Some unpleasant arithmetics of regional unemployment in the EU. Are there any lessons for EMU?

Several studies have documented the weak response of regional wage differentials and labour mobility following region-specific (“idiosyncraticâ€) shocks in the average of the EU countries. This has been often taken as evidence of the rigidity of labour markets in European countries, as opposed to the flexibility of the USA. However, as such shocks by definition average to zero, one cannot make an explicit link between the (lack of) adjustment at regional level and aggregate unemployment. Moreover, the emphasis on the reaction to short-run idiosyncratic shocks is unlikely to explain the permanent differentials across regions, which characterise the regional distribution of unemployment in many EU countries. This paper tries to provide a better understanding of the regional distribution of unemployment and why region-specific shocks can matter for aggregate unemployment. It does so by explicitly considering the possibility of asymmetric reactions, so that unemployment rises more in poorer areas suffering an adverse shock than it declines in richer regions experiencing a favourable shock. The reason behind such asymmetries is the presence of a wage floor in the poorer regions resulting from policy centralisation, as for instance in the case of a national unemployment compensation system, which provides benefits that are uniform across regions. If such a mechanism is at work, aggregate unemployment tends to be “inflated†by region-specific shocks that are inequality- increasing. After presenting an illustrative model of the mechanism, the paper proposes a simple measure of the resulting “excess unemploymentâ€, based on the difference between the average (national) unemployment rate and the unemployment rate of the median region. It also examines the relationship between regional asymmetries in unemployment and the dispersion of productivity across regions, taken as proxy of the inequality-increasing shocks. The evidence, while not entirely conclusive, justifies two tentative policy conclusions, which are particularly relevant in the context of EMU: a) to avoid centralisation of labour market institutions at the EU level that may end up inflating aggregate unemployment; b) to effectively deploy regional policies to combat inequality- increasing shocks.regional policy, unemployment, disparities

Some Unpleasant Arithmetics of Regional Unemployment in the EU. Are there any lessons for EMU? European Commission Forward Studies Unit, 1999

Several studies have documented the weak response of regional wage differentials and labour mobility following region-specific ("idiosyncratic ") shocks in the average of the EU countries. This has been often taken as evidence of the rigidity of labour markets in European countries, as opposed to the flexibility of the USA. However, as such shocks by definition average to zero, one cannot make an explicit link between the (lack of) adjustment at regional level and aggregate unemployment. Moreover, the emphasis on the reaction to short-run idiosyncratic shocks is unlikely to explain the permanent differentials across regions, which characterise the regional distribution of unemployment in many EU countries. This paper tries to provide a better understanding of the regional distribution of unemployment and why region-specific shocks can matter for aggregate unemployment. It does so by explicitly considering the possibility of asymmetric reactions, so that unemployment rises more in poorer areas suffering an adverse shock than it declines in richer regions experiencing a favourable shock. The reason behind such asymmetries is the presence of a wage floor in the poorer regions resulting from policy centralisation, as for instance in the case of a national unemployment compensation system, which provides benefits that are uniform across regions. If such a mechanism is at work, aggregate unemployment tends to be "inflated" by region-specific shocks that are inequality-increasing. After presenting an illustrative model of the mechanism, the paper proposes a simple measure of the resulting "excess unemployment ", based on the difference between the average (national) unemployment rate and the unemployment rate of the median region. It also examines the relationship between regional asymmetries in unemployment and the dispersion of productivity across regions, taken as proxy of the inequality-increasing shocks. The evidence, while not entirely conclusive, justifies two tentative policy conclusions, which are particularly relevant in the context of EMU: a) to avoid centralisation of labour market institutions at the EU level that may end up inflating aggregate unemployment; b) to effectively deploy regional policies to combat inequality- increasing shocks

