Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909.

The induction of potent CD8+ T cell responses by vaccines to fight microbes or tumors remains a major challenge, as many candidates for human vaccines have proved to be poorly immunogenic. Deoxycytidyl-deoxyguanosin oligodeoxynucleotides (CpG ODNs) trigger Toll-like receptor 9, resulting in dendritic cell maturation that can enhance immunogenicity of peptide-based vaccines in mice. We tested whether a synthetic ODN, CpG 7909, could improve human tumor antigen-specific CD8+ T cell responses. Eight HLA-A2+ melanoma patients received 4 monthly vaccinations of low-dose CpG 7909 mixed with melanoma antigen A (Melan-A; identical to MART-1) analog peptide and incomplete Freund's adjuvant. All patients exhibited rapid and strong antigen-specific T cell responses: the frequency of Melan-A-specific T cells reached over 3% of circulating CD8+ T cells. This was one order of magnitude higher than the frequency seen in 8 control patients treated similarly but without CpG and 1-3 orders of magnitude higher than that seen in previous studies with synthetic vaccines. The enhanced T cell populations consisted primarily of effector memory cells, which in part secreted IFN- and expressed granzyme B and perforin ex vivo. In vitro, T cell clones recognized and killed melanoma cells in an antigen-specific manner. Thus, CpG 7909 is an efficient vaccine adjuvant that promotes strong antigen-specific CD8+ T cell responses in humans.

Survival, development and growth of larvae of the blue swimmer crab, Portunus pelagicus, cultured under different photoperiod conditions

The blue swimmer crab is a commercially important species of the tropical Indo-Pacific regions that shows substantial potential as a candidate species for aquaculture. Optimization of larval rearing conditions, including photoperiod, is therefore important to establish a method for the intensive hatchery culture of this species. Newly hatched larvae of Portunuspelagicus in first zoeal stage (ZI) were reared under five photoperiod regimes 0L: 24D, 6L: 18D, 12L: 12D, 18L: 6D, and 24L: 0D (5 replicates per treatment) till they metamorphosed to megalopae (ranged from 8.5 ± 0.3 days (18L: 6D) to 10.8 ± 1.8 days (0L: 24D) at 29 ± 1 °C). Daily, larvae of each treatment were fed an identical diet of mixed rotifer and Artemia nauplii, and the survival and molt to successive stages was monitored. Newly hatched ZI larvae of P. pelagicus could successfully develop to the megalopal stage under all tested photoperiod conditions, but we detected significant differences in survival among treatments (p & 0.05). The constant darkness treatment (0L: 24D) had the lowest (19.2 ± 7.2%, mean ± S.E.) cumulative survival from ZI to the megalopal stage, while the 18L: 6D treatment achieved the highest survival (51.2 ± 23.6%). Similarly, the photoperiod significantly affected zoeal development. Constant darkness led to the longest cumulative zoeal duration (10.8 ± 1.8 days), whereas the 18L: 6D treatment rendered the shortest larval development (8.5 ± 0.3 days). In addition, larvae reared under constant darkness resulted in the smallest megalopae (carapace length = 1.44 ± 0.09 mm) and the lowest dry weight (0.536 ± 0.188 mg). In conclusion, photoperiod significantly affected the survival, development, and growth of P. pelagicus zoeal larvae. Constant darkness led to the lowest larval survival and developmental rate, while a photoperiod regime of 18L: 6D appeared to be the most suitable condition for the rearing of zoeal larvae of P. pelagicus.

Visual stimulus-dependent changes in interhemispheric EEG coherence in humans.

We analyzed the coherence of electroencephalographic (EEG) signals recorded symmetrically from the two hemispheres, while subjects (n = 9) were viewing visual stimuli. Considering the many common features of the callosal connectivity in mammals, we expected that, as in our animal studies, interhemispheric coherence (ICoh) would increase only with bilateral iso-oriented gratings located close to the vertical meridian of the visual field, or extending across it. Indeed, a single grating that extended across the vertical meridian significantly increased the EEG ICoh in normal adult subjects. These ICoh responses were obtained from occipital and parietal derivations and were restricted to the gamma frequency band. They were detectable with different EEG references and were robust across and within subjects. Other unilateral and bilateral stimuli, including identical gratings that were effective in anesthetized animals, did not affect ICoh in humans. This fact suggests the existence of regulatory influences, possibly of a top-down kind, on the pattern of callosal activation in conscious human subjects. In addition to establishing the validity of EEG coherence analysis for assaying cortico-cortical connectivity, this study extends to the human brain the finding that visual stimuli cause interhemispheric synchronization, particularly in frequencies of the gamma band. It also indicates that the synchronization is carried out by cortico-cortical connection and suggests similarities in the organization of visual callosal connections in animals and in man.

