Magistri Petri de Vineis epistolae : initium desideratur.

Tellerianus

Magistri Petri de Vineis epistolae.

Colbertinus

Role of prohormone convertases in pro-neuropeptide Y processing: coexpression and in vitro kinetic investigations.

Proneuropeptide Y (ProNPY) undergoes cleavage at a single dibasic site Lys38-Arg39 resulting in the formation of 1-39 amino acid NPY which is further processed successively by carboxypeptidase-like and peptidylglycine alpha-amidating monooxygenase enzymes. To investigate whether prohormone convertases are involved in ProNPY processing, a vaccinia virus derived expression system was used to coexpress recombinant ProNPY with each of the prohormone convertases PC1/3, PC2, furin, and PACE4 in Neuro2A and NIH 3T3 cell lines as regulated neuroendocrine and constitutive prototype cell lines, respectively. The analysis of processed products shows that only PC1/3 generates NPY in NIH 3T3 cells while both PC1/3 and PC2 are able to generate NPY in Neuro2A cells. The convertases furin and PACE4 are unable to process ProNPY in either cell line. Moreover, comparative in vitro cleavage of recombinant NPY precursor by the enzymes PC1/3, PC2 and furin shows that only PC1/3 and PC2 are involved in specific cleavage of the dibasic site. Kinetic studies demonstrate that PC1/3 cleaves ProNPY more efficiently than PC2. The main difference between the cleavage efficiency is observed in the Vmax values whereas no major difference is observed in Km values. In addition the cleavage by PC1/3 and PC2 of two peptides reproducing the dibasic cleavage site with different amino acid sequence lengths namely (20-49)-ProNPY and (28-43)-ProNPY was studied. These shortened ProNPY substrates, when recognized by the enzymes, are more efficiently cleaved than ProNPY itself. The shortest peptide is not cleaved by PC2 while it is by PC1/3. On the basis of these observations it is proposed, first, that the constitutive secreted NPY does not result from the cleavage carried out by ubiquitously expressed enzymes furin and PACE4; second, that PC1/3 and PC2 are not equipotent in the cleavage of ProNPY; and third, substrate peptide length might discriminate PC1/3 and PC2 processing activity.

Aplicação dos conceitos de modelagem e de redes de Petri na análise do processo produtivo da indústria sucroalcooleira

A modelagem, como meio de análise de processos do agronegócio, bem como de cadeias produtivas, atende à demanda por métodos apropriados. O presente trabalho objetivou avaliar a aderência dos conceitos de modelagem e de rede de Petri aplicados ao complexo agroindustrial da cana-de-açúcar. Utilizou-se uma empresa real para a aquisição das informações. Os modelos das cadeias de atividades foram validados com o uso da rede de Petri, por meio de um método de análise em que são simulados todos os caminhos possíveis e os estados que o sistema modelado pode atingir. O estudo resultou em 14 conjuntos de etapas de produção, englobando todas as operações unitárias das cadeias produtivas do açúcar e do álcool, desde o plantio da cana até o armazenamento do açúcar e do álcool.

fragmenta varia simul compacta hoc ordine : — 1.° Anonymi libellus de nativitatibus. — 2.° Excerptum è libro Petri de Alliaco, Cameracensis Episcopi, de imagine mundi. — 3.° Fragmentum registri cujusdam Procuratoris nomine Guaillardi. — 4.° Fragmentum Ciceronis de optimo genere Oratorum. — 5.° Fragmentum libri cui titulus : manipulus florum, è variis sanctorum Patrum locis collectus à Magistro Thoma de Hybernia, quondam Socio de Sorbona. — 6.° Catalogus operum quorum authores feruntur Dionysius, Augustinus, Ambrosius, Hieronymus, Gregorius, Bernardus, Hilarius, Isidorus, Chrysostomus, Rabanus, Prosper, Damascenus, Anselmus, Richardus et Hugo de Sancto Victore, Alanus, Cicero, Boëtius et Seneca : finis desideratur. — Hujusce codicis pars duodecimo, pars decimo quarto saeculo videtur exarata.

