4,682 research outputs found
Eating with a Purpose:Consumer Response to Functional Food Health Claims in Conflicting Versus Complementary Information Environments
Marketers of food products have recently introduced a variety of âfunctional foodsâ that promise consumers improvements in targeted physiological functions. However, despite the proliferation of functional food health claims promising more than basic nutrition, little is known about consumer responses to these claims, particularly in information environments in which inconsistent information may be available about the efficacy of a particular functional ingredient
Molecular characterisation of PDIp : the pancreas-specific isoform of PDI
PDIp is a close homolog of the well known protein folding catalyst PDI. Unlike PDI
however, PDIp exhibits restricted protein expression and is found predominantly in
the exocrine pancreas. Currently, the physiological function of PDIp is unknown but
previous work has shown a clear specificity for substrates containing a hydroxyaryl
group. Again this is in contrast to PDI which exhibits more general specificity. This
work to investigate the in vitro activities of PDIp, was stimulated by the hypothesis
that PDIp has an essential role in folding a specific subset of secretory proteins. The
identity of these proteins is currently unknown.
In this work, the redox-mediated conformational changes of PDIp have been studied
and compared using far UV CD, dynamic light scattering and limited proteolysis.
Compared to PDI, these changes are conservative in PDIp. Also, unlike PDI for
which bâxaâc is the minimal redox-active cassette, the PDIp a and b domains seem to
be involved in modulating these conformational changes. This may indicate that
PDIp has a unique substrate binding mechanism that may work synergistically with
its restricted substrate specificity.
Using the insulin reduction assay, PDIp was shown to have ~50% of the oxidoreductase
activity of PDI and this was not due to the aberrant threonine residue in the
aâ domain active site motif (CTHC). Further investigation by stopped flow kinetic
studies showed that the low activity could be due to the abnormally high pKa for the
PDIp a domain N-terminal catalytic cysteine. This result was unexpected because
PDI and PDIp a share the same catalytic active site motif (CGHC) indicating that
nearby residues may act as mediators of activity. Future work to clarify this will be
essential.
This is the first study of the structure of PDIp and its molecular basis for activity.
Through investigation of these two areas, it is hoped that the general understanding
of the role of PDIp and its contribution to oxidative folding in secretory tissues will
be improved
Medication adherence in patients with myotonic dystrophy and facioscapulohumeral muscular dystrophy
Myotonic dystrophy (DM) and facioscapulohumeral muscular dystrophy (FSHD) are the two most common adult muscular dystrophies and have progressive and often disabling manifestations. Higher levels of medication adherence lead to better health outcomes, especially important to patients with DM and FSHD because of their multisystem manifestations and complexity of care. However, medication adherence has not previously been studied in a large cohort of DM type 1 (DM1), DM type 2 (DM2), and FSHD patients. The purpose of our study was to survey medication adherence and disease manifestations in patients enrolled in the NIH-supported National DM and FSHD Registry. The study was completed by 110 DM1, 49 DM2, and 193 FSHD patients. Notable comorbidities were hypertension in FSHD (44 %) and DM2 (37 %), gastroesophageal reflux disease in DM1 (24 %) and DM2 (31 %) and arrhythmias (29 %) and thyroid disease (20 %) in DM1. Each group reported high levels of adherence based on regimen complexity, medication costs, health literacy, side effect profile, and their beliefs about treatment. Only dysphagia in DM1 was reported to significantly impact medication adherence. Approximately 35 % of study patients reported polypharmacy (taking 6 or more medications). Of the patients with polypharmacy, the DM1 cohort was significantly younger (mean 55.0 years) compared to DM2 (59.0 years) and FSHD (63.2 years), and had shorter disease duration (mean 26 years) compared to FSHD (26.8 years) and DM2 (34.8 years). Future research is needed to assess techniques to ease pill swallowing in DM1 and to monitor polypharmacy and potential drug interactions in DM and FSHD
Triggered Electrical Stimulation Cueing to Address Hypofunctioning Peroneus Muscle in the Treatment of Chronic Ankle Instability: Two Repeated Single Case Designs
