The Role of the Right Posterior Parietal Cortex in Letter Migration between Words

When briefly presented with pairs of words, skilled readers can sometimes report words with migrated letters (e.g., they report hunt when presented with the words hint and hurt). These letter migration phenomena have been often used to investigate factors that influence reading such as letter position coding. However, the neural basis of letter migration is poorly understood. Previous evidence has implicated the right posterior parietal cortex (PPC) in processing visuospatial attributes and lexical properties during word reading. The aim of this study was to assess this putative role by combining an inhibitory TMS protocol with a letter migration paradigm, which was designed to examine the contributions of visuospatial attributes and lexical factors. Temporary interference with the right PPC led to three specific effects on letter migration. First, the number of letter migrations was significantly increased only in the group with active stimulation (vs. a sham stimulation group or a control group without stimulation), and there was no significant effect on other error types. Second, this effect occurred only when letter migration could result in a meaningful word (migration vs. control context). Third, the effect of active stimulation on the number of letter migrations was lateralized to target words presented on the left. Our study thus demonstrates that the right PPC plays a specific and causal role in the phenomenon of letter migration. The nature of this role cannot be explained solely in terms of visuospatial attention, rather it involves an interplay between visuospatial attentional and word reading-specific factors.

β2 integrin-mediated crawling on endothelial ICAM-1 and ICAM-2 is a prerequisite for transcellular neutrophil diapedesis across the inflamed blood-brain barrier

In acute neuroinflammatory states such as meningitis, neutrophils cross the blood-brain barrier (BBB) and contribute to pathological alterations of cerebral function. The mechanisms that govern neutrophil migration across the BBB are ill defined. Using live-cell imaging, we show that LPS-stimulated BBB endothelium supports neutrophil arrest, crawling, and diapedesis under physiological flow in vitro. Investigating the interactions of neutrophils from wild-type, CD11a(-/-), CD11b(-/-), and CD18(null) mice with wild-type, junctional adhesion molecule-A(-/-), ICAM-1(null), ICAM-2(-/-), or ICAM-1(null)/ICAM-2(-/-) primary mouse brain microvascular endothelial cells, we demonstrate that neutrophil arrest, polarization, and crawling required G-protein-coupled receptor-dependent activation of β2 integrins and binding to endothelial ICAM-1. LFA-1 was the prevailing ligand for endothelial ICAM-1 in mediating neutrophil shear resistant arrest, whereas Mac-1 was dominant over LFA-1 in mediating neutrophil polarization on the BBB in vitro. Neutrophil crawling was mediated by endothelial ICAM-1 and ICAM-2 and neutrophil LFA-1 and Mac-1. In the absence of crawling, few neutrophils maintained adhesive interactions with the BBB endothelium by remaining either stationary on endothelial junctions or displaying transient adhesive interactions characterized by a fast displacement on the endothelium along the direction of flow. Diapedesis of stationary neutrophils was unchanged by the lack of endothelial ICAM-1 and ICAM-2 and occurred exclusively via the paracellular pathway. Crawling neutrophils, although preferentially crossing the BBB through the endothelial junctions, could additionally breach the BBB via the transcellular route. Thus, β2 integrin-mediated neutrophil crawling on endothelial ICAM-1 and ICAM-2 is a prerequisite for transcellular neutrophil diapedesis across the inflamed BBB.

The generation of neutrophils in the bone marrow is controlled by autophagy.

