On the Role of NAO Driven Interannual Variability in Rainfall Seasonality on Water Resources and Hydrologic Design in a Typical Mediterranean Basin

In the last several decades, extended dry periods have affected the Mediterranean area with dramatic impacts on water resources. Climate models are predicting further warming, with negative effects on water availability. The authors analyze the hydroclimatic tendencies of a typical Mediterranean basin, the Flumendosa basin located in Sardinia, an island in the center of the Mediterranean Sea, where in the last 30 years a sequence of dry periods has seriously impacted the water management system. Interestingly, in the historic record the annual runoff reductions have been more pronounced than the annual precipitation reductions. This paper performs an analysis that links this runoff decrease to changes in the total annual precipitation and its seasonal structure. The seasonality is a key determinant of the surface runoff process, as it reflects the degree to which rainfall is concentrated during the winter. The observed reductions in winter precipitation are shown here to be well correlated (Pearson correlation coefficient of −0.5) with the North Atlantic Oscillation (NAO) index. Considering the predictability of the winter NAO, there is by extension an opportunity to predict future winter precipitation and runoff tendencies. The recent hydroclimatic trends are shown to impact hydrologic design criteria for water resources planning. The authors demonstrate that there is a dangerous increase of the drought severity viewed from the perspective of water resources planning

Rhizosphere water content drives hydraulic redistribution : Implications of pore-scale heterogeneity to modeling diurnal transpiration in water-limited ecosystems

Trees typically survive prolonged droughts by absorbing water from deeper layers. Where soils are shallow, roots may be extract water from the underlying fractured bedrocks. In dry seasons, surface-soil moisture dynamics reflect hydraulic redistribution (HR). HR is usually estimated based on the gradient of mean, or bulk, soil water potential among layers in the rooting zone (HRB). This approach neglects the potential effect of spatial heterogeneity of water content at the millimeter scale between the rhizosphere and bulk soil. We proposed to account for the rhizosphere water balance, estimating HR to the rhizosphere (HRR) of the dry surface soil from the underlying fractured rock. The model was evaluated using a 15-year dataset collected in Sardinia. When the typical approach, based on moisture gradients among bulk soil layers, was used for estimating HRB, tree transpiration was underpredicted in all seasons, especially in spring and summer. Forcing the model with measured tree transpiration, HRB decreased during spring and summer, while the contribution of the underlying rock layer to tree transpiration was threefold that estimated using HRR-based model. The average water content of the bulk surface soil layer was very low, reaching 0.06 in the driest summers while showing little diurnal dynamics; however, concentrating water in roughly estimated rhizosphere volume, produced rhizosphere water content appreciably higher (approximate to 0.16), and much more dynamic. Predicted HRR dominated evapotranspiration (60% - 65%) in dry springs and summers reaching 80% of tree transpiration. Most importantly, the proposed rhizosphere-HR model correctly predicts the diurnal dynamics of tree transpiration year-round, and the grass transpiration in its active spring period. Eco-hydrological models operating at sub-daily scale should consider partitioning the soil to rhizosphere volume, thus allowing both diagnostic and prognostic estimates of diurnal biosphere-atmosphere mass and energy exchanges.Peer reviewe

On the transpiration of wild olives under water-limited conditions in a heterogeneous ecosystem with shallow soil over fractured rock

Mediterranean ecosystems are typically heterogeneous and savanna-like, with trees and grass competing for water use. By measuring sap flow, we estimated high transpiration of wild olive, a common Mediterranean tree, in Sardinia despite dry conditions. This estimate agrees with independent estimates of tree transpiration based on energy balance, highlighting the wild olive’s strong tolerance of dry conditions. The wild olive can develop an adaptation strategy to tolerate dry conditions. In this Sardinian case study, the wild olive grew in shallow soil, and the tree roots expanded into the underlying fractured basalt. The trees survived in dry periods using water infiltrated during wet seasons into fractured rocks and held in soil pockets. We estimated a high upward vertical flux through the bottom soil layer from the underlying substrate, which reached 97% evapotranspiration in August 2011. The water taken up by tree roots from bedrock hollows is usually neglected in ecohydrological modeling

