New version of a laboratory impact device for firmness sensing of fruits.

Results of previous studies conducted by different researchers have shown that impact techniques can be used to evaluate firmness (Delwiche et al., 1989; Delwiche et al.;1996; Jaren et al., 1992; Ruiz Altisent et al., 1996). To impact the fruit with a small spherical impactor of known mass and radius of curvature and measure the acceleration of the impactor is a technique described by Chen et al. (1985) and used by several researchers for sensing fruit firmness (Jaren et al., 1992; Correa et al.; 1992). The advantages of this method vs. a force sensor that measures the force as a function of time is that the measured impact-acceleration response is independent of the fruit mass and is less sensitive to the variation in the radius of curvature of the fruit (Chen et al., 1996). Ruiz Altisent et al. (1993) developed and used a 50 g impactor with a 19 mm diameter spherical tip, dropping from different height for fruits (apples, pears, avocados, melons, peaches ...). Another impact device for firmness sensing of fruits was developed by Chen and Ruiz Altisent (1996). They designed and fabricated an experimental low-mass impact sensor for high-speed sensing of fruit firmness. The impactor consisted of a semi-spherical impacting tip attached to the end (near the centre of percussion) of a pivoting arm. Impact is done by swinging the impactor to collide with the fruit. It has been implemented for on-line use. In both devices a small accelerometer is mounted behind the impacting tip. Lateral impactor and vertical impactor have been used in laboratory and the results from non-destructive impact tests have contributed to standardise methods to measure fruit firmness: Barreiro (1992) compared impact parameters and results of Magness-Taylor penetration tests for apples, pears, apricots [and peaches; Agulheiro (1994) studied the behaviour of the impact parameters during seven weeks of cold storage of two melon varieties; Ortiz (1998) used low energy impact and NIR procedures to segregate non crispy, non firm and soft peaches. Steinmetz (1996) compared various non-destructive firmness sensors, based on sound, impact and micro-deformation

Genetic heterogeneity in the toxicity to systemic adenoviral gene transfer of interleukin-12

Despite the efficacy of IL-12 in cancer experimental models, clinical trials with systemic recombinant IL-12 showed unacceptable toxicity related to endogenous IFNgamma production. We report that systemic administration of a recombinant adenovirus encoding IL-12 (AdCMVmIL-12) has a dramatically different survival outcome in a number of mouse pure strains over a wide range of doses. For instance at 2.5 x 10(9) p.f.u., systemic AdCMVmIL-12 killed all C57BL/6 mice but spared all BALB/c mice. Much higher IFNgamma concentrations in serum samples of C57BL/6 than in those from identically treated BALB/c were found. Causes for heterogeneous toxicity can be traced to differences among murine strains in the levels of gene transduction achieved in the liver, as assessed with adenovirus coding for reporter genes. In accordance, IL-12 serum concentrations are higher in susceptible mice. In addition, sera from C57BL/6 mice treated with AdCMVmIL-12 showed higher levels of IL-18, a well-known IFNgamma inducer. Interestingly, lethal toxicity in C57BL/6 mice was abolished by administration of blocking anti-IFNgamma mAbs and also by simultaneous depletion of T cells, NK cells, and macrophages. These observations together with the great dispersion of IFNgamma produced by human PBMCs upon in vitro stimulation with IL-12, or infection with recombinant adenovirus encoding IL-12, suggest that patients might also show heterogeneous degrees of toxicity in response to IL-12 gene transfer

Beta interferon production is regulated by P38 mitogen-activated protein kinase in macrophages via both MSK1/2-and tristetraprolin-dependent pathways

Autocrine or paracrine signaling by beta interferon (IFN-β) is essential for many of the responses of macrophages to pathogen-associated molecular patterns. This feedback loop contributes to pathological responses to infectious agents and is therefore tightly regulated. We demonstrate here that macrophage expression of IFN-β is negatively regulated by mitogen- and stress-activated kinases 1 and 2 (MSK1/2). Lipopolysaccharide (LPS)-induced expression of IFN-β was elevated in both MSK1/2 knockout mice and macrophages. Although MSK1 and -2 promote the expression of the anti-inflammatory cytokine interleukin 10, it did not strongly contribute to the ability of MSKs to regulate IFN-β expression. Instead, MSK1 and -2 inhibit IFN-β expression via the induction of dual-specificity phosphatase 1 (DUSP1), which dephosphorylates and inactivates the mitogen-activated protein kinases p38 and Jun N-terminal protein kinase (JNK). Prolonged LPS-induced activation of p38 and JNK, phosphorylation of downstream transcription factors, and overexpression of IFN-β mRNA and protein were similar in MSK1/2 and DUSP1 knockout macrophages. Two distinct mechanisms were implicated in the overexpression of IFN-β: first, JNKmediated activation of c-jun, which binds to the IFN-β promoter, and second, p38-mediated inactivation of the mRNA-destabilizing factor tristetraprolin, which we show is able to target the IFN-β mRNA

