Role of ABC-Transporters in Epileptogenesis and Pharmacoresistant Epilepsy

According to a recently published article by our group [The complexity of roles of P-glycoprotein in refractory epilepsy: pharmacoresistance, epileptogenesis, SUDEP and relapsing marker after surgical treatment ADMET & DMPK 3(2) (2015) 110-121], we have written a chapter related to these concepts

Un nuevo desafío de trabajo: la discapacidad psicosocial

Institucionalmente, la UNAJ se encuentra dividida para su funcionamiento en el Centro de Política Educativa y en el Centro de Política y Territorio. Del primero depende la Unidad de Asuntos estudiantiles que lleva como objetivo central el acompañamiento, contención y orientación de los estudiantes; con diversos recursos que contribuyan a alentar las posibilidades individuales, más allá de las diferencias sociales. De esta Unidad de asuntos estudiantiles (dividida a su vez en tres departamentos: Alumnos, Bienestar Estudiantil y Orientación Educativa), y atravesada transversalmente, depende un área de discapacidad que se aboca al tema específico. Existe además una comisión institucional que depende de la Universidad. Al momento de la inscripción, se realiza un relevamiento donde los alumnos informan en caso de tener una discapacidad lo que nos permite realizar el primer contacto con ellos y conocer sus dificultades lo que nos ordena en las adaptaciones futuras a que realizar.Secretaría de Asuntos Académico

Suwerenność Ukrainy w latach 1917-1921 w kontekście sytuacji międzynarodowej

Sovereigny of Ukraine in 1917-1921 in the context of international situationThis article discusses Ukrainian independence war 1917-1921, Polish-Ukrainian relations in this time and Polish-Russian war as a background of building the Ukrainian state. The article relates to international public law. The author explains how and if the West Ukrainian People’s Republic reached sovereignty and independence. Suwerenność Ukrainy w latach 1917-1921 w kontekście sytuacji międzynarodowejNiniejszy artykuł podejmuje zagadnienie ukraińskiej walki o niepodległość w latach 1917-1921, polsko ukraińskich relacji w tym czasie oraz polsko rosyjskiej wojny jako tła dla budowy ukraińskiej państwowości. Artykuł dotyczy prawa międzynarodowego publicznego. Autor wyjaśnia, jak i czy Zachodnio-Ukraińska Republika Ludowa uzyskała suwerenność i niepodległość

A new topology of the HK97-like fold revealed in Bordetella bacteriophage by cryoEM at 3.5 A resolution.

Bacteriophage BPP-1 infects and kills Bordetella species that cause whooping cough. Its diversity-generating retroelement (DGR) provides a naturally occurring phage-display system, but engineering efforts are hampered without atomic structures. Here, we report a cryo electron microscopy structure of the BPP-1 head at 3.5 Å resolution. Our atomic model shows two of the three protein folds representing major viral lineages: jellyroll for its cement protein (CP) and HK97-like ('Johnson') for its major capsid protein (MCP). Strikingly, the fold topology of MCP is permuted non-circularly from the Johnson fold topology previously seen in viral and cellular proteins. We illustrate that the new topology is likely the only feasible alternative of the old topology. β-sheet augmentation and electrostatic interactions contribute to the formation of non-covalent chainmail in BPP-1, unlike covalent inter-protein linkages of the HK97 chainmail. Despite these complex interactions, the termini of both CP and MCP are ideally positioned for DGR-based phage-display engineering. DOI: http://dx.doi.org/10.7554/eLife.01299.001

The complexity of roles of P-glycoprotein in refractory epilepsy: Pharmacoresistance, epileptogenesis, SUDEP and relapsing marker after surgical treatment

As described initially from clinical and experimental studies, P-glycoprotein (P-gp) plays a central role in the pharmacoresistance of epilepsy, acting by efflux of AEDs mainly at blood brain barrier (BBB) level. However, repetitive seizures can produce both brain and heart P-gp overexpression. Because P-gp activity induces membrane depolarization, its neuronal expression could be acting in the intrinsic mechanism of epileptogenesis, and its heart expression, can be a high risk factor of death, after severe-continuo convulsive stresses as in fatal status epilepticus or in SUDEP. Additionally, because P-gp is also a stem cell marker, we suggests that its constitutive overexpression in dysplastic neurons from brain epileptogenic areas observed in patients with refractory epilepsies, should be addressed as a risk factor of seizures relapse after surgical treatment. Here we discuss these concepts, based on our own clinical and experimental experiences, and reviewing the current literature on these subjects

Discovery and Characterization of Iron Sulfide and Polyphosphate Bodies Coexisting in Archaeoglobus fulgidus

