Molecular Characterization of Tick Salivary Gland Glutaminyl Cyclase

Glutaminyl cyclase (QC) catalyzes the cyclization of N-terminal glutamine residues into pyroglutamate. This post-translational modification extends the half-life of peptides and, in some cases, is essential in binding to their cognate receptor. Due to its potential role in the post-translational modification of tick neuropeptides, we report the molecular, biochemical and physiological characterization of salivary gland QC during the prolonged blood feeding of the black-legged tick (Ixodes scapularis) and the gulf-coast tick (Amblyomma maculatum). QC sequences from I. scapularis and A. maculatum showed a high degree of amino acid identity to each other and other arthropods and residues critical for zinc binding/catalysis (D159, E202, and H330) or intermediate stabilization (E201, W207, D248, D305, F325, and W329) are conserved. Analysis of QC transcriptional gene expression kinetics depicts an upregulation during the bloodmeal of adult female ticks prior to fast-feeding phases in both I. scapularis and A. maculatum suggesting a functional link with bloodmeal uptake. QC enzymatic activity was detected in saliva and extracts of tick salivary glands and midguts. Recombinant QC was shown to be catalytically active. Furthermore, knockdown of QC transcript by RNA interference resulted in lower enzymatic activity, and small, unviable egg masses in both studied tick species as well as lower engorged tick weights for I. scapularis. These results suggest that the post-translational modification of neurotransmitters and other bioactive peptides by QC is critical to oviposition and potentially other physiological processes. Moreover, these data suggest that tick-specific QC-modified neurotransmitters/hormones or other relevant parts of this system could potentially be used as novel physiological targets for tick control

Moderate-to-Vigorous Physical Activity is Related With Retinal Neuronal and Axonal Integrity in Persons With Multiple Sclerosis

Background Moderate-to-vigorous physical activity (MVPA) may confer benefits for axonal and/or neuronal integrity in adults with multiple sclerosis (MS). Purpose Examine the association between device-measured MVPA with optical coherence tomography (OCT) metrics of retinal nerve fiber layer (RNFL) thickness and total macular volume (TMV) in persons with and without MS. Methods Adults with MS (N = 41), along with sex-matched healthy control (HC) participants (N = 79), underwent measurements of retinal morphology via OCT and wore an accelerometer for a period of 7 days as a measure of MVPA. Results Persons with MS had significantly lower MVPA, RNFL thickness, and TMV compared with HCs. MVPA was correlated with RNFL (r = .38, P \u3c .01) thickness and TMV (r = .49, P \u3c .01). Hierarchical linear regression analyses indicated that addition of MVPA attenuated the Group effect on RNFL and TMV. MVPA accounted for 8% and 3% of the variance in TMV (β = .343, P \u3c .01) and RNFL thickness (β = .217, P = .03), respectively. Conclusion MVPA was positively associated with axonal and neuronal integrity assessed by OCT and partially explained group differences in those metrics. These results present possible future targets for MS management by increasing MVPA

The clinical effectiveness of self-care interventions with an exercise component to manage knee conditions: a systematic review

Objective. Treatment of knee conditions should include approaches to support self-care and exercise based interventions. The most effective way to combine self-care and exercise has however not been determined sufficiently. Therefore the aim was to evaluate the clinical effectiveness of self-care programmes with an exercise component for individuals with any type of knee conditions. Methods. A keyword search of Medline, CINAHL, Amed, PsycInfo, Web of Science, and Cochrane databases was conducted up until January 2015. Two reviewers independently assessed manuscript eligibility against inclusion/exclusion criteria. Study quality was assessed using the Downs and Black quality assessment tool and the Cochrane Risk of Bias Tool. Data were extracted about self-care and exercise intervention type, control intervention, participants, length of follow-up, outcome measures, and main findings. Results. From the 7392 studies identified through the keyword search the title and abstract of 5498 were screened. The full text manuscripts of 106 studies were retrieved to evaluate their eligibility. Twenty-one manuscripts met the inclusion/exclusion criteria. Conclusion. The treatment potential of combined self-care and exercise interventions has not been maximised because of limitations in study design and failure to adequately define intervention content. Potentially the most beneficial self-care treatment components are training self-management skills, information delivery, and goal setting. Exercise treatment components could be strengthened by better attention to dose and progression. Modern technology to streamline delivery and support self-care should be considered. More emphasis is required on using self-care and exercise programmes for chronic condition prevention in addition to chronic condition management

Effect of Particle Size on Droplet Infiltration into Hydrophobic Porous Media As a Model of Water Repellent Soil

The wettability of soil is of great importance for plants and soil biota, and in determining the risk for preferential flow, surface runoff, flooding,and soil erosion. The molarity of ethanol droplet (MED) test is widely used for quantifying the severity of water repellency in soils that show reduced wettability and is assumed to be independent of soil particle size. The minimum ethanol concentration at which droplet penetration occurs within a short time (≤10 s) provides an estimate of the initial advancing contact angle at which spontaneous wetting is expected. In this study, we test the assumption of particle size independence using a simple model of soil, represented by layers of small (0.2–2 mm) diameter beads that predict the effect of changing bead radius in the top layer on capillary driven imbibition. Experimental results using a three-layer bead system show broad agreement with the model and demonstrate a dependence of the MED test on particle size. The results show that the critical initial advancing contact angle for penetration can be considerably less than 90° and varies with particle size, demonstrating that a key assumption currently used in the MED testing of soil is not necessarily valid