Background: Approximately two million ankle sprains occur in the United States annually. Lateral ankle sprains (LAS) account for 85% of all ankle sprains, 74% of those individuals report continued symptoms following the initial insult. Persistent pain and instability following ankle sprain is indicative of chronic ankle instability (CAI). There are many interventions to address hypofunctioning muscle including electrical stimulation (ES) and it is known that peripheral ES changes muscle behavior. The purpose of this pilot study was to investigate the effect of electrical stimulation of the peroneal muscles combined with 3 exercises for the treatment of CAI.Methods: Two participants with CAI were recruited for this repeated single case design. The Cumberland Ankle Instability Tool (CAIT), the modified Star Excursion Balance Test (mSEBT), and center of pressure (CoP) was measured. A single limb hop to stabilization protocol and single limb stance activities were combined with manual triggered electrical stimulation for six sessions.Results: Improvements in CAIT scores for both patients were observed. There was no statistically significant change in mSEBT scores. Center of Pressure measurement improvements varied between subjects. For subject 1, there was no significant change in CoP in eyes open and eyes closed conditions. For subject 2, there was a significant change in the anterior/posterior CoP data points in both conditions.Discussion: In individuals with CAI, the addition of electrical stimulation to a single limb stance and hop stabilization protocol for hypofunctioning peroneal muscles led to positive CAI outcomes as measured by improved CAIT scores and improved CoP measurement in one subject
Measuring longitudinal amplitudes for electroproduction of pseudoscalar mesons using recoil polarization in parallel kinematics
We propose a new method for measuring longitudinal amplitudes for
electroproduction of pseudoscalar mesons that exploits a symmetry relation for
polarization observables in parallel kinematics. This polarization technique
does not require variation of electron scattering kinematics and avoids the
major sources of systematic errors in Rosenbluth separation.Comment: intended for Phys. Rev. C as a Brief Repor
Levels of organochlorine pesticides are associated with amyloid aggregation in apex avian brains
Organochlorine (OC) pesticides pose a significant environmental risk to wildlife and humans and have been associated with Alzheimerâs disease (AD). This study aims to spectroscopically analyse brains from free-flying birds and link the results to OC exposure and consequent amyloid aggregation. As long-lived apex predators, predatory birds represent a sentinel species similar to humans. Therefore, the results have implications for both species and may also add to our understanding of the role OC pesticides play in the development of AD. Brains of wild sparrowhawks were analysed using ATR-FTIR and Raman spectroscopy and Congo red staining; results were correlated with OC pesticide concentrations in livers. Effects of OC exposure were sex and age dependant and associated alterations were seen in lipids and protein secondary structure. A shift from α-helix to ÎČ-sheet conformation of proteins indicated that concentrations of OC pesticides > 7.18 ”g/g may lead to cerebral amyloid aggregation
Interviewer: 'Are women and girls ever responsible for the domestic violence they encounter?' Student: 'No, well, unless they did something really, really badââŠ'
Research shows the âgendered natureâ of domestic violence, with Womenâs Aid (a UK-based charity) estimating that 1 in 4 women are affected (2014). This paper reports on a project - funded by Comic Relief, completed by Nottinghamshire Domestic Violence Forum (now known as Equation) and evaluated by Nottingham Trent University. The project adopts a Whole School Approach in seeking to prevent domestic violence. Students at three secondary schools attended between one and five blocks of work, and special events. There is evidence of positive developments - with young people showing understanding of domestic violence as well as the margins between healthy and unhealthy relationships. However, not all students could reply âneverâ to the question of âare women and girls to blame for the domestic violence they experience?â, remarking that if the woman had done something âreally, really badâ then violence might be justified. We argue that young peopleâs uncertainties need to be situated within the gender-unequal socio-contexts of contemporary society, and further call for a WSA to domestic violence prevention to be a compulsory part of the UK national curriculum
Utility of Whole Genome Sequencing in Assessing and Enhancing Partner Notification of Neisseria gonorrhoeae Infection
Background:
Gonorrhea is a sexually transmitted infection of global concern. We investigated whole genome sequencing (WGS) as a tool to measure and enhance partner notification (PN) in gonorrhea management. /
Methods:
Between May-November 2018, all N. gonorrhoeae isolated from patients attending Leeds Sexual Health, UK, underwent WGS. Reports listing sequences within 20 single nucleotide polymorphisms (SNPs) of study isolates within a database containing select isolates from April 1 2016 to November 15 2018 were issued to clinicians. The proportion of cases with a potential transmission partner identified by PN was determined from patient and PN data. WGS reports were reviewed to identify additional cases within â€6 SNPs and verified for PN concordance. /
Results:
380 isolates from 377 cases were successfully sequenced; 292 had traceable/contactable partners and 69 (18%) had a potential transmission partner identified by PN. Concordant PN and WGS links were identified in 47 partner pairs. Of 308 cases with no transmission partner by PN, 185 (60%) had a case within â€6 SNPs; examination of these casesâ PN data identified seven partner pairs with previously unrecognized PN link, giving a total of 54 pairs; all had â€4 SNP differences. WGS clusters confirmed gaps in partner finding, at individual and group levels. Despite the clinic providing sexual health services to the whole city, 35 cases with multiple partners had no genetically related case, suggesting multiple undiagnosed infections. /
