Intrinsic changes in developing retinal neurons result in regenerative failure of their axons.

The failure of mature mammalian central nervous system axons to regenerate after transection is usually attributed to influences of the extraneuronal milieu. Using explant cocultures of retina and midbrain tectum from hamsters, we have found evidence that these influences account for failure of regrowth of only a small minority of retinal axons. For most of the axons, there is a programmed loss of ability to elongate in the central nervous system. We show that there is a precipitous decline in the ability of retinal axons to reinnervate tectal targets when the retina is derived from pups on or after postnatal day 2, even when the target is embryonic. By contrast, embryonic retinal axons can regrow into tectum of any age, overcoming growth-inhibiting influences of glial factors.

Chromosomal insertion of foreign (adenovirus type 12, plasmid, or bacteriophage lambda) DNA is associated with enhanced methylation of cellular DNA segments.

Insertion of foreign DNA into an established mammalian genome can extensively alter the patterns of cellular DNA methylation. Adenovirus type 12 (Ad12)-transformed hamster cells, Ad12-induced hamster tumor cells, or hamster cells carrying integrated DNA of bacteriophage lambda were used as model systems. DNA methylation levels were examined by cleaving cellular DNA with Hpa II, Msp I, or Hha I, followed by Southern blot hybridization with 32P-labeled, randomly selected cellular DNA probes. For several, but not all, cellular DNA segments investigated, extensive increases in DNA methylation were found in comparison with the methylation patterns in BHK21 or primary Syrian hamster cells. In eight different Ad12-induced hamster tumors, moderate increases in DNA methylation were seen. Increased methylation of cellular genes was also documented in two hamster cell lines with integrated Ad12 DNA without the Ad12-transformed phenotype, in one cloned BHK21 cell line with integrated plasmid DNA, and in at least three cloned BHK21 cell lines with integrated lambda DNA. By fluorescent in situ hybridization, the cellular hybridization probes were located to different hamster chromosomes. The endogenous intracisternal A particle genomes showed a striking distribution on many hamster chromosomes, frequently on their short arms. When BHK21 hamster cells were abortively infected with Ad12, increases in cellular DNA methylation were not seen. Thus, Ad12 early gene products were not directly involved in increasing cellular DNA methylation. We attribute the alterations in cellular DNA methylation, at least in part, to the insertion of foreign DNA. Can alterations in the methylation profiles of hamster cellular DNA contribute to the generation of the oncogenic phenotype?

Species specificity in the cell-free conversion of prion protein to protease-resistant forms: a model for the scrapie species barrier.

Scrapie is a transmissible neurodegenerative disease that appears to result from an accumulation in the brain of an abnormal protease-resistant isoform of prion protein (PrP) called PrPsc. Conversion of the normal, protease-sensitive form of PrP (PrPc) to protease-resistant forms like PrPsc has been demonstrated in a cell-free reaction composed largely of hamster PrPc and PrPsc. We now report studies of the species specificity of this cell-free reaction using mouse, hamster, and chimeric PrP molecules. Combinations of hamster PrPc with hamster PrPsc and mouse PrPc with mouse PrPsc resulted in the conversion of PrPc to protease-resistant forms. Protease-resistant PrP species were also generated in the nonhomologous reaction of hamster PrPc with mouse PrPsc, but little conversion was observed in the reciprocal reaction. Glycosylation of the PrPc precursors was not required for species specificity in the conversion reaction. The relative conversion efficiencies correlated with the relative transmissibilities of these strains of scrapie between mice and hamsters. Conversion experiments performed with chimeric mouse/hamster PrPc precursors indicated that differences between PrPc and PrPsc at residues 139, 155, and 170 affected the conversion efficiency and the size of the resultant protease-resistant PrP species. We conclude that there is species specificity in the cell-free interactions that lead to the conversion of PrPc to protease-resistant forms. This specificity may be the molecular basis for the barriers to interspecies transmission of scrapie and other transmissible spongiform encephalopathies in vivo.

