Distribution of events of positive selection and population differentiation in a metabolic pathway: the case of asparagine N-glycosylation

Background: Asparagine N-Glycosylation is one of the most important forms of protein post-translational modification in eukaryotes. This metabolic pathway can be subdivided into two parts: an upstream sub-pathway required for achieving proper folding for most of the proteins synthesized in the secretory pathway, and a downstream sub-pathway required to give variability to trans-membrane proteins, and involved in adaptation to the environment andinnate immunity. Here we analyze the nucleotide variability of the genes of this pathway in human populations, identifying which genes show greater population differentiation and which genes show signatures of recent positive selection. We also compare how these signals are distributed between the upstream and the downstream parts of the pathway, with the aim of exploring how forces of population differentiation and positive selection vary among genes involved in the same metabolic pathway but subject to different functional constraints. Results:Our results show that genes in the downstream part of the pathway are more likely to show a signature of population differentiation, while events of positive selection are equally distributed among the two parts of the pathway. Moreover, events of positive selection arefrequent on genes that are known to be at bifurcation points, and that are identified as beingin key position by a network-level analysis such as MGAT3 and GCS1.Conclusions: These findings indicate that the upstream part of the Asparagine N-Glycosylation pathway has lower diversity among populations, while the downstream part is freer to tolerate diversity among populations. Moreover, the distribution of signatures of population differentiation and positive selection can change between parts of a pathway, especially between parts that are exposed to different functional constraints. Our results support the hypothesis that genes involved in constitutive processes can be expected to show lower population differentiation, while genes involved in traits related to the environment should show higher variability. Taken together, this work broadens our knowledge on how events of population differentiation and of positive selection are distributed among different parts of a metabolic pathway.

The infected aorta.

BACKGROUND: Despite the improvements achieved in antibiotic therapy, severe aortic infection resulting in mycotic aneurysms is still a highly lethal disease and surgical management remains a challenging task. PATIENTS AND METHODS: A total of 43 patients with severe aortic infections were analyzed and separated in four groups: (1) Infections of the aortic root Ventriculo-aortic disconnection due to deep aortic infection (6 patients). Two patients were operated using homo-composit grafts. Of the 6 patients total, one died early and two died late during a mean follow-up of 6 years. The two patients with homografts are still alive. (2) Infections of the ascending aorta and the aortic arch. In situ repair for mycotic aneurysmal lesions of the ascending aorta was performed in 6 patients using synthetic graft material in 4/6, biological material in 1/6 and direct suture in 1/6. Two patients had to be reoperated; one of them died early. There was no recurrent infection during a mean follow-up of 6 years. (3) Infections of the descending thoracic and thoraco-abdominal aorta in-situ repair for mycotic aneurysmal lesions of the descending and thoraco-abdominal aorta was performed in 12 patients using homografts in five. Two patients died early and two other patients died late during a mean follow-up of 6 years. (4) Infections of the infrarenal abdominal aorta. In this series of 19 patients with mycotic infrarenal aortic aneurysms, in situ reconstruction was performed in 12 (5/12 with homografts) and extra-anatomic reconstruction (axillo-femoral bypass) was performed in 7. Hospital mortality was 5/19 patients and another 5/19 patients died during a mean follow-up of 6 years. One of the early deaths was due to aortic stump rupture. Two patients with axillo-femoral reconstructions were later converted to descending-thoracic-aortic-bifemoral bypasses. Five thromboses of axillo-femoral bypasses were observed in three of the seven patients with extra-anatomic repairs. RESULTS: Infections of the aortic root, the ascending aorta and the aortic arch are approached with total cardio-pulmonary bypass, using cardioplegic myocardial protection and deep hypothermia with circulatory arrest if necessary. Proximal unloading and distal support using partial cardiopulmonary bypass is preferred for repair of infected descending and thoracoabdominal aortic lesions, whereas no such adjuncts are required for repair of infected infrarenal aortic lesions. CONCLUSIONS: The anatomical location of the aortic infection and the availability of homologous graft material are the main factors determining the surgical strategy.

