprogrammed 3TF-piHeps display a hepatocyte-like morphology and show functional characteristics of hepatic cells, including albumin secretion, Dil-AcLDL uptake, storage of lipids and glycogen and activity of cytochrome P450 enzymes CYP1A2 and CYP2C33 (CYP2C9 in humans). Moreover, we show that markers of mature hepatocytes are highly expressed in 3TF-piHeps, while fibroblastic markers are reduced. We envision piHeps as useful cell sources for future studies on drug metabolism and toxicity as well as in vitro models for investigation of pig-to-human infectious diseases.
Apoptotic cells in mouse blastocysts are eliminated by neighbouring blastomeres
Authors: Pisko Jozef , Špirková Alexandra , Čikoš Štefan , Olexiková Lucia , Kovaříková Veronika , Šefčíková Zuzana , Fabian Dušan 
Published: April 2021

AbstractApoptosis is a physiological process that occurs commonly during the development of the preimplantation embryo. The present work examines the ability of apoptotic embryonic cells to express a signal promoting their phagocytosis, and quantifies the ability of neighbouring, normal embryonic cells to perform that task. Microscopic analysis of mouse blastocysts revealed phosphatidylserine externalization to be 10 times less common than incidence of apoptotic cells (as detected by TUNEL). In spite of the low frequency of phosphatidylserine-flipping (in inner cell mass, no annexin V staining was recorded), fluorescence staining of the plasma membrane showed more than 20% of apoptotic cells to have been engulfed by neighbouring blastomeres. The mean frequency of apoptotic cells escaping phagocytosis by their extrusion into blastocyst cavities did not exceed 10%. Immunochemically visualised RAC1 (an enzyme important in actin cytoskeleton rearrangement) was seen in phagosome-like structures containing a nucleus with a condensed morphology. Gene transcript analysis showed that the embryonic cells expressed 12 receptors likely involved in phagocytic process (Scarf1, Msr1, Cd36, Itgav, Itgb3, Cd14, Scarb1, Cd44, Stab1, Adgrb1, Cd300lf, Cd93). In conclusion, embryonic cells possess all the necessary mechanisms for recognising, engulfing and digesting apoptotic cells, ensuring the clearance of most dying blastomeres.
Cytocompatibility of stabilized black phosphorus nanosheets tailored by directly conjugated polymeric micelles for human breast cancer therapy
Authors: Biedulska M. , Jakóbczyk P. , Sosnowska M. , Dec B. , Muchlińska A. , Zaczek A. J. , Nidzworski D. , Bogdanowicz R. 
Published: April 2021

AbstractThe novel procedure of few-layer black phosphorus (FLBP) stabilization and functionalisation was here proposed. The cationic polymer PLL and non-ionic PEG have been involved into encapsulation of FLBP to allow sufficient time for further nanofabrication process and overcome environmental degradation. Two different spacer chemistry was designed to bind polymers to tumor-homing peptides. The efficiency of functionalisation was examined by RP-HPLC, microscopic (TEM and SEM) and spectroscopic (FT-IR and Raman) techniques as well supported by ab-initio modelling. The cell and dose dependent cytotoxicity of FLBP and its bioconjugates was evaluated against HB2, MCF-7 and MDA-MB-231 cell lines. Functionalisation allowed not only for improvement of environmental stability, but also enhances therapeutic effect by abolished the cytotoxicity of FLBP against HB2 cell line. Moreover, modification of FLBP with PLL caused increase of selectivity against highly aggressive breast cancer cell lines. Results indicate the future prospect application of black phosphorus nanosheets as nanocarrier, considering its unique features synergistically with conjugated polymeric micelles.
Clinicopathological analysis of hepatic immune-related adverse events in comparison with autoimmune hepatitis and graft-versus host disease
Authors: Hagiwara Satoru , Watanabe Tomohiro , Kudo Masatoshi , Minaga Kosuke , Komeda Yoriaki , Kamata Ken , Kimura Masatomo , Hayashi Hidetoshi , Nakagawa Kazuhiko , Ueshima Kazuomi , Minami Yasunori , Aoki Tomoko , Takita Masahiro , Morita Masahiro , Cishina Hirokazu , Ida Hiroshi , Park Ah-Mee , Nishida Naoshi 
Published: April 2021

