Phylogeny of the kinetoplastida: taxonomic problems and insights into the evolution of parasitism

To further investigate phylogeny of kinetoplastid protozoa, the sequences of small subunit (18S) ribosomal RNA of nine bodonid isolates and ten isolates of insect trypanosomatids have been determined. The root of the kinetoplastid tree was attached to the branch of Bodo designis and/or Cruzella marina. The suborder Trypanosomatina appeared as a monophyletic group, while the suborder Bodonina was paraphyletic. Among bodonid lineages, parasitic organisms were intermingled with free-living ones, implying multiple transitions to parasitism and supporting the `vertebrate-first hypothesis'. The tree indicated that the genera Cryptobia and Bodo are artificial taxa. Separation of fish cryptobias and Trypanoplasma borreli as different genera was not supported. In trypanosomatids, the genera Leptomonas and Blastocrithidia were polyphyletic, similar to the genera Herpetomonas and Crithidia and in contrast to the monophyletic genera Trypanosoma and Phytomonas. This analysis has shown that the morphological classification of kinetoplastids does not in general reflect their genetic affinities and needs a revision.

Juli Cèsar, tirà i visionari? : l'esfondrament de la República romana

Aquest treball emmarca la vida de Juli Cèsar en el procés d'esfondrament de la República romana i la guerra civil. La seva vida n'és el fil conductor. També hi ha anàlisis descontextualitzades d'aquesta vida (la lluita entre optimates i populares, els mandats extraordinaris, la figura dels tribuns de la plebs i l'imperialisme romà), necessaris per a entendre aquest pas de República a Principat.

Continuous monitoring of cerebrovascular pressure reactivity in patients with head injury.

OBJECT: Cerebrovascular pressure reactivity is the ability of cerebral vessels to respond to changes in transmural pressure. A cerebrovascular pressure reactivity index (PRx) can be determined as the moving correlation coefficient between mean intracranial pressure (ICP) and mean arterial blood pressure. METHODS: The authors analyzed a database consisting of 398 patients with head injuries who underwent continuous monitoring of cerebrovascular pressure reactivity. In 298 patients, the PRx was compared with a transcranial Doppler ultrasonography assessment of cerebrovascular autoregulation (the mean index [Mx]), in 17 patients with the PET-assessed static rate of autoregulation, and in 22 patients with the cerebral metabolic rate for O(2). Patient outcome was assessed 6 months after injury. RESULTS: There was a positive and significant association between the PRx and Mx (R(2) = 0.36, p < 0.001) and with the static rate of autoregulation (R(2) = 0.31, p = 0.02). A PRx > 0.35 was associated with a high mortality rate (> 50%). The PRx showed significant deterioration in refractory intracranial hypertension, was correlated with outcome, and was able to differentiate patients with good outcome, moderate disability, severe disability, and death. The graph of PRx compared with cerebral perfusion pressure (CPP) indicated a U-shaped curve, suggesting that too low and too high CPP was associated with a disturbance in pressure reactivity. Such an optimal CPP was confirmed in individual cases and a greater difference between current and optimal CPP was associated with worse outcome (for patients who, on average, were treated below optimal CPP [R(2) = 0.53, p < 0.001] and for patients whose mean CPP was above optimal CPP [R(2) = -0.40, p < 0.05]). Following decompressive craniectomy, pressure reactivity initially worsened (median -0.03 [interquartile range -0.13 to 0.06] to 0.14 [interquartile range 0.12-0.22]; p < 0.01) and improved in the later postoperative course. After therapeutic hypothermia, in 17 (70.8%) of 24 patients in whom rewarming exceeded the brain temperature threshold of 37 degrees C, ICP remained stable, but the average PRx increased to 0.32 (p < 0.0001), indicating significant derangement in cerebrovascular reactivity. CONCLUSIONS: The PRx is a secondary index derived from changes in ICP and arterial blood pressure and can be used as a surrogate marker of cerebrovascular impairment. In view of an autoregulation-guided CPP therapy, a continuous determination of a PRx is feasible, but its value has to be evaluated in a prospective controlled trial.

Sources of pre-analytical variations in yield of DNA extracted from blood samples: analysis of 50,000 DNA samples in EPIC.