Autophagy has been demonstrated to have an essential function in several cellular hematopoietic differentiation processes, for example, the differentiation of reticulocytes. To investigate the role of autophagy in neutrophil granulopoiesis, we studied neutrophils lacking autophagy-related (Atg) 5, a gene encoding a protein essential for autophagosome formation. Using Cre-recombinase mediated gene deletion, Atg5-deficient neutrophils showed no evidence of abnormalities in morphology, granule protein content, apoptosis regulation, migration, or effector functions. In such mice, however, we observed an increased proliferation rate in the neutrophil precursor cells of the bone marrow as well as an accelerated process of neutrophil differentiation, resulting in an accumulation of mature neutrophils in the bone marrow, blood, spleen, and lymph nodes. To directly study the role of autophagy in neutrophils, we employed an in vitro model of differentiating neutrophils that allowed modulating the levels of ATG5 expression, or, alternatively, intervening pharmacologically with autophagy-regulating drugs. We could show that autophagic activity correlated inversely with the rate of neutrophil differentiation. Moreover, pharmacological inhibition of p38 MAPK or mTORC1 induced autophagy in neutrophilic precursor cells and blocked their differentiation, suggesting that autophagy is negatively controlled by the p38 MAPK-mTORC1 signaling pathway. On the other hand, we obtained no evidence for an involvement of the PI3K-AKT or ERK1/2 signaling pathways in the regulation of neutrophil differentiation. Taken together, these findings show that, in contrast to erythropoiesis, autophagy is not essential for neutrophil granulopoiesis, having instead a negative impact on the generation of neutrophils. Thus, autophagy and differentiation exhibit a reciprocal regulation by the p38-mTORC1 axis.

Migration and population expansion of Abies, Fagus, Picea, and Quercus since 15000 years in and across the Alps, based on pollen-percentage threshold values

Aims: The aim of this study is to explore the migration (colonization of new areas) and subsequent population expansion (within an area) since 15 ka cal BP of Abies, Fagus, Picea, and Quercus into and through the Alps solely on the basis of high-quality pollen data. Methods: Chronologies of 101 pollen sequences are improved or created. Data from the area delimited by 45.5–48.1°N and 6–14°E are summarized in three ways: (1) in a selection of pollen-percentage threshold maps (thresholds 0.5%, 1%, 2%, 4%, 8%, 16%, and 32% of land pollen); (2) in graphic summaries of 250-year time slices and geographic segments (lengthwise and transverse in relation to the main axis of the Alps) as pollen-percentage curves, pollen-percentage difference curves, and pollen-percentage threshold ages cal BP graphed against both the length and the transverse Alpine axes; and (3) in tables showing statistical relationships of either pollen-percentage threshold ages cal BP or pollen expansion durations (=time lapse between different pollen-percentage threshold ages cal BP) with latitude, longitude, and elevation; to establish these relationships we used both simple linear regression and multiple linear regression after stepwise-forward selection. Results: The statistical results indicate that (a) the use of pollen-percentage thresholds between 0.5% and 8% yield mostly similar directions of tree migration, so the method is fairly robust, (b) Abies migrated northward, Fagus southward, Picea westward, and Quercus northward; more detail does not emerge due to an extreme scarcity of high-quality data especially along the southern foothills of the Alps and in the eastern Alps. This scarcity allows the reconstruction of one immigration route only of Abies into the southern Alps. The speed of population expansion (following arrival) of Abies increased and of Picea decreased during the Holocene, of Fagus it decreased especially during the later Holocene, and of Quercus it increased especially at the start of the Holocene.

Mechanical restoration and failure analyses of a hydrogel and scaffold composite strategy for annulus fibrosus repair

Unrepaired defects in the annulus fibrosus of intervertebral disks are associated with degeneration and persistent back pain. A clinical need exists for a disk repair strategy that can seal annular defects, be easily delivered during surgical procedures, and restore biomechanics with low risk of herniation. Multiple annulus repair strategies were developed using poly(trimethylene carbonate) scaffolds optimized for cell delivery, polyurethane membranes designed to prevent herniation, and fibrin-genipin adhesive tuned to annulus fibrosus shear properties. This three-part study evaluated repair strategies for biomechanical restoration, herniation risk and failure mode in torsion, bending and compression at physiological and hyper-physiological loads using a bovine injury model. Fibrin-genipin hydrogel restored some torsional stiffness, bending ROM and disk height loss, with negligible herniation risk and failure was observed histologically at the fibrin-genipin mid-substance following rigorous loading. Scaffold-based repairs partially restored biomechanics, but had high herniation risk even when stabilized with sutured membranes and failure was observed histologically at the interface between scaffold and fibrin-genipin adhesive. Fibrin-genipin was the simplest annulus fibrosus repair solution evaluated that involved an easily deliverable adhesive that filled irregularly-shaped annular defects and partially restored disk biomechanics with low herniation risk, suggesting further evaluation for disk repair may be warranted. Statement of significance Lower back pain is the leading cause of global disability and commonly caused by defects and failure of intervertebral disk tissues resulting in herniation and compression of adjacent nerves. Annulus fibrosus repair materials and techniques have not been successful due to the challenging mechanical and chemical microenvironment and the needs to restore biomechanical behaviors and promote healing with negligible herniation risk while being delivered during surgical procedures. This work addressed this challenging biomaterial and clinical problem using novel materials including an adhesive hydrogel, a scaffold capable of cell delivery, and a membrane to prevent herniation. Composite repair strategies were evaluated and optimized in quantitative three-part study that rigorously evaluated disk repair and provided a framework for evaluating alternate repair techniques.