MECHANISMS OF THE IL-22 ACTIVITY REGULATION IN HUMAN PRIMARY KERATINOCYTES

L\u2019Interleuchina (IL)-22, in gran parte prodotta dalle cellule T helper (Th) di tipo Th17 e Th22, \ue8 considerata una citochina chiave nella patogenesi della psoriasi poich\ue9, responsabile della marcata iperplasia e dell\u2019alterato differenziamento tipici della cute lesionale. In particolare, l\u2019IL-22 induce la proliferazione dei cheratinociti, inibisce il loro differenziamento terminale e stimola la produzione di peptidi antimicrobici e chemochine. Signal transducer and activator of transcription (STAT) 3 \ue8 il mediatore principale del segnale indotto dall\u2019IL-22 e la sua completa attivazione richiede la fosforilazione dei residui di tirosina (Tyr) 705 e serina (Ser) 727. La fosforilazione di STAT3 in Tyr705 \ue8 inoltre proporzionale all\u2019acetilazione del residuo di lisina (Lys) 685. I livelli di acetilazione di STAT3 sono finemente regolati da processi di acetilazione e deacetilazione controllati, rispettivamente, dagli enzimi acetilasi p300 ed istone deacetilasi (HDAC). Dato che STAT3 appare altamente attivato nell\u2019epidermide psoriasica, lo scopo del lavoro \ue8 di identificare molecole target capaci di contrastare l\u2019attivazione di STAT3 mediata dall\u2019IL-22 in cheratinociti umani. Per tale ragione \ue8 stato studiato l\u2019effetto di Sirtuina (SIRT) 1, il rappresentante pi\uf9 caratterizzato della famiglia degli enzimi HDAC di classe III, nel controllo dell\u2019attivazione di STAT3 e degli effetti biologici indotti dall\u2019IL-22 in cheratinociti umani. E\u2019 stato, infatti, precedentemente dimostrato che SIRT1 \ue8 in grado di deacetilare STAT3 nella Lys685 e, di conseguenza, di inibirne la fosforilazione in Tyr705 in cellule epatocitarie. E\u2019 stato inoltre riportato che la sirtuina induce il differenziamento e blocca la proliferazione di cheratinociti umani. L\u2019attivit\ue0 di ricerca ha permesso di dimostrare che la proteina SIRT1 \ue8 costitutivamente espressa in cellule primarie umane cheratinocitarie, dove essa contribuisce efficientemente alla deacetilazione di STAT3. Durante i processi d\u2019infiammazione cutanea, caratterizzati dalla presenza concomitante dell\u2019Interferone (IFN)-gamma e dell\u2019IL-22, l\u2019IFN-gamma riduce l\u2019espressione di SIRT1, consentendo cos\uec all\u2019IL-22 di attivare STAT3. La riduzione dei livelli di SIRT1 determina, infatti, l\u2019accumulo di STAT3 acetilato in Lys685 e favorisce cos\uec la fosforilazione di STAT3 in Tyr705 e le risposte dei cheratinociti all\u2019IL-22. SIRT1 modula negativamente il Proliferating cellular nuclear antigen (PCNA), la ciclina D1 ed il phospho-Retinoblastoma (pRB), molecole indotte dall\u2019IL-22 attraverso STAT3 e che giocano un ruolo fondamentale nella proliferazione cellulare. Inoltre, la sirtuina aumentando i livelli di cheratina (KRT)1, contrasta gli effetti anti-differenziativi esercitati dall\u2019IL-22 in cheratinociti. Nelle lesioni psoriasiche, l\u2019inibizione di SIRT1 potrebbe essere responsabile della forte attivazione di STAT3 e, quindi, delle risposte esagerate dei cheratinociti all\u2019IL-22 e ad altre citochine pro-infiammatorie che segnalano attraverso STAT3 (IL-6 e oncostatina M). Un\u2019altra molecola potenzialmente capace di controllare le cascate molecolari e gli effetti biologici indotti dall\u2019IL-22 in cheratinociti umani \ue8 il Suppressor of cytokine signalling (SOCS) 3. In cellule epatocitarie, infatti, l\u2019aumento dell\u2019espressione di SOCS3 riduce l\u2019attivazione di STAT3 mediata dall\u2019IL-22. Tale studio ha permesso di dimostrare che SOCS3 \ue8 l\u2019unico membro della famiglia dei SOCS ad essere indotto dall\u2019IL-22 in cheratinociti umani. Anche se i livelli di SOCS1 non sono modulati dall\u2019IL-22, la sua aumentata espressione in cheratinociti trasfettati stabilmente, inibisce le fosforilazioni di STAT3 in Tyr705 e Ser727 mediate dall\u2019IL-22 in modo simile ai cloni SOCS3. Parallelamente, la trasfezione transiente dei cheratinociti con plasmidi per SOCS1 e SOCS3 riduce l\u2019attivit\ue0 trascrizionale di STAT3 dipendente dall\u2019IL-22. Viceversa, SOCS2 non \ue8 coinvolto nella regolazione dell\u2019attivazione di STAT3. Conseguentemente all\u2019inattivazione di STAT3, cheratinociti che esprimono alti livelli di SOCS1 e SOCS3 proliferano di meno dopo trattamento con IL-22 rispetto alle cellule MOCK. Al contrario, l\u2019effetto mitogenico dell\u2019IL-22 \ue8 potenziato in cheratinociti che non esprimono il SOCS3. Inoltre, SOCS3 \ue8 in grado di ridurre l\u2019espressione di geni pro-infiammatori e di opporsi al de-differenziamento cheratinocitario dipendente dall\u2019IL-22. Gli effetti inibitori di SOCS3 sull\u2019attivazione di STAT3 dipendente dall\u2019IL-22 sono esercitati dalla sua regione