The European Prospective Investigation into Cancer and nutrition (EPIC) is a long-term, multi-centric prospective study in Europe investigating the relationships between cancer and nutrition. This study has served as a basis for a number of Genome-Wide Association Studies (GWAS) and other types of genetic analyses. Over a period of 5 years, 52,256 EPIC DNA samples have been extracted using an automated DNA extraction platform. Here we have evaluated the pre-analytical factors affecting DNA yield, including anthropometric, epidemiological and technical factors such as center of subject recruitment, age, gender, body-mass index, disease case or control status, tobacco consumption, number of aliquots of buffy coat used for DNA extraction, extraction machine or procedure, DNA quantification method, degree of haemolysis and variations in the timing of sample processing. We show that the largest significant variations in DNA yield were observed with degree of haemolysis and with center of subject recruitment. Age, gender, body-mass index, cancer case or control status and tobacco consumption also significantly impacted DNA yield. Feedback from laboratories which have analyzed DNA with different SNP genotyping technologies demonstrate that the vast majority of samples (approximately 88%) performed adequately in different types of assays. To our knowledge this study is the largest to date to evaluate the sources of pre-analytical variations in DNA extracted from peripheral leucocytes. The results provide a strong evidence-based rationale for standardized recommendations on blood collection and processing protocols for large-scale genetic studies.

[12 phot. des Alpes suisses (Valais et canton de Berne) par J. Beck, don E. Reclus en 1886]

Donateur : Reclus, Élisée (1830-1905)

[7 phot.des Alpes de Berne et du Valais, et du Tyrol, par J. Beck, don du général Parmentier en 1880]

Donateur : Parmentier, Théodore (1821-1910)

Exploring the environmental diversity of kinetoplastid flagellates in the high-throughput DNA sequencing era

The class Kinetoplastea encompasses both free-living and parasitic species from a wide range of hosts. Several representatives of this group are responsible for severe human diseases and for economic losses in agriculture and livestock. While this group encompasses over 30 genera, most of the available information has been derived from the vertebrate pathogenic genera Leishmaniaand Trypanosoma. Recent studies of the previously neglected groups of Kinetoplastea indicated that the actual diversity is much higher than previously thought. This article discusses the known segment of kinetoplastid diversity and how gene-directed Sanger sequencing and next-generation sequencing methods can help to deepen our knowledge of these interesting protists.

Vitae sanctorum.