SUPERFUND: AN ANALYSIS OF IMPLEMENTATION FAILURE (CERCLA, HEALTH LAW POLICY)

In December, 1980, following increasing congressional and constituent-interest in problems associated with hazardous waste, the Comprehensive Environmental Recovery, Compensation and Liability Act (CERCLA) was passed. During its development, the legislative initiative was seriously compromised which resulted in a less exhaustive approach than was formerly sought. Still, CERCLA (Superfund) which established, among other things, authority to clean up abandoned waste dumps and to respond to emergencies caused by releases of hazardous substances was welcomed by many as an important initial law critical to the cleanup of the nation's hazardous waste. Expectations raised by passage of this bill were tragically unmet. By the end of four years, only six sites had been declared by the EPA as cleaned. Seemingly, even those determinations were liberal; of the six sites, two were identified subsequently as requiring further cleanup.^ This analysis is focused upon the implementation failure of the Superfund. In light of that focus, discussion encompasses development of linkages between flaws in the legislative language and foreclosure of chances for implementation success. Specification of such linkages is achieved through examination of the legislative initiative, identification of its flaws and characterization of attendant deficits in implementation ability. Subsequent analysis is addressed to how such legislative frailities might have been avoided and to attendant regulatory weaknesses which have contributed to implementation failure. Each of these analyses are accomplished through application of an expanded approach to the backward mapping analytic technique as presented by Elmore. Results and recommendations follow.^ Consideration is devoted to a variety of regulatory issues as well as to those pertinent to legislative and implementation analysis. Problems in assessing legal liability associated with hazardous waste management are presented, as is a detailed review of the legislative development of Superfund, and its initial implementation by Gorsuch's EPA. ^

Returns to migration : the role of educational attainment in rural Tanzania

Given the migration premium previously identified in an impact evaluation approach, this paper asks the question of why migration is not more prominent, given such high premium associated with it. Using long-term household panel data drawn from rural Tanzania, Kagera for the period 1991-2004, this study aims to answer this question by exploring the contribution of education in the migration premium. By separating migrants into those that moved out of original villages but remained within Kagera and those who left the region, this study finds that, in consumption, the return on investment in education is higher at both destinations. However, whilst the higher return on education fully explains the gains associated with migration within Kagera, it only partly explains those of external migration. These findings suggest that welfare opportunities are higher at the destination and that an individual's limited investment in education plays a major role in preventing short-distance migration from becoming a significant source of raising welfare, which is not the case for long-distance migration. While education plays a role, it appears that other mechanisms may prohibit rural agents from exploiting the arbitrage opportunity when they migrate to the destination at a great distance from the source.

Failure and impact behavior of facade panels made of glass fiber reinforced cement(GRC)

GRC is a cementitious composite material made up of a cement mortar matrix and chopped glass fibers. Due to its outstanding mechanical properties, GRC has been widely used to produce cladding panels and some civil engineering elements. Impact failure of cladding panels made of GRC may occur during production if some tool falls onto the panel, due to stone or other objects impacting at low velocities or caused by debris projected after a blast. Impact failure of a front panel of a building may have not only an important economic value but also human lives may be at risk if broken pieces of the panel fall from the building to the pavement. Therefore, knowing GRC impact strength is necessary to prevent economic costs and putting human lives at risk. One-stage light gas gun is an impact test machine capable of testing different materials subjected to impact loads. An experimental program was carried out, testing GRC samples of five different formulations, commonly used in building industry. Steel spheres were shot at different velocities on square GRC samples. The residual velocity of the projectiles was obtained both using a high speed camera with multiframe exposure and measuring the projectile’s penetration depth in molding clay blocks. Tests were performed on young and artificially aged GRC samples to compare GRC’s behavior when subjected to high strain rates. Numerical simulations using a hydrocode were made to analyze which parameters are most important during an impact event. GRC impact strength was obtained from test results. Also, GRC’s embrittlement, caused by GRC aging, has no influence on GRC impact behavior due to the small size of the projectile. Also, glass fibers used in GRC production only maintain GRC panels’ integrity but have no influence on GRC’s impact strength. Numerical models have reproduced accurately impact tests.

