Carotenoid accumulation during tomato fruit ripening is modulated by the auxin-ethylene balance

Background : Tomato fruit ripening is controlled by ethylene and is characterized by a shift in color from green to red, a strong accumulation of lycopene, and a decrease in β-xanthophylls and chlorophylls. The role of other hormones, such as auxin, has been less studied. Auxin is retarding the fruit ripening. In tomato, there is no study of the carotenoid content and related transcript after treatment with auxin. Results : We followed the effects of application of various hormone-like substances to “Mature-Green” fruits. Application of an ethylene precursor (ACC) or of an auxin antagonist (PCIB) to tomato fruits accelerated the color shift, the accumulation of lycopene, α-, β-, and δ-carotenes and the disappearance of β-xanthophylls and chlorophyll b. By contrast, application of auxin (IAA) delayed the color shift, the lycopene accumulation and the decrease of chlorophyll a. Combined application of IAA + ACC led to an intermediate phenotype. The levels of transcripts coding for carotenoid biosynthesis enzymes, for the ripening regulator Rin, for chlorophyllase, and the levels of ethylene and abscisic acid (ABA) were monitored in the treated fruits. Correlation network analyses suggest that ABA, may also be a key regulator of several responses to auxin and ethylene treatments. Conclusions : The results suggest that IAA retards tomato ripening by affecting a set of (i) key regulators, such as Rin, ethylene and ABA, and (ii) key effectors, such as genes for lycopene and β-xanthophyll biosynthesis and for chlorophyll degradation

Microsatellite instability and intratumoural heterogeneity in 100 right-sided sporadic colon carcinomas

Microsatellite instability has been proposed as an alternative pathway of colorectal carcinogenesis. The aim of this study was to evaluate the interest of immunohistochemistry as a new tool for highlighting mismatch repair deficiency and to compare the results with a PCR-based microsatellite assay. A total of 100 sporadic proximal colon adenocarcinomas were analysed. The expression of hMLH1, hMSH2 and hMSH6 proteins evaluated by immunohistochemistry was altered in 39% of the cancers, whereas microsatellite instability assessed by PCR was detected in 43%. There was discordance between the two methods in eight cases. After further analyses performed on other tumoural areas for these eight cases, total concordance between the two techniques was observed (Kappa=100%). Our results demonstrate that immunohistochemistry may be as efficient as microsatellite amplification in the detection of unstable phenotype provided that at least two samples of each carcinoma are screened, because of intratumoural heterogeneity

MLP (muscle LIM protein) as a stress sensor in the heart

Muscle LIM protein (MLP, also known as cysteine rich protein 3 (CSRP3, CRP3)) is a muscle-specific-expressed LIM-only protein. It consists of 194 amino-acids and has been described initially as a factor involved in myogenesis (Arber et al. Cell 79:221–231, 1994). MLP soon became an important model for experimental cardiology when it was first demonstrated that MLP deficiency leads to myocardial hypertrophy followed by a dilated cardiomyopathy and heart failure phenotype (Arber et al. Cell 88:393–403, 1997). At this time, this was the first genetically altered animal model to develop this devastating disease. Interestingly, MLP was also found to be down-regulated in humans with heart failure (Zolk et al. Circulation 101:2674–2677, 2000) and MLP mutations are able to cause hypertrophic and dilated forms of cardiomyopathy in humans (Bos et al. Mol Genet Metab 88:78–85, 2006; Geier et al. Circulation 107:1390–1395, 2003; Hershberger et al. Clin Transl Sci 1:21–26, 2008; Knöll et al. Cell 111:943–955, 2002; Knöll et al. Circ Res 106:695–704, 2010; Mohapatra et al. Mol Genet Metab 80:207–215, 2003). Although considerable efforts have been undertaken to unravel the underlying molecular mechanisms—how MLP mutations, either in model organisms or in the human setting cause these diseases are still unclear. In contrast, only precise knowledge of the underlying molecular mechanisms will allow the development of novel and innovative therapeutic strategies to combat this otherwise lethal condition. The focus of this review will be on the function of MLP in cardiac mechanosensation and we shall point to possible future directions in MLP research

Time course and mechanisms of left ventricular systolic and diastolic dysfunction in monocrotaline-induced pulmonary hypertension

Although pulmonary hypertension (PH) selectively overloads the right ventricle (RV), neuroendocrine activation and intrinsic myocardial dysfunction have been described in the left ventricle (LV). In order to establish the timing of LV dysfunction development in PH and to clarify underlying molecular changes, Wistar rats were studied 4 and 6 weeks after subcutaneous injection of monocrotaline (MCT) 60 mg/kg (MCT-4, n = 11; MCT-6, n = 11) or vehicle (Ctrl-4, n = 11; Ctrl-6, n = 11). Acute single beat stepwise increases of systolic pressure were performed from baseline to isovolumetric (LVPiso). This hemodynamic stress was used to detect early changes in LV performance. Neurohumoral activation was evaluated by measuring angiotensin-converting enzyme (ACE) and endothelin-1 (ET-1) LV mRNA levels. Cardiomyocyte apoptosis was evaluated by TUNEL assay. Extracellular matrix composition was evaluated by tenascin-C mRNA levels and interstitial collagen content. Myosin heavy chain (MHC) composition of the LV was studied by protein quantification. MCT treatment increased RV pressures and RV/LV weight ratio, without changing LV end-diastolic pressures or dimensions. Baseline LV dysfunction were present only in MCT-6 rats. Afterload elevations prolonged tau and upward-shifted end-diastolic pressure dimension relations in MCT-4 and even more in MCT-6. MHC-isoform switch, ACE upregulation and cardiomyocyte apoptosis were present in both MCT groups. Rats with severe PH develop LV dysfunction associated with ET-1 and tenascin-C overexpression. Diastolic dysfunction, however, could be elicited at earlier stages in response to hemodynamic stress, when only LV molecular changes, such as MHC isoform switch, ACE upregulation, and myocardial apoptosis were present.Supported by Portuguese grants from FCT (POCI/SAU-FCF/60803/2004 and POCI/SAU-MMO/61547/2004) through Cardiovascular R&D Unit (FCT No. 51/94)