Amalan Etika Kerja Dalam Perkhidmatan Awam Malaysia : Satu Kajian di Kementerian Pembangunan Usahawan dan Koperasi Malaysia

The objectives of this study is to determine the level of work ethic among the employees of the Ministry of Entrepreneur and Cooperative Development (MECD) and also to determine whether there are significant difference in work ethic characteristics among the MECD employees based on demographic variables namely gender, age, marital status and educational level as well as work variables namely job category, income and tenure of service. This study was conducted on a sample of 187 MECD employees using a 73-item questionnaire to measure all 12 pillars of The Twelve Pillars Work Ethic. T-test, one-way ANOVA test and Post HOC Tukey HSD test were used in the analysis to test whether there are significant difference in work ethic characteristics based on demographic and work variables among the MECD employees. The empirical results indicate that the level of work ethic among the MECD employees are good with a mean score of 3.89. Results further reveal that MECD work ethic characteristics differs significantly across gender, age, educational level, job category, income and tenure of service whereas there is no difference based on marital status. The findings have theoritical implications towards a better understanding of the relationship between demographic variables as well as work variables and work ethic. It is also hope that the findings of this study could assist the MECD management formulate sound strategies to improve the present programs and to implement new programs towards enhancing the work ethic of MECD employees

Oxidative Stress and Cellular Senescence Are Involved in the Aging Kidney

Chronic kidney disease (CKD) can be considered as a clinical model for premature aging. However, non‐invasive biomarkers to detect early kidney damage and the onset of a senescent phenotype are lacking. Most of the preclinical senescence studies in aging have been done in very old mice. Furthermore, the precise characterization and over-time development of age-related senes-cence in the kidney remain unclear. To address these limitations, the age-related activation of cellular senescence-associated mechanisms and their correlation with early structural changes in the kidney were investigated in 3- to 18-month-old C57BL6 mice. Inflammatory cell infiltration was ob-served by 12 months, whereas tubular damage and collagen accumulation occurred later. Early activation of cellular-senescence-associated mechanisms was found in 12-month-old mice, character-ized by activation of the DNA-damage-response (DDR), mainly in tubular cells; activation of the antioxidant NRF2 pathway; and klotho downregulation. However, induction of tubular-cell-cycle-arrest (CCA) and overexpression of renal senescent-associated secretory phenotype (SASP) components was only found in 18-month-old mice. In aging mice, both inflammation and oxidative stress (marked by elevated lipid peroxidation and NRF2 inactivation) remained increased. These findings support the hypothesis that prolonged DDR and CCA, loss of nephroprotective factors (klotho), and dysfunctional redox regulatory mechanisms (NRF2/antioxidant defense) can be early drivers of age-related kidney-damage progressionThis research was funded by grants from the Instituto de Salud Carlos III (ISCIII); Fondos FEDER European Union (PI17/00119, PI20/00140; and DTS20/00083 to M.R.-O.; PI18/01133 to A.M.R.); Sara Borrell’ program from Instituto de Salud Carlos III (ISCIII) (grant number CD20/00042 to R.R.R.-D.); Red de Investigación Renal REDINREN: RD16/0009/0003 and RICORS program to RICORS2040 496 (RD21/0005), to M.R.-O., Sociedad Española de Nefrología; “NOVELREN-CM: Enfermedad renal crónica: nuevas Estrategias para la prevención, Diagnóstico y tratamiento” (B2017/BMD3751 to M.R.-O.); “Convocatoria Dinamización Europa Investigación 2019” MINECO (EIN2019-103294 to M.R.-O.); Juan de la Cierva incorporacion grant: IJC2018-035187-I to S.R.-M.; innovation program under the Marie Skłodowska-Curie grant of the European Union’s Horizon 2020 (IMProvePD ID: 812699) to M.R.-O.; and Fundacion Conchita Rabago to L.T.-

Statins: Could an old friend help the fight against COVID-19?

