Modelling actin polymerization: the effect on confined cell migration

The aim of this work is to model cell motility under conditions of mechanical confinement. This cell migration mode may occur in extravasation of tumour and neutrophil-like cells. Cell migration is the result of the complex action of different forces exerted by the interplay between myosin contractility forces and actin processes. Here, we propose and implement a finite element model of the confined migration of a single cell. In this model, we consider the effects of actin and myosin in cell motility. Both filament and globular actin are modelled. We model the cell considering cytoplasm and nucleus with different mechanical properties. The migration speed in the simulation is around 0.1 µm/min, which is in agreement with existing literature. From our simulation, we observe that the nucleus size has an important role in cell migration inside the channel. In the simulation the cell moves further when the nucleus is smaller. However, this speed is less sensitive to nucleus stiffness. The results show that the cell displacement is lower when the nucleus is stiffer. The degree of adhesion between the channel walls and the cell is also very important in confined migration. We observe an increment of cell velocity when the friction coefficient is higher

A role for SUMO modification in transcriptional repression and activation

Since the discovery of the SUMO (small ubiquitin-like modifier) family of proteins just over a decade ago, a plethora of substrates have been uncovered including many regulators of transcription. Conjugation of SUMO to target proteins has generally been considered as a repressive modification. However, there are now a growing number of examples where sumoylation has been shown to activate transcription. Here we discuss whether there is something intrinsically repressive about sumoylation, or if the outcome of this modification in the context of transcription will prove to be largely substrate-dependent. We highlight some of the technical challenges that will be faced by attempting to answer this question

Reproducibility and clinical relevance of the ocular response analyzer in nonoperated eyes: corneal biomechanical and tonometric implications

To assess the reproducibility of the ocular response analyzer (ORA) in nonoperated eyes and the impact of corneal biomechanical properties on intraocular pressure (IOP) measurements in normal and glaucomatous eyes. METHODS: In the reliability study, two independent examiners obtained repeated ORA measurements in 30 eyes. In the clinical study, the examiners analyzed ORA and IOP-Goldmann values from 220 normal and 42 glaucomatous eyes. In both studies, Goldmann-correlated IOP measurement (IOP-ORAg), corneal-compensated IOP (IOP-ORAc), corneal hysteresis (CH), and corneal resistance factor (CRF) were evaluated. IOP differences of 3 mm Hg or greater between the IOP-ORAc and IOP-ORAg were considered outcome significant. RESULTS: Intraexaminer intraclass correlation coefficients and interexaminer concordance correlation coefficients ranged from 0.78 to 0.93 and from 0.81 to 0.93, respectively, for all parameters. CH reproducibility was highest, and the IOP-ORAg readings were lowest. The median IOP was 16 mm Hg with the Goldmann tonometer, 14.5 mm Hg with IOP-ORAg (P < 0.001), and 15.7 mm Hg with IOP-ORAc (P < 0.001). Outcome-significant results were found in 77 eyes (29.38%). The IOP-ORAc, CH, and CRF were correlated with age (r = 0.22, P = 0.001; r = -0.23, P = 0.001; r = -0.14, P = 0.02, respectively), but not the IOP-ORAg or IOP-Goldmann. CONCLUSIONS: The ORA provides reproducible corneal biomechanical and IOP measurements in nonoperated eyes. Considering the effect of ORA, corneal biomechanical metrics produces an outcome-significant IOP adjustment in at least one quarter of glaucomatous and normal eyes undergoing noncontact tonometry. Corneal viscoelasticity (CH) and resistance (CRF) appear to decrease minimally with increasing age in healthy adults

The spectrum of an open vertex model based on the U_q[SU(2)] at roots of unity

We study the exact solution of an $N$-state vertex model based on the representation of the $U_q[SU(2)]$ algebra at roots of unity with diagonal open boundaries. We find that the respective reflection equation provides us one general class of diagonal $K$-matrices having one free-parameter. We determine the eigenvalues of the double-row transfer matrix and the respective Bethe ansatz equation within the algebraic Bethe ansatz framework. The structure of the Bethe ansatz equation combine a pseudomomenta function depending on a free-parameter with scattering phase-shifts that are fixed by the roots of unity and boundary variables.Comment: 21 page

