The fast transient sky with Gaia

The ESA Gaia satellite scans the whole sky with a temporal sampling ranging from seconds and hours to months. Each time a source passes within the Gaia field of view, it moves over 10 CCDs in 45 s and a lightcurve with 4.5 s sampling (the crossing time per CCD) is registered. Given that the 4.5 s sampling represents a virtually unexplored parameter space in optical time domain astronomy, this data set potentially provides a unique opportunity to open up the fast transient sky. We present a method to start mining the wealth of information in the per CCD Gaia data. We perform extensive data filtering to eliminate known on-board and data processing artefacts, and present a statistical method to identify sources that show transient brightness variations on ~2 hours timescales. We illustrate that by using the Gaia photometric CCD measurements, we can detect transient brightness variations down to an amplitude of 0.3 mag on timescales ranging from 15 seconds to several hours. We search an area of ~23.5 square degrees on the sky, and find four strong candidate fast transients. Two candidates are tentatively classified as flares on M-dwarf stars, while one is probably a flare on a giant star and one potentially a flare on a solar type star. These classifications are based on archival data and the timescales involved. We argue that the method presented here can be added to the existing Gaia Science Alerts infrastructure for the near real-time public dissemination of fast transient events.Comment: 10 pages, 5 figures and 5 tables; MNRAS in pres

A novel adenovirus of Western lowland gorillas (Gorilla gorilla gorilla)

Adenoviruses (AdV) broadly infect vertebrate hosts including a variety of primates. We identified a novel AdV in the feces of captive gorillas by isolation in cell culture, electron microscopy and PCR. From the supernatants of infected cultures we amplified DNA polymerase (DPOL), preterminal protein (pTP) and hexon gene sequences with generic pan primate AdV PCR assays. The sequences in-between were amplified by long-distance PCRs of 2 - 10 kb length, resulting in a final sequence of 15.6 kb. Phylogenetic analysis placed the novel gorilla AdV into a cluster of primate AdVs belonging to the species Human adenovirus B (HAdV-B). Depending on the analyzed gene, its position within the cluster was variable. To further elucidate its origin, feces samples of wild gorillas were analyzed. AdV hexon sequences were detected which are indicative for three distinct and novel gorilla HAdV-B viruses, among them a virus nearly identical to the novel AdV isolated from captive gorillas. This shows that the discovered virus is a member of a group of HAdV-B viruses that naturally infect gorillas. The mixed phylogenetic clusters of gorilla, chimpanzee, bonobo and human AdVs within the HAdV-B species indicate that host switches may have been a component of the evolution of human and non-human primate HAdV-B viruses

Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder

Glucose transporter-1 deficiency syndrome is caused by mutations in the SLC2A1 gene in the majority of patients and results in impaired glucose transport into the brain. From 2004-2008, 132 requests for mutational analysis of the SLC2A1 gene were studied by automated Sanger sequencing and multiplex ligation-dependent probe amplification. Mutations in the SLC2A1 gene were detected in 54 patients (41%) and subsequently in three clinically affected family members. In these 57 patients we identified 49 different mutations, including six multiple exon deletions, six known mutations and 37 novel mutations (13 missense, five nonsense, 13 frame shift, four splice site and two translation initiation mutations). Clinical data were retrospectively collected from referring physicians by means of a questionnaire. Three different phenotypes were recognized: (i) the classical phenotype (84%), subdivided into early-onset (<2 years) (65%) and late-onset (18%); (ii) a non-classical phenotype, with mental retardation and movement disorder, without epilepsy (15%); and (iii) one adult case of glucose transporter-1 deficiency syndrome with minimal symptoms. Recognizing glucose transporter-1 deficiency syndrome is important, since a ketogenic diet was effective in most of the patients with epilepsy (86%) and also reduced movement disorders in 48% of the patients with a classical phenotype and 71% of the patients with a non-classical phenotype. The average delay in diagnosing classical glucose transporter-1 deficiency syndrome was 6.6 years (range 1 month-16 years). Cerebrospinal fluid glucose was below 2.5 mmol/l (range 0.9-2.4 mmol/l) in all patients and cerebrospinal fluid : blood glucose ratio was below 0.50 in all but one patient (range 0.19-0.52). Cerebrospinal fluid lactate was low to normal in all patients. Our relatively large series of 57 patients with glucose transporter-1 deficiency syndrome allowed us to identify correlations between genotype, phenotype and biochemical data. Type of mutation was related to the severity of mental retardation and the presence of complex movement disorders. Cerebrospinal fluid : blood glucose ratio was related to type of mutation and phenotype. In conclusion, a substantial number of the patients with glucose transporter-1 deficiency syndrome do not have epilepsy. Our study demonstrates that a lumbar puncture provides the diagnostic clue to glucose transporter-1 deficiency syndrome and can thereby dramatically reduce diagnostic delay to allow early start of the ketogenic die

a high level of genetic diversity and evidence of recombination and zoonotic transmission