Abdo et Sennes (262-263v) ; Acisclus et Victoria (163-165) ; Adrianus (72v-77) ; Affra (45v) ; Amancius (122-125v) ; Andochius (90v-92v) ; Andreas (186-194v) ; Antoninus (68v-70v, 221v) ; Apollinaris (1bis-1bis v); Audardus (254-259) ; Augustinus (231-232v) ; Bartholomeus (55v-59v) ; Bricius Turonensis (162v-163) ; Caprasius (107-108) ; Caprasius et Fides (218-219v) ; Cassianus (48v) ; Cecilia (168v-174v) ; Christina (12-16v) ; Christoforus (22-24) ; Ciricus et Julita (2v-6, 260v-262) ; Cirillus (2-2v) ; Ciprianus (47v-48v) ; Claudius, Asterius, Neo (54v-55v) ; Clemens (174v-176) ; Cosmas et Damianus (97v-98v) ; Crisantus et Daria (179-182v) ; Crucis exaltatio (83-84) ; Cucufas (24-25) ; Dalmacius Rutenae urbis (131-132v) ; Desiderius Caturcensis (207v-217v) ; Dionisius (105-106v) ; Donatus (263v-265v) ; Eleazarus (38-38v) ; Eptadius (59v-61v) ; Eufemia (84-86) ; Eugenia (78-83) ; Eulalia (195v-199) ; Eustachius (125v-129v) ; Fabius (34v-36v) ; Fausta (52-53v) ; Faustus, Januarius et Marcialis (106v-107) ; Felix (36v-38) ; Felix Nolensis ep. (25-27) ; Filibertus (227v-231) ; Genesius Arelatensis (61v-62v) ; Germanus Autissiodorensis (33-34) ; Gervasius et Protasius (259v-260v) ; Gregorius papa (222-224v) ; Grisogonus (176v-178) ; Jacobus major (20v-21v) ; Jeronimus (100-102) ; Johannis Baptistae decollatio (66v-68v) ; Johannes et Paulus (227-227v) ; Julia (11-12) ; Julianus (64-64v) ; Julianus, auct. Gregorio Turonense (265v-272) ; Julius (178-178v) ; Justa et Rufina (6v-7) ; Justina et Ciprianus (92v-97v) ; Justus et Pastor (44v-45) ; Laurianus (167v-168v) ; Leochadia (195-195v) ; Leodegarius (102-104v) ; Licerius (62v-64) ; Longinus (195) ; Lucia (199-200v) ; Machabei (34-34v) ; Mammes (45v-47v) ; Marcellinus et Petrus (259-259v) ; Marcellus (114) ; Marcellus Cavalonis (219v-220) ; Marcellus Kavilonensis (1v-1bis) ; Marcus (224v-225) ; Marciana (129v-131) ; Marcianus (206-206v) ; Margarita (7-11) ; Mariae assumptio (48v-51) ; Martinus, auct. Sulpicio Severo (133-160v) ; Matheus (86-89) ; Mauricius (89-90v) ; Mauricius, Exuperius, Candidus, Innocentius, Victor cum sociis eorum (272-272v) ; Maurinus (245-247v) ; Maximus (241-244v) ; Medardus (225-227) ; Mennas (160v-162v) ; Michael (98v-100) ; Mimius (39v-40) ; Nazarius et Celsus (27-31v) ; Omnes Sancti (118v-122) ; Pantaleo (31v-32v) ; Petri cathedra (220-221v, 249-250) ; Petrus, ep. Alexandriae (248-249) ; Procopius (39-39v) ; Quintinus (114-118v) ; Regina (70v-72v) ; Reparata (104v-105) ; Romanus (165-167) ; Sabina (64v-66v) ; Salvius (77-78) ; Saturninus et Sisinnius (178v) ; Saturninus Tolosanensis (182v-185v, 232v-239) ; Segolena (16v-20v) ; Servandus et Germanus (108-109) ; Sixtus, Laurentius et Ypolitus (40-44v); Symo et Judas (109-112v) ; Symphorianus (53v-54v) ; Teodota (38v-39) ; Terencianus (239-241) ; Theodardus Narbonensis (250-254) ; Thomas (200v-206) ; Valerianus (206v-207) ; Vamnes (51-52) ; Vincentius et Savina (112v-114). Le f. 220v contient un catalogue ancien de la bibliothèque de Moissac.

Varicella Zoster Virus CNS disease in hematopoietic cell transplantation: A single center experience

Background: Varciella Zoster Virus (VZV) can lead to serious complications in Hematopoietic Cell Transplant (HCT) recipients. Central nervous system (CNS) VZV can be one of the most devastating infections in transplant recipients, yet little is known about this rare disease. Objectives: To describe CNS VZV in the post-transplant period and to define potential risk factors in the HCT population. Methods: We reviewed the course of all patients who received a first HCT at the Fred Hutchinson Cancer Center (FHCRC) in Seattle, WA from 1/1996 through 12/2007. Data were collected retrospectively using the Long-Term Follow-Up database, which includes on-site examinations, outside records, laboratory tests, and yearly questionnaires. Patients were classified as CNS VZV if they had laboratory confirmation of VZV in the cerebrospinal fluid (CSF), or had zoster with associated clinical and laboratory findings consistent with CNS disease. Results: A total of six patients developed VZV CNS disease during the evaluation period (table 1). Diagnosis was confirmed in 3/6 by detection of VZV in CSF by PCR. All other patients had a clinical diagnosis based on the presence of CNS symptoms, zoster, lymphocytic pleiocytosis, and response to IV acyclovir. Patients who developed CNS disease had a mean age of 42 years (range 34-51) at time of transplant. CNS disease developed at a mean of 9 months posttransplantation (range 0.5-24 months), and severity varied, ranging from meningitis (3/6) to encephalitis/myelitis (3/6). All had active graft-versus host disease (GHVD) and all were being treated with immunosuppressive therapy at time of diagnosis. Fever and headache were the most common symptoms, but patients who developed focal CNS findings or seizures (3/6) had a more complicated clinical course. While most patients presented with classic VZV/zoster skin lesions, 2/6 patients had no dermatologic findings associated with their presentation. Four (66%) of patients who developed VZV CNS disease died, two related to VZV complications despite aggressive antiviral therapy. Conclusions: In this cohort of HCT patients, VZV CNS disease was a rare complication. Mortality due to CNS VZV is high, particularly in patients who develop focal neurologic findings or seizures. Even in the absence of skin lesions, VZV CNS disease should be considered in patients who develop fevers and neurologic symptoms.

