Comparison of drought stress response and gene expression between a GM maize variety and a near-isogenic non-GM variety

Maize MON810, grown and commercialised worldwide, is the only cultivated GM event in the EU. Maize MON810, variety DKC6575, and the corresponding near-isogenic line Tietar were studied in different growth conditions, to compare their behaviour in response to drought. Main photosynthetic parameters were significantly affected by water stress in both GM and non –GM varieties to a similar extents. Though DKC6575 (GM) had a greater sensitivity in the early phase of stress response as compared with Tietar (non GM), after six days of stress they behaved similarly, and both varieties recovered from stress damage. Profiling gene expression in water deficit regimes and in a generalised water stress condition showed an up-regulation of many stress- responsive genes, but a greater number of differentially expressed genes was observed in Tietar, with genes belonging to transcription factor families and genes encoding HSPs, LEAs and detoxification enzymes. Since induction of these genes have been indicated from the literature as typical of stress responses, their activation in Tietar rather than in DKC6575 may be reminiscent of a more efficient response to drought. DKC6575 was also analysed for the expression of the transgene CryIAb (encoding the delta-endotoxin insecticidal protein) in water deficit conditions. In all the experiments, the CryIAb transcript was not influenced by water stress, but was expressed at a constant level.. This suggests that though possessing a different pattern of sensitivity to stress, the GM variety maintains the same expression level for the transgene

Imatinib-associated hyperpigmentation, a side effect that should be recognized

Introduction & Objectives: Imatinib mesylate is a tyrosine-kinase inhibitor used as the first-line treatment in chronic myeloid leukemia patients who are not candidate for allogeneic bone marrow transplantation. The most frequently reported drug-related side effects are edema, nausea, vomiting, muscle cramps, musculoskeletal pain, diarrhea and rash. Imatinib treatment is often associated with hypopigmentation, but only a few cases of mucocutaneous hyperpigmentation are described in literature. We are reporting an additional case of mucocutaneous blue hyperpigmentation in a patient affected by chronic myeloid leukemia and treated with imatinib since 2003. Material & Methods: A review of the available literature regarding the hyperpigmentation related to imatinib was performed and one additional case was analysed. Results: In our case imatinib therapy was well tolerated for several years and it led to an excellent hematological and cytogenetic response. However, the patient gradually developed an intense blue hyperpigmentation that involved the oral mucosa and part of the skin. Other causes of hyperpigmentation were excluded. Conclusions: Since 2001, when imatinib was approved from Food and Drug Administration for chronic myeloid leukemia, some cases of secondary hyperpigmentation were reported. This rare side effect should be recognized by the physicians. Moreover, the patient should be informed about this benign event before starting the therapy. Currently, no treatment is required for this condition and there is not indication to discontinue imatinib treatment. Further insight into the mechanisms of the pigmentary alterations caused by this drug is suggested for better treatment and prevention of these manifestations

Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More

Increasing interest has recently focused on determining whether several natural compounds, collectively referred to as nutraceuticals, may exert neuroprotective actions in the developing, adult, and aging nervous system. Quercetin, a polyphenol widely present in nature, has received the most attention in this regard. Several studies in vitro, in experimental animals and in humans, have provided supportive evidence for neuroprotective effects of quercetin, either against neurotoxic chemicals or in various models of neuronal injury and neurodegenerative diseases. The exact mechanisms of such protective effects remain elusive, though many hypotheses have been formulated. In addition to a possible direct antioxidant effect, quercetin may also act by stimulating cellular defenses against oxidative stress. Two such pathways include the induction of Nrf2-ARE and induction of the antioxidant/anti-inflammatory enzyme paraoxonase 2 (PON2). In addition, quercetin has been shown to activate sirtuins (SIRT1), to induce autophagy, and to act as a phytoestrogen, all mechanisms by which quercetin may provide its neuroprotection

The combination of oral and topical photoprotection with a standardized Polypodium leucotomos extract is beneficial against actinic keratosis

