Ecological and evolutionary implications of food subsidies from humans

Human activities are the main current driver of global change. From hunter‐gatherers through to Neolithic societies–and particularly in contemporary industrialised countries–humans have (voluntarily or involuntarily) provided other animals with food, often with a high spatio‐temporal predictability. Nowadays, as much as 30–40% of all food produced in Earth is wasted. We argue here that predictable anthropogenic food subsidies (PAFS) provided historically by humans to animals has shaped many communities and ecosystems as we see them nowadays. PAFS improve individual fitness triggering population increases of opportunistic species, which may affect communities, food webs and ecosystems by altering processes such as competition, predator–prey interactions and nutrient transfer between biotopes and ecosystems. We also show that PAFS decrease temporal population variability, increase resilience of opportunistic species and reduce community diversity. Recent environmental policies, such as the regulation of dumps or the ban of fishing discards, constitute natural experiments that should improve our understanding of the role of food supply in a range of ecological and evolutionary processes at the ecosystem level. Comparison of subsidised and non‐subsidised ecosystems can help predict changes in diversity and the related ecosystem services that have suffered the impact of other global change agents.     

Synthesis,HPLC Enantioresolution,and X‐ray Analysis of a New Series of C5‐methyl Pyridazines as N‐Formyl Peptide Receptor (FPR) Agonists

The synthesis of three racemates and the corresponding non‐chiral analogues of a C5‐methyl pyridazine series is described here, as well as the isolation of pure enantiomers and their absolute configuration assignment. In order to obtain optically active compounds, direct chromatographic methods of separation by HPLC‐UV were investigated using four chiral stationary phases (CSPs: Lux Amylose‐2, Lux Cellulose‐1, Lux Cellulose‐2 and Lux Cellulose‐3). The best resolution was achieved using amylose tris(5‐chloro‐2‐methylphenylcarbamate) (Lux Amylose‐2), and single enantiomers were isolated on a semipreparative scale with high enantiomeric excess, suitable for biological assays. The absolute configuration of optically active compounds was unequivocally established by X‐ray crystallographic analysis and comparative chiral HPLC‐UV profile. All compounds of the series were tested for formyl peptide receptor (FPR) agonist activity, and four were found to be active, with EC₅₀ values in the micromolar range. Chirality 25:400–408, 2013. © 2013 Wiley Periodicals, Inc.     

Practical considerations over spectral quality in solid state NMR spectroscopy of soluble proteins

Great theoretical and methodological advances are pushing the limits of resolution and sensitivity in solid state NMR (SSNMR). However, sample preparation remains a critical issue for the success of an experiment. The factors affecting spectral quality in SSNMR samples are discussed, examining cases encountered in the literature and presenting new experimental data. A discussion on resolution and sensitivity in sedimented solutes is framed in this context.     

Susceptibility of Human Placenta Derived Mesenchymal Stromal/Stem Cells to Human Herpesviruses Infection

Fetal membranes (FM) derived mesenchymal stromal/stem cells (MSCs) are higher in number, expansion and differentiation abilities compared with those obtained from adult tissues, including bone marrow. Upon systemic administration, ex vivo expanded FM-MSCs preferentially home to damaged tissues promoting regenerative processes through their unique biological properties. These characteristics together with their immune-privileged nature and immune suppressive activity, a low infection rate and young age of placenta compared to other sources of SCs make FM-MSCs an attractive target for cell-based therapy and a valuable tool in regenerative medicine, currently being evaluated in clinical trials. In the present study we investigated the permissivity of FM-MSCs to all members of the human Herpesviridae family, an issue which is relevant to their purification, propagation, conservation and therapeutic use, as well as to their potential role in the vertical transmission of viral agents to the fetus and to their potential viral vector-mediated genetic modification. We present here evidence that FM-MSCs are fully permissive to infection with Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), Varicella zoster virus (VZV), and Human Cytomegalovirus (HCMV), but not with Epstein-Barr virus (EBV), Human Herpesvirus-6, 7 and 8 (HHV-6, 7, 8) although these viruses are capable of entering FM-MSCs and transient, limited viral gene expression occurs. Our findings therefore strongly suggest that FM-MSCs should be screened for the presence of herpesviruses before xenotransplantation. In addition, they suggest that herpesviruses may be indicated as viral vectors for gene expression in MSCs both in gene therapy applications and in the selective induction of differentiation.     