KIR (Kinase Inhibitory Region). L\u2019uso di attivatori di SIRT1 o di molecole che mimano la regione KIR del SOCS3, in grado quindi di ridurre la fosforilazione di STAT3 in Tyr705 in cheratinociti epidermici, potrebbe essere utile per la cura della psoriasi, ma anche di altre patologie cutanee caratterizzate da un\u2019aberrante attivazione di STAT3.Interleukin (IL)-22 is a cytokine mainly released by T helper (Th) 17 and Th22 lymphocytes having a pathogenetic role in psoriasis. In this skin disorder, IL-22 is responsible for the altered proliferative and differentiative processes observed in the epidermis, and induces inflammatory molecules in keratinocytes. Signal transducer and activator of transcription (STAT) 3 is the principal mediator of IL-22 signaling and its complete activation requires the phosphorylation in tyrosine (Tyr) 705 and in serine (Ser) 727 residues. Moreover, STAT3 phosphorylation in Tyr705 is proportional to the acetylation in lysine (Lys) 685 residue. STAT3 acetylation is tightly regulated by the acetylation and deacetylation processes, which are controlled by p300 acetylase and histone deacetylase enzymes (HDAC), respectively. Due to the aberrant STAT3 activation in psoriatic epidermis, the aim of this study was to identify the target molecules able to inhibit the IL-22-triggered STAT3 phosphorylation and down-stream effects in human keratinocytes. For this purpose the role of Sirtuin (SIRT) 1, the most characterized Class III HDAC family member, has been studied in the control of IL-22-dependent signaling in keratinocytes. Indeed, it has previously demonstrated that SIRT1 is able to deacetylate STAT3 in Lys685 residue and, consequently, to inhibit STAT3 phosphorylation in Tyr705 in hepatocyte cells. Moreover, it was reported that the sirtuin is able to induce the differentiation and inhibit the proliferation of human keratinocytes. The research activity allowed us to demonstrate that SIRT1 is constitutively expressed by keratinocytes and that it efficiently contributes to STAT3 deacetylation in these cells. During inflammatory skin processes characterized by a concomitant presence of Interferon (IFN)-gamma and IL-22, IFN-gamma strongly down-regulates the keratinocyte expression of SIRT1 and IL-22 activates STAT3. In fact, SIRT1 decrement determines an accumulation of STAT3 acetylated in Lys685, thus favoring STAT3 phosphorylation in Tyr705 and keratinocyte responses to IL-22. SIRT1 negatively modulates the Proliferating cellular nuclear antigen (PCNA), cyclin D1 and phospho-Retinoblastoma (pRB), that is STAT3-dependent and IL-22-induced molecules and play a fundamental role in cellular proliferation. In addition, the sirtuin, by enhancing the level of keratin (KRT) 1, counter-acts the IL-22-triggered de-differentiate effect in keratinocytes. In psoriatic lesions, SIRT1 inhibition could be responsible for the strong activation of STAT3 and, thus, for the exaggerated responses of epidermal keratinocytes to IL-22 and other pro-inflammatory cytokines signaling through STAT3 (i.e., IL-6 and oncostatin M). Suppressor of cytokine signalling (SOCS) 3 represents another possible candidate able to control the IL-22-derived molecular cascades and the biological effects in keratinocytes. Indeed, in hepatocyte cells, the enhanced expression of SOCS3 level reduces the IL-22-dependent STAT3 activation. In this study it has been demonstrated that SOCS3 is the only SOCS family member induced by IL-22 in human keratinocytes. Interestingly, even though SOCS1 was not up-regulated by IL-22, its over-expression in stably trasfected keratinocytes potently inhibited the IL-22-induced Tyr705 and Ser727 phosphorylations of STAT3, likewise to what observed in SOCS3 clones. Consistently, transient transfection of keratinocytes with SOCS1 or SOCS3 plasmids markedly reduced the IL-22-induced STAT3 transcriptional activity. In contrast, stable or transient SOCS2 over-expression in keratinocytes had no effects on STAT3 activation by IL-22. As consequence of STAT3 inactivation, the IL-22-induced proliferation was impaired in SOCS3 and SOCS1 clones compared to mock-trasfected keratinocytes. Vice versa, the mitogenic effect exerted by IL-22 on keratinocytes depleted of SOCS3 was more pronounced. Moreover, SOCS3 reduces the expression of IL-22-dependent pro-inflammatory genes and opposes to the de-differentiative effect of the cytokine in keratinocytes. The SOCS3 inhibitory effect on the IL-22-induced STAT3 activation is executed by SOCS3 KIR (kinase inhibitory region) domain. Therefore, the use of SIRT1 activators or molecules able to mimic SOCS3-KIR region, able to reduce the STAT3 Tyr705 phosphorylation in epidermal keratinocytes, could be therapeutically useful for the treatment of psoriasis as well as other skin diseases characterized by an aberrant STAT3 activation

