ROS (reactive oxygen species) have long been regarded as a series of destructive molecules that have a detrimental effect on cell homoeostasis. In support of this are the myriad antioxidant defence ...systems nearly all eukaryotic cells have that are designed to keep the levels of ROS in check. However, research data emerging over the last decade have demonstrated that ROS can influence a range of cellular events in a manner similar to that seen for traditional second messenger molecules such as cAMP. Hydrogen peroxide (H2O2) appears to be the main ROS with such signalling properties, and this molecule has been shown to affect a wide range of cellular functions. Its localized synthesis by the Nox (NADPH oxidase) family of enzymes and how these enzymes are regulated is of particular interest to those who work in the field of tumour biology.
Quantum coherence and control is foundational to the science and engineering of quantum systems
. In van der Waals materials, the collective coherent behaviour of carriers has been probed ...successfully by transport measurements
. However, temporal coherence and control, as exemplified by manipulating a single quantum degree of freedom, remains to be verified. Here we demonstrate such coherence and control of a superconducting circuit incorporating graphene-based Josephson junctions. Furthermore, we show that this device can be operated as a voltage-tunable transmon qubit
, whose spectrum reflects the electronic properties of massless Dirac fermions travelling ballistically
. In addition to the potential for advancing extensible quantum computing technology, our results represent a new approach to studying van der Waals materials using microwave photons in coherent quantum circuits.
Abstract In this study, a folate targeted cyclodextrin (CD) nanoparticle was prepared by co-formulating CD.siRNA complexes with DSPE-PEG5000 -folate to target the prostate specific membrane antigen ...(PSMA). Targeted formulations showed increased uptake, relative to untargeted controls, in two prostate cancer cell lines expressing PSMA (VCaP and LNCaP). Competitive uptake studies, using excess folate, significantly reduced uptake of targeted nanoparticles in PSMA positive cell lines ( P < 0.001) Relative to untreated controls, folate-targeted nanoparticles significantly reduced the levels of RelA mRNA in VCaP and LNCaP cells by 44% and 22% respectively ( P < 0.001). In contrast there was no significant reduction in RelA mRNA in these cell lines by untargeted complexes. Pharmacokinetic (PK) data indicated that the incorporation of PEG into the formulation increased the circulation time of siRNA 8-fold. This study highlights the ability of incorporating a folate ligand into CD.siRNA nanoparticles to allow for targeted delivery of siRNA to prostate cancer cells via the PSMA.
Abstract Osteoarthritis (OA) is a chronic disorder resulting in degenerative changes to the knee joint. Three-dimensional gait analysis provides a unique method of measuring knee dynamics during ...activities of daily living such as walking. The purpose of this study was to identify biomechanical features characterizing the gait of patients with mild-to-moderate knee OA and to determine if the biomechanical differences become more pronounced as the locomotor system is stressed by walking faster. Principal component analysis was used to compare the gait patterns of a moderate knee OA group ( n =41) and a control group ( n =43). The subjects walked at their self-selected speed as well as at 150% of that speed. The two subject groups did not differ in knee joint angles, stride length, and stride time or walking speed. Differences in the magnitude and shape of the knee joint moment waveforms were found between the two groups. The OA group had larger adduction moment magnitudes during stance and this higher magnitude was sustained for a longer portion of the gait cycle. The OA group also had a reduced flexion moment and a reduced external rotation moment during early stance. Increasing speed was associated with an increase in the magnitude of all joint moments. The fast walks did not, however, increase or bring out any biomechanical differences between the OA and control groups that did not exist at the self-selected walks.
