130 research outputs found
The Influence of Lumbopelvic Function on Perceived Ankle Function in Individuals with Chronic Ankle Instability
Perceived functional impairments measured via patient-reported outcomes (PROs) are associated with reduced postural control ability in CAI patients. Furthermore, hip and trunk neuromuscular impairments are critical factors that can cause decreased postural stability in those with CAI. Identifying the relevance between reduced lumbopelvic function and impaired sensory-perceptual outcomes might direct clinicians to novel methods for CAI patients to improve postural control ability and perceived ankle function. Therefore, the aim of this study was to examine the relationship between tests of lumbopelvic function and PROs in individuals with CAI. Thirty-three individuals with CAI underwent assessment of transversus abdominis and lumbar multifidus muscle contractility using diagnostic ultrasound; lumbopelvic stability via the unilateral hip bridge, trunk flexion endurance, Biering-Sorensen, and side plank tests; and isometric hip extension, abduction, and external rotation strength via hand-held dynamometry. We assessed PROs including the Foot and Ankle Ability Measure (FAAM-ADL and FAAM-Sport), the Tampa Scale of Kinesiophobia-11 and Fear-Avoidance Beliefs Questionnaire, and the Self-Efficacy of Balance Scale. Pearson product moment correlations and Separate backward linear regression analyses were used to identify the relationship between lumbopelvic function and PROs’ scores. Alpha was set a priori at P2=0.20, P2=0.29, Phttps://digitalcommons.odu.edu/gradposters2021_healthsciences/1006/thumbnail.jp
Low-scale warped extra dimension and its predilection for multiple top quarks
Within warped extra dimension models that explain flavor through geometry,
flavor changing neutral current constraints generally force the Kaluza-Klein
scale to be above many TeV. This creates tension with a natural electroweak
scale. On the other hand, a much lower scale compatible with precision
electroweak and flavor changing neutral current constraints is allowed if we
decouple the Kaluza-Klein states of Standard Model gauge bosons from light
fermions bulk mass parameters). The main
signature for this approach is four top quark production via the Kaluza-Klein
excitations' strong coupling to top quarks. We study single lepton, like-sign
dilepton, and trilepton observables of four-top events at the Large Hadron
Collider. The like-sign dilepton signature typically has the largest discovery
potential for a strongly coupled right-handed top case (M_{KK} \sim 2-2.5
\TeV), while single lepton is the better when the left-handed top couples most
strongly (M_{KK} \sim 2 \TeV). We also describe challenging lepton-jet
collimation issues in the like-sign dilepton and trilepton channels. An
alternative single lepton observable is considered which takes advantage of the
many bottom quarks in the final state. Although searches of other particles may
compete, we find that four top production via Kaluza-Klein gluons is most
promising in a large region of this parameter space.Comment: 35 pages, 8 figures. discussions improved, references adde
Scalable production of human mesenchymal stromal cell-derived extracellular vesicles under serum-/xeno-free conditions in a microcarrier-based bioreactor culture system
Copyright © 2020 de Almeida Fuzeta, Bernardes, Oliveira, Costa, Fernandes-Platzgummer, Farinha, Rodrigues, Jung, Tseng, Milligan, Lee, Castanho, Gaspar, Cabral and da Silva. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Mesenchymal stromal cells (MSC) hold great promise for tissue engineering and cell-based therapies due to their multilineage differentiation potential and intrinsic immunomodulatory and trophic activities. Over the past years, increasing evidence has proposed extracellular vesicles (EVs) as mediators of many of the MSC-associated therapeutic features. EVs have emerged as mediators of intercellular communication, being associated with multiple physiological processes, but also in the pathogenesis of several diseases. EVs are derived from cell membranes, allowing high biocompatibility to target cells, while their small size makes them ideal candidates to cross biological barriers. Despite the promising potential of EVs for therapeutic applications, robust manufacturing processes that would increase the consistency and scalability of EV production are still lacking. In this work, EVs were produced by MSC isolated from different human tissue sources [bone marrow (BM), adipose tissue (AT), and umbilical cord matrix (UCM)]. A serum-/xeno-free microcarrier-based culture system was implemented in a Vertical-WheelTM bioreactor (VWBR), employing a human platelet lysate culture supplement (UltraGROTM-PURE), toward the scalable production of MSC-derived EVs (MSC-EVs). The morphology and structure of the manufactured EVs were assessed by atomic force microscopy, while EV protein markers were successfully identified in EVs by Western blot, and EV surface charge was maintained relatively constant (between −15.5 ± 1.6 mV and −19.4 ± 1.4 mV), as determined by zeta potential measurements. When compared to traditional culture systems under static conditions (T-flasks), the VWBR system allowed the production of EVs at higher concentration (i.e., EV concentration in the conditioned medium) (5.7-fold increase overall) and productivity (i.e., amount of EVs generated per cell) (3-fold increase overall). BM, AT