Human mobility networks, travel restrictions, and the global spread of 2009 H1N1 pandemic

After the emergence of the H1N1 influenza in 2009, some countries responded with travel-related controls during the early stage of the outbreak in an attempt to contain or slow down its international spread. These controls along with self-imposed travel limitations contributed to a decline of about 40% in international air traffic to/from Mexico following the international alert. However, no containment was achieved by such restrictions and the virus was able to reach pandemic proportions in a short time. When gauging the value and efficacy of mobility and travel restrictions it is crucial to rely on epidemic models that integrate the wide range of features characterizing human mobility and the many options available to public health organizations for responding to a pandemic. Here we present a comprehensive computational and theoretical study of the role of travel restrictions in halting and delaying pandemics by using a model that explicitly integrates air travel and short-range mobility data with high-resolution demographic data across the world and that is validated by the accumulation of data from the 2009 H1N1 pandemic. We explore alternative scenarios for the 2009 H1N1 pandemic by assessing the potential impact of mobility restrictions that vary with respect to their magnitude and their position in the pandemic timeline. We provide a quantitative discussion of the delay obtained by different mobility restrictions and the likelihood of containing outbreaks of infectious diseases at their source, confirming the limited value and feasibility of international travel restrictions. These results are rationalized in the theoretical framework characterizing the invasion dynamics of the epidemics at the metapopulation level.     

Adenoviral Gene Transfer of PLD1-D4 Enhances Insulin Sensitivity in Mice by Disrupting Phospholipase D1 Interaction with PED/PEA-15

Over-expression of phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (PED/PEA-15) causes insulin resistance by interacting with the D4 domain of phospholipase D1 (PLD1). Indeed, the disruption of this association restores insulin sensitivity in cultured cells over-expressing PED/PEA-15. Whether the displacement of PLD1 from PED/PEA-15 improves insulin sensitivity in vivo has not been explored yet. In this work we show that treatment with a recombinant adenoviral vector containing the human D4 cDNA (Ad-D4) restores normal glucose homeostasis in transgenic mice overexpressing PED/PEA-15 (Tg _ped/pea-15) by improving both insulin sensitivity and secretion. In skeletal muscle of these mice, D4 over-expression inhibited PED/PEA-15-PLD1 interaction, decreased Protein Kinase C alpha activation and restored insulin induced Protein Kinase C zeta activation, leading to amelioration of insulin-dependent glucose uptake. Interestingly, Ad-D4 administration improved insulin sensitivity also in high-fat diet treated obese C57Bl/6 mice. We conclude that PED/PEA-15-PLD1 interaction may represent a novel target for interventions aiming at improving glucose tolerance.     

Anti-tissue transglutaminase antibodies activate intracellular tissue transglutaminase by modulating cytosolic Ca2+ homeostasis

Anti-tissue transglutaminase (tTG) antibodies are specifically produced in the small-intestinal mucosa of celiac disease (CD) patients. It is now recognized that these antibodies, acting on cell-surface tTG, may play an active role in CD pathogenesis triggering an intracellular response via the activation of different signal transduction pathways. In this study, we report that anti-tTG antibodies, both commercial and from a CD patient, induce a rapid Ca²⁺ mobilization from intracellular stores in Caco-2 cells. We characterized the mechanism of Ca²⁺ release using thapsigargin and carbonylcyanide-p-trifluoromethoxyphenylhydrazone, which are able to deplete specifically endoplasmic reticulum and mitochondria of Ca²⁺, respectively. Our data highlight that both pathways of calcium release were involved, thus indicating that the spectrum of cellular responses downstream can be very wide. In addition, we demonstrate that the increased Ca²⁺ level in the cells evoked by anti-tTG antibodies was sufficient to activate tTG, which is normally present as a latent protein due to the presence of low Ca²⁺ and to the inhibitory effect of GTP/GDP. Herein, we discuss the importance of intracellular tTG activation as central in the context of CD pathogenesis.     