Conhecimento, atitude e prática do uso de preservativos por presidiárias: prevenção das DST/HIV no cenário prisional

Objetivou-se avaliar o conhecimento, a atitude e a prática de presidiárias quanto ao uso do preservativo masculino e feminino como medida preventiva às DST/HIV. Pesquisa quantitativa e avaliativa do tipo Conhecimento, Atitude e Prática (CAP), envolvendo 155 presidiárias. A coleta de dados realizou-se de janeiro a março de 2010 na penitenciária feminina do estado do Ceará. Embora tivessem ouvido falar e/ou soubessem as finalidades do uso, apenas 35 mulheres (22,6%) tinham conhecimento adequado sobre o preservativo masculino e 11 (7,1%) a respeito do feminino. As atitudes foram menos favoráveis quanto ao uso no sexo oral. A prática adequada apresentou pouca representatividade, em especial, do feminino. A homo/bissexualidade, as questões de gênero, a falta de conhecimento e o difícil acesso aos preservativos representaram obstáculos a serem considerados na promoção da saúde sexual do grupo estudado.

HIV infection and suicide risk: an epidemiological inquiry among male homosexuals in Switzerland.

Conflicting results have been published about suicidality among HIV+ subjects; part of the alleged increased risk may be linked to premorbid risk factors such as drug addiction and homosexuality. In order to cope with these confounding factors, we assessed the degree of suicidal ideation in a sample of Swiss male homo- and bisexuals, comparing HIV- and HIV+ subjects. A total of 164 subjects returned a self-administered, home-completed questionnaire, which had been circulated among homosexuals in the French speaking part of Switzerland. Suicidal ideation was assessed through Pöldinger's scale. Serostatus was known for 149 subjects, among whom 65 were HIV+. A high rate of suicide attempts was found among homosexuals, both HIV- and HIV+. Scores on Pöldinger's scale are significantly, though moderately, higher among HIV+ subjects, and this finding seems to be a direct consequence of HIV infection.

Proteinaceous infectious behavior in non-pathogenic proteins is controlled by molecular chaperones.

External stresses or mutations may cause labile proteins to lose their distinct native conformations and seek alternatively stable aggregated forms. Molecular chaperones that specifically act on protein aggregates were used here as a tool to address the biochemical nature of stable homo- and hetero-aggregates from non-pathogenic proteins formed by heat-stress. Confirmed by sedimentation and activity measurements, chaperones demonstrated that a single polypeptide chain can form different species of aggregates, depending on the denaturing conditions. Indicative of a cascade reaction, sub-stoichiometric amounts of one fast-aggregating protein strongly accelerated the conversion of another soluble, slow-aggregating protein into insoluble, chaperone-resistant aggregates. Chaperones strongly inhibited seed-induced protein aggregation, suggesting that they can prevent and cure proteinaceous infectious behavior in homo- and hetero-aggregates from common and disease-associated proteins in the cell.

Genetic team composition and level of selection in the evolution of cooperation

In cooperative multiagent systems, agents interac to solve tasks. Global dynamics of multiagent teams result from local agent interactions, and are complex and difficult to predict. Evolutionary computation has proven a promising approach to the design of such teams. The majority of current studies use teams composed of agents with identical control rules ("geneti- cally homogeneous teams") and select behavior at the team level ("team-level selection"). Here we extend current approaches to include four combinations of genetic team composition and level of selection. We compare the performance of genetically homo- geneous teams evolved with individual-level selection, genetically homogeneous teams evolved with team-level selection, genetically heterogeneous teams evolved with individual-level selection, and genetically heterogeneous teams evolved with team-level selection. We use a simulated foraging task to show that the optimal combination depends on the amount of cooperation required by the task. Accordingly, we distinguish between three types of cooperative tasks and suggest guidelines for the optimal choice of genetic team composition and level of selection

Engineering polyhydroxyalkanoate content and monomer composition in the oleaginous yeast Yarrowia lipolytica by modifying the ß-oxidation multifunctional protein.