Migration of keratinocytes through tunnels of digested fibrin

We report here a hitherto undescribed form of cell migration. When a suspension of human keratinocytes is plated on a fibrin matrix, single cells invade the matrix and progress through it as rounded cells by dissolving the fibrin and thereby creating tunnels. These tunnels are cylindrical or helical, the latter being the result of constant change in the path of cellular advance around the helical axis. Helical tunnel formation is strongly promoted by epidermal growth factor. The rate of migration of the cell through the track of a helical tunnel (up to 2.1 mm per day) is about 7-fold greater than through a cylindrical tunnel. Pericellular fibrinolysis leading to tunnel formation depends on the presence of plasminogen in the medium and its conversion to plasmin by a cellular activator. Formation of tunnels requires that plasminogen activator be localized on the advancing surface of the keratinocyte; we propose that the tunnel is cylindrical when the site of release of plasmin is located at a fixed point on the cell surface and helical when the site of release precesses.

Virulence of a Mycobacterium tuberculosis clinical isolate in mice is determined by failure to induce Th1 type immunity and is associated with induction of IFN-α/β

To understand how virulent mycobacteria subvert host immunity and establish disease, we examined the differential response of mice to infection with various human outbreak Mycobacterium tuberculosis clinical isolates. One clinical isolate, HN878, was found to be hypervirulent, as demonstrated by unusually early death of infected immune-competent mice, compared with infection with other clinical isolates. The differential effect on survival required lymphocyte function because severe combined immunodeficiency (SCID) mice infected with HN878 or other clinical isolates all died at the same rate. The hypervirulence of HN878 was associated with failure to induce M. tuberculosis-specific proliferation and IFN-γ production by spleen and lymph node cells from infected mice. In addition, 2- to 4-fold lower levels of tumor necrosis factor-α (TNF-α), IL-6, IL-12, and IFN-γ mRNAs were observed in lungs of HN878-infected mice. IL-10, IL-4, and IL-5 mRNA levels were not significantly elevated in lungs of HN878 infected mice. In contrast, IFN-α mRNA levels were significantly higher in lungs of these mice. To further investigate the role of Type 1 IFNs, mice infected with HN878 were treated intranasally with purified IFN-α/β. The treatment resulted in increased lung bacillary loads and even further reduced survival. These results suggest that the hypervirulence of HN878 may be due to failure of this strain to stimulate Th1 type immunity. In addition, the lack of development of Th1 immunity in response to HN878 appears to be associated with increased induction of Type 1 IFNs.

Combined effects of cellulose nanocrystals and silver nanoparticles on the barrier and migration properties of PLA nano-biocomposites

Poly(lactic acid) (PLA)-based high performance nano-biocomposites were prepared to be used in active food packaging. Pristine (CNC) and surfactant modified cellulose nanocrystals (s-CNC) with silver (Ag) nanoparticles were used as the matrix modifiers. Binary and ternary systems were prepared. Morphological investigations revealed the good distribution of silver nanoparticles in PLA ternary systems. The combination of s-CNC and Ag nanoparticles increased the barrier effect of the produced films while the results of overall migration for the PLA nano-biocomposites revealed that none of the samples exceeded the overall migration limit, since results were well below 60 mg kg−1 of simulant.