Pressure Load: The Main Factor for Altered Gene Expression in Right Ventricular Hypertrophy in Chronic Hypoxic Rats

BACKGROUND: The present study investigated whether changes in gene expression in the right ventricle following pulmonary hypertension can be attributed to hypoxia or pressure loading. METHODOLOGY/PRINCIPAL FINDINGS: To distinguish hypoxia from pressure-induced alterations, a group of rats underwent banding of the pulmonary trunk (PTB), sham operation, or the rats were exposed to normoxia or chronic, hypobaric hypoxia. Pressure measurements were performed and the right ventricle was analyzed by Affymetrix GeneChip, and selected genes were confirmed by quantitative PCR and immunoblotting. Right ventricular systolic blood pressure and right ventricle to body weight ratio were elevated in the PTB and the hypoxic rats. Expression of the same 172 genes was altered in the chronic hypoxic and PTB rats. Thus, gene expression of enzymes participating in fatty acid oxidation and the glycerol channel were downregulated. mRNA expression of aquaporin 7 was downregulated, but this was not the case for the protein expression. In contrast, monoamine oxidase A and tissue transglutaminase were upregulated both at gene and protein levels. 11 genes (e.g. insulin-like growth factor binding protein) were upregulated in the PTB experiment and downregulated in the hypoxic experiment, and 3 genes (e.g. c-kit tyrosine kinase) were downregulated in the PTB and upregulated in the hypoxic experiment. CONCLUSION/SIGNIFICANCE: Pressure load of the right ventricle induces a marked shift in the gene expression, which in case of the metabolic genes appears compensated at the protein level, while both expression of genes and proteins of importance for myocardial function and remodelling are altered by the increased pressure load of the right ventricle. These findings imply that treatment of pulmonary hypertension should also aim at reducing right ventricular pressure

Field hyperspectral imagery as a tool for plant monitoring: application to wheat nitrogen content

International audienceIn the study presented here, we used a pushbroom CCD camera fitted on a motorised tractor rail to take hyperspectral images of wheat plots. Reflectance correction was performed using a ceramic plate as a reference. The hyperspectral images have been used to build nitrogen (N) content images for wheat plots using two Partial Least Square regression models. The first chemometrical model was calibrated on nitrogen contents (in percentage of dry matter, % DM) obtained in laboratory and flat leaf normalised spectra (5 latent variables, R² = 0.907, RMSEP = 0.326 N % DM); the second one on greenhouse pot plant leaf spectra (8 latent variables, R² = 0.919, RMSEP = 0.412 N % DM). Subsequently, they were directly applied to field plant spectra, providing images of nitrogen content. The range of nitrogen content values in these images was not satisfactory. Due to important spectral differences between greenhouse pot plant leaf spectra and field leaf spectra, a model calibrated directly on field leaves is necessary

N-heterocyclic carbene-palladium complexes [(NHC)Pd(acac)Cl]: Improved synthesis and catalytic activity in large-scale cross-coupling reactions

From two commercially available starting materials, improved one-step, multigram-scale syntheses of [(IPr)Pd(acac)Cl] [IPr=N,N'-bis(2,6-diisopropylphenyl)imidazol-2-ylidene; acac=acetylacetonate] and [(IMes)Pd(acac)Cl] [IMes = N,]Vbis(2,4,6-trimethylphenyl)imidazol-2-ylidene] are described. The catalytic activity of both complexes in cross-coupling reactions has been examined. The most active pre-catalyst, [(IPr)Pd(acac)Cl], has allowed for efficient large-scale (10 mmol) Buch-wald-Hartwig and a-ketone arylation reactions to be carried out.</p

Early Onset Delirium During Hospitalization Increases In-Hospital and Postdischarge Mortality in COVID-19 Patients: A Multicenter Prospective Study

Objective: Delirium is a common feature in COVID-19 patients. Although its association with in-hospital mortality has previously been reported, data concerning postdischarge mortality and delirium subtypes are scarce. We evaluated the association between delirium and its subtypes and both in-hospital and postdischarge mortality. Methods: This multicenter longitudinal clinical-based study was conducted in Monza and Brescia, Italy. The study population included 1,324 patients (median age: 68 years) with COVID-19 admitted to 4 acute clinical wards in northern Italy during the first pandemic waves (February 2020 to January 2021). Delirium within 48 hours of hospital admission was assessed through validated scores and/or clinically according to DSM-5 criteria. The association of delirium—and its subtypes—with in-hospital and postdischarge mortality (over a median observation period of 257 [interquartile range: 189–410] days) was evaluated through Cox proportional hazards models. Results: The 223 patients (16.8%) presenting delirium had around 2-fold increased in-hospital (hazard ratio [HR] = 1.94; 95% CI, 1.38–2.73) and postdischarge (HR = 2.01; 95% CI, 1.48–2.73) mortality than those without delirium. All delirium subtypes were associated with greater risk of death compared to the absence of delirium, but hypoactive delirium revealed the strongest associations with both in-hospital (HR=2.03; 95% CI, 1.32–3.13) and postdischarge (HR=2.22; 95% CI, 1.52–3.26) mortality. Conclusions: In patients with COVID-19, early onset delirium is associated not only with in-hospital mortality but also with shorter postdischarge survival. This suggests that delirium detection and management are crucial to improving the prognosis of COVID-19 patients