A 20-year experience with urgent percutaneous cardiopulmonary bypass for salvage of potential survivors of refractory cardiovascular collapse

In-hospital cardiac arrest or refractory shock carries a high mortality despite the use of advanced resuscitative measures. We have implemented an in-hospital, nurse-based, continuously available, percutaneous, venoarterial cardiopulmonary bypass system, also known as extracorporeal life support (ECLS), as an adjunct to resuscitation when initial measures are ineffective.In 1986, a system for the rapid initiation of ECLS, was created in which trained critical care nurses primed an ECLS circuit and in-house physicians percutaneously placed required cannulas. From a prospective registry, we assessed long-term survival (LTS) (≥30 days, cardiopulmonary support weaned), short-term survival (<30 days, CPS weaned), or death on CPS.One hundred fifty patients (age, 57 ± 17 years) were urgently started on CPS for cardiac arrest (n = 127; witnessed, n = 124; unwitnessed, n = 3) and refractory shock (n = 23). Sixty-nine patients were weaned from CPS, and 81 could not be weaned. Overall, 39 (26.0%) patients achieved LTS with a subsequent Kaplan–Meier median survival of 9.5 years. Duration of CPS was 32 ± 38 hours for LTS and 21 ± 38 hours for non-LTS. LTS occurred in 29 (23.4%) of 124 patients started on CPS for witnessed cardiac arrest and 11 (47.8%) of 23 for refractory shock ( < .05). Among patients with CPS initiated in the cardiac catheterization laboratory, LTS was seen in 24 (50.0%) of 48 versus 15 (14.7%) of 102 in patients with CPS initiated in other locations ( < .001). Cardiopulmonary resuscitation times greater than or equal to 30 minutes were associated with lower LTS ( < .05). The most common cause of death during CPS was refractory cardiac dysfunction (39.5%), and the most common cause associated with short-term survival was neurologic/pulmonary dysfunction (53.6%). Seven patients were bridged to a left ventricular assist device, and 1 subsequently underwent heart transplantation. Multivariate analysis revealed only cardiac catheterization laboratory site of initiation as a significant independent predictor of LTS ( < .01). When dividing the 20-year experience in tertiles, recent recipients have had more common prearrest insertion. Rates of long-term survival have not changed.Of patients started on CPS, 46% were weaned, and 26.0% were long-time survivors. Rapid initiation of CPS permits LTS for some inpatients with cardiovascular collapse when initial advanced resuscitation fails. Strategies to improve end-organ function associated with use of CPS should lead to greater LTS. This practical application of inexpensive available technology should be more widely used

Cardiac mitochondrial function depends on BUD23 mediated ribosome programming.

Efficient mitochondrial function is required in tissues with high energy demand such as the heart, and mitochondrial dysfunction is associated with cardiovascular disease. Expression of mitochondrial proteins is tightly regulated in response to internal and external stimuli. Here we identify a novel mechanism regulating mitochondrial content and function, through BUD23-dependent ribosome generation. BUD23 was required for ribosome maturation, normal 18S/28S stoichiometry and modulated the translation of mitochondrial transcripts in human A549 cells. Deletion of Bud23 in murine cardiomyocytes reduced mitochondrial content and function, leading to severe cardiomyopathy and death. We discovered that BUD23 selectively promotes ribosomal interaction with low GC-content 5'UTRs. Taken together we identify a critical role for BUD23 in bioenergetics gene expression, by promoting efficient translation of mRNA transcripts with low 5'UTR GC content. BUD23 emerges as essential to mouse development, and to postnatal cardiac function

Injectable semaglutide and reductions in HbA1c and weight in the real world in people switched from alternative glucagon-like peptide-1 receptor agonists

The ABCD semaglutide audit was designed to capture the routine clinical outcomes of people commenced on semaglutide in the UK. Previous work showed differential reductions in HbA1c and weight dependent on previous glucagon-like peptide-1 receptor agonist (GLP-1RA) exposure. The analysis, in this research letter, shows that decreases in HbA1c and weight associated with semaglutide occur irrespective of previous GLP-1RA use. However, HbA1c reductions were less if switched from dulaglutide or liraglutide and weight changes were attenuated if switched from dulaglutide or exenatide, potentially suggesting differing potencies between GLP-1RAs. Dedicated studies with head-to-head comparisons are needed to confirm these findings

Costa Rica Rift hole deepened and logged

During Leg 111 of the Ocean Drilling Program, scientists on the drilling vessel JOIDES Resolution studied crustal structure and hydrothermal processes in the eastern equatorial Pacific. Leg 111 spent 43 days on its primary objective, deepening and logging Hole 5048, a deep reference hole in 5.9-million-year-old crust 200 km south of the spreading axis of the Costa Rica Rift. Even before Leg 111 , Hole 5048 was the deepest hole drilled into the oceanic crust, penetrating 274.5 m of sediments and 1,075.5 m of pillow lavas and sheeted dikes to a total depth of 1,350 m below sea floor (mbsf). Leg 111 deepened the hole by 212.3 m to a total depth of 1,562.3 mbsf (1,287.8 m into basement), and completed a highly successful suite of geophysical logs and experiments, including sampling of borehole waters