A dual role for Integrin α6β4 in modulating hereditary neuropathy with liability to pressure palsies

Peripheral myelin protein 22 (PMP 22) is a component of compact myelin in the peripheral nervous system. The amount of PMP 22 in myelin is tightly regulated, and PMP 22 over or under‐expression cause Charcot‐Marie‐Tooth 1A (CMT 1A) and Hereditary Neuropathy with Pressure Palsies (HNPP ). Despite the importance of PMP 22 , its function remains largely unknown. It was reported that PMP 22 interacts with the β4 subunit of the laminin receptor α6β4 integrin, suggesting that α6β4 integrin and laminins may contribute to the pathogenesis of CMT 1A or HNPP . Here we asked if the lack of α6β4 integrin in Schwann cells influences myelin stability in the HNPP mouse model. Our data indicate that PMP 22 and β4 integrin may not interact directly in myelinating Schwann cells, however, ablating β4 integrin delays the formation of tomacula, a characteristic feature of HNPP . In contrast, ablation of integrin β4 worsens nerve conduction velocities and non‐compact myelin organization in HNPP animals. This study demonstrates that indirect interactions between an extracellular matrix receptor and a myelin protein influence the stability and function of myelinated fibers.

     

Morphological Analysis of the Transfer of VSV ts-045 G Glycoprotein from the Endoplasmic Reticulum to the Intermediate Compartment in Vero Cells

Vero cells were infected with the ts-045 strain of vesicular stomatitis virus, and the cells were incubated at 39°C to accumulate the mutant G glycoprotein in the ER as a misfolded aggregate. Cycloheximide was added to the culture medium 3.5 h after infection to prevent further protein synthesis, and the temperature was lowered to 10, 15, or 31°C. At these temperatures, the mutant G glycoprotein correctly folds and oligomerizes. Immunofluorescence light microscopy showed that the G glycoprotein was exported to the Golgi complex at 31°C and to the intermediate compartment (IC) at 15°C, but no export was observed at 10°C. However, incubations at 10°C followed by shift to 15 or 31°C resulted in the normal transfer of the glycoprotein to the IC and the Golgi, respectively. Immunoelectron microscopical analysis confirmed all these results, but showed also that the glycoprotein was frequently clustered in the ER at 10°C. Conventional electron microscopy showed that the morphology of the ER, IC, and Golgi complex remained essentially unchanged at all temperatures. The only significant difference detectable in cells incubated at 10°C was the increased number of partially coated ER protrusions, longer than those detected at higher temperatures. These results demonstrate that the transport toward the Golgi complex of G glycoprotein can be arrested at a step preceding the entry into the IC, thus suggesting that ER and IC are separate stations in the exocytic pathway.     

An environmental and economic analysis of the wood-pellet chain: two case studies in Southern Italy

Purpose

Wood pellet heating systems are considered as an essential component of European plans to reduce greenhouse gas (GHG) emissions. The goal of this analysis was to estimate and compare the environmental impacts and the costs of the production of packed wood pellets. Two pellet production systems, using roundwood logs (case 1) and mainly sawdust (case 2), have been analysed in 2015 in Basilicata region (Southern Italy).

Methods

A life cycle assessment (LCA) analysis was applied to calculate the environmental impact indicators of each system, whilst a life cycle cost (LCC) analysis was implemented to evaluate the pellets’ cost production. Hence, the functional unit chosen was 1 t of produced pellets. The system boundaries considered for the purpose of the current investigation were from the tree felling to the pellet packaging. In particular, the following activities were considered: motor-manual felling and delimbing with a chainsaw, timber yarding with a tractor along the forest track, loading and transportation of the logs to the collection point, transportation of timber to the factories for a distance of 35 km, pellet production and pellet packaging in low-density polyethylene bags with a total weight of 15 kg bag^?1.

Results and discussion

The production of 1 t of pellets emitted about 83 kg of CO₂eq in case 1 and 38 kg in case 2. In addition, 2.7 kg of SO₂eq and 0.005 kg of PO³ ₄-eq were produced in case 1 and 1.4 kg of SO₂eq and 0.002 kg of PO³ ₄-eq in case 2. Mineral extraction was equal to 0.9 MJ surplus energy in both cases. Case 1 led to higher environmental impacts (about 50% more), essentially for the operation of pelletisation, and in particular for the higher consumption of electricity that characterised it, whereas the production costs were 172 and 113 € t^?1 in case 1 and case 2, respectively. In both study cases, consumption costs (costs for raw material, electricity consumption, fuel usage) were the most important cost items.

Conclusions

Our studies highlight how, in both cases, the operations carried out in the forest produced the minor part of the environmental impact but, at the same time, were the most expensive operations. Further, our studies show how mixing lumbering by-products (sawdust) and forest management products (lumbers) can be an efficient solution to reduce both manufacturing costs and environmental impacts to produce wood pellets.