Potential Effects of Climate Change on the Water Level,Flora and Macro-fauna of a Large Neotropical Wetland

Possible consequences of climate change in one of the world’s largest wetlands (Ibera, Argentina) were analysed using a multi-scale approach. Climate projections coupled to hydrological models were used to analyse variability in wetland water level throughout the current century. Two potential scenarios of greenhouse gas emissions were explored, both resulting in an increase in the inter-annual fluctuations of the water level. In the scenario with higher emissions, projections also showed a long-term negative trend in water-level. To explore the possible response of biota to such water-level changes, species-area relationships of flora and aerial censuses of macro-fauna were analysed during an extraordinary dry period. Plant species richness at the basin scale was found to be highly resistant to hydrological changes, as the large dimension of the wetland acts to buffer against the water-level variations. However, local diversity decreased significantly with low water levels, leading to the loss of ecosystem resilience to additional stressors. The analysis of macro-fauna populations suggested that wetland provides refuge, in low water periods, for the animals with high dispersal ability (aquatic and migratory birds). On the contrary, the abundance of animals with low dispersal ability (mainly herbivorous species) was negatively impacted in low water periods, probably because they are required to search for alternative resources beyond the wetland borders. This period of resource scarcity was also related to increased mortality of large mammals (e.g. marsh deer) around water bodies with high anthropogenic enrichment and cyanobacteria dominance. The synergy between recurrent climatic fluctuations and additional stressors (i.e. biological invasions, eutrophication) presents an important challenge to the conservation of neotropical wetlands in the coming decades.     

Prevalence of Disease and Relationships between Laboratory Phenotype and Bleeding Severity in Platelet Primary Secretion Defects

Background

The prevalence of platelet primary secretion defects (PSD) among patients with bleeding diathesis is unknown. Moreover, there is paucity of data on the determinants of bleeding severity in PSD patients.

Objective

To determine the prevalence of PSD in patients with clinical bleeding and to study the relationships between the type of platelet defect and bleeding severity.

Methods

Data on patients referred for bleeding to the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan (Italy) in the years between 2008 and 2012 were retrieved to study the prevalence of PSD. Demographic, clinical and laboratory information on 32 patients with a diagnosis of PSD was used to compare patients with or without associated medical conditions and to investigate whether or not the type and extension of platelet defects were associated with the bleeding severity score (crude and age-normalized) or with the age at first bleeding requiring medical attention.

Results

The estimated prevalence of PSD among 207 patients with bleeding diathesis and bleeding severity score above 4 was 18.8% (95% confidence interval [CI]: 14.1–24.7%). Patients without associated medical conditions had earlier age of first bleeding (18 vs 45 years; difference: -27 years; 95% CI: -46 to -9 years) and different platelet functional defect patterns (Fisher''s exact test of the distribution of patterns, P = 0.007) than patients with accompanying medical conditions. The type and extension of platelet defect was not associated with the severity of bleeding.

Conclusions

PSD is found in approximately one fifth of patients with clinical bleeding. In patients with PSD, the type and extension of laboratory defect was not associated with bleeding severity.     

Expression of the Wnt inhibitor Dickkopf-1 is required for the induction of neural markers in mouse embryonic stem cells differentiating in response to retinoic acid

Cultured mouse D3 embryonic stem (ES) cells differentiating into embryoid bodies (EBs) expressed several Wnt isoforms, nearly all isotypes of the Wnt receptor Frizzled and the Wnt/Dickkopf (Dkk) co-receptor low-density lipoprotein receptor-related protein (LRP) type 5. A 4-day treatment with retinoic acid (RA), which promoted neural differentiation of EBs, substantially increased the expression of the Wnt antagonist Dkk-1, and induced the synthesis of the Wnt/Dkk-1 co-receptor LRP6. Recombinant Dkk-1 applied to EBs behaved like RA in inducing the expression of the neural markers nestin and distal-less homeobox gene (Dlx-2). Recombinant Dkk-1 was able to inhibit the Wnt pathway, as shown by a reduction in nuclear beta-catenin levels. Remarkably, the antisense- or small interfering RNA-induced knockdown of Dkk-1 largely reduced the expression of Dlx-2, and the neuronal marker beta-III tubulin in EBs exposed to RA. These data suggest that induction of Dkk-1 and the ensuing inhibition of the canonical Wnt pathway is required for neural differentiation of ES cells.     

Graph-based identification of cancer signaling pathways from published gene expression signatures using PubLiME

Gene expression technology has become a routine application in many laboratories and has provided large amounts of gene expression signatures that have been identified in a variety of cancer types. Interpretation of gene expression signatures would profit from the availability of a procedure capable of assigning differentially regulated genes or entire gene signatures to defined cancer signaling pathways. Here we describe a graph-based approach that identifies cancer signaling pathways from published gene expression signatures. Published gene expression signatures are collected in a database (PubLiME: Published Lists of Microarray Experiments) enabled for cross-platform gene annotation. Significant co-occurrence modules composed of up to 10 genes in different gene expression signatures are identified. Significantly co-occurring genes are linked by an edge in an undirected graph. Edge-betweenness and k-clique clustering combined with graph modularity as a quality measure are used to identify communities in the resulting graph. The identified communities consist of cell cycle, apoptosis, phosphorylation cascade, extra cellular matrix, interferon and immune response regulators as well as communities of unknown function. The genes constituting different communities are characterized by common genomic features and strongly enriched cis-regulatory modules in their upstream regulatory regions that are consistent with pathway assignment of those genes.