Contaminants in Buildings and Occupied Spaces as Risk Factors forOccupant Symptoms in U.S. Office Buildings: Findings from the U.S. EPABASE Study

Nonspecific building-related symptoms among occupants of modern office buildings worldwide are common and may be associated with important reductions in work performance, but their etiology remains uncertain. Most reported research into environmental risk factors for these symptoms has focused on ventilation system-related factors, dampness, and particle removal through filtration and cleaning, with relatively few studies of other potential sources of indoor contaminants. We analyzed data collected by the U.S. Environmental Protection Agency (EPA) from a representative sample of 100 large U.S. office buildings--the Building Assessment and Survey Evaluation (BASE) study--using multivariate-adjusted logistic regression models with generalized estimating equations. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between seven building-related symptom outcomes and a diverse set of potential indoor and outdoor sources for indoor pollutants. Although most of the investigated risk factors showed no apparent association with building-related symptoms, some interesting associations resulted. Increased prevalence of symptoms was associated with carpets older than one year (lower respiratory symptoms), non-carpeted floors (upper and lower respiratory symptoms), older furniture (eye and skin symptoms), infrequent vacuuming (upper respiratory, eye, and skin symptoms and headache), and masonry exterior walls (cough, eye symptoms, and fatigue/concentration difficulty). For the many potential risk factors assessed, almost none had been investigated previously, and many associations found here may have been by chance. Additional confirmatory research focused on risk factors initially identified here is needed, using more objective measures of health outcomes and risk factors or exposures

Incidence of zygomycosis in transplant recipients

AbstractRecently, a remarkable increase in the incidence of zygomycosis has been reported from institutions in the USA and Europe. The use of voriconazole for the treatment of aspergillosis and, less frequently, the use of echinocandins as empirical treatment for invasive fungal infections are thought to be responsible for the increase. In addition, an increased incidence of this infection has been observed in transplant recipients, including both haematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) patients. There are no global surveys on the prevalence or incidence of zygomycosis, but data from individual institutions and countries show that zygomycosis is an emerging infection. The increased incidence of zygomycosis most probably reflects a greater frequency of predisposing factors, such as higher numbers of patients undergoing HSCT and immunosuppressive chemotherapy. In addition, the emergence of rare pathogens as a result of the rise in the use of antifungal therapy against common species can be postulated. Further, the availability of antifungal agents with activity profiles that are more specific for selected fungi increases the necessity of identifying pathogenic fungi; the frequency of Zygomycetes infections may have been underestimated until now because therapeutic decisions did not depend on the precise identification of pathogenic fungi

Mental Health Patients' Expectations about the Non-Medical Care They Receive in Primary Care: A Cross-Sectional Descriptive Study

A health system's responsiveness is the result of patient expectations for the non-medical care they receive. The objective of this study was to assess mental patients' responsiveness to the health system in primary care, as related to the domains of dignity, autonomy, confidentiality, and communication. Data were collected from 215 people over the age of 18 with mental disorders, using the Multi-Country Survey Study (MCSS) developed by the World Health Organization. Of them, 95% reported a good experience regarding the dignity, confidentiality, communication, and autonomy domains. Regarding responsiveness, patients valued the dignity domain as the most important one (25.1%). Among the patients who experienced poor confidentiality, five out of seven earned less than 900 euros per month (X-2 = 10.8, p = 0.004). Among those who experienced good autonomy, 85 out of 156 belonged to the working social class (90.4%), and among those who valued it as poor (16.1%), the highest proportion was for middle class people (X-2 = 13.1, p = 0.028). The two students and 87.5% of retirees experienced this dimension as good, and most patients who valued it as poor were unemployed (43.5%) (X-2 = 13.0, p = 0.011). Patients with a household income higher than 900 euros more frequently valued responsiveness as good, regarding those domains related to communication, with OR = 3.84, 95% CI = 1.05-14.09, and confidentiality, with OR = 10.48, 95% CI = 1.94-56.59. To conclude, as regards responsiveness in primary care, the dignity domain always obtained the best scores by people with mental disorders. Low economic income is related to a poor assessment of confidentiality. Working class patients, students, and retirees value autonomy as good