Acute hypersensitivity pneumonitis in a paint quality controller : a case report

Introduction: Isocyanates are sensitizing chemicals used in various industries such as polyurethane foam production or paint-related purposes. Acting as haptens recognized by T-lymphocytes, they can cause allergic asthma and rarely hypersensitivity pneumonitis (HP). We aim to present a case report of acute HP due to hexamethylene diisocyanate (HDI) in a paint quality controller, a profession not generally considered at a high risk for work-related Isocyanates exposure. Case report: A 30-yr-old otherwise healthy female, light smoker working as a paint quality controller developed shortness of breath, malaise, sweating and chills at workplace six hours after handling a HDI-based hardener. Upon admission to emergency department, symptoms had progressed to severe respiratory failure. HR computer tomography (HRCT) showed bilateral ground-glass attenuation without pleural effusion. Rapid clinical and radiological improvement occurred under facial oxygen supply and systemic steroid therapy. Occupational medicine investigations revealed regular handling of HDI using latex gloves without respiratory protection. Assessment at workplace showed insufficient air renewal (1.5 times per hour), inadequate local aspiration and HDI exposure at levels of 1-4.25 ppb/m3 (Swiss Occupation Exposure Limit 5 ppb/m3). Biological monitoring after identical work procedure executed by a co-worker showed HDI exposure (5.1 micrograms hexamethylene diamine/g creatinine). Resumption of work was disadvised because of the life-threatening event. Discussion: The diagnosis of occupational HP is highly supported by classical findings on imagery and typical symptoms occurring within approved latency interval, associated with rapid clinical improvement. Although neither broncho-alveolar lavage nor specific IgG diagnosis (en route) were performed during the acute episode, various blood tests managed to rule out evidence of an infection or autoimmune disease. Other causes of HP seem unlikely as the patient did not have any recurrence of symptoms since absence from work. Workplace evaluation provided significant information on HDI exposure and allowed substantial recommendations to diminish Isocyanate exposure for the 20 still healthy laboratory co-workers. Although the entryways (air or skin) and precise mechanism of toxicity remain unclear, the present case clearly shows that Isocyanates may trigger acute HP in susceptible workers in a profession not generally considered at a high risk.

Fatty Acid and Sterol Composition of Three Phytomonas Species

Fatty acid and sterol analysis were performed on Phytomonas serpens and Phytomonas sp. grown in chemically defined and complex medium, and P. françai cultivated in complex medium. The three species of the genus Phytomonas had qualitatively identical fatty acid patterns. Oleic, linoleic, and linolenic were the major unsaturated fatty acids. Miristic and stearic were the major saturated fatty acids. Ergosterol was the only sterol isolated from Phytmonas sp. and P. serpens grown in a sterol-free medium, indicating that it was synthesized de novo. When P. françai that does not grow in defined medium was cultivated in a complex medium, cholesterol was the only sterol detected. The fatty acids and sterol isolated from Phytomonas sp. and P. serpens grown in a chemically defined lipid-free medium indicated that they were able to biosynthesize fatty acids and ergosterol from acetate or from acetate precursors such as glucose or threonine.

Novel H3K4me3 marks are enriched at human- and chimpanzee-specific cytogenetic structures.

Human and chimpanzee genomes are 98.8% identical within comparable sequences. However, they differ structurally in nine pericentric inversions, one fusion that originated human chromosome 2, and content and localization of heterochromatin and lineage-specific segmental duplications. The possible functional consequences of these cytogenetic and structural differences are not fully understood and their possible involvement in speciation remains unclear. We show that subtelomeric regions-regions that have a species-specific organization, are more divergent in sequence, and are enriched in genes and recombination hotspots-are significantly enriched for species-specific histone modifications that decorate transcription start sites in different tissues in both human and chimpanzee. The human lineage-specific chromosome 2 fusion point and ancestral centromere locus as well as chromosome 1 and 18 pericentric inversion breakpoints showed enrichment of human-specific H3K4me3 peaks in the prefrontal cortex. Our results reveal an association between plastic regions and potential novel regulatory elements.