Adenoviren sind in der Lage, ein breites Wirbeltierspektrum zu infizieren, unter ihnen eine Vielzahl nicht-humaner Primaten. Die vorliegende Arbeit beschäftigte sich mit folgenden Fragestellungen: (i) Kommen AdVs bei wildlebenden nicht-humanen Primaten vor? (ii) Wie sind ihre phylogenetischen Eigenschaften? (iii) Besteht Potenzial einer zoonotischen Übertragung zwischen Menschen und nicht menschlichen Primaten? (iv) Lassen sich Rekombinationen bei AdVs wildlebender Primaten beobachten? Hierzu wurden 1285 Proben simianer Herkunft untersucht. Kot erwies sich als sehr geeignetes Probenmaterial zum AdV-Nachweis. Es konnten insgesamt 46 neuartige AdVs mittels degenerierter PCR Assays detektiert werden. Von ihnen stehen DPOL-Teilsequenzen zur Verfügung. Bei 29 gelang zusätzlich aus der gleichen Probe die Amplifikation des nahezu gesamten Hexon-Gens. Ob DPOL- und Hexon-Sequenzen aus einer Probe vom gleichen Virusgenom stammten, war nicht zu ermitteln. Deshalb wurden DPOL- und Hexon- Teilsequenzen getrennt betrachtet. Zusätzlich gelang es, ein AdV aus im Münsteraner Allwetterzoo gehaltenen Gorillas anzuzüchten und zu sequenzieren. Bei diesem AdV konnten DPOL- und Hexonsequenzen miteinander verbunden werden, wodurch eine Teilsequenz von 15.6 kb Länge für Vergleiche mit Genomen anderer AdVs und phylogenetische Untersuchungen zur Verfügung stand. Die Berechnungen phylogenetischer Stammbäume ergaben für Nukleinsäureteilsequenzen des DPOL- und Hexon-Gens eine hohe genetische Diversität. Die neuartigen AdVs gruppierten sich innerhalb aller etablierten humanen und simianen AdV-Spezies ein. Sieben AdVs von Altweltaffen bildeten eigene Kluster und konnten keiner bekannten AdV-Spezies zugeordnet werden. Zusätzlich konnten erstmalig Sequenzen von zwei distinkten AdVs aus Neuweltaffen nachgewiesen und phylogenetisch analysiert werden. Fünf in wildlebenden Schimpansen gefundene AdVs gaben Hinweise auf zoonotische Übertragungen zwischen Mensch und Schimpanse [PtroAdV-8 [HAdV-A], PtroAdV-10 [HAdV-D], PtroAdV-3 [HAdV-F], PtroAdV-7 [HAdV-B] und PtroAdV-14 [HAdV-E]]. Dies zeigt erstmalig, dass AdVs aus wildlebenden Menschenaffen große phylogenetische Ähnlichkeiten zu humanen AdVs aufweisen können. Allerdings wurden nur für einige AdVs Hinweise auf die Richtung der Übertragung erhalten. Um das zoonotische Potential von AdVs nicht humaner Primaten besser abzuklären zu können, sollten in Zukunft auch humane AdVs der gleichen Regionen identifiziert werden und Eingang in die phylogenetische Untersuchungen finden. Trotz Bemühungen, DPOL- und Hexon- Genteilsequenzen der AdVs wilder NHP miteinander zu verbinden, gelang dies nur bei dem angezüchteten AdV GgorAdV-B7. Deshalb wurde auch nur die Genom- Teilsequenz dieses AdV (15.6kb Länge) auf Rekombinationsereignisse untersucht. Die BLAST-Analyse der gesamten Nukleinsäureteilsequenz ergab, dass GgorAdV-B7 die größte Ähnlichkeit zu dem Schimpansen AdV SAdV-35.1 und dem humanen AdV HAdV-21 hat. Zusätzlich wurden phylogenetische Stammbäume der Gene DPOL, pTP, Penton und Hexon berechnet. Sie zeigten, dass GgorAdV-B7 in jedem Gen mit unterschiedlichen AdVs Gruppen bildete. So ist GgorAdV-B7 im DPOL- und pTP-Gen eng mit einer Vielzahl von AdVs von Gorillas und Schimpansen gruppiert. Im Hexon-Gen gruppiert es sich mit dem Schimpansen AdV SAdV-35.1, dem Bonobo AdV SAdV-35.2 und drei humanen AdVs (HAdV-11, HAdV-21 und HAdV-35). Die Nukleinsäuresequenz des Penton-Gens von GgorAdV-B7 hingegen ist nahezu