and UCM MSC cultured in the VWBR system yielded an average of 2.8 ± 0.1 × 1011, 3.1 ± 1.3 × 1011, and 4.1 ± 1.7 × 1011 EV particles (n = 3), respectively, in a 60 mL final volume. This bioreactor system also allowed to obtain a more robust MSC-EV production, regarding their purity, compared to static culture. Overall, we demonstrate that this scalable culture system can robustly manufacture EVs from MSC derived from different tissue sources, toward the development of novel therapeutic products.unding received by iBB-Institute for Bioengineering and Biosciences from the Portuguese Foundation for Science and Technology (FCT) (UID/BIO/04565/2020) and through the projects PTDC/EQU-EQU/31651/2017, PTDC/BBB-BQB/1693/2014, and PTDC/BTM-SAL/31057/2017 is acknowledged. Funding received from POR de Lisboa 2020 through the project PRECISE – Accelerating progress toward the new era of precision medicine (Project N. 16394) is also acknowledged. MAF (PD/BD/128328/2017) and FO (PD/BD/135046/2017) acknowledge FCT for the Ph.D. fellowships and DG (SFRH/BPD/109010/2015) for the Post-Doctoral fellowship.info:eu-repo/semantics/publishedVersio
Co-production of hydrogen and ethanol from glucose in Escherichia coli by activation of pentose-phosphate pathway through deletion of phosphoglucose isomerase (pgi) and overexpression of glucose-6-phosphate dehydrogenase (zwf) and 6-phosphogluconate dehydrogenase (gnd)
Background: Biologically, hydrogen (H-2) can be produced through dark fermentation and photofermentation. Dark fermentation is fast in rate and simple in reactor design, but H-2 production yield is unsatisfactorily low as < 4 mol H-2/ mol glucose. To address this challenge, simultaneous production of H-2 and ethanol has been suggested. Co-production of ethanol andH(2) requires enhanced formation of NAD(P) H during catabolism of glucose, which can be accomplished by diversion of glycolytic flux from the Embden-Meyerh-of-Parnas (EMP) pathway to the pentose-phosphate (PP) pathway in Escherichia coli. However, the disruption of pgi (phosphoglucose isomerase) for complete diversion of carbon flux to the PP pathway made E. coli unable to grow on glucose under anaerobic condition. Results: Here, we demonstrate that, when glucose-6-phosphate dehydrogenase (Zwf) and 6-phosphogluconate dehydrogenase (Gnd), two major enzymes of the PP pathway, are homologously overexpressed, E. coli.pgi can recover its anaerobic growth capability on glucose. Further, with additional deletions of Delta hycA,Delta hyaAB,Delta hybBC,Delta ldhA, and Delta frdAB, the recombinant.pgi mutant could produce 1.69 mol H-2 and 1.50 mol ethanol from 1 mol glucose. However, acetate was produced at 0.18 mol mol(-1) glucose, indicating that some carbon is metabolized through the Entner-Doudoroff (ED) pathway. To further improve the flux via the PP pathway, heterologous zwf and gnd from Leuconostoc mesenteroides and Gluconobacter oxydans, respectively, which are less inhibited by NADPH, were overexpressed. The new recombinant produced more ethanol at 1.62 mol mol(-1) glucose along with 1.74 mol H-2 mol(-1) glucose, which are close to the theoretically maximal yields, 1.67 mol mol(-1) each for ethanol andH(2). However, the attempt to delete the ED pathway in the.pgi mutant to operate the PP pathway as the sole glycolytic route, was unsuccessful. Conclusions: By deletion of pgi and overexpression of heterologous zwf and gnd in E. coli Delta hycA Delta hyaAB Delta hybBC Delta ldhA Delta frdAB, two important biofuels, ethanol andH(2), could be successfully co-produced at high yields close to their theoretical maximums. The strains developed in this study should be applicable for the production of other biofuels and biochemicals, which requires supply of excessive reducing power under anaerobic conditions
Comparison of two high-throughput semiconductor chip sequencing platforms in noninvasive prenatal testing for Down syndrome in early pregnancy
Background: Noninvasive prenatal testing (NIPT) to detect fetal aneuploidy using next-generation sequencing on ion semiconductor platforms has become common. There are several sequencers that can generate sufficient DNA reads for NIPT. However, the approval criteria vary among platforms and countries. This can delay the introduction of such devices and systems to clinics. A comparison of the sensitivity and specificity of two different platforms using the same sequencing chemistry could be useful in NIPT for fetal chromosomal aneuploidies. This would improve healthcare authorities' confidence in decision-making on sequencing-based tests.
Methods: One hundred and one pregnant women who were predicted at high risk of fetal defects using conventional prenatal screening tests, and who underwent definitive diagnosis by full karyotyping, were enrolled from three hospitals in Korea. Most of the pregnant women (69.79 %) received NIPT during weeks 11-13 of gestation and 30.21 % during weeks 14-18. We used Ion Torrent PGM and Proton semi-conductor-based sequencers with 0.3x sequencing coverage depth. The average total reads of 101 samples were approximately 4.5 and 7.6 M for PGM and Proton, respectively. A Burrows-Wheeler Aligner (BWA) algorithm was used for the alignment, and a z-score was used to decide fetal trisomy 21. Interactive dot diagrams from the sequencing data showed minimal z-score values of 2.07 and 2.10 to discriminate negative versus positive cases of fetal trisomy 21 for the two different sequencing systems.