Recombinant strains of the oleaginous yeast Yarrowia lipolytica expressing the PHA synthase gene (PhaC) from Pseudomonas aeruginosa in the peroxisome were found able to produce polyhydroxyalkanoates (PHA). PHA production yield, but not the monomer composition, was dependent on POX genotype (POX genes encoding acyl-CoA oxidases) (Haddouche et al. FEMS Yeast Res 10:917-927, 2010). In this study of variants of the Y. lipolytica β-oxidation multifunctional enzyme, with deletions or inactivations of the R-3-hydroxyacyl-CoA dehydrogenase domain, we were able to produce hetero-polymers (functional MFE enzyme) or homo-polymers (with no 3-hydroxyacyl-CoA dehydrogenase activity) of PHA consisting principally of 3-hydroxyacid monomers (>80%) of the same length as the external fatty acid used for growth. The redirection of fatty acid flux towards β-oxidation, by deletion of the neutral lipid synthesis pathway (mutant strain Q4 devoid of the acyltransferases encoded by the LRO1, DGA1, DGA2 and ARE1 genes), in combination with variant expressing only the enoyl-CoA hydratase 2 domain, led to a significant increase in PHA levels, to 7.3% of cell dry weight. Finally, the presence of shorter monomers (up to 20% of the monomers) in a mutant strain lacking the peroxisomal 3-hydroxyacyl-CoA dehydrogenase domain provided evidence for the occurrence of partial mitochondrial β-oxidation in Y. lipolytica.

Trois sortes d'altruisme et leur rapport à la morale

Nombreux sont les philosophes et psychologues qui voient en l'altruisme une des plus grandes vertus humaines. Certains en font même une composante nécessaire à la morale. Sachant cela, il est assez piquant de constater que les biologistes trouvent de l'altruisme dans le monde animal et que, plus récemment, il est également devenu un objet de recherche en économie. L'hétérogénéité des disciplines qui traitent de l'altruisme en ont fait une notion extrêmement complexe et difficile à saisir. L'objectif de cet article est d'explorer les différents sens donnés à cette notion et de comprendre le rôle qu'elle joue dans les débats propres aux sciences qui l'utilisent. Il s'agira également de réfléchir aux liens qu'entretiennent les diverses formes d'altruisme, entre elles d'une part, et avec la morale d'autre part.La première partie de l'article est consacrée à trois types de débats faisant usage de la notiond'altruisme. Nous verrons que chacun d'eux prend place dans le cadre d'une science ou d'un groupe de sciences différentes et que la signification de l'altruisme s'y adapte. Le premier débat a pour cadre la biologie et utilise la notion d'« altruisme biologique » ; il s'agit d'expliquer comment un comportement désavantageux du point de vue de la survie et de la reproduction a pu être sélectionné au fil de l'évolution. Le second débat a lieu au sein des sciences sociales (plus particulièrement en économie et anthropologie évolutionniste) et se centre sur la notion d'« altruisme comportemental » ; il s'agit de montrer que des personnes ordinaires ne se comportement souvent pas en maximisateurs rationnels de leur gains propres, comme le prédirait la théorie économique néoclassique. Le troisième débat repose sur la notion d'« altruisme psychologique » et engage particulièrement les philosophes, les psychologues mais également certains économistes et neuroscientifiques ; il s'agit de déterminer si les êtres humains sont capables d'agir en fonction de motivations dirigées vers le bien-être d'autrui. La seconde partie de l'article a pour objectif de mettre en relation ces trois formes d'altruisme ainsi que leur rapport avec la morale.

Pi*-pi* bonding interactions generated by halogen oxidation of zirconium(IV) redox-active ligand complexes.