Dynamic features of human mitochondrial DNA maintenance and transcription

Mitochondria are the primary sites for cellular energy production and are required for many essential cellular processes. Mitochondrial DNA (mtDNA) is a 16.6 kb circular DNA molecule that encodes only 13 gene products of the approximately 90 different proteins of the respiratory chain complexes and an estimated 1,200 mitochondrial proteins. MtDNA is, however, crucial for organismal development, normal function, and survival. MtDNA maintenance requires mitochondrially targeted nuclear DNA repair enzymes, a mtDNA replisome that is unique to mitochondria, and systems that control mitochondrial morphology and quality control. Here, we provide an overview of the current literature on mtDNA repair and transcription machineries and discuss how dynamic functional interactions between the components of these systems regulate mtDNA maintenance and transcription. A profound understanding of the molecular mechanisms that control mtDNA maintenance and transcription is important as loss of mtDNA integrity is implicated in normal process of aging, inflammation, and the etiology and pathogenesis of a number of diseases

Rock Water as a Key Resource for Patchy Ecosystems on Shallow Soils : Digging Deep Tree Clumps Subsidize Surrounding Surficial Grass

Mediterranean mountainous areas of shallow soil often display a mosaic of tree clumps surrounded by grass. The combined role and dynamics of water extracted from the underlying rock, and the competition between adjacent patches of trees and grass, has not been investigated. We quantified the role rock water plays in the seasonal dynamics of evapotranspiration (ET), over a patchy landscape in the context of current and past seasonal climate changes, and land-cover change strategies. Soil water budget suggests deep water uptake by roots of trees (0.8-0.9 mm/d), penetrating into the fractured basalt, subsidized grass transpiration in spring through hydraulic redistribution. However, in summer trees used all the rock water absorbed (0.79 mm/d). A 15-year data set shows that, with increasing seasonal drought-severity (potential ET/precipitation) to >1.04, the vertical water flux through the bottom of the thin soil layer transitions from drainage to uptake in support of ET. A hypothetical grass-covered landscape, with no access to deep water, would require 0.68-0.85 mm/d more than is available, forcing shortened growing season and/or reduced leaf area. Long-term decreasing winter precipitation and increasing spring potential ET suggest drying climate, so far with stable vegetation mosaic but progressively earlier peak of grass leaf area. Intervention policies to increase water yield by reducing tree cover will curtail grass access to rock moisture, while attempting to increase tree-related products (including carbon sequestration) by increasing forest cover will limit water availability per tree leaf area. Both changes may further reduce ecosystem stability.Peer reviewe

Human metapneumovirus driven IFN-β production antagonizes macrophage transcriptional induction of IL1-β in response to bacterial pathogens

Human metapneumovirus (HMPV) is a pneumovirus that may cause severe respiratory disease in humans. HMPV infection has been found to increase susceptibility to bacterial superinfections leading to increased morbidity and mortality. The molecular mechanisms underlying HMPV-mediated increase in bacterial susceptibility are poorly understood and largely understudied. Type I interferons (IFNs), while critical for antiviral defenses, may often have detrimental effects by skewing the host immune response and cytokine output of immune cells. It is currently unknown if HMPV skews the inflammatory response in human macrophages triggered by bacterial stimuli. Here we report that HMPV pre-infection impacts production of specific cytokines. HMPV strongly suppresses IL-1β transcription in response to LPS or heat-killed Pseudomonas aeruginosa and Streptococcus pneumonia, while enhancing mRNA levels of IL-6, TNF-α and IFN-β. We demonstrate that in human macrophages the HMPV-mediated suppression of IL-1β transcription requires TANK-binding kinase 1 (TBK1) and signaling via the IFN-β-IFNAR axis. Interestingly, our results show that HMPV pre-infection did not impair the LPS-stimulated activation of NF-κB and HIF-1α, transcription factors that stimulate IL-1β mRNA synthesis in human cells. Furthermore, we determined that sequential HMPV-LPS treatment resulted in accumulation of the repressive epigenetic mark H3K27me3 at the IL1B promoter. Thus, for the first time we present data revealing the molecular mechanisms by which HMPV shapes the cytokine output of human macrophages exposed to bacterial pathogens/LPS, which appears to be dependent on epigenetic reprogramming at the IL1B promoter leading to reduced synthesis of IL-1β. These results may improve current understanding of the role of type I IFNs in respiratory disease mediated not only by HMPV, but also by other respiratory viruses that are associated with superinfections.</p