Nutraceutical approach to the modulation of cholesterol metabolism: in vitro and in vivo studies

Negli ultimi anni, si sono diffusi nuove strategie per il trattamento delle malattie cardiovascolari, che possano supportare una terapia medica, o in alcuni casi, sostituirla. Infatti, l’abbandono delle terapie è il più importante problema di salute pubblica del mondo occidentale, soprattutto per le malattie croniche. Ciò è dovuto alla complessità delle terapie farmacologiche e ai numerosi e in alcuni casi gravi effetti collaterali dei farmaci somministrati. Di conseguenza, una riduzione di questi effetti migliorerebbe le condizioni di vita del paziente e quindi diminuirebbe il rischio di abbandono della terapia. Per ottenere ciò, è possibile affiancare al trattamento farmacologico una terapia nutraceutica, consistente nella somministrazione di complessi molecolari o microorganismi, provenienti da piante, latte o cibi funzionali. Lo scopo generale di questo studio è indagare le attività ipolipidemizzanti di un composto nutraceutico e di un ceppo batterio specifico nel modello animale che presenta elevati alti livelli plasmatici di colesterolo. Inoltre, sono stati analizzati gli effetti del trattamento nutraceutico sui meccanismi fisiologici che contrastano la creazione della placca aterosclerotica come l’efflusso di colesterolo dalle “foam cells” presenti nell’ateroma, o la riduzione dell’assorbimento intestinale di colesterolo. La presente tesi è divisa in due parti. Nella prima parte, abbiamo analizzato la capacità dei Bifidobacteria di ridurre i livelli di colesterolo nel medium di crescita. Dall’analisi, si è osservato che vari ceppi del genere Bifidobacteria presentano un’ampia capacità di assimilazione del colesterolo all’interno della cellula batterica, in particolare il Bifidobacterium bifidum PRL2010. Le analisi di trascrittomica del Bb PRL2010 incubato in presenza di colesterolo, hanno rivelato un significativo aumento dei livelli di trascrizione di geni codificanti trasportatori e riduttasi, responsabili del meccanismo di accumulo all’interno della cellula batterica e della conversione del colesterolo in coprostanolo. L’attività ipolipidemizzante del Bb PRL2010 è stata poi valutata nel modello murino, mostrando la modificazione del microbiota dei topi trattati dopo somministrazione del batterio in questione. Nella seconda parte del progetto di ricerca, abbiamo indagato sugli effetti di un composto coperto da brevetto, chiamato “Ola”, sull’efflusso di colesterolo di criceti trattati con questo composto nutraceutico. L’efflusso di colesterolo è il primo step del meccanismo fisiologico noto come Trasporto Inverso del Colesterolo, che consente l’eliminazione del colesterolo dalle placche aterosclerotiche, attraverso l’interazione fra le HDL, presenti nella circolazione sanguigna, e specifici trasportatori delle foam cells, come ABCA1/G1 e SR-BI. In seguito, le lipoproteine rilasciano il colesterolo alle cellule epatiche, dove è metabolizzato ed escreto attraverso le feci. Per valutare l’effetto dell’Ola sul profilo lipidico dei criceti, sono state condotte analisi in vitro. I risultati mostrano un aumento dell’efflusso di colesterolo in cellule che esprimono il trasportatore ABCA1, comparato con il gruppo controllo. Questi due studi mostrano come l’approccio nutraceutico può essere un importante modo per contrastare l’aterosclerosi. Come mostrato in letteratura, gli effetti dei composti nutraceutici sull’aterosclerosi e su altre malattie croniche, hanno portato a un ampio uso come supporto alle terapie farmacologiche, ed in alcuni casi hanno rimpiazzato la terapia farmacologica stessa.

The EU and Syria – Time to Play behind Closed Doors. Jean Monnet/Robert Schuman Paper Series Special Issue, September 13, 2013

From the Introduction. Since the – presumed – utilization of chemical weapons against civilians by the Assad regime late August, the members of the Euro-Atlantic community have been building the case for a military intervention, a punishing mission against Bashar al-Assad. Despite evidences that sarin gas was used, the UK and Germany seem to be out of the race – for a similar reason: domestic politics –, leaving the US and France in the starting blocks. French President Hollande has expressed his commitment to go to war. The world is now on hold waiting for the US as President Obama, after asking US Congress to postpone a vote on a military intervention, is working on a possible diplomatic solution with Russian President Putin. Since Kerry’s comments in London earlier this week, Russian President Putin has been seeking for a diplomatic solution that would put all Syrian chemical arsenals under international supervision.