The new complex, [Zr(pda)2]n (1, pda2- = N,N'-bis(neo-pentyl)-ortho-phenylenediamide, n = 1 or 2), prepared by the reaction of 2 equiv of pdaLi2 with ZrCl4, reacts rapidly with halogen oxidants to afford the new product ZrX2(disq)2 (3, X = Cl, Br, I; disq- = N,N'-bis(neo-pentyl)-ortho-diiminosemiquinonate) in which each redox-active ligand has been oxidized by one electron. The oxidation products 3a-c have been structurally characterized and display an unusual parallel stacked arrangement of the disq- ligands in the solid state, with a separation of approximately 3 A. Density functional calculations show a bonding-type interaction between the SOMOs of the disq- ligands to form a unique HOMO while the antibonding linear combination forms a unique LUMO. This orbital configuration leads to a closed-shell-singlet ground-state electron configuration (S = 0). Temperature-dependent magnetism measurements indicate a low-lying triplet excited state at approximately 750 cm-1. In solution, 3a-c show strong disq--based absorption bands that are invariant across the halide series. Taken together these spectroscopic measurements provide experimental values for the one- and two-electron energies that characterize the pi-stacked bonding interaction between the two disq- ligands.

Fission yeast rad51 and dmc1, two efficient DNA recombinases forming helical nucleoprotein filaments.

Homologous recombination is important for the repair of double-strand breaks during meiosis. Eukaryotic cells require two homologs of Escherichia coli RecA protein, Rad51 and Dmc1, for meiotic recombination. To date, it is not clear, at the biochemical level, why two homologs of RecA are necessary during meiosis. To gain insight into this, we purified Schizosaccharomyces pombe Rad51 and Dmc1 to homogeneity. Purified Rad51 and Dmc1 form homo-oligomers, bind single-stranded DNA preferentially, and exhibit DNA-stimulated ATPase activity. Both Rad51 and Dmc1 promote the renaturation of complementary single-stranded DNA. Importantly, Rad51 and Dmc1 proteins catalyze ATP-dependent strand exchange reactions with homologous duplex DNA. Electron microscopy reveals that both S. pombe Rad51 and Dmc1 form nucleoprotein filaments. Rad51 formed helical nucleoprotein filaments on single-stranded DNA, whereas Dmc1 was found in two forms, as helical filaments and also as stacked rings. These results demonstrate that Rad51 and Dmc1 are both efficient recombinases in lower eukaryotes and reveal closer functional and structural similarities between the meiotic recombinase Dmc1 and Rad51. The DNA strand exchange activity of both Rad51 and Dmc1 is most likely critical for proper meiotic DNA double-strand break repair in lower eukaryotes.

Similarities and differences of polyadenylation signals in human and fly.

BACKGROUND: Cleavage of messenger RNA (mRNA) precursors is an essential step in mRNA maturation. The signal recognized by the cleavage enzyme complex has been characterized as an A rich region upstream of the cleavage site containing a motif with consensus AAUAAA, followed by a U or UG rich region downstream of the cleavage site. RESULTS: We studied these signals using exhaustive databases of cleavage sites obtained from aligning raw expressed sequence tags (EST) sequences to genomic sequences in Homo sapiens and Drosophila melanogaster. These data show that the polyadenylation signal is highly conserved in human and fly. In addition, de novo motif searches generated a refined description of the U-rich downstream sequence (DSE) element, which shows more divergence between the two species. These refined motifs are applied, within a Hidden Markov Model (HMM) framework, to predict mRNA cleavage sites. CONCLUSION: We demonstrate that the DSE is a specific motif in both human and Drosophila. These findings shed light on the sequence correlates of a highly conserved biological process, and improve in silico prediction of 3' mRNA cleavage and polyadenylation sites.

Mutations in the DNA-binding domain of NR2E3 affect in vivo dimerization and interaction with CRX.