Yin Yang 1 (YY1) is a multifunctional zinc-finger-containing transcription factor that plays crucial roles in numerous biological processes by selectively activating or repressing transcription, ...depending upon promoter contextual differences and specific protein interactions. In mice, Yy1 null mutants die early in gestation whereas Yy1 hypomorphs die at birth from lung defects. We studied how the epithelial-specific inactivation of Yy1 impacts on lung development. The Yy1 mutation in lung epithelium resulted in neonatal death due to respiratory failure. It impaired tracheal cartilage formation, altered cell differentiation, abrogated lung branching and caused airway dilation similar to that seen in human congenital cystic lung diseases. The cystic lung phenotype in Yy1 mutants can be partly explained by the reduced expression of Shh, a transcriptional target of YY1, in lung endoderm, and the subsequent derepression of mesenchymal Fgf10 expression. Accordingly, SHH supplementation partially rescued the lung phenotype in vitro. Analysis of human lung tissues revealed decreased YY1 expression in children with pleuropulmonary blastoma (PPB), a rare pediatric lung tumor arising during fetal development and associated with DICER1 mutations. No evidence for a potential genetic interplay between murine Dicer and Yy1 genes during lung morphogenesis was observed. However, the cystic lung phenotype resulting from the epithelial inactivation of Dicer function mimics the Yy1 lung malformations with similar changes in Shh and Fgf10 expression. Together, our data demonstrate the crucial requirement for YY1 in lung morphogenesis and identify Yy1 mutant mice as a potential model for studying the genetic basis of PPB.
Childhood overweight and obesity (OWO) has become a major public concern worldwide including in Shanghai, one of the most developed areas of China. Understanding perceptions and challenges of ...tackling childhood OWO among caregivers of children is critical to provide services in need.
A qualitative descriptive study including in-depth interviews with seven parents and six focus group discussions with a total of 32 parents or grandparents of children zero to 6 years of age. Participants lived in three districts of Shanghai and indexed children included both those with OWO or non-OWO children. Data were analyzed using qualitative thematic analysis.
Caregivers tended to underestimate children's weight status, and to regard chubby children as a sign of good parental care. Some caregivers even suggested that there were positive effects of childhood overweight. Caregivers identified a number of challenges to prevention of OWO in children, including difficulties in controlling dietary intake or increasing children's physical activities; discordant views between parents and grandparents, and barriers to accessing professional guidance. Caregivers desired more detailed advice regarding children's nutrition intake and physical activity, and preferred online approaches.
Misconceptions regarding childhood overweight were found in caregivers of children in Shanghai. Professional guidance on childhood weight control for caregivers is desired via digital applications such as mobile phone applications and social media.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Female athletes are 2 to 8 times more likely than male athletes to injure the anterior cruciate ligament during a non-contact
athletic maneuver. Identifying anterior cruciate ligament ...injury risk factors in female athletes may help with the development
of preventive training programs aimed at reducing injury rates.
Hypothesis: Differences between genders in lower limb kinematics, kinetics, and neuromuscular patterns will be identified in an adolescent
soccer population during an unanticipated side-cut maneuver.
Study Design: Controlled laboratory study.
Methods: Forty-two elite adolescent soccer players (21 male and 21 female) performed an unanticipated side-cut maneuver, with the
3-dimensional kinematic, kinetic, and electromyographic lower limb data being analyzed using principal component analysis.
Results: The female athletes had higher gastrocnemius activity, normalized to maximal voluntary isometric contractions, and a mediolateral
gastrocnemius activation imbalance that was not present in the male athletes during early stance to midstance of the side-cut.
Female athletes demonstrated greater rectus femoris muscle activity throughout stance, and the only hamstring difference identified
was a mediolateral activation imbalance in male athletes only. Female athletes performed the side-cut with less hip flexion
and more hip external rotation and also generated a smaller hip flexion moment compared with the male athletes.
Conclusion: This is the first study to identify gender-related differences in gastrocnemius muscle activity during an unanticipated cutting
maneuver.
Clinical Relevance: The increased and imbalanced gastrocnemius muscle activity, combined with increased rectus femoris muscle activity and reduced
hip flexion angles and moments in female subjects, may all have important contributing roles in the higher noncontact ACL
injury rates observed in female athletes.
