A crucial sequence for transglutaminase type 2 extracellular trafficking in renal tubular epithelial cells lies in its N-terminal {beta}-sandwich domain

Transglutaminase type 2 (TG2) catalyzes the formation of an -( -glutamyl)-lysine isopeptide bond between adjacent peptides or proteins including those of the extracellular matrix (ECM). Elevated extracellular TG2 leads to accelerated ECM deposition and reduced clearance that underlie tissue scarring and fibrosis. The extracellular trafficking of TG2 is crucial to its role in ECM homeostasis; however, the mechanism by which TG2 escapes the cell is unknown as it has no signal leader peptide and therefore cannot be transported classically. Understanding TG2 transport may highlight novel mechanisms to interfere with the extracellular function of TG2 as isoform-specific TG2 inhibitors remain elusive. Mammalian expression vectors were constructed containing domain deletions of TG2. These were transfected into three kidney tubular epithelial cell lines, and TG2 export was assessed to identify critical domains. Point mutation was then used to highlight specific sequences within the domain required for TG2 export. The removal of -sandwich domain prevented all TG2 export. Mutations of Asp94 and Asp97 within the N-terminal -sandwich domain were identified as crucial for TG2 externalization. These form part of a previously identified fibronectin binding domain (88WTATVVDQQDCTLSLQLTT106). However, siRNA knockdown of fibronectin failed to affect TG2 export. The sequence 88WTATVVDQQDCTLSLQLTT106 within the -sandwich domain of TG2 is critical to its export in tubular epithelial cell lines. The extracellular trafficking of TG2 is independent of fibronectin

Energy bands and Landau levels of ultracold fermions in the bilayer honeycomb optical lattice

We investigate the spectrum and eigenstates of ultracold fermionic atoms in the bilayer honeycomb optical lattice. In the low energy approximation, the dispersion relation has parabolic form and the quasiparticles are chiral. In the presence of the effective magnetic field, which is created for the system with optical means, the energy spectrum shows an unconventional Landau level structure. Furthermore, the experimental detection of the spectrum is proposed with the Bragg scattering techniques.Comment: To appear in Journal of Modern Optic

Durable and ductile double-network material for dust control

Dust generation is a world-wide issue due to its serious deleterious effects on the environment, human health and safety, and the economy. Although various dust suppression methods have been used for decades, some critical drawbacks in state-of-the-art technology still remain unsolved, such as short-lasting, ground water impact, and prone to water. This work reports a soil stabilizer based on non-toxic material and forms a ductile and durable double-network in soil, namely “D3 soil stabilizer”, which not only improves soil mechanical toughness of surface soil but also suppresses dust generation. A copolymer comprising hydrophilic and hydrophobic components combined with enzyme-induced carbonate precipitation is utilized as an in-situ gelation binder to soil particle. The tunable hydrophobic-to-hydrophilic component ratio minimizes undesirable soil matrix expansion and mechanical strength loss upon experiencing wet-dry processes, while still retains good water affinity. We further demonstrated controllable treatment depth by fine-tuning precursor composition, which is essential to minimize environmental impact. The double-network morphology with carbonate precipitate embedded uniformly in polymer matrix is observed via microscopic imaging. The nature of outstanding ductility, high durability against water, and good long-term stability were supported by systematic unconfined compressive strength (UCS) measurements on treated soil, which show strong inter-particles binding, good retention of peak strength, increased strain at peak strength, and increased toughness after soil samples have experienced wet-dry processes

A survey of befriending services for people with intellectual disabilities in the UK

Background: Individuals with intellectual disability (ID) may benefit from befriending services, which can help to widen their social networks and reduce social isolation. This study examined the characteristics and challenges encountered by befriending services in the United Kingdom and motivations and experiences of volunteers working with people with ID. // Methods: This is a cross-sectional study using two separate online surveys, one for befriending services and one for volunteers. // Results: Eight services and 58 volunteers (aged 15 to 72) responded to the survey. The two major issues faced by befriending services were related to funding and recruitment of volunteers. The most common volunteering motivation was “To give something back” (75.9%). While unemployed volunteers were more likely to be motivated by wanting to do something useful with their spare time (OR 3.62, 95% CI 1.09–12.05), young volunteers expressed wanting to gain work experience through volunteering (OR 11.37, 95% CI 1.31–98.59). Most volunteers reported that volunteering had a positive impact on them and would like to continue volunteering in the future. Both positive and negative volunteer experiences were explored. // Discussion: Volunteers experienced unique difficulties in interacting with service users with ID due to physical and cognitive barriers. More training and support could be provided to volunteers to help them manage these difficulties and to improve outcomes and experiences of both volunteers and individuals with ID. Policy guidance should be developed on how to set up high-quality befriending services for this group