BACKGROUND: NR2E3 (PNR) is an orphan nuclear receptor essential for proper photoreceptor determination and differentiation. In humans, mutations in NR2E3 have been associated with the recessively inherited enhanced short wavelength sensitive (S-) cone syndrome (ESCS) and, more recently, with autosomal dominant retinitis pigmentosa (adRP). NR2E3 acts as a suppressor of the cone generation program in late mitotic retinal progenitor cells. In adult rod photoreceptors, NR2E3 represses cone-specific gene expression and acts in concert with the transcription factors CRX and NRL to activate rod-specific genes. NR2E3 and CRX have been shown to physically interact in vitro through their respective DNA-binding domains (DBD). The DBD also contributes to homo- and heterodimerization of nuclear receptors. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed NR2E3 homodimerization and NR2E3/CRX complex formation in an in vivo situation by Bioluminescence Resonance Energy Transfer (BRET(2)). NR2E3 wild-type protein formed homodimers in transiently transfected HEK293T cells. NR2E3 homodimerization was impaired in presence of disease-causing mutations in the DBD, except for the p.R76Q and p.R104W mutant proteins. Strikingly, the adRP-linked p.G56R mutant protein interacted with CRX with a similar efficiency to that of NR2E3 wild-type and p.R311Q proteins. In contrast, all other NR2E3 DBD-mutant proteins did not interact with CRX. The p.G56R mutant protein was also more effective in abolishing the potentiation of rhodospin gene transactivation by the NR2E3 wild-type protein. In addition, the p.G56R mutant enhanced the transrepression of the M- and S-opsin promoter, while all other NR2E3 DBD-mutants did not. CONCLUSIONS/SIGNIFICANCE: These results suggest different disease mechanisms in adRP- and ESCS-patients carrying NR2E3 mutations. Titration of CRX by the p.G56R mutant protein acting as a repressor in trans may account for the severe clinical phenotype in adRP patients.

Rapid and selective surveillance of Arabidopsis thaliana genome annotations with Centrifuge.

Centrifuge is a user-friendly system to simultaneously access Arabidopsis gene annotations and intra- and inter-organism sequence comparison data. The tool allows rapid retrieval of user-selected data for each annotated Arabidopsis gene providing, in any combination, data on the following features: predicted protein properties such as mass, pI, cellular location and transmembrane domains; SWISS-PROT annotations; Interpro domains; Gene Ontology records; verified transcription; BLAST matches to the proteomes of A.thaliana, Oryza sativa (rice), Caenorhabditis elegans, Drosophila melanogaster and Homo sapiens. The tool lends itself particularly well to the rapid analysis of contigs or of tens or hundreds of genes identified by high-throughput gene expression experiments. In these cases, a summary table of principal predicted protein features for all genes is given followed by more detailed reports for each individual gene. Centrifuge can also be used for single gene analysis or in a word search mode. AVAILABILITY: http://centrifuge.unil.ch/ CONTACT: edward.farmer@unil.ch.

Brevia de fide catholica (f. 1-52v). Acta paparum (f. 53-139v).