Keywords:
anterior cruciate ligament injury
electromyography
gender
kinematics
kinetics
side-cut
unanticipated
It is currently not known if there are different mechanical factors involved in accelerated rates of knee osteoarthritis structural progression. Data regarding the role of the transverse plane moment ...along with the contributions to joint loading from muscle activity, a primary contributor to the joint loading environment, is not well represented in the current literature on knee OA radiographic progression. The objective of this study was to understand if a 3-year end point corroborates what has been shown for longer term radiographic progression or provides more insight into factors that may be implicated in more accelerated radiographic progression than those shown previously.
52 participants visited the Dynamics of Human Motion laboratory at baseline for three-dimensional, self-selected speed over ground walking gait analysis. Differences in magnitude and patterns of 3D knee moments and electromyography waveforms between participants who progressed radiographically from those that did not were compared using t-tests (P < 0.05).
Features of the frontal and transverse plane knee moments along with muscle activation patterns for the lateral gastrocnemius and lateral hamstrings differentiated the progression group from the non-progression group at baseline.
In general, the walking gait biomechanics of the progression group in this 3-year radiographic study aligned well with previously reported characteristics of diagnosed or symptomatic osteoarthritis. The higher rotation moment range during stance found with the progression group is a novel finding that points to a need to better understand torsional joint loading and its implications for loading of the knee joint tissues.
•Higher peak knee adduction moment is linked to 3-year medial joint space narrowing.•Mid-stance knee adduction moment unloading may not be relevant to structural progression.•The link between the knee rotation moment and structural progression requires further research.•Differences in activation of the lateral muscles may contribute to structural degradation.
Pleuropulmonary blastoma (PPB) is a very rare pediatric lung disease. It can progress from abnormal epithelial cysts to an aggressive sarcoma with poor survival. PPB is difficult to diagnose as it ...can be confounded with other cystic lung disorders, such as congenital pulmonary airway malformation (CPAM). PPB is associated with mutations in
that perturb the microRNA (miRNA) profile in lung. How
and miRNAs act during PPB pathogenesis remains unsolved. Lung epithelial deletion of the Yin Yang1 (
) gene in mice causes a phenotype mimicking the cystic form of PPB and affects the expression of key regulators of lung development. Similar changes in expression were observed in PPB but not in CPAM lung biopsies, revealing a distinctive PPB molecular signature. Deregulation of molecules promoting epithelial-mesenchymal transition (EMT) was detected in PPB specimens, suggesting that EMT might participate in tumor progression. Changes in miRNA expression also occurred in PPB lung biopsies. miR-125a-3p, a candidate to regulate
expression and lung branching, was abnormally highly expressed in PPB samples. Together, these findings support the concept that reduced expression of YY1, due to the abnormal miRNA profile resulting from
mutations, contributes to PPB development via its impact on the expression of key lung developmental genes.This article has an associated First Person interview with the joint first authors of the paper.
Abstract Constitutive expression of the Bcr–Abl kinase in Chronic Myelogenous Leukaemia (CML) is known to produce elevated levels of Reactive Oxygen Species (ROS) which can enhance cell survival as ...well as generate genomic instability. Our laboratory has previously demonstrated that NADPH oxidase (Nox) activity contributes to intracellular-ROS levels in Bcr–Abl-positive cells, while inducing increased pro-survival signalling through the PI3K/Akt pathway. How Bcr–Abl signalling regulates Nox activity still remains to be elucidated. In this study, using the K562 CML cell line we showed that inhibition of Bcr–Abl signalling, by either Imatinib or Nilotinib, led to a significant reduction in ROS levels which was concurrent with the GSK-3β dependent, post-translational down-regulation of the small membrane-bound protein p22phox, an essential component of the Nox complex. Furthermore, siRNA knockdown of p22phox in these cells established its importance in ROS production and proliferation. Taken together we believe our results provide a possible link between Bcr–Abl signalling and ROS production through Nox activity and demonstrate a novel mechanism of action associated with Imatinib and Nilotinib treatment in CML.
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