Spatial heterogeneity enhances and modulates excitability in a mathematical model of the myometrium

The muscular layer of the uterus (myometrium) undergoes profound changes in global excitability prior to parturition. Here, a mathematical model of the myocyte network is developed to investigate the hypothesis that spatial heterogeneity is essential to the transition from local to global excitation which the myometrium undergoes just prior to birth. Each myometrial smooth muscle cell is represented by an element with FitzHugh–Nagumo dynamics. The cells are coupled through resistors that represent gap junctions. Spatial heterogeneity is introduced by means of stochastic variation in coupling strengths, with parameters derived from physiological data. Numerical simulations indicate that even modest increases in the heterogeneity of the system can amplify the ability of locally applied stimuli to elicit global excitation. Moreover, in networks driven by a pacemaker cell, global oscillations of excitation are impeded in fully connected and strongly coupled networks. The ability of a locally stimulated cell or pacemaker cell to excite the network is shown to be strongly dependent on the local spatial correlation structure of the couplings. In summary, spatial heterogeneity is a key factor in enhancing and modulating global excitability

Herpes zoster and its neurological complications

Ninety-three Chinese patients with cutaneous herpes zoster were seen during a 4-year period. Thoracic zoster occurred most commonly, followed by ophthalmic, cervical and lumbosacral zoster. Neurological complications were present in eleven patients (11.8%), the commonest being Ramsay-Hunt syndrome and segmental limb paresis. The clinical picture, pathogenesis, treatment and outcome of segmental limb paresis, myelitis and delayed contralateral hemiparesis following zoster ophthalmicus are discussed. Nine immunocompromised patients received intravenous adenine arabinoside (vidarabine) or acycloguanosine (acyclovir), and no cutaneous or visceral spread occurred in these patients.published_or_final_versio

Two semi-Lagrangian fast methods for Hamilton-Jacobi-Bellman equations

In this paper we apply the Fast Iterative Method (FIM) for solving general Hamilton-Jacobi-Bellman (HJB) equations and we compare the results with an accelerated version of the Fast Sweeping Method (FSM). We find that FIM can be indeed used to solve HJB equations with no relevant modifications with respect to the original algorithm proposed for the eikonal equation, and that it overcomes FSM in many cases. Observing the evolution of the active list of nodes for FIM, we recover another numerical validation of the arguments recently discussed in [Cacace et al., SISC 36 (2014), A570-A587] about the impossibility of creating local single-pass methods for HJB equations

Quantifying variability of intrafractional target motion in stereotactic body radiotherapy for lung cancers

published_or_final_versio

Human papilloma virus and breast cancer

PubMe

Very short answer questions: a novel approach to summative assessments in pathology

Background A solid understanding of the science underpinning treatment is essential for all doctors. Pathology teaching and assessment are fundamental components of the undergraduate medicine curriculum. Assessment drives learning and the choice of assessments influences students’ learning behaviours. The use of multiple-choice questions is common but is associated with significant cueing and may promote ‘rote learning’. Essay-type questions and Objective Structured Clinical Examinations (OSCEs) are resource-intensive in terms of delivery and marking, and do not allow adequate sampling of the curriculum. To address these limitations, we used a novel online tool to administer Very Short Answer questions (VSAQs) and evaluated the utility of the VSAQs in an undergraduate summative pathology assessment. Methods A group of 285 medical students took the summative assessment, comprising 50 VSAQs, 50 single best answer questions (SBAQs), and 75 extended matching questions (EMQs). The VSAQs were machine-marked against pre-approved responses, and subsequently reviewed by a panel of pathologists, with the software remembering all new marking judgements. Results The total time taken to mark all 50 VSAQs for all 285 students was 5 hours, compared to 70 hours required to manually mark an equivalent number of questions in a paper-based pathology exam. The median percentage score for the VSA test (72%) was significantly lower than that of the SBAQs (80%) and EMQs (84%), p <0.0001. VSAQs had a higher Cronbach alpha (0.86) than SBAQs (0.76), and EMQs (0.77). VSAQs, SBAQs and EMQs had a mean point-biserial of 0.35, 0.30 and 0.28, respectively. Conclusions VSAQs are an acceptable, reliable and discriminatory method for assessing pathology, and may enhance students’ understanding of how pathology supports clinical decision-making and clinical care by changing learning behaviour