Covalent functionalization of N-doped graphene by N-alkylation

[EN] Nitrogen doped graphene was modified by N-alkylation using a combination of phase transfer catalysis and microwave irradiation. The resulting derivatives of N-doped graphene were analysed showing that the bandgap of the material varied depending on the alkylation agent used.Financial support from MINECO (Spain) (CTQ2013-48252-P and CTQ2012-32315), Junta de Comunidades de Castilla-La Mancha (PEII-2014-014-P) and Generalidad Valenciana (Prometeo 13/19) is gratefully acknowledged. M.B. thanks the MINECO for a doctoral FPI grant.Barrejon, M.; Primo Arnau, AM.; Gomez-Escalonilla, M.; Fierro, JLG.; García Gómez, H.; Langa, F. (2015). Covalent functionalization of N-doped graphene by N-alkylation. Chemical Communications. 51(95):16916-16919. https://doi.org/10.1039/c5cc06285cS16916169195195Wang, H., Maiyalagan, T., & Wang, X. (2012). Review on Recent Progress in Nitrogen-Doped Graphene: Synthesis, Characterization, and Its Potential Applications. 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Cocaine Selectively Reorganizes Excitatory Inputs to Substantia Nigra Pars Compacta Dopamine Neurons

Substantia nigra pars compacta (SNc) dopamine neurons and their targets are involved in addiction and cue-induced relapse. However, afferents onto SNc dopamine neurons themselves appear insensitive to drugs of abuse, such as cocaine, when afferents are collectively stimulated electrically. This contrasts with ventral tegmental area (VTA) dopamine neurons, whose glutamate afferents react robustly to cocaine. We used an optogenetic strategy to isolate identified SNc inputs and determine whether cocaine sensitivity in the mouse SNc circuit is conferred at the level of three glutamate afferents: dorsal raphé nucleus (DR), pedunculopontine nucleus (PPN), and subthalamic nucleus (STN). We found that excitatory afferents to SNc dopamine neurons are sensitive to cocaine in an afferent-specific manner. A single exposure to cocaine in vivo led to PPN-innervated synapses reducing the AMPA-to-NMDA receptor-mediated current ratio. In contrast to work in the VTA, this was due to increased NMDA receptor function with no change in AMPA receptor function. STN synapses showed a decrease in calcium-permeable AMPA receptors after cocaine, but no change in the AMPA-to-NMDA ratio. Cocaine also increased the release probability at DR-innervated and STN-innervated synapses, quantified by decreases in paired-pulse ratios. However, release probability at PPN-innervated synapses remained unaffected. By examining identified inputs, our results demonstrate a functional distribution among excitatory SNc afferent nuclei in response to cocaine, and suggest a compelling architecture for differentiation and separate parsing of inputs within the nigrostriatal system

Combined zinc and nitrogen fertilization in different bread wheat genotypes grown under mediterranean conditions

The combined application of nitrogen (N) and zinc (Zn) appears to be a promising agronomic strategy for the biofortification with Zn. To evaluate such efficiency, a field experiment was conducted in south-eastern Portugal under Zn-deficient soil. Four advanced breeding lines and two commercial varieties of bread wheat (Triticum aestivum L.) were fertilized with five treatments: i) control, ii) two foliar Zn applications, iii) one foliar Zn+N application, iv) soil and two foliar Zn applications, and v) soil and one foliar Zn+N application. Grain Zn content varied greatly across treatments and INIAV-1 and the commercial varieties were the most interesting cultivars in all the treatments. Grain Zn concentrations higher than the target level of 38 mg Zn kg−1 were obtained only when two foliar Zn applications were applied, alone or in combination with soil Zn applications, and grain Zn bioavailability also was more adequate (phytate:Zn ratios similar to 15). Soil Zn application resulted in grain yield increases between 7–10%, which virtually offset the extra application cost. The combined soil and two foliar treatment could be a good option for biofortifying bread wheat under Zn-deficient soils