Comparison of the efficacy and longevity of nonpenetrating glaucoma surgery with and without a new, nonabsorbable hydrophilic implant.

BACKGROUND AND OBJECTIVE: To compare the efficacy and longevity of nonpenetrating glaucoma surgery with and without the use of a nonabsorbable hydrophilic implant at the Oxford Eye Centre, Johannesburg, South Africa, and the Glaucoma Unit, Jules Gonin Ophthalmic Hospital, Lausanne, Switzerland. PATIENTS AND METHODS: In a nonrandomized, prospective study between March 1997 and December 2001, 48 eyes of 32 patients aged 18 to 86 years with primary open-angle glaucoma underwent nonpenetrating glaucoma surgery; 25 eyes with the implant and 23 eyes without it. Intraocular pressure (IOP) was recorded preoperatively and postoperatively at 1, 7, and 14 days, at 1, 3, and 6 months, and thereafter every 6 months. RESULTS: The mean preoperative IOP was 27.5 +/- 11.8 mm Hg (range, 20 to 64 mm Hg) in the implant group and 24.8 +/- 7.1 mm Hg (range, 16 to 38 mm Hg) in the control group. During the first 18 months of follow-up, both groups showed identical IOP progression and the mean IOP remained less than 14 mm Hg. After 2 years of follow-up, the IOP started to rise in the control group but remained stable in the implant group. After 30 months, the mean IOP was 12.4 +/- 2 mm Hg and the IOP decrease in percentage was 62% +/- 6% in the implant group (n = 13) versus 16.1 +/- 3 mm Hg and 34% +/- 13% in the control group (n = 15) (mean IOP, P = .0022; mean IOP decrease in percentage, P = .01). CONCLUSIONS: During the first 18 months, there was no difference in the outcomes between the two groups. After 2 years of follow-up, the mean IOP was lower and the IOP decrease in percentage was greater in the implant group compared with the control group.

Strategies of use of a specific immunoglobulin-rich egg yolk powder in weaning piglets

Two experiments were performed to determine the best strategy of use of the product TRACTcare® 4P (ITPSA) (TC, specific immunoglobulin-rich egg yolk powder within an energetic fatty acid matrix) in piglets from weaning and for 6 weeks, in diets without or with inclusion of antibiotics. Each trial was performed with 144 piglets in 24 pens, in a completely randomized design blocked by initial body weight. Feeds were formulated according to animal requirements in two periods. In the first trial no antibiotics were included in the feeds and no room disinfection from previous trial was performed; treatments were: 1) Negative control (NC); 2) NC+TC on top of the feed within the hopper for the first 3 days on trial (30 g/pig×day), and eventually if diarrhea appeared (TCOT); 3) NC+TC ad libitum provided in an extra hopper within the pen (TCAL); and 4) NC+TC at 5 g/kg added to the feed in the mixer (TC5). In the second trial, treatments were: 1) Positive control: basal diet that included 250 mg/kg amoxiciline (BD)+100 mg/kg colistine (AC); 2) BD+2 g/kg TC (TC2A); 3) BD+5 g/kg TC (TC5A); and 4) BD+8 g/kg TC (TC8A). In diets without antibiotics, the product TC at 5 g/kg in the feed numerically improved BW by 8% compared to Control animals, while G:F was almost identical between both groups. When antibiotics were used in the feed, replacement of colistin at 100 mg/kg for TC at 2 g/kg in feed numerically improved the performance compared to Positive control animals (for the whole trial period ADG 8% better: 390 g vs. 361 g; G:F 1% better: 0.748 kg/kg vs. 0.742 kg/kg), possibly due to the stimulation of feed consumption at weaning. In both trials, the lower number of dead and culled animals from TC5 and TC2A together with higher BW represented an advantage over Control treatments of 6% to 10% animals more and 15% to 17% total BW more at the end of the trial.

Some solutions to obtain very efficient separations in isocratic and gradient modes using small particles size and ultra-high pressure.