F. 1-52v. Recueil de textes de piété, en italien sauf le premier. « Confiteor Deo omnipotenti Patri et Filio et Spiritui sancto (...) martiribus tuis Grisanto et Darie, confessoribus tuis Prospero et Venerio atque beato Francisco... - ... eternam amen » (1). — [Rubrique :] « Quisti son li X comandam. de la leze ». « Primo non adorare altro che uno solo dio et per questo commandamento se veta le idole... - ... non e » (1v-3v). — [Rubrique :] « Quisti son li XII articoli de la fede ». « Credo in Dio padre omnipotente creatore del celo et de la terra. 1. S. Petro. Et in Yesu... - ... alli boni. 11. S. Thadeo. 12. S. Mathia » (3v). — [Rubrique :] « Quisti son li septe peccati mortali. Lo primo Elatio ». « Superbia cio e reputare de havere bene per propria virtu et non da Dio... - ... tante fiade pecca mortalmente » (3v-10). — [Rubriques :] « Quisti son li dexe comandamenti soto brevita » (...) « Quisti sono li septe sacramenti » (...) « Que son le VII opere de la misericordia temporale » (...) « Queste son le spirituale » (...) « Questi son li setti peccati mortali » (...) « Circha de sopra in li dexe comandamenti. Quista sun li V sentimenti de lo corpo » (...) « Quisti sono li septi doni del Spirito sancto che sono contra li VII peccati mortali » (...) « Queste sono le III virtu theologie » (...) « Quatuor sono le cardinale » (...) « Queste son le conditione de la confessione » (...) « Quisti son li casi de la papa sive papali » (...) « Casus exclusi » (...) « Quisti sun li cassi de lo episcopo sive episcopali » (...) (10-12). — [NICOLAUS DE AUXIMO, O. F. M. (Nicolò da Osimo), Compendio de salute], cf. Umberto Picciafuoco, Fr. Nicolò da Osimo: vita, opera, spiritualità, 1980 ; « Per dare breve introductione delle cose necessarie ad la salute ad ciaschuno simplice lo quale desidera de salvarse, me sono studiato de redirre le dicte cose sotto breve compendio, retracto de uno libro dicto Quadriga spirituale... - ... molto cose secondo li doctori » (12-52v).F. 53-139v. Actes pontificaux et varia. EUGENIUS IV papa, Bulla [ad Jacobum de Primadiciis de Bononia, O. F. M. (Giacomo Primadizzi) ?], de communione pascali, [07/07/1446], cf. Archivum Franciscanum Historicum, 21, 1928, p. 270 n. 1, 282-283 « Eugenius papa IIIIus. Dilecte fili salutem et apostolicam benedictionem. Fidedigna relatione percepimus in civitate Licii non parvam... - ... VIII kal. julii 1446, po. no. anno XVI° » (éd. ibid., p. 282-283, avec une date corrigée) (53-54). — [PAULUS II papa], Bulla, 14/04/1469 « I ». [Rubrique :] « Bulla que quotannis in cena Domini publicari per summum pontificem consuevit ». « Dilecti filii salutem et apostolicam benedictionem. Consueverunt predecessores nostri romani pontifices annis singulis in die cene Domini sedentes...-... die XIIII° aprilis 1469 p. n. anno quinto. L. Dathus » (55-56). — PAULUS II papa, Bulla, 30/03/1469 « 2. Bulla. Paulus (...). Consueverunt sancte memorie romani pontifices predecessoris [sic] nostri ad retinendam puritatem... - ... tertio kal. aprilis, p. n. anno quinto. De curia. Signata A. Ingherannus, L. Dathus » (56v-64). — PAULUS II papa, Bulla, 06/06/1469 « 3. Paulus (...). Decet romanum pontificem sic in suis fore gratiis liberalem quod in ecclesiarum... - ... octavo id. junii, p. n. anno quinto. De curia, B. Lunensis » (64v-67). — PAULUS II papa, Bulla, 02/07/1469 « Paulus papa II. 4. [Rubrique :] Presidenti monasteriorum Sancte Justine de Padua ». « Dilecte fili salutem et apostolicam benedictionem. Bullam presentibus alligatam constitutionis et decreti nostri circa annexa et juncta beneficia... - ... die IIa julii M° CCCC LXVIIII p. n. anno quinto. L. Dathus » (67v-68). — PAULUS II papa, Bulla, de casibus reservatis, [03/03/1470] cf. Cesare Censi, Manoscritti