Results: Our z-score-based discrimination method resulted in 100 % positive and negative prediction values for both ion semiconductor PGM and Proton sequencers, regardless of their sequencing chip and chemistry differences. Both platforms performed well at an early stage (11-13 weeks of gestation) compared with previous studies.
Conclusions: These results suggested that, using two different sequencers, NIPT to detect fetal trisomy 21 in early pregnancy is accurate and platform-independent. The data suggested that the amount of sequencing and the application of common, simple, and robust statistical analyses are more important than sequencing chemistry and platform types. This result has practical implications in countries where PGM is approved for NIPT but the Proton system is not.ope
Biphasic Electrical Currents Stimulation Promotes both Proliferation and Differentiation of Fetal Neural Stem Cells
The use of non-chemical methods to differentiate stem cells has attracted
researchers from multiple disciplines, including the engineering and the
biomedical fields. No doubt, growth factor based methods are still the most
dominant of achieving some level of proliferation and differentiation control -
however, chemical based methods are still limited by the quality, source, and
amount of the utilized reagents. Well-defined non-chemical methods to
differentiate stem cells allow stem cell scientists to control stem cell biology
by precisely administering the pre-defined parameters, whether they are
structural cues, substrate stiffness, or in the form of current flow. We have
developed a culture system that allows normal stem cell growth and the option of
applying continuous and defined levels of electric current to alter the cell
biology of growing cells. This biphasic current stimulator chip employing ITO
electrodes generates both positive and negative currents in the same culture
chamber without affecting surface chemistry. We found that biphasic electrical
currents (BECs) significantly increased the proliferation of fetal neural stem
cells (NSCs). Furthermore, BECs also promoted the differentiation of fetal NSCs
into neuronal cells, as assessed using immunocytochemistry. Our results clearly
show that BECs promote both the proliferation and neuronal differentiation of
fetal NSCs. It may apply to the development of strategies that employ NSCs in
the treatment of various neurodegenerative diseases, such as Alzheimer's
and Parkinson's diseases
Biphasic Electrical Currents Stimulation Promotes both Proliferation and Differentiation of Fetal Neural Stem Cells
The use of non-chemical methods to differentiate stem cells has attracted
researchers from multiple disciplines, including the engineering and the
biomedical fields. No doubt, growth factor based methods are still the most
dominant of achieving some level of proliferation and differentiation control -
however, chemical based methods are still limited by the quality, source, and
amount of the utilized reagents. Well-defined non-chemical methods to
differentiate stem cells allow stem cell scientists to control stem cell biology
by precisely administering the pre-defined parameters, whether they are
structural cues, substrate stiffness, or in the form of current flow. We have
developed a culture system that allows normal stem cell growth and the option of
applying continuous and defined levels of electric current to alter the cell
biology of growing cells. This biphasic current stimulator chip employing ITO
electrodes generates both positive and negative currents in the same culture
chamber without affecting surface chemistry. We found that biphasic electrical
currents (BECs) significantly increased the proliferation of fetal neural stem
cells (NSCs). Furthermore, BECs also promoted the differentiation of fetal NSCs
into neuronal cells, as assessed using immunocytochemistry. Our results clearly
show that BECs promote both the proliferation and neuronal differentiation of
fetal NSCs. It may apply to the development of strategies that employ NSCs in
the treatment of various neurodegenerative diseases, such as Alzheimer's
and Parkinson's diseases
Entamoeba lysyl-tRNA Synthetase Contains a Cytokine-Like Domain with Chemokine Activity towards Human Endothelial Cells
Immunological pressure encountered by protozoan parasites drives the selection of strategies to modulate or avoid the immune responses of their hosts. Here we show that the parasite Entamoeba histolytica has evolved a chemokine that mimics the sequence, structure, and function of the human cytokine HsEMAPII (Homo sapiens endothelial monocyte activating polypeptide II). This Entamoeba EMAPII-like polypeptide (EELP) is translated as a domain attached to two different aminoacyl-tRNA synthetases (aaRS) that are overexpressed when parasites are exposed to inflammatory signals. EELP is dispensable for the tRNA aminoacylation activity of the enzymes that harbor it, and it is cleaved from them by Entamoeba proteases to generate a standalone cytokine. Isolated EELP acts as a chemoattractant for human cells, but its cell specificity is different from that of HsEMAPII. We show that cell specificity differences between HsEMAPII and EELP can be swapped by site directed mutagenesis of only two residues in the cytokines' signal sequence. Thus, Entamoeba has evolved a functional mimic of an aaRS-associated human cytokine with modified cell specificity
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