The UHPLC strategy which combines sub-2 microm porous particles and ultra-high pressure (>1000 bar) was investigated considering very high resolution criteria in both isocratic and gradient modes, with mobile phase temperatures between 30 and 90 degrees C. In isocratic mode, experimental conditions to reach the maximal efficiency were determined using the kinetic plot representation for DeltaP(max)=1000 bar. It has been first confirmed that the molecular weight of the compounds (MW) was a critical parameter which should be considered in the construction of such curves. With a MW around 1000 g mol(-1), efficiencies as high as 300,000 plates could be theoretically attained using UHPLC at 30 degrees C. By limiting the column length to 450 mm, the maximal plate count was around 100,000. In gradient mode, the longest column does not provide the maximal peak capacity for a given analysis time in UHPLC. This was attributed to the fact that peak capacity is not only related to the plate number but also to column dead time. Therefore, a compromise should be found and a 150 mm column should be preferentially selected for gradient lengths up to 60 min at 30 degrees C, while the columns coupled in series (3x 150 mm) were attractive only for t(grad)>250 min. Compared to 30 degrees C, peak capacities were increased by about 20-30% for a constant gradient length at 90 degrees C and gradient time decreased by 2-fold for an identical peak capacity.

Mitochondrial DNA variation of Triatoma infestans populations and its implication on the specific status of T. melanosoma

DNA sequence comparison of 412 base-pairs fragments of the mitochondrial cytochrome B gene was used to infer the genetic structure of nine geographical Triatoma infestans populations and their phylogenetic relationship with T. melanosoma and T. brasiliensis. T. infestans and T. melanosoma were compared by morphometry, allozyme and cytogenetic analyses, as well as subjected to reciprocal crosses, in order to clarify the taxonomic status of the latter. No differences were found to distinguish the two species and the crosses between them yielded progeny. T. infestans populations presented four haplotypes that could be separated in two clusters: one formed by the samples from Bolivia (Andes and Chaco) and the other formed by samples from Argentina and Brazil. Silvatic and domestic T. infestans populations from Bolivia (Andes) were genetically identical.

Oxidative and nonoxidative glucose metabolism following graded doses of oral glucose in man.

The oxidative and nonoxidative glucose metabolism represent the two major mechanisms of the utilization of a glucose load. Eight normal subjects were administered oral loads of 50, 100 and 150 g glucose and gas exchange measurements were performed for eight hours by means of computerized continuous indirect calorimetry. The glycemic peaks were almost identical with all three doses with a rise to between 141 and 147 mg/dl at 60 min. The fall back to basal level was reached later with the high than with the low glucose doses. The glucose oxidation rate rose to values between 223 and 253 mg/min after the three glucose doses, but while falling immediately after the peak at 120 min following the 50 g load, the glucose oxidation rate remained at its maximum rate until 210 min for the 100 g glucose load and plateaued up to 270 min for the 150 g glucose dose. The oxidation rates then fell gradually to reach basal levels at 270, 330 and 420 min according to the increasing size of the load. Altogether 55 +/- 3 g glucose were oxidized during the 8 hours following the 50 g glucose load, 75 +/- 3 g after the 100 g load and 80 +/- 5 g after the 150 g load. The nonoxidative glucose disposal, which corresponds essentially to glucose storage, varied according to the size of the glucose load, with uptakes of 20 +/- 1, 60 +/- 1 and 110 +/- 1 g glucose 180 min after the 50, 100 and 150 g glucose loads respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The Irish Infancy Narratives and their Relationship with Latin Sources