Element abundances of unevolved stars in the open cluster M 67

We determined the metallicity ([Fe/H]), together with O, Na, Mg, Al, Si, Ca, Ti, Cr and Ni abundances for a sample of 10 unevolved or slightly evolved stars belonging to the open cluster M 67. We find an average metallicity [Fe/H]=0.03 +/- 0.01, in very good agreement with previous determinations. All the [X/Fe] abundance ratios are very close to solar. The star-to-star scatter in [Fe/H] and [X/Fe] ratios for all elements, including oxygen, is lower than 0.05 dex, implying that the large dispersion in lithium reported in previous studies is not due to differences in these element abundances. We also find that, when using a homogeneous scale, the abundance pattern of unevolved stars in our sample is very similar to that of evolved stars, suggesting that, at least in this cluster, RGB and clump stars have not undergone any chemical processing. Finally, our results show that M 67 has a chemical composition that is representative of the solar neighborhood.Comment: 18 pages, 5 figures, accepted for publication in A&

Open clusters as key tracers of Galactic chemical evolution. III. Element abundances in Berkeley 20, Berkeley 29, Collinder 261, and Melotte 66

Galactic open clusters are since long recognized as one of the best tools for investigating the radial distribution of iron and other metals. We employed FLAMES at VLT to collect UVES spectra of bright giant stars in a large sample of open clusters, spanning a wide range of Galactocentric distances, ages, and metallicities. We present here the results for four clusters: Berkeley 20 and Berkeley 29, the two most distant clusters in the sample; Collinder 261, the oldest and the one with the minimum Galactocentric distance; Melotte 66. Equivalent width analysis was carried out using the spectral code MOOG and Kurucz model atmospheres to derive abundances of Fe, Al, Mg, Si, Ca, Ti, Cr, Ni, Ba; non-LTE Na abundances were derived by direct line-profile fitting. We obtain subsolar metallicities for the two anticenter clusters Be 20 ([Fe/H]=-0.30, rms=0.02) and Be 29 ([Fe/H]=-0.31, rms=0.03), and for Mel 66 ([Fe/H]=-0.33, rms=0.03), located in the third Galactic quadrant, while Cr 261, located toward the Galactic center, has higher metallicity ([Fe/H]=+0.13, rms=0.05 dex). The alpha-elements Si, Ca and Ti, and the Fe-peak elements Cr and Ni are in general close to solar; the s-process element Ba is enhanced. Non-LTE computations of Na abundances indicate solar scaled values, suggesting that the enhancement in Na previously determined in giants in open clusters could be due to neglected non-LTE effects. Our results support the presence of a steep negative slope of the Fe radial gradient up to about 10-11 kpc from the Galactic center, while in the outer disk the [Fe/H] distribution seems flat. All the elemental ratios measured are in very good agreement with those found for disk stars of similar metallicity and no trend with Galactocentric distance seems to be present.Comment: Accepted for publication on A&