This is the peer reviewed version of the following article: "Statins: Could an old friend help the fight against COVID-19?" . British Journal of Pharmacology (2020): 19 June, which has been published in final form at https://doi.org/10.1111/bph.15166. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versionshe COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has overwhelmed healthcare systems requiring the rapid development of treatments, at least, to reduce COVID-19 severity. Drug repurposing offers a fast track. Here, we discuss the potential beneficial effects of statins in COVID-19 patients based on evidence that they may target virus receptors, replication, degradation, and downstream responses in infected cells, addressing both basic research and epidemiological information. Briefly, statins could modulate virus entry, acting on the SARS-CoV-2 receptors, ACE2 and CD147, and/or lipid rafts engagement. Statins, by inducing autophagy activation, could regulate virus replication or degradation, exerting protective effects. The well-known anti-inflammatory properties of statins, by blocking several molecular mechanisms, including NF-κB and NLRP3 inflammasomes, could limit the "cytokine storm" in severe COVID-19 patients which is linked to fatal outcome. Finally, statin moderation of coagulation response activation may also contribute to improving COVID-19 outcomesThis work and data discussed here were supported by grants from the Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union (PI17/00119 and Red de Investigación Renal (REDINREN): RD16/0009, to M.R-O, PI17/01495 to J.E, PI18/01133 to AMR, PI19/00815 to A.O); Comunidad de Madrid (“NOVELREN” B2017/BMD3751 to M.R-O, B2017/BMD-3686 CIFRA2-CM to A.O); Spanish Ministry of Economy and Competitiveness MINECO (DTS17/00203, DTS19/00093) to J,E; “Convocatoria Dinamización Europa Investigación 2019” MINECO (EIN2019-103294 to M.R-O and SR-M); ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071) and DTS18/00032 to A.O; The “Sara Borrell” postdoctoral training program of the ISCIII supported the salary of SR-M (CD19/00021), IMPROVE-PD project (“Identification and Management of Patients at Risk–Outcome and Vascular Events in Peritoneal Dialysis”) funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant Agreement No. 812699 to M.R.O

Is telomere length socially patterned? Evidence from the West of Scotland Twenty-07 study

Lower socioeconomic status (SES) is strongly associated with an increased risk of morbidity and premature mortality, but it is not known if the same is true for telomere length, a marker often used to assess biological ageing. The West of Scotland Twenty-07 Study was used to investigate this and consists of three cohorts aged approximately 35 (N = 775), 55 (N = 866) and 75 years (N = 544) at the time of telomere length measurement. Four sets of measurements of SES were investigated: those collected contemporaneously with telomere length assessment, educational markers, SES in childhood and SES over the preceding twenty years. We found mixed evidence for an association between SES and telomere length. In 35-year-olds, many of the education and childhood SES measures were associated with telomere length, i.e. those in poorer circumstances had shorter telomeres, as was intergenerational social mobility, but not accumulated disadvantage. A crude estimate showed that, at the same chronological age, social renters, for example, were nine years (biologically) older than home owners. No consistent associations were apparent in those aged 55 or 75. There is evidence of an association between SES and telomere length, but only in younger adults and most strongly using education and childhood SES measures. These results may reflect that childhood is a sensitive period for telomere attrition. The cohort differences are possibly the result of survival bias suppressing the SES-telomere association; cohort effects with regard different experiences of SES; or telomere possibly being a less effective marker of biological ageing at older ages

A western route of prehistoric human migration from Africa into the Iberian Peninsula

Being at the western fringe of Europe, Iberia had a peculiar prehistory and a complex pattern of Neolithization. A few studies, all based on modern populations, reported the presence of DNA of likely African origin in this region, generally concluding it was the result of recent gene flow, probably during the Islamic period. Here, we provide evidence of much older gene flow from Africa to Iberia by sequencing whole genomes from four human remains from northern Portugal and southern Spain dated around 4000 years BP (from the Middle Neolithic to the Bronze Age). We found one of them to carry an unequivocal sub-Saharan mitogenome of most probably West or West-Central African origin, to our knowledge never reported before in prehistoric remains outside Africa. Our analyses of ancient nuclear genomes show small but significant levels of sub-Saharan African affinity in several ancient Iberian samples, which indicates that what we detected was not an occasional individual phenomenon, but an admixture event recognizable at the population level. We interpret this result as evidence of an early migration process from Africa into the Iberian Peninsula through a western route, possibly across the Strait of Gibraltar

Rapid assessment of nonlinear optical propagation effects in dielectrics

Ultrafast laser processing applications need fast approaches to assess the nonlinear propagation of the laser beam in order to predict the optimal range of processing parameters in a wide variety of cases. We develop here a method based on the simple monitoring of the nonlinear beam shaping against numerical prediction. The numerical code solves the nonlinear Schrödinger equation with nonlinear absorption under simplified conditions by employing a state-of-the art computationally efficient approach. By comparing with experimental results we can rapidly estimate the nonlinear refractive index and nonlinear absorption coefficients of the material. The validity of this approach has been tested in a variety of experiments where nonlinearities play a key role, like spatial soliton shaping or fs-laser waveguide writing. The approach provides excellent results for propagated power densities for which free carrier generation effects can be neglected. Above such a threshold, the peculiarities of the nonlinear propagation of elliptical beams enable acquiring an instantaneous picture of the deposition of energy inside the material realistic enough to estimate the effective nonlinear refractive index and nonlinear absorption coefficients that can be used for predicting the spatial distribution of energy deposition inside the material and controlling the beam in the writing process