First flowering of wind‐pollinated species with the greatest phenological advances in Europe

Increasing risk of pollinosis (hay fever) is one of the most anticipated consequences of climate change on human health. Wind‐pollinated plants are representative of allergenic species because they include species with the highest capability of causing allergy‐related diseases in humans. Therefore, changes in wind‐pollinated species may reflect impacts of climate change on allergenic plants. In particular, flowering is one of the developmental stages most affected by climate change. This report specifically addresses changes in flowering dates that have occurred during the three decades 1971–2000 as a function of pollination mode and woodiness. The assessment is made using a phenological data set comprising trends of flowering dates of 29 species in 983 locations in Europe. Linear mixed models assessing the statistical significance of trends while adjusting for spatial correlation are used. The main results indicate for the first time that the onset of flowering of wind‐pollinated plants advanced more than for insect‐pollinated plants, while full flowering phases tended to advance less. These novel findings are contrary to the results of Fitter and Fitter (2002) for Oxfordshire, who reported larger advances of insect‐pollinated plants. Onset of flowering and full flowering of insect‐pollinated species are more likely to advance for seasons early in the year; instead, wind‐pollinated plants showed no dependence of trends on the season (first flowering) or a decreased advance of phases that are early in the year (full flowering). The effect of woodiness could not be unambiguously defined, but seems to be of minor importance. The presented findings suggest a lengthening of the flowering period in general, which might lead to an increasing time of exposure to airborne pollen of allergic subjects, with consequent likely increment in severity and incidence of allergic symptoms.     

The Deoxynucleoside Triphosphate Triphosphohydrolase Activity of SAMHD1 Protein Contributes to the Mitochondrial DNA Depletion Associated with Genetic Deficiency of Deoxyguanosine Kinase

The dNTP triphosphohydrolase SAMHD1 is a nuclear antiviral host restriction factor limiting HIV-1 infection in macrophages and a major regulator of dNTP concentrations in human cells. In normal human fibroblasts its expression increases during quiescence, contributing to the small dNTP pool sizes of these cells. Down-regulation of SAMHD1 by siRNA expands all four dNTP pools, with dGTP undergoing the largest relative increase. The deoxyguanosine released by SAMHD1 from dGTP can be phosphorylated inside mitochondria by deoxyguanosine kinase (dGK) or degraded in the cytosol by purine nucleoside phosphorylase. Genetic mutations of dGK cause mitochondrial (mt) DNA depletion in noncycling cells and hepato-cerebral mtDNA depletion syndrome in humans. We studied if SAMHD1 and dGK interact in the regulation of the dGTP pool during quiescence employing dGK-mutated skin fibroblasts derived from three unrelated patients. In the presence of SAMHD1 quiescent mutant fibroblasts manifested mt dNTP pool imbalance and mtDNA depletion. When SAMHD1 was silenced by siRNA transfection the composition of the mt dNTP pool approached that of the controls, and mtDNA copy number increased, compensating the depletion to various degrees in the different mutant fibroblasts. Chemical inhibition of purine nucleoside phosphorylase did not improve deoxyguanosine recycling by dGK in WT cells. We conclude that the activity of SAMHD1 contributes to the pathological phenotype of dGK deficiency. Our results prove the importance of SAMHD1 in the regulation of all dNTP pools and suggest that dGK inside mitochondria has the function of recycling the deoxyguanosine derived from endogenous dGTP degraded by SAMHD1 in the nucleus.     