IntroductionThis study describes a prospective, multicentre, randomized controlled, open-label study with three arms aimed at studying the differences between: [Cnt], self-administered sun protection; [T], topical treatment; and [TO], topical + oral treatment; for the management of Actinic Keratosis (AK) in a cohort of subjects of advanced age displaying severe actinic damage (SAD). MethodsTreatments administered to groups [T] and [TO] had a common component, which is a botanical extract, Fernblock, with demonstrated photoprotective activity. ResultsIn total, 131 subjects were distributed randomly in the three groups, and followed up clinically at three separate time points, beginning of the study (t = 0) and after 6 and 12 months. Analysis of clinical data and examination using reflectance confocal microscopy (RCM) revealed that group [T] and [TO] displayed decreased clinical AK and field cancerization parameters, including the number of new lesions, and reduced the need for additional interventions in these patients. RCM revealed normalization of the keratinocyte layer. Improvements in AK and field cancerization parameters were greatest in the group [TO], suggesting that topical and oral photoprotection improves the clinical and anatomical outcome compared to control conditions. ConclusionsThe combination of topical and oral immune photoprotection provides an advantage compared to topical photoprotection alone

Misato Controls Mitotic Microtubule Generation by Stabilizing the TCP-1 Tubulin Chaperone Complex

Mitotic spindles are primarily composed of microtubules (MTs), generated by polymerization of α- and β-Tubulin hetero-dimers. Tubulins undergo a series of protein folding and post-translational modifications in order to fulfill their functions. Defects in Tubulin polymerization dramatically affect spindle formation and disrupt chromosome segregation. We recently described a role for the product of the conserved misato (mst) gene in regulating mitotic MT generation in flies, but the molecular function of Mst remains unknown. Here, we use affinity purification mass spectrometry (AP-MS) to identify interacting partners of Mst in the Drosophila embryo. We demonstrate that Mst associates stoichiometrically with the hetero-octameric Tubulin Chaperone Protein-1 (TCP-1) complex, with the hetero-hexameric Tubulin Prefoldin complex, and with proteins having conserved roles in generating MT-competent Tubulin. We show that RNAi-mediated in vivo depletion of any TCP-1 subunit phenocopies the effects of mutations in mst or the Prefoldin-encoding gene merry-go-round (mgr), leading to monopolar and disorganized mitotic spindles containing few MTs. Crucially, we demonstrate that Mst, but not Mgr, is required for TCP-1 complex stability and that both the efficiency of Tubulin polymerization and Tubulin stability are drastically compromised in mst mutants. Moreover, our structural bioinformatic analyses indicate that Mst resembles the three-dimensional structure of Tubulin monomers and might therefore occupy the TCP-1 complex central cavity. Collectively, our results suggest that Mst acts as a co-factor of the TCP-1 complex, playing an essential role in the Tubulin-folding processes required for proper assembly of spindle MTs

Teleangectasie del volto: una questione di profilo

Si presenta il caso di una donna di 48 anni che giungeva alla nostra osservazione per la comparsa da circa 1 anno di un’eruzione eritematosa asintomatica della parte superiore dell’emivolto sinistro. La paziente non riferiva patologie note, non assumeva farmaci e non consumava abitualmente bevande alcoliche. L’esame obiettivo evidenziava alcune macule eritematose della regione periorbitaria e fini teleangectasie diffuse nel territorio di distribuzione del trigemino. Le lesioni scomparivano alla digito-vitro-pressione. Nessuna anomalia si riscontrava sul resto della cute ed a carico delle mucose. La dermoscopia e la microscopia laser confocale rivelavano patterns aspecifici, mentre la tomografia a coerenza ottica evidenziava un aumento della vascolarizzazione rispetto all’emivolto controlaterale. Veniva eseguita una biopsia cutanea su una delle macule e l’esame istologico mostrava la presenza di teleangectasie nel derma circondate da lieve infiltrato linfocitario, senza un aumento significativo di mastociti. Questi elementi hanno permesso di escludere alcune ipotesi diagnostiche iniziali e, guidati anche dalla particolare localizzazione delle lesioni, di formulare la diagnosi di una rara dermatosi vascolare. Gli esami di funzionalità epatica, le sierologie per HBV ed HCV, il dosaggio degli ormoni sessuali e l’ecografia addome completo venivano richiesti per valutare la presenza di patologie sistemiche associate