Enhanced Amphiphilic Profile of a Short β-Stranded Peptide Improves Its Antimicrobial Activity

SB056 is a novel semi-synthetic antimicrobial peptide with a dimeric dendrimer scaffold. Active against both Gram-negative and -positive bacteria, its mechanism has been attributed to a disruption of bacterial membranes. The branched peptide was shown to assume a β- stranded conformation in a lipidic environment. Here, we report on a rational modification of the original, empirically derived linear peptide sequence [WKKIRVRLSA-NH$_{2}$, SB056-lin]. We interchanged the first two residues [KWKIRVRLSA-NH$_{2}$, β-SB056-lin] to enhance the amphipathic profile, in the hope that a more regular β-strand would lead to a better antimicrobial performance. MIC values confirmed that an enhanced amphiphilic profile indeed significantly increases activity against both Gram-positive and -negative strains. The membrane binding affinity of both peptides, measured by tryptophan fluorescence, increased with an increasing ratio of negatively charged/zwitterionic lipids. Remarkably, β- SB056-lin showed considerable binding even to purely zwitterionic membranes, unlike the original sequence, indicating that besides electrostatic attraction also the amphipathicity of the peptide structure plays a fundamental role in binding, by stabilizing the bound state. Synchrotron radiation circular dichroism and solid-state $^{19}$F-NMR were used to characterize and compare the conformation and mobility of the membrane bound peptides. Both SB056- lin and β-SB056-lin adopt a β-stranded conformation upon binding POPC vesicles, but the former maintains an intrinsic structural disorder that also affects its aggregation tendency. Upon introducing some anionic POPG into the POPC matrix, the sequence-optimized β- SB056-lin forms well-ordered β-strands once electro-neutrality is approached, and it aggregates into more extended β-sheets as the concentration of anionic lipids in the bilayer is raised. The enhanced antimicrobial activity of the analogue correlates with the formation of these extended β-sheets, which also leads to a dramatic alteration of membrane integrity as shown by $^{31}$P-NMR. These findings are generally relevant for the design and optimization of other membrane-active antimicrobial peptides that can fold into amphipathic β-strands

A regulatory network comprising let-7 miRNA and SMUG1 is associated with good prognosis in ER+ breast tumours

Single-strand selective uracil–DNA glycosylase 1 (SMUG1) initiates base excision repair (BER) of uracil and oxidized pyrimidines. SMUG1 status has been associated with cancer risk and therapeutic response in breast carcinomas and other cancer types. However, SMUG1 is a multifunctional protein involved, not only, in BER but also in RNA quality control, and its function in cancer cells is unclear. Here we identify several novel SMUG1 interaction partners that functions in many biological processes relevant for cancer development and treatment response. Based on this, we hypothesized that the dominating function of SMUG1 in cancer might be ascribed to functions other than BER. We define a bad prognosis signature for SMUG1 by mapping out the SMUG1 interaction network and found that high expression of genes in the bad prognosis network correlated with lower survival probability in ER(+) breast cancer. Interestingly, we identified hsa-let-7b-5p microRNA as an upstream regulator of the SMUG1 interactome. Expression of SMUG1 and hsa-let-7b-5p were negatively correlated in breast cancer and we found an inhibitory auto-regulatory loop between SMUG1 and hsa-let-7b-5p in the MCF7 breast cancer cells. We conclude that SMUG1 functions in a gene regulatory network that influence the survival and treatment response in several cancers