Mélanges de Peiresc.

Litanies de S. Victor de Marseille (1). - Vie de s. Trophyme (5). - Philippus Cabassole, de B. M. Magdalena (7). - Lettres sur l'ancienne division de la Gaule (9 v°). - Notice de Besly sur la chronique de Julius Florus (15). - Antiquité des séparations dans les églises (17). - Commencement d'un traité historique sur les évêchés d'Angleterre (22). - Notes autographes de Peiresc sur des antiquités chrétiennes de Vienne (28). - Mémoires sur Embrun (32, 55 v°, 94 v°), le Dauphiné, le Comtat, la Provence, le Languedoc, les évêques de Digne (60 v°), de Sisteron (63) et de Vence (68 v°), Avignon (76), les évêques de Marseille (92), et ceux de Fréjus (95). - Vita b. Lamberti, ep. Venciensis (68 v°). - Origines de l'église de Reims (96). - Antiquités d'Orange (110). - Droits du roi en Bourgogne (140). - Pont du S. Esprit (153). - Seigneurie de Sault (154 v°). - Notes et documents généalogiques. - Copies de lettres et de documents du XVII s. - Idea sive designatio aliquot operum quae Jo. Ba. Donius partim absolvit partim incaepit (236). - Copie des anciens priviléges de l'église d'Arles (254).

Recherche de l'expression de la lamine A et de la progérine chez des patients avec un syndrome myélodysplasique/syndrome myéloprolifératif avec thrombocytose

Les syndromes myélodysplasiques (SMD) et myéloprolifératifs (SMP) sont des maladies qui touchent les cellules souches de la moelle hématopoïétique. Les symptômes varient selon le sous-type de SMD ou SMP allant de l'anémie à la polyglobulie, de la leucopénie à la leucocytose et de la thrombopénie à la thrombocytose. Ces syndromes se développent à la suite de mutations acquises qui provoquent des anomalies des cellules souches. En outre, plusieurs études ont mis en évidence des anomalies de processus épigénétiques comme l'hyperméthylation de l'ADN et la déacéthylation des histones. La maladie de Hutchinson-Gilford ou progéria est provoquée par une mutation sur le gène de la lamine A (protéine de l'enveloppe nucléaire) qui a pour conséquence l'augmentation de l'utilisation d'un site de splicing normalement peu utilisé ce qui engendre une protéine anormale, la progérine. Cette protéine a pour effet de modifier les processus épigénétiques. Une étude récente sur des patients souffrant de progéria a révélé la présence d'une thrombocytose chez tous les patients. Le but du présent travail a été d'étudier l'expression de la lamine A et de la progérine chez les patients souffrant de SMD ou SMP avec une thrombocytose suivis par le Service d'hématologie du CHUV. Nous avons sélectionné parmi les patients souffrant de SMD ou SMP ceux avec une thrombocytose supérieure à 400 G/l au moment du diagnostic. Nous avons ensuite effectué une PCR pour détecter la lamine A et la mutation de la lamine A que l'on trouve dans la progéria. Sur les 33 patients sélectionnés, nous avons pu analyser les échantillons de 18 d'entre eux. Le matériel était issu de cellules mononucléées ou de granulocytes. Les résultats démontrent la présence de la lamine A et l'absence de la mutation trouvée dans la progéria chez 16 patients. Cependant, chez 2 patients, la PCR laisse suspecter la présence de progérine en plus de celle de la lamine A. D'autres investigations seront nécessaires pour confirmer cette dernière observation. S'il s'avère que la progérine est effectivement présente chez ces deux patients, il faudrait étendre l'analyse à d'autres patients avec une hémopathie maligne. Plusieurs publications rapportent l'absence de lamine A dans les cellules hématopoïétiques. Cependant, le présent travail démontre clairement que les cellules mononucléées du sang ou de la moelle osseuse de certains patients avec SMP/SMD expriment la lamine A. Nous n'avons toutefois pas étudié si la lamine A et, éventuellement la progérine, sont exprimées par les cellules hématopoïétiques normales. En conclusion, ce travail a révélé qu'il serait très intéressant d'étudier le rôle potentiel des lamines nucléaires et en particulier de la lamine A et de la progérine dans l'hématopoïèse et le développement des SMD/SMP et d'autres hémopathies malignes. Il a donc ouvert la voie pour de futurs projets de recherche.