francescani della Biblioteca Nazionale di Napoli, 2 vol., 1971 (Spicilegium bonaventurianum, VII-VIII), t. I, p. 222, qui renvoie au ms. Napoli, Biblioteca Nazionale, V H 33 (n° 125 a de la liste de Cenci) ; incomplet de la fin « 5. [Rubrique :] Bulla pro casibus reservatis ». « Paulus (...). Etsi dominici gregis saluti semper intenti singulis cum humilitate poscentibus ea benigne... - ... omnipotentis Dei et beatorum » [Petri et Pauli...] (68v-70). — PAULUS II papa, Bulla, 23/11/1464 « 6. [Rubrique :] Contra symoniacos ». « Paulus (...). Cum detestabile scelus simoniace pravitates tam divinorum quam sacrorum canonum... - ... nono kal. decembres, p. n. anno primo » (70v-72). — PAULUS II papa, Bulla, [01/03/1468], cf. C. Censi, op. cit., ms. Napoli, Bibl. Naz., I H 43 et V H 33 (n° 50 ap et 125 d) « 7. [Rubrique :] Bulla prohibens ne bona ecclesiarum et Dei alienari possint ultra triennium ». « Paulus (...). Ambitiose perversorum cupiditati illorum precipue qui divinis et humanis legibus affectata... - ... M° CCCC LXVII kalendis martii p. n. anno quarto » (72v-74). — PAULUS II papa, Bulla, 31/01/1468 « 8. [Rubrique :] De celebratione dierum festorum in terris ecclesie ». « Paulus (...). Perniciosa consuetudo aut verius corruptela que in gravem divine majestatis ac sanctorum... - ... M° CCCC LXVII pridie kal. febr. anno p. n. IIII° » (74v-76v). — Exemplum de Raymundo cardinale nepote Honorii pape et beata Maria virgine et Annunciatione ejus. [Rubrique :] « Pro jejunio domine nostre ». « Honorius summus pontifex habuit ex sorore nepotem Raymundum nomine tituli sanctorum Johannis et Pauli cardinalem libidini ita deditum... - ... regna migravit » (77-79). — PAULUS II papa, Bulla, de jubilaeo, 19/04/1470 « 10 ( ?). [Rubrique :] De publicatione anni jubilei redacti ad M CCCC LXXV ». « Paulus (...). Ineffabilis providentia summi patris qui pro redemptione humani generis ejusque reconcilianda natura... - ... tertiodecimo kalendas maii p. n. anno sexto » (79-85). — PAULUS II papa, Breve, ad episcopum Cumanensem, 22/04/1471 « Breve pontificis ad episcopum Cumanensem. Paulus II. Venerabilis frater (...). Expositum fuit nobis nonnullos istius civitatis Cumane ejusque diocesis existere qui contra libertatem... - ... XXII aprilis 1471 p. n. anno septimo » (86-86v). — PAULUS II papa, Breve, ad episcopum Cumanensem, 07/06/1471 « Suprascriptum breve non habuit locum sed reformatum fuit in formam infrascriptam : Paulus II. Ven. (...). Expositum nobis fuit pro parte dilecti filii nobilis viri Galeaz Marie ducis Mediolani nonnullos istius civitatis Cumane... - ... 7° junii 1471 p. n. anno 7° » (86v-87v). — PAULUS II papa, Breve, [ad Galeazzum Mariam Sforza ducem Mediolanensem], 31/05/1471 « Dilecte fili (...). Diligenter exposuit nobis dilectus filius Augustinus de Rubeis eques et doctor Parmensis consiliarius et orator ad nos tuus... - ... ultimo maii 1471, p. n. anno septimo » (87v-88v). — NICODEMUS [TRANCHEDINI], Littera ad Galeazzum Mariam Sforza ducem Mediolanensem, 13/05/1471, cf. Paola Sverzelatti, « Per la biografia di Nicodemo Tranchedini [1413-1481] di Pontremoli, ambasciatore sforzesco », Aevum, 1998, LXII, 485-557 [4° Z 4794] « Littere Nicodemi ad illustrissimum d. ducem. El papa me ha dicto questa sera che heri sera deputo et immediate hebbe ad se li inferri... - ... Johachinus et Franciscus de Padua advocati consistoriales ». « Suprascriptis videnda commissa fuit bulla pontificis » (89-89v). — AUGUSTINUS DE RUBEIS (Agostino de’Rossi) et NICODEMUS [TRANCHEDINI], Littera ad Galeazzum Mariam Sforza ducem Mediolanensem, 25/05/1471 « Littere d. Augustini et Nicodemi ad principem. Illustrissimo (...). Questi xi sonno mo stati piu volte insieme et col papa anchora et heri se fece el