Inorganic storage granules have long been recognized in bacterial and eukaryotic cells but were only recently identified in archaeal cells. Here, we report the cellular organization and chemical compositions of storage granules in the Euryarchaeon, Archaeoglobus fulgidus strain VC16, a hyperthermophilic, anaerobic, and sulfate-reducing microorganism. Dense granules were apparent in A. fulgidus cells imaged by cryo electron microscopy (cryoEM) but not so by negative stain electron microscopy. Cryo electron tomography (cryoET) revealed that each cell contains one to several dense granules located near the cell membrane. Energy dispersive X-ray (EDX) spectroscopy and scanning transmission electron microscopy (STEM) show that, surprisingly, each cell contains not just one but often two types of granules with different elemental compositions. One type, named iron sulfide body (ISB), is composed mainly of the elements iron and sulfur plus copper; and the other one, called polyphosphate body (PPB), is composed of phosphorus and oxygen plus magnesium, calcium, and aluminum. PPBs are likely used for energy storage and/or metal sequestration/detoxification. ISBs could result from the reduction of sulfate to sulfide via anaerobic energy harvesting pathways and may be associated with energy and/or metal storage or detoxification. The exceptional ability of these archaeal cells to sequester different elements may have novel bioengineering applications

Target Site Recognition by a Diversity-Generating Retroelement

Diversity-generating retroelements (DGRs) are in vivo sequence diversification machines that are widely distributed in bacterial, phage, and plasmid genomes. They function to introduce vast amounts of targeted diversity into protein-encoding DNA sequences via mutagenic homing. Adenine residues are converted to random nucleotides in a retrotransposition process from a donor template repeat (TR) to a recipient variable repeat (VR). Using the Bordetella bacteriophage BPP-1 element as a prototype, we have characterized requirements for DGR target site function. Although sequences upstream of VR are dispensable, a 24 bp sequence immediately downstream of VR, which contains short inverted repeats, is required for efficient retrohoming. The inverted repeats form a hairpin or cruciform structure and mutational analysis demonstrated that, while the structure of the stem is important, its sequence can vary. In contrast, the loop has a sequence-dependent function. Structure-specific nuclease digestion confirmed the existence of a DNA hairpin/cruciform, and marker coconversion assays demonstrated that it influences the efficiency, but not the site of cDNA integration. Comparisons with other phage DGRs suggested that similar structures are a conserved feature of target sequences. Using a kanamycin resistance determinant as a reporter, we found that transplantation of the IMH and hairpin/cruciform-forming region was sufficient to target the DGR diversification machinery to a heterologous gene. In addition to furthering our understanding of DGR retrohoming, our results suggest that DGRs may provide unique tools for directed protein evolution via in vivo DNA diversification

Georg Philipp Telemann (1681-1767) : his relationship to Carl Heinrich Graun and the Berlin circle

The history of music in Germany in the first half of the eighteenth century is best understood within the context of the social, cultural and intellectual history of the German people during this period.The intellectual coming of age of the middle classes during the first decades of the century occurred as a result of growing confidence in the establishment of a national spoken and literary language. In a gradual progression of liberation and purification, the German language broke away from the dominant voices and cultures of its closest neighbours, leading to the crystalization of a clearly indigenous culture later in the century. Few other art forms followed this development more closely and indeed benefitted more from it than music.At the beginning of the century German music, and German culture in general, was still very much subjected to vassalage to foreign powers. Only in its church music, however, could a small but distinctly native voice be detected. With the growth of literary confidence, in particular in devotional poetry, music received considerable creative impetus. The figure who most closely followed these linguistic and literary developments is Georg Philipp Telemann (1681-1767).The object of this thesis is to place in its proper context the highly influential musical personality of Telemann, in particular through a study of his relationship to a younger generation of composers and theorists: the 'Berlin Circle'. In a detailed study of the composer's relationship to Carl Heinrich Graun(1703 or 1704-1759), the court Capellmeister at Berlin, the association between words and music, between musical and literary languages, will be discussed and, furthermore, they will be seen to be interdependen

“The fundamental, perpetual and irrevocable law of the Monarchy”. The Albertine Statute and its significance for the development of the constitutional system of Italy

The Albertine Statute was the constitution of the Kingdom of Sardinia enacted in March 1848. After unification under Piedmontese leadership, the Albertine Statute became the constitution of the Kingdom of Italy. The article contains a history of codification, its modifications especially under the Fascist regime and finally abrogation when Italy became a republic in 1948. Furthermore, the text shows a special role of the constitutional principles for the history of Italy. There is also presented the difference between flexible act of 1848 and rigid constitution of 1947