Lithium evolution in intermediate age and old open clusters: NGC 752 revisited

We present new high resolution spectroscopic observations of the intermediate age (~2 Gyr) open cluster NGC 752. We investigate the Li vs. Teff distribution and we obtain a new accurate determination of the cluster metallicity. We compare the results for NGC 752 with other intermediate age and old clusters spanning the age range from the Hyades (~0.6 Gyr) to NGC 188 (~6-8 Gyr). We find that NGC 752 has a solar iron content ([Fe/H]=+0.01+/-0.04), at variance with early reports of sub-solar metallicity. We find that NGC 752 is only slightly more Li depleted than the younger Hyades and has a Li pattern almost identical to that observed in the ~2 Gyr old IC 4651 and NGC 3680. As for the latter clusters, we find that NGC 752 is characterized by a tight Li vs. Teff distribution for solar-type stars, with no evidence for a Li spread as large as the one observed in the solar age solar metallicity M 67. We discuss these results in the framework of mixing mechanisms and Li depletion on the main sequence (MS). We conclude that the development of a large scatter in Li abundances in old open clusters might be an exception rather than the rule (additional observations of old clusters are required), and that metallicity variations of the order of ~0.2 dex do not affect Li depletion after the age of the Hyades.Comment: A&A accepted, 10 pages, 5 ps figure

The sensitivity to -carotene growth-inhibitory and proapoptotic effects is regulated by caveolin-1 expression in human colon and prostate cancer cells

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Inhibition of enterovirus a71 by a novel 2-phenyl-benzimidazole derivative

Enterovirus A71 (EV-A71) infection has emerged as a significant public health concern at the global level. Epidemic events of EV-A71 have been reported worldwide, and this succession of outbreaks has heightened concern that EV-A71 may become a public health threat. In recent years, widespread A71 enterovirus also occurred in European countries. EV-A71 infection causes hand-foot-mouth disease (HFMD), herpangina, and fever. However, it can sometimes induce a variety of neurological complications, including encephalitis, aseptic meningitis, pulmonary edema, and acute flaccid paralysis. We identified new benzimidazole derivatives and described theirin vitrocytotoxicity and broad-spectrum anti-enterovirus activity. Among them, derivative 2b resulted in interesting activity against EV-A71, and therefore it was selected for further investigations. Compound 2b proved to be able to protect cell monolayers from EV-A71-induced cytopathogenicity, with an EC50 of 3 µM. Moreover, Vero-76 cells resulted in being significantly protected from necrosis and apoptosis when treated with 2b at 20 and 80 µM. Compound 2b reduced viral adsorption to Vero-76 cells, and when evaluated in a time-of-addition assay, the derivative had the highest effect when added during the infection period. Moreover, derivative 2b reduced viral penetration into host cells. Besides, 2b did not affect intestinal monolayers permeability, showing no toxic effects. A detailed insight into the efficacy of compound 2b against EV-A71 showed a dose-dependent reduction in the viral titer, also at low concentrations. Mechanism of action investigations suggested that our derivative can inhibit viral endocytosis by reducing viral attachment to and penetration into host cells. Pharmacokinetic and toxicity predictions validated compound 2b as a good candidate for furtherin vivoassays

A New Fast Silicon Photomultiplier Photometer

The Crab pulsar is one of the most intensively studied X-ray/optical objects, but up to now only a small number of research groups have based their photometers on SiPM technology. In early February 2011, the Crab pulsar signal was observed with our photometer prototype. With low-cost instrumentation, the results of the analysis are very significant: the processed data acquired on the Crab pulsar gave both a good light curve and a good power spectrum, in comparison with the data analysis results of other more expensive photometer instrumentation

Nature-based molecules combined with rivastigmine: A symbiotic approach for the synthesis of new agents against Alzheimer's disease

Starting from nature as original source, new potential agents with pleiotropic activities have been synthesized and evaluated as neuroprotective agents. In this work, novel nature-based hybrids, combining antioxidant motifs with rivastigmine, have been designed and synthesized. The biological results revealed that the new compounds inhibit both AChE and BuChE. In particular, lipoic acid hybrids LA1, LA2, LA3 resulted to be the most potent inhibitors of BuChE showing IC50 values ranging from 340 to 378 nM. Analogously, all the compounds were able to inhibit the self β-amyloid1-42 aggregation. The gallic acid hybrid GA2 as well as the 2-chromonecarboxylic acid hybrids CA1 and CA2 prevented the self-mediated Aβ aggregation with percentages of inhibition ranging from 53% to 59%. Finally, some of them also show potent neuroprotective effects against glutamate-induced cell death and low toxicity in HT22 cells