consistorio... - ... XXV maii 1471. Augustinus et Nicodemus » (89v-91). — Iidem ad eumdem, 27/05/1471 « Eorundem. Illustrissimo (...). Credace la vestra signoria per cosa se havesse ad agitar. qua postquam questo nostro sancto patre fu facto papa... - ... XXVII maii 1471 » (91-94v). — [EUGENIUS IV papa, Gratiae concessae Francisco de Platea de Bononia, O. F. M., 01/1440], cf. Cesare Censi, Manoscritti francescani della Biblioteca Nazionale di Napoli, 2 vol., 1971 (Spicilegium bonaventurianum, VII-VIII), t. II, p. 1060, qui renvoie à deux exemplaires du texte, mss. Napoli, Biblioteca Nazionale, cod. VII G 50 et VII G 66 [n° 371 et 383 de la liste de Cenci] « Copia. Ego frater Franciscus de Bononia frater venerabilis viri fratris Jacobi de Primidiciis de Bononia Florentiam accessi... - ... M CCCC XL die III et die decima januarii » (95-98v). — PAULUS II papa, Breve ( ?), ad Julium Cesari de Varano domicellum, incomplet de la fin « Paulus episcopus (...) dilecto filio nobili viro Julio Cesari de Varano domicello civitatis nostre Camerini et pro nobis (...) gubernatori (...). Inter cura multiplices quibus assidue permimur illa precipue sollicitat mentem nostram... - ... merito commendari » (100-106v). — NICOLAUS V papa, Breve ( ?), ad Franciscum Sforza, 24/07/1447 « Nicolaus (...) dilecto filio nobili viro Francisco Sfortie vicecomiti, comiti et marchioni (...). Sedes apostolica pia mater recurrentibus ad eam cum humilitate filiis post excessum libenter... - ... nono kal. augusti, p. n. anno primo. Pe. de Noxeto » (107-111v). — FRANCISCUS PHILELPHUS ( ?), [De Sacerdotio Christi (extractum et translatum e graeco Souda), versio italica], cf. Giovanni Mercati, Ultimi contributi alla storia degli Umanistici, 1939, I, p. 74-76 (4° Z 1722 (90)) « Tractatello traducto per messere Francescho Philelpho singularissimo poetha de greco in latino per luy trovato presso autentici et antiqui autori, reducto in volgare ad contemplatione d’alcuni devoti cortesani del illustrissimo signiore duca di Milano, ad confirmatione de la fede nostra et confusione de Judei. Regnando Justiniano imperatore clementissimo fo uno homo principe de Judei chiamato Theodosio... - ... teneva occulto » (112-118v). — « Electi beneficii et superni doni data ad quella anima che oldira la sancta messa integramente monifestati per li sancti doctori... - ... ligno de la vita » (118v-119). — MARTINUS V papa, Bulla, de excommunicatione hereticorum, [28/03/1426 ?], incomplète de la fin ; cf. C. Censi, op. cit., I, p. 501-502 (n° 304 f) « 1. Excommunicationes plures contente in processu qui fit annuatim in curia in cena Domini. Martinus (...). Excommunicamus et anathematizamus ex parte omnipotentis Dei Patris et Filii et Spiritus sancti auctoritate Petri... - ... incursurum. Datum Rome etc » (120-122v). — « Item excommunicamus et anathematizamus omnes illos qui per se vel per alium vel alios directe vel indirecte... - ... cautione prestitis » (122v-123v). — PAULUS II papa, Bulla, 11/04/1471 « 2. Paulus (...). Consueverunt sancte memorie romani pontifices predecessores nostri ad retinendam puritatem... - ... tertio idus aprilis, p. n. anno VII° » (124-130v). — SIXTUS IV papa, Bulla, de excommunicatione hereticorum, 26/03/1472 « 2. Sixtus (...). Excommunicamus et anathematizamus ex parte omnipotentis Dei Patris et Filii et Spiritus sancti auctoritate quoque beatorum... - ... septimo kal. aprilis etc. anno primo » (131-134v). — SIXTUS IV papa, Breve ( ?), ad Ferdinandum I regem Sicilie, 01/03/1472 « 4. Sixtus (...) carissimo in Christo filio Ferdinando regi Sicilie illustri (...). Dum eximie fidelitatis devotionis atque prudentie tue ceterasque tibi a Domino traditas virtutes...-... kalendis martiis [sic] p. n. anno primo. M. Milinus » (135-139v).