Conclusions:
WGS could improve gonorrhea PN and control by identifying new links and clusters with significant gaps in partner finding
Heart Rate Responses to Unaided Orion Side Hatch Egress in the Neutral Buoyancy Laboratory
NASA is developing the Orion capsule as a vehicle for transporting crewmembers to and from the International Space Station (ISS) and for future human space exploration missions. Orion and other commercial vehicles are designed to splash down in the ocean where nominally support personnel will assist crewmembers in egressing the vehicle. However, off-nominal scenarios will require crewmembers to egress the vehicle unaided, deploy survival equipment, and ingress a life raft. PURPOSE: To determine the heart rate (HR) responses to unaided Orion side hatch egress and raft ingress as a part of the NASA Crew Survival Engineering Team's evaluation of the PORT Orion mockup in the Neutral Buoyancy Laboratory (NBL). METHODS: Nineteen test subjects, including four astronauts (N=19, 14 males/5 females, 38.6+/-8.4 y, 174.4+/-9.6 cm, 75.7+/-13.1 kg), completed a graded maximal test on a cycle ergometer to determine VO2peak and HRpeak and were divided into five crews of four members each; one subject served on two crews. Each crew was required to deploy a life raft, egress the Orion vehicle from the side hatch, and ingress the life raft with two 8 kg emergency packs per crew. Each crew performed this activity one to three times; a total of ten full egresses were completed. Subjects wore a suit that was similar in form, mass, and function to the Modified Advanced Crew Escape Suit (MACES) including helmet, gloves, boots, supplemental O2 bottles, and a CO2-inflated life preserver (approx.18 kg); subjects began each trial seated supine in the PORT Orion mockup with seat belts and mockup O2 and communication connections and ended each trial with all four crewmembers inside the life raft. RESULTS: VO2peak was 40.8+/-6.8 mL/kg/min (3.1+/-0.7 L/min); HRpeak was 181+/-10 bpm. Total egress time across trials was 5.0+/-1.6 min (range: 2.8-8.0 min); all subjects were able to successfully complete all trials. Average maximum HR at activity start, at the hatch opening, in the water, and in the raft, was 108, 137, 147, and 153 bpm, respectively; these values corresponded to 59+/-10%, 73+/-8%, 82+/-3%, and 84+/-6% of HRpeak, respectively. The highest HRs were seen after raft ingress and ranged from 72-99% HRpeak. Across all trials, cumulative averages of 5.4, 3.0, 1.1, and 0.2 min were spent at HRs >60%, >70%, >80%, and >90% HRpeak, respectively. CONCLUSION: Unaided Orion side hatch egress in the NBL is a relatively short-duration activity that elicits a high HR response for several min. Although all crewmembers successfully completed this activity, additional factors such as high seas, poor visibility, an incapacitated crewmember, neurovestibular perturbation, and neuromuscular deconditioning characteristic of a true operational environment may increase the physiologic demand (or decrease crewmembers' physiologic capacity) of unaided Orion side hatch egress. Additionally, landing conditions may require the crewmembers to egress from the top hatch, which is expected to be even more physiologically demanding; this condition will be evaluated in subsequent collaborative testing with the NASA Crew Survival Engineering Team
The Bacillus subtilis TatAdCd system exhibits an extreme level of substrate selectivity
The Tat system preferentially transports correctly folded proteins across the bacterial membrane although little is known of the proofreading mechanism. Most research has focused on TatABC systems from Gram-negative bacteria, especially Escherichia coli, and much less is known of the TatAC-type systems from Gram-positive organisms. We have previously shown that the Bacillus subtilis TatAdCd system is functional in an E. coli tat null background and able to transport TorA-GFP and native TorA (TMAO reductase); here, we examined its ability to transport other proteins bearing a TorA signal sequence. We show that whereas E. coli TatABC transports a wide range of biotherapeutics including human growth hormone, interferon ?2b, a VH domain protein and 2 different scFvs, TatAdCd transports the scFvs but completely rejects the other proteins. The system also rejects two native E. coli substrates, NrfC and FhuD. Moreover, we have shown that TatABC will transport a wide range of folded scFv variants with the surface altered to incorporate multiple salt bridges, charged residues (5 glutamate, lysine or arginine), or hydrophobic residues (up to 6 leucines). In contrast, TatAdCd completely rejects many of these variants including those with 5 or 6 added Leu residues. The combined data show that the TatABC and TatAdCd systems have very different substrate selectivities, with the TatAdCd system displaying an extreme level of selectivity when compared to the E. coli system. The data also provide a preliminary suggestion that TatAdCd may not tolerate surface domains with a level of hydrophobicity above a certain threshold
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