Migration and asylum: The movement of people in the Mediterranean Region - Future scenarios and the EU response. Jean Monnet Occasional Paper No. 11/2014

Introduction. In recent years, the global discussion on migration and asylum has evolved from polarization of perspectives and mistrust, to improving partnerships and fostering cooperation between countries and regions. The paradigm has shifted from control and security exclusively to an increased awareness of the ramifications of migration in development and labour markets, the increasing demographic gap1 and the dangers of exclusion faced by migrant workers (regular or irregular). Eastern Europe will suffer the biggest population decline in the coming years, and Nigeria’s population will reach one billion by 2100. In Europe, the work replacement ratio will be two pensioners for one active worker. It has become clear that these facts cannot be ignored and that there is a need for greater convergence of policies (migration/mobility, fundamental rights, and economic growth), with a migrant-centred approach.2. The assumption that Europe will remain a geopolitical and economic hub that attracts immigrants at all skill levels might not hold water in the long run. The evolving demographic and economic changes have made it evident that the competitiveness of the EU (Europe 2020 Strategy) is also at stake, particularly if an adaptable workforce with the necessary skills is not secured in view of shortfalls in skill levels and because of serious labour mismatches. Therefore, it is the right moment to develop more strategic and long-term migration policies that take into account the evolving position of Europe and its neighbours in the world. By the same token, labour market strategies that meet needs and promote integration of regular migrants are still a pending task for the Member States (MS) in terms of the free movement of people, but also in relation with neighbouring and partner countries.

EU labour migration policy by other means? The potential impact of EU economic governance reforms on labour migration policymaking. EPC Policy Brief, 13 February 2015

Over the last 15 years, Member States have been quite reluctant to address labour migration issues at EU level. Will the forthcoming years reverse the tide and lead to the developement of ambitious and common actions in this policy field? There are currently no strong signs of such a move towards a greater management of labour migration policy at EU level. However, Yves Pascouau argues in this FIERI Working paper that the deadlock may be broken with the development of new policy tools taking place in the field of economic governance. More precisely, he underlines that recipes adopted to overcome the so-called ‘euro crisis’ may well have an impact on labour migration issues.As a consequence, this could initiate a coordination process which was not called for by home affairs decision-makers.

The migration of Ukrainians in times of crisis. OSW COMMENTARY Number 187, 2015-10-19

Before the Russian annexation of Crimea and the outbreak of the conflict in eastern Ukraine, the scale of labour outward migration of Ukrainians had been characterised by a slight downward trend. Back in 2014, an increase in the number of Ukrainians who migrated to Russia was observed, although no similar increase was recorded for EU countries (excluding Poland). The year 2015 brought a more rapid surge in the number of Ukrainians migrating to the EU, again mainly to Poland. Due to the lack of current EU-wide data, estimates can be made based only on data compiled by national statistical offices in countries which are the most popular with Ukrainian migrants. In Poland, as of October 2015 Ukrainians held 52,000 valid residence cards. Much greater migration dynamics have been observed in the case of temporary migration – the number of declarations which enable an individual to take up a temporary job in Poland, issued in the first half of 2015, was a staggering 400,000. This means a more than twofold increase – in the whole of 2014 372,000 declarations were issued to Ukrainian citizens. No similar increase has so far been observed in other EU states, including Italy and the Czech Republic, which have always been popular destinations for Ukrainian migration. In late 2014, 233,000 Ukrainian migrants were registered in Italy (in late 2013 the figure was 191,000), whereas in the Czech Republic the number of Ukrainian migrants remains stable – 104,000 in June 2015.

Irregular Migration, Trafficking and Smuggling of Human Beings: Policy Dilemmas in the EU. CEPS Paperback, 22 February 2016

The expert contributors to this edited volume, representing a multidisciplinary selection of academics, examine the treatment of irregular migration, human trafficking and smuggling in EU law and policy. The various chapters explore the policy dilemmas encountered in efforts to criminalise irregular migration and humanitarian assistance to irregular immigrants. The book aims to provide academic input to informed policy-making in the next phase of the European Agenda on Migration. In his Foreword, Matthias Ruete, Director General of DG Home Affairs of the European Commission, writes: “This initiative aims to stimulate evidence-based policy-making and to bring fresh thinking to develop more effective policies. The European Commission welcomes the valuable contribution of this initiative to help close the wide gap in our knowledge about the smuggling of migrants, and especially the functioning of smuggling networks.”