Road to Proscription: The EU and Hezbollah since the Arab Spring. EU Diplomacy Paper 07/2013

The European Union (EU) has traditionally taken a rather nuanced view of the activities of Hezbollah. Despite historic links to violent activity, Europe always remained reluctant to place the Lebanese militant group on its list of terrorist organisations. Internal divergences among member states, as well as the strategic-realist goals of the EU in both Lebanon and the Middle East more generally meant that such a listing never materialised. This remained the case even in the initial turmoil following the Arab uprisings, when Hezbollah’s relatively moderating objectives were viewed as a force for stability. However, the EU shifted policy in July 2013 by listing the military wing of Hezbollah as a terrorist entity. This paper will investigate the reasons behind this decision, as well as the likely implications and effectiveness of the new policy. Two principal catalysts were behind the decision. The first was a Hezbollah-linked bombing in Bulgaria which provided the focal point around which a consensus of the EU member states could emerge in the Council. Secondly, the escalation both of the Syrian conflict and Hezbollah’s role in it provided a more political and strategic impetus for the decision. This paper maintains that although a change in policy was somewhat necessary, it is questionable whether the artificial separation of Hezbollah’s political and military wings and the symbolic proscription of the latter is the most propitious choice to achieve European objectives.

Shaping the emerging consensus on Syria. CEPS Commentaries, 26 February 2014

Notwithstanding the failure on February 15th of the second round of the Geneva II talks on Syria, Luigi Scazzieri and Steven Blockmans take note in this CEPS commentary of several welcome signs that the international community as a whole is starting to move in a more coordinated manner on the Syrian peace process.

Helpless and lonely: Turkey's attitude towards the war in Syria. OSW Commentary No. 136, 09.05.2014

The conflict in Syria, which has lasted since 2011, has become the most significant test of the efficiency of Turkey’s foreign policy and the biggest challenge to Turkey’s security in recent decades. The lack of a clear prospect of an end to the war does not allow us to come to a final conclusion regarding the Syrian civil war’s importance for Turkey. However, it can be said today that with the exception of the initial phase of the conflict, Ankara’s influence over the course of events in Syria has been limited, and the war itself is evolving in a direction that is unfavourable for Turkey: the hostile regime of Bashar al-Assad is still in power, the opposition has proved to be an unreliable or even a dangerous ally, and in northern Syria militant jihadist groups and Kurds are gaining importance. It is also quite unlikely that the West will take any greater responsibility for stabilising the situation in the region. In response to such an unfortunate situation, and out of fear of risking deeper involvement in the conflict, during the past year Turkey’s policy towards Syria has been restrained, reactive and focused mainly on defending Turkey’s territory. However, this policy offers no security guarantees and does not prevent the country’s regional position from weakening, especially in the context of the reinforcement of the jihadist militants and the Kurdish autonomy in northern Syria. The arguments for Turkey continuing its defensive policy are strong: the country fears the possible results of an open confrontation with Assad’s forces; most probably it could not count on support for such actions from within its own society or its Western allies. It also does not have enough acceptance within the anti-Assad opposition circles. On the other hand, though, the risk of uncontrolled development of events is still present; the risk of confrontations with armed jihadist militants is growing; and the potential operation of Turkish forces, either against the jihadists or against Assad’s army, could be considered as a method of diverting attention from the political problems with which the AKP government has been struggling at home.

Syria: A Roadmap for a Sustainable Political Settlement. Egmont Security Policy Brief No. 52, January 2014

On the eve of the Geneva II conference and amid continued fighting on the ground, this short paper seeks to draw up a roadmap, indicating the different stages and steps on the way to a sustainable political settlement of the conflict in Syria. A longer term perspective is put forward, adopting a broad-based and inclusive approach, focused on a Syrian-led transition process under international supervision with the assistance of key third countries, thus preparing the way for a multi-party democratic post-Baath future.

China on Russia’s intervention in Syria. OSW Commentary Number 193|19.01.2016

China has reacted positively to Russia’s military intervention in Syria. The Chinese government perceives it as an element of the global fight against terrorism, and has emphasised the fact that Russia was acting in response to a request by the Syrian government. At the same time, Beijing has argued that the Syrian conflict cannot be resolved by military means and that a political compromise is necessary.

EU-Turkey plan for handling refugees is fraught with legal and procedural challenges. CEPS Commentary, 10 March 2016

EU-Turkey relations in the scope of the ongoing refugee crisis were at the heart of the European Council meeting of 7 March 2016. Among the set of initiatives proposed, the following two have attracted the most attention: First, for every Syrian readmitted by Turkey from the Greek islands, another Syrian from Turkey would be resettled in an EU member state. This has come to be known as the ‘one for one’ resettlement approach. Second, all new irregular migrants and asylum-seekers crossing from Turkey to the Greek islands would be returned to Turkey without offering any guarantee of protection.

Clinical anatomy of the European hamster Cricetus cricetus, L. /

Mode of access: Internet.

Chronique de Michel le Syrien : patriarche jacobite d'Antioche (1166-1199) /

Syriac text at the end of each vol. making tome IV.