nuper comparatus

1.° Venerabilis Bedae tractatus de orthographia ; nono saeculo exaratus. — 2.° Wandelberti, Prumiensis Monachi, martyrologium, carmine heroïco ; uncialibus litteris nono saeculo exaratum. — 3.° Prisciani epitome : authore Gosberto ; undecimo saeculo exarata. — 4.° Anonymi opusculum de lectione sacrarum Scripturarum ; duodecimo saeculo exaratum. — 5.° Mag. Petri Hispani secreta contra aegritudines oculorum ; decimo quarto saeculo exarata. — 6.° Miracula sanctorum Martyrum Urgeliensium, Mauri Episcopi, Sergii et Pantaleonis ; italico idiomate, anno 1475. exarata.

Puteanus

Differential effects of pro- and anti-inflammatory cytokines alone or in combinations on the metabolic profile of astrocytes.

We have previously reported that the pro-inflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) induce profound modifications of the metabolic profile of astrocytes. The present study was undertaken to further characterize the effects of cytokines in astrocytes and to determine whether similar effects could also be observed in neurons. To do so, selected pro-inflammatory (IL-6 and interferon-γ, in addition to the above-mentioned TNFα and IL-1β) and anti-inflammatory cytokines (IL-4, IL-10, transforming growth factor-β1 and interferon-β) were applied to primary neuronal and astrocytic cultures, and key metabolic parameters were assessed. As a general pattern, we observed that pro-inflammatory cytokines increased glucose utilization in astrocytes while the anti-inflammatory cytokines IL-4 and IL-10 decreased astrocytic glucose utilization. In contrast, no significant change could be observed in neurons. When pairs of pro-inflammatory cytokines were co-applied in astrocytes, several additive or synergistic modifications could be observed. In contrast, IL-10 partially attenuated the effects of pro-inflammatory cytokines. Finally, the modifications of the astrocytic metabolism induced by TNFα + IL-1β and interferon-γ modulated neuronal susceptibility to an excitotoxic insult in neuron-astrocyte co-cultures. Together, these results suggest that pro- and anti-inflammatory cytokines differentially affect the metabolic profile of astrocytes, and that these changes have functional consequences for surrounding neurons.

C/EBP homologous protein contributes to cytokine-induced pro-inflammatory responses and apoptosis in β-cells.

Induction of the C/EBP homologous protein (CHOP) is considered a key event for endoplasmic reticulum (ER) stress-mediated apoptosis. Type 1 diabetes (T1D) is characterized by an autoimmune destruction of the pancreatic β-cells. Pro-inflammatory cytokines are early mediators of β-cell death in T1D. Cytokines induce ER stress and CHOP overexpression in β-cells, but the role for CHOP overexpression in cytokine-induced β-cell apoptosis remains controversial. We presently observed that CHOP knockdown (KD) prevents cytokine-mediated degradation of the anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia sequence 1 (Mcl-1), thereby decreasing the cleavage of executioner caspases 9 and 3, and apoptosis. Nuclear factor-κB (NF-κB) is a crucial transcription factor regulating β-cell apoptosis and inflammation. CHOP KD resulted in reduced cytokine-induced NF-κB activity and expression of key NF-κB target genes involved in apoptosis and inflammation, including iNOS, FAS, IRF-7, IL-15, CCL5 and CXCL10. This was due to decreased IκB degradation and p65 translocation to the nucleus. The present data suggest that CHOP has a dual role in promoting β-cell death: (1) CHOP directly contributes to cytokine-induced β-cell apoptosis by promoting cytokine-induced mitochondrial pathways of apoptosis; and (2) by supporting the NF-κB activation and subsequent cytokine/chemokine expression, CHOP may contribute to apoptosis and the chemo attraction of mononuclear cells to the islets during insulitis.