AbstractImmune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) are widely used to treat advanced metastatic cancers. Neutralisation of PD-1 or CTLA-4 by ICIs results in immune-related adverse events (irAEs). The clinicopathological features of twelve patients with hepatic irAEs were evaluated and compared to those of ten patients with autoimmune hepatitis (AIH) or graft-versus-host disease (GVHD). No significant difference was seen in serum levels of transaminases, whereas serum levels of IgG and anti-nuclear antibody were higher in patients with AIH than in those with GVHD or hepatic irAEs. Inflammation was limited to the liver lobes in patients with GVHD or hepatic irAEs, whereas patients with AIH exhibited both portal and lobular inflammation. Immunohistochemical analyses revealed a predominant infiltration of CD8+ T cells and defective accumulation of regulatory T cells (Tregs) expressing forkhead box p3 (FOXP3) in the lobular areas of patients with hepatic irAEs and GVHD. In contrast, periportal lesions of patients with AIH were characterised by an infiltration of CD4+ T cells, CD8+ T cells, CD20+ B cells, and FOXP3+ Tregs. Overall, the activation of CD8+ T cells in the absence of activation of Tregs potentially underlies the immunopathogenesis of hepatic irAEs.
Improved chondrogenic performance with protective tracheal design of Chitosan membrane surrounding 3D-printed trachea
Authors: Kim Hyeonji , Lee Jae Yeon , Han Hyeonseok , Cho Won-Woo , Han Hohyeon , Choi Andrew , Hong Hyeonjun , Kim Jae Yun , Park Jeong Hun , Park Sun Hwa , Kim Sung Won , Kim Dong Sung , Cho Dong-Woo 
Published: April 2021

AbstractIn recent tracheal tissue engineering, limitations in cartilage reconstruction, caused by immature delivery of chondrocyte-laden components, have been reported beyond the complete epithelialization and integration of the tracheal substitutes with the host tissue. In an attempt to overcome such limitations, this article introduces a protective design of tissue-engineered trachea (TraCHIM) composed of a chitosan-based nanofiber membrane (CHIM) and a 3D-printed biotracheal construct. The CHIM was created from chitosan and polycaprolactone (PCL) using an electrospinning process. Upon addition of chitosan to PCL, the diameter of electrospun fibers became thinner, allowing them to be stacked more closely, thereby improving its mechanical properties. Chitosan also enhances the hydrophilicity of the membranes, preventing them from slipping and delaminating over the cell-laden bioink of the biotracheal graft, as well as protecting the construct. Two weeks after implantation in Sprague–Dawley male rats, the group with the TraCHIM exhibited a higher number of chondrocytes, with enhanced chondrogenic performance, than the control group without the membrane. This study successfully demonstrates enhanced chondrogenic performance of TraCHIM in vivo. The protective design of TraCHIM opens a new avenue in engineered tissue research, which requires faster tissue formation from 3D biodegradable materials, to achieve complete replacement of diseased tissue.
A modified clot-based assay to measure negatively charged procoagulant phospholipids
Authors: Ramberg Cathrine , Jamaly S. , Latysheva N. , Wilsgård L. , Sovershaev T. , Snir O. , Hansen J.-B. 
Published: April 2021

AbstractGrowing evidence supports a role for extracellular vesicles (EVs) in haemostasis and thrombosis due to exposure of negatively charged procoagulant phospholipids (PPL). Current commercial PPL-dependent clotting assays use chemically phospholipid depleted plasma to measure PPL activity. The purpose of our study was to modify the PPL assay by substituting the chemically phospholipid depleted plasma with PPL depleted plasma obtained by ultracentrifugation This in order to get readily access to a sensitive and reliable assay to measure PPL activity in human plasma and cell supernatants. The performance of the assay was tested, including the influence of individual coagulation factors and postprandial lipoproteins and compared to a commercial PPL assay (STA-Procoag-PPL). The two PPL assays displayed similar sensitivity to exogenously added standardized phospholipids. The PPL activity measured by the modified assay strongly correlates with the results from the commercial assay. The intraday- and between-days coefficients of variation ranged from 2–4% depending on the PPL activity in the sample. The modified PPL assay was insensitive to postprandial lipoprotein levels in plasma, as well as to tissue factor (TF) positive EVs from stimulated whole blood. Our findings showed that the modified assay performed equal to the comparator, and was insensitive to postprandial lipoproteins and TF+ EVs.
Relationship between spinal structural damage on radiography and bone fragility on CT in ankylosing spondylitis patients
Authors: Fauny Marine , Verhoeven Frank , Allado Edem , Albuisson Eliane , Pinzano Astrid , Morizot Caroline , Chary-Valckenaere Isabelle , Loeuille Damien 
Published: April 2021