Seborrheic keratoses mimicking melanoma unveiled by in vivo reflectance confocal microscopy

Background: Seborrheic keratoses (SebK) with atypical dermoscopy presentation are increasingly reported. These lesions do not exhibit typical dermoscopy features of SebK and sometimes mimic melanoma, thus complicating the differential diagnosis. Reflectance confocal microscopy (RCM) is a non-invasive tool, which allows an in vivo imaging of the skin. Objective: To evaluate the agreement between RCM classification and histological diagnoses, and the reliability of well-known RCM criteria for SebK in the identification of SebK with atypical dermoscopy presentation. Methodology: We retrospectively analysed at RCM excised lesions presenting in dermoscopy 651 score at revisited 7-point checklist. The study population consisted of cases showing no melanocytic RCM findings. Lesions were investigated for distinct non-melanocytic RCM features, blinded from histopathology diagnoses. Histopathology matching was then performed before statistical analysis. Results: The study consisted of 117 cases, classified at RCM as SebK (71 cases), dermatofibroma (DF; 18 cases), basal cell carcinoma (BCC; 13 cases), squamous cell carcinoma (SCC; 2 cases), and \u201cnon specific\u201d (13 cases). Overall K strength of agreement at histopathology matching proved 0.76. Of the 71 cases classified at RCM with SebK, agreement was achieved in 97%. Conclusions: RCM classification proved high agreement with histopathology for SebK with atypical dermoscopy presentations, allowing an early differential diagnosis. RCM features in this group of lesions were similar to those described for typical cases of SebK, and may assist clinician therapy decision making, whilst avoiding unnecessary excisions

Moonlighting in mitosis:Analysis of the mitotic functions of transcription and splicing factors

Moonlighting proteins can perform one or more additional functions besides their primary role. It has been posited that a protein can acquire a moonlighting function through a gradual evolutionary process, which is favored when the primary and secondary functions are exerted in different cellular compartments. Transcription factors (TFs) and splicing factors (SFs) control processes that occur in interphase nuclei and are strongly reduced during cell division, and are therefore in a favorable situation to evolve moonlighting mitotic functions. However, recently published moonlighting protein databases, which comprise almost 400 proteins, do not include TFs and SFs with secondary mitotic functions. We searched the literature and found several TFs and SFs with bona fide moonlighting mitotic functions, namely they localize to specific mitotic structure(s), interact with proteins enriched in the same structure(s), and are required for proper morphology and functioning of the structure(s). In addition, we describe TFs and SFs that localize to mitotic structures but cannot be classified as moonlighting proteins due to insufficient data on their biochemical interactions and mitotic roles. Nevertheless, we hypothesize that most TFs and SFs with specific mitotic localizations have either minor or redundant moonlighting functions, or are evolving towards the acquisition of these functions

Cyclin F-Mediated Degradation of Ribonucleotide Reductase M2 Controls Genome Integrity and DNA Repair

F-box proteins are the substrate binding subunits of SCF (Skp1-Cul1-F-box protein) ubiquitin ligase complexes. Using affinity purifications and mass spectrometry, we identified RRM2 (the ribonucleotide reductase family member 2) as an interactor of the F-box protein cyclin F. Ribonucleotide reductase (RNR) catalyzes the conversion of ribonucleotides to deoxyribonucleotides (dNTPs), which are necessary for both replicative and repair DNA synthesis. We found that, during G2, following CDK-mediated phosphorylation of Thr33, RRM2 is degraded via SCFcyclin F to maintain balanced dNTP pools and genome stability. After DNA damage, cyclin F is downregulated in an ATR-dependent manner to allow accumulation of RRM2. Defective elimination of cyclin F delays DNA repair and sensitizes cells to DNA damage, a phenotype that is reverted by expressing a nondegradable RRM2 mutant. In summary, we have identified a biochemical pathway that controls the abundance of dNTPs and ensures efficient DNA repair in response to genotoxic stress