(Résumé de l'ouvrage) In 1927 M. R. James published Latin Infancy Gospels, identified by him in two related but not identical manuscripts (one the British Library Arundel 404; the other from Hereford), together with a parallel text from the Irish manuscript known as the Leabhar Breac. Later researches brought to light more manuscripts of this Latin work, and also of the Irish text. James recognized that his apocryphal Latin Infancy text was compiled from a combination of the Protevangelium of James and a hitherto unknown text which he named "The Source". Recent research has identified a full Latin translation of the Protevangelium of James. A hitherto unrecognized Irish Infancy Narrative has also been identified in the Dublin manuscript known as the Liber Flavus Fergusiorum. A deep study of this related tradition was called for. This has been carried out over the past ten years by an Irish team in conjunction with Professor Daniel Kaestli and AELAC. The fruits of this labour are published in these two volumes. Volume 13 has a general introduction with a historical sketch of New Testament apocrypha in Ireland and a history of research on the subject. This is followed by a comparison of the Infancy Narratives in the Leabhar Breac and the Liber Flavus Fergusiorum. There are special introductions to these Infancy texts, followed by critical editions of the Irish texts, accompanied by English translations and rich annotation. Next there is similar treatment of the Irish versified Narrative (from ca. 700) of the Childhood Deeds of Jesus (commonly known as the Infancy Narrative (or Gospel) of Thomas. There is then (in volume 14, but with continuous pagination) the edition and translation of an Irish thirteenth-century poem with elements from Infancy Narratives, and both Latin and Irish texts on the wonders at Christ's birth, accompanied by translations and notes. The edition of the Irish material is followed by a critical edition of the full Arundel and Hereford forms of the Infancy Narrative (here referred to as the "J Compilation"), together with a detailed study of all the questions relating to this work. The volume concludes with a critical edition (by Rita Beyers) of the Latin text of the Protevangelium of James, accompanied by a detailed study of the work.. The work contains a detailed study of the Latin translations of the Protevangelium of James and the transmission of this work in the West. The "J Compilation" (a combination of the Protevangelium and texts of Pseudo-Matthew) can be traced back in manuscript transmission to ca. 800,and must have originated some time earlier. Behind it stands an earlier "I ("I" for Irish) Compilation" without influence from Pseudo-Matthew, the form found in the Irish witnesses. It is argued that M. R. James's "Source" may be of Judaeo-Christian origin and may really be the Gospel of the Nazoreans. Among the indexes there is a list of all the Irish words found in the texts. This edition of the Irish and related Latin texts is a major contribution to the study of the apocryphal Infancy Narratives. It should also be of particular interest to Celtic scholars, to students of Irish ecclesiastical learning, and in general to all medievalists.

Latin Infancy Gospels: The J Compilation. Introduction and Edition

(Résumé de l'ouvrage) In 1927 M. R. James published Latin Infancy Gospels, identified by him in two related but not identical manuscripts (one the British Library Arundel 404; the other from Hereford), together with a parallel text from the Irish manuscript known as the Leabhar Breac. Later researches brought to light more manuscripts of this Latin work, and also of the Irish text. James recognized that his apocryphal Latin Infancy text was compiled from a combination of the Protevangelium of James and a hitherto unknown text which he named "The Source". Recent research has identified a full Latin translation of the Protevangelium of James. A hitherto unrecognized Irish Infancy Narrative has also been identified in the Dublin manuscript known as the Liber Flavus Fergusiorum. A deep study of this related tradition was called for. This has been carried out over the past ten years by an Irish team in conjunction with Professor Daniel Kaestli and AELAC. The fruits of this labour are published in these two volumes. Volume 13 has a general introduction with a historical sketch of New Testament apocrypha in Ireland and a history of research on the subject. This is followed by a comparison of the Infancy Narratives in the Leabhar Breac and the Liber Flavus Fergusiorum. There are special introductions to these Infancy texts, followed by critical editions of the Irish texts, accompanied by English translations and rich annotation. Next there is similar treatment of the Irish versified Narrative (from ca. 700) of the Childhood Deeds of Jesus (commonly known as the Infancy Narrative (or Gospel) of Thomas. There is then (in volume 14, but with continuous pagination) the edition and translation of an Irish thirteenth-century poem with elements from Infancy Narratives, and both Latin and Irish texts on the wonders at Christ's birth, accompanied by translations and notes. The edition of the Irish material is followed by a critical edition of the full Arundel and Hereford forms of the Infancy Narrative (here referred to as the "J Compilation"), together with a detailed study of all the questions relating to this work. The volume concludes with a critical edition (by Rita Beyers) of the Latin text of the Protevangelium of James, accompanied by a detailed study of the work.. The work contains a detailed study of the Latin translations of the Protevangelium of James and the transmission of this work in the West. The "J Compilation" (a combination of the Protevangelium and texts of Pseudo-Matthew) can be traced back in manuscript transmission to ca. 800,and must have originated some time earlier. Behind it stands an earlier "I ("I" for Irish) Compilation" without influence from Pseudo-Matthew, the form found in the Irish witnesses. It is argued that M. R. James's "Source" may be of Judaeo-Christian origin and may really be the Gospel of the Nazoreans. Among the indexes there is a list of all the Irish words found in the texts. This edition of the Irish and related Latin texts is a major contribution to the study of the apocryphal Infancy Narratives. It should also be of particular interest to Celtic scholars, to students of Irish ecclesiastical learning, and in general to all medievalists.