Walking Performance: Correlation between Energy Cost of Walking and Walking Participation. New Statistical Approach Concerning Outcome Measurement

Walking ability, though important for quality of life and participation in social and economic activities, can be adversely affected by neurological disorders, such as Spinal Cord Injury, Stroke, Multiple Sclerosis or Traumatic Brain Injury. The aim of this study is to evaluate if the energy cost of walking (CW), in a mixed group of chronic patients with neurological diseases almost 6 months after discharge from rehabilitation wards, can predict the walking performance and any walking restriction on community activities, as indicated by Walking Handicap Scale categories (WHS). One hundred and seven subjects were included in the study, 31 suffering from Stroke, 26 from Spinal Cord Injury and 50 from Multiple Sclerosis. The multivariable binary logistical regression analysis has produced a statistical model with good characteristics of fit and good predictability. This model generated a cut-off value of.40, which enabled us to classify correctly the cases with a percentage of 85.0%. Our research reveal that, in our subjects, CW is the only predictor of the walking performance of in the community, to be compared with the score of WHS. We have been also identifying a cut-off value of CW cost, which makes a distinction between those who can walk in the community and those who cannot do it. In particular, these values could be used to predict the ability to walk in the community when discharged from the rehabilitation units, and to adjust the rehabilitative treatment to improve the performance.     

Latent profile analysis in frontotemporal lobar degeneration and related disorders: clinical presentation and SPECT functional correlates

Background  

Frontotemporal Lobar Degeneration (FTLD) thus recently renamed, refers to a spectrum of heterogeneous conditions. This same heterogeneity of presentation represents the major methodological limit for the correct evaluation of clinical designation and brain functional correlates. At present, no study has investigated clinical clusters due to specific cognitive and behavioural disturbances beyond current clinical criteria.     

Association of Thyroid Diseases with Primary Extra-Thyroidal Malignancies in Women: Results of a Cross-Sectional Study of 6,386 Patients

We here analyzed the prevalence of extra-thyroidal malignancies (EM) in 6,386 female patients affected by different thyroid disease (TD). At first, an age-matched analysis of EM in all patients was performed. We then evaluated EM prevalence in four TD diagnostic categories: non-nodular TD (n = 2,159); solitary nodule (n = 905); multinodular TD (n = 2,871); differentiated thyroid cancers (n = 451). Finally, patients were grouped based on the absence (n = 3,820) or presence of anti-thyroglobulin (TgAb) and/or anti-thyroperoxidase (TPOAb) (n = 2,369), or anti-Thyroid Stmulating Hormone (TSH) receptor autoantibodies (n = 197). A total of 673 EM were recorded. EM prevalence in TD patients was higher compared to the general population (Odds Ratio, OR 3.21) and the most frequent EM was breast cancer (OR 3.94), followed by colorectal (OR 2.18), melanoma (OR 6.71), hematological (OR 8.57), uterus (OR 2.52), kidney (OR 3.40) and ovary (OR 2.62) neoplasms. Age-matched analysis demonstrated that the risk of EM was maximal at age 0–44 yr (OR 11.28), remaining lower, but significantly higher that in the general population, in the 45–59 and 60–74 year age range. Breast and hematological malignancies showed an increased OR in all TD, while other cancers associated with specific TD. An increased OR for melanoma, breast and hematological malignancies was observed in both TPOAb and/or TgAb autoantibody negative and positive patients, while colorectal, uterus, kidney and ovary cancers showed an increased OR only in thyroid autoantibody negative patients. In conclusions, women affected by both benign and malignant TD, especially at a younger age and in absence of thyroid autoimmunity, have an increased risk of developing primary EM, thus requiring a careful follow-up and surveillance.     

Transforming Growth Factor-β1 Induces Transdifferentiation of Myoblasts into Myofibroblasts via Up-Regulation of Sphingosine Kinase-1/S1P3 Axis