AbstractTo evaluate whether the risk of bone fragility on computed tomography (CT) (scanographic bone attenuation coefficient of the first lumbar vertebra (SBAC-L1)) is associated with the severity of spine structural involvement (mSASSS) in patients with ankylosing spondylitis (AS). This retrospective study included AS patients, followed from 2009 to 2017, who fulfilled the New York criteria and who underwent thoraco-abdomino-pelvic CT and radiography (spine, pelvis). The structural involvement was retained for mSASSS ≥ 2. The SBAC-L1 was measured in Hounsfield units (HU). A SBAC-L1 ≤ 145 HU was used to define patients at risk of vertebral fracture (VF). A total of 73 AS patients were included (mean age: 60.3 (± 10.7) years, 8 women (11%), mean disease duration: 24.6 years (± 13.9)). Sixty patients (82.2%) had a mSASSS ≥ 2 (mean score 20.7 (± 21.2)). The mean SBAC-L1 was 141.1 HU (± 45), 138.1 HU (± 44.8) and 154.8 HU (± 44.9) in the total, mSASSS ≥ 2 and mSASSS < 2 populations, respectively. Patients with bone bridges had lower SBAC-L1 than mSASSS ≥ 2 patients without ankylosis (p = 0.02) and more often SBAC-L1 ≤ 145 HU (73% vs 41.9%, p = 0.006). A SBAC-L1 ≤ 145 HU was not associated with structural spine involvement, but patients with bone bridges had significantly decreased SBAC-L1 and an increased probability of being under the fracture threshold.
Comparison of blood pressure values and expression of genes associated with hypertension in children before and after hematopoietic cell transplantation
Authors: Strojny Wojciech , Kwiecińska Kinga , Fijorek Kamil , Korostyński Michał , Piechota Marcin , Balwierz Walentyna , Skoczeń Szymon 
Published: April 2021

AbstractHypertension is a well-known late effect of hematopoietic cell transplantation (HCT), but no markers predicting its development are known. Our aim was to assess short-term blood pressure (BP) values and expressions of hypertension-associated genes as possible markers of hypertension in children treated with HCT. We measured systolic blood pressure (SBP) and diastolic blood pressure (DBP), using both office procedure and ambulatory BP monitoring (ABPM) in children before HCT and after a median of 6 months after HCT. We compared the results with two control groups, one of healthy children and another of children with simple obesity. We also performed microarray analysis of hypertension-associated genes in patients treated with HCT and children with obesity. We found no significant differences in SBP and DBP in patients before and after HCT. We found significant differences in expressions of certain genes in patients treated with HCT compared with children with obesity. We concluded that BP values in short-term follow-up after HCT do not seem to be useful predictors of hypertension as a late effect of HCT. However, over expressions of certain hypertension-associated genes might be used as markers of hypertension as a late effect of HCT if this is confirmed in larger long-term studies.
Track distance runners exhibit bilateral differences in the plantar fascia stiffness
Authors: Shiotani Hiroto , Yamashita Ryo , Mizokuchi Tomohiro , Sado Natsuki , Naito Munekazu , Kawakami Yasuo 
Published: April 2021

AbstractHuman steady-state locomotion modes are symmetrical, leading to symmetric mechanical function of human feet in general; however, track distance running in a counterclockwise direction exposes the runner’s feet to asymmetrical stress. This may induce asymmetrical adaptation in the runners’ foot arch functions, but this has not been experimentally tested. Here, we show that the plantar fascia (PF), a primary structure of the foot arch elasticity, is stiffer for the left than the right foot as a characteristic of runners, via a cross-sectional study on 10 track distance runners and 10 untrained individuals. Shear wave velocity (index of tissue stiffness: SWV) and thickness of PF and foot dimensions were compared between sides and groups. Runners showed higher PF SWV in their left (9.4 ± 1.0 m/s) than right (8.9 ± 0.9 m/s) feet, whereas untrained individuals showed no bilateral differences (8.5 ± 1.5 m/s and 8.6 ± 1.7 m/s, respectively). Additionally, runners showed higher left to right (L/R) ratio of PF SWV than untrained men (105.1% and 97.7%, respectively). PF thickness and foot dimensions were not significantly different between sides or groups. These results demonstrate stiffer PF in the left feet of runners, which may reflect adaptation to their running-specific training that involves asymmetrical mechanical loading.
Lanthanide-porphyrin species as Kondo irreversible switches through tip-induced coordination chemistry
Authors: Cirera B. , Gallego J. M. , Martínez J. I. , Miranda R. , Écija D. 
Published: April 2021

This work reports the in-situ design of premetallated dysprosium porphyrin complexes (Dy-2H-4FTPP) on Au(111), whose Kondo resonance can be switched off with atomic precision by sequential transformation into partially and fully metallated species.
Prix Nobel de Médecine 2016 : Autophagie
Authors: Ohsumi Yoshinori 
Published: April 2021

Au moment où nous apportions la dernière main à un numéro thématique « Autophagie », sous la direction de Patrice Codogno, nous apprenons que le Prix Nobel de médecine 2016 a été décerné au Japonais Yoshinori Ohsumi pour ses travaux sur l’autophagie.
Yoshinori Ohsumi est né le 9 février 1945 à Fukuoka (Japon). Il obtient un Ph.D. à l’université de Tokyo en 1974. Après 3 ans (1974-1977) à l’Université Rockefeller de New York, il revient à l’université de Tokyo où il crée son unité de recherche en 1988. Depuis 2009, il est professeur à l’Institut de technologie de Tokyo.