Pandemic Influenza Background (PDF 99 KB)

The Presence of highly pathogenicH5N1 avian influenza has been confirmed in birds in Turkey, Romania, Russia and Kazakhstan. There have been a total of 4 confirmed cases of human infection in Eastern/South Eastern Turkey that has resulted in 2 deaths. Background Avian influenza naturally circulates in wild waterfowl such as ducks and geese often causing little or no symptoms. Many other bird species are susceptible to infection with these influenza viruses and in many of these species it may cause severe disease associated with high mortality. Outbreaks associated with high bird mortality are called Highly Pathogenic Avian Influenza (HPAI) to distinguish them from less pathogenic influenza. In January 2004 avian influenza in poultry was confirmed in Vietnam. Subsequently, there have been very substantial outbreaks of avian influenza associated with high mortality affecting poultry in various countries throughout Asia including Vietnam, Thailand, China, Malaysia, Mongolia, North & South Korea, Cambodia, Indonesia, Laos and Japan. These outbreaks are caused by H5N1 subtype of influenza A virus, the same subtype (but not identical to the virus) that caused the outbreak in Hong Kong in 1997. åÊ

Cleusonite, (Pb,Sr)(U4+,U6+)(Fe2+ Zn)2(Ti,Fe2+ Fe3+)18(O,OH)38, a new mineral species of the crichtonite group from the western Swiss Alps

Cleusonite, (Pb,Sr)(U4+,U6+) (Fe2+,Zn)(2) (Ti,Fe2+,Fe3+)(18) (O,OH)(38), is a new member of the crichtonite group. It was found at two occurrences in greenschist facies metamorphosed gneissic series of the Mont Fort and Siviez-Mischabel Nappes in Valais, Switzerland (Cleuson and Bella Tolla summit), and named after the type locality. It occurs as black opaque cm-sized tabular crystals with a bright sub-metallic lustre. The crystals consist of multiple rhombohedra and hexagonal prisms that are generally twinned. Measured density is 4.74(4) g/cm(3) and can be corrected to 4.93(12) g/cm(3) for macroscopic swelling due to radiation damage; the calculated density varies from 5.02(6) (untreated) to 5.27(5) (heat-treated crystals); the difference is related to the cell swelling due to the metamictisation. The empirical formula for cleusonite from Cleuson is (Pb0.89Sr0.12)(Sigma=1.01) (U0.79+4U0.30+6)(Sigma=1.09) (Fe1.91+2Zn0.09)(Sigma=2.00) (Ti11.80Fe3.44+2Fe2.33+3V0.19+5Mn0.08Al0.07)(Sigma=17.90) [O-35.37(OH)(2.63)](Sigma=38). Cations were measured by electron microprobe, the presence of structural (OH) was confirmed by infrared spectroscopy and the U6+/U4+ and Fe2+/Fe3+ ratios were determined by X-ray photoelectron spectroscopy. Cleusonite is partly metamict, and untreated crystals only show three major X-ray diffraction peaks. Because of this radiation-damaged state, the mineral appears optically isotropic and shows a light-grey to white colour in reflected polarized light. Cleusonite is trigonal, space group R $(3) over bar $, and unit-cell parameters are varying from a = 10.576(3), c = 21.325(5) angstrom (untreated crystal) to a = 10.4188(6), c = 20.942(1) angstrom (800 degrees C treatment) and to a = 10.385(2), c = 20.900(7) angstrom (1000 degrees C treatment). The three cells give a common axial ratio 2.01 (1), which is identical to the measured morphological one 2.04(6). ne name cleusonite also applies to the previously described ``uranium-rich senaite'' from Alinci (Macedonia) and the ``plumbodavidite'' from Huanglongpu (China).