The pleiotropic cytokine transforming growth factor (TGF)-β1 is a key player in the onset of skeletal muscle fibrosis, which hampers tissue repair. However, the molecular mechanisms implicated in TGFβ1-dependent transdifferentiation of myoblasts into myofibroblasts are presently unknown. Here, we show that TGFβ1 up-regulates sphingosine kinase (SK)-1 in C2C12 myoblasts in a Smad-dependent manner, and concomitantly modifies the expression of sphingosine 1-phosphate (S1P) receptors (S1PRs). Notably, pharmacological or short interfering RNA-mediated inhibition of SK1 prevented the induction of fibrotic markers by TGFβ1. Moreover, inhibition of S1P₃, which became the highest expressed S1PR after TGFβ1 challenge, strongly attenuated the profibrotic response to TGFβ1. Furthermore, downstream of S1P₃, Rho/Rho kinase signaling was found critically implicated in the profibrotic action of TGFβ1. Importantly, we demonstrate that SK/S1P axis, known to play a key role in myogenesis via S1P₂, consequently to TGFβ1-dependent S1PR pattern remodeling, becomes responsible for transmitting a profibrotic, antidifferentiating action. This study provides new compelling information on the mechanism by which TGFβ1 gives rise to fibrosis in skeletal muscle, opening new perspectives for its pharmacological treatment. Moreover, it highlights the pleiotropic role of SK/S1P axis in skeletal myoblasts that, depending on the expressed S1PR pattern, seems capable of eliciting multiple, even contrasting biological responses.     

Sexually dimorphic phrase organization in the song of the indris (Indri indri)

Animal acoustic communication often takes the form of complex sequences, composed of multiple distinct acoustic units, which can vary in their degree of stereotypy. Studies of sequence variation may contribute to our understanding of the structural flexibility of primates' songs, which can provide essential ecological and behavioral information about variability at the individual, population, and specific level and provide insights into the mechanisms and drivers responsible for the evolutionary change of communicative traits. Several methods have been used for investigating different levels of structural information and sequence similarity in acoustic displays. We studied intra and interindividual variation in the song structuring of a singing primate, the indri (Indri indri), which inhabits the montane rain forests of Madagascar. Indri groups emit duets and choruses in which they combine long notes, short single units, and phrases consisting of a variable number of units (from two to six) with slightly descending frequency. Males' and females' contributions to the song differ in the temporal and frequency structure of song units and repertoire size. We calculated the similarity of phrase organization across different individual contributions using the Levenshtein distance, a logic distance that expressed the minimum cost to convert a sequence into another and can measure differences between two sequences of data. We then analyzed the degree of similarity within and between individuals and found that: (a) the phrase structure of songs varied between reproductive males and females: female structuring of the song showed a higher number of phrases if compared to males; (b) male contributions to the song were overall more similar to those of other males than were female contributions to the song of other females; (c) male contributions were more stereotyped than female contributions, which showed greater individual flexibility. The picture emerging from phrase combinatorics in the indris is in agreement with previous findings of rhythmic features and song repertoire size of the indris, which also suggested that female songs are potentially less stereotyped than those of males.     

Latent Membrane Protein LMP2A Impairs Recognition of EBV-Infected Cells by CD8+ T Cells

The common pathogen Epstein-Barr virus (EBV) transforms normal human B cells and can cause cancer. Latent membrane protein 2A (LMP2A) of EBV supports activation and proliferation of infected B cells and is expressed in many types of EBV-associated cancer. It is not clear how latent EBV infection and cancer escape elimination by host immunity, and it is unknown whether LMP2A can influence the interaction of EBV-infected cells with the immune system. We infected primary B cells with EBV deleted for LMP2A, and established lymphoblastoid cell lines (LCLs). We found that CD8+ T cell clones showed higher reactivity against LMP2A-deficient LCLs compared to LCLs infected with complete EBV. We identified several potential mediators of this immunomodulatory effect. In the absence of LMP2A, expression of some EBV latent antigens was elevated, and cell surface expression of MHC class I was marginally increased. LMP2A-deficient LCLs produced lower amounts of IL-10, although this did not directly affect CD8+ T cell recognition. Deletion of LMP2A led to several changes in the cell surface immunophenotype of LCLs. Specifically, the agonistic NKG2D ligands MICA and ULBP4 were increased. Blocking experiments showed that NKG2D activation contributed to LCL recognition by CD8+ T cell clones. Our results demonstrate that LMP2A reduces the reactivity of CD8+ T cells against EBV-infected cells, and we identify several relevant mechanisms.