identisch mit der Nukleinsäuresequenz des Penton-Gens des Schimpansen AdV SAdV-29. Diese unterschiedliche Gruppenbildung ist nicht durch eine koevolutionäre Entwicklung von GgorAdV-B7 mit seinem Wirt erklärbar, sondern Inter-Spezies-Übertragungen und Rekombinationsereignisse müssen ebenso eine Rolle gespielt haben. Insbesondere im Penton-Gen gibt es Hinweise auf ein Rekombinationsereignis zwischen AdVs unterschiedlicher Wirte. Elternviren konnten jedoch nicht identifiziert werden. Die Erkenntnisse dieser Arbeit lassen davon ausgehen, dass AdVs über ein nicht zu vernachlässigendes zoonotisches Potential verfügen und ihre phylogenetische Diversität durch Rekombinationsereignisse erhöht wird. Ob AdVs nicht humanen Ursprungs bereits in lokalen afrikanischen Bevölkerungsgruppen oder AdVs humanen Ursprungs in Affenpopulationen zirkulieren, ist bisher kaum abschätzbar. Im Hinblick auf die Gefährdung der Bevölkerung durch Pathogene zoonotischen Ursprungs und einhergehende Belastung der öffentlichen Gesundheitssysteme können Erkenntnisse und Nachweissysteme, wie die hier vorgelegten helfen, frühzeitig Risiken zu erkennen und Gegenmaßnahmen einzuleiten.Adenoviruses (AdVs) broadly infect vertebrate hosts including a variety of primates. The present study assessed the following questions: (i) Are AdVs present in wild nonhuman primates (NHPs)? (ii) How are their phylogenetic properties? (iii) Is there evidence for interspecies transmission between humans and NHPs? (iv) Do recombination events occur among AdVs of NHPs? A total of 1285 samples of simian origin were analyzed for the presence of AdVs with a panprimate AdV-specific PCR targeting a highly conserved region of the DNA polymerase (DPOL) gene. With this approach a plethora of novel AdV sequences were identified, representing at least 46 distinct AdVs. Of these, 29 nearly complete hexon genes could be amplified. DPOL and hexon sequence from a given sample could not be connected by longdistance PCR. Therefore, only the hexon sequences were the basis for tentative virus names. In addition we identified a novel AdV in the faeces of captive gorillas living in the Zoological gardens of Münster by isolation in cell culture and PCR. Hexon and DPOL gene sequences of this particular virus could be connected by amplification of the in-between sequence resulting in a final sequence of 15.6 kb. Phylogenetic analysis performed in Maximum Likelihood frameworks revealed a high level of genetic diversity of the novel AdVs. They exhibited a broad evolutionary spectrum and were tentatively allocated to all established human and simian AdV species. Seven AdVs of Old World monkeys (OWMs) grouped separately and could not be assigned to any known AdV species. Furthermore, three DPOL sequences were identified in New World monkeys (NWMs) that clustered in a well-separated clade at the base of the primate AdV tree, possibly reflecting the split between NWMs and OWMs. Five AdVs detected in wild chimpanzees revealed a remarkably close relationship to human AdVs over their entire hexon gene sequence, and thus provide evidence for interspecies transmission events between humans and chimpanzees. The directionality of these transmissions could not be firmly determined. Namely these viruses are: PtroAdV-8 [HAdV-A], PtroAdV-10 [HAdV-D], PtroAdV-3 [HAdV-F], PtroAdV-7 [HAdV-B], and PtroAdV- 14 [HAdV-E]. The 15.6 kb sequence of GgorAdV-B7 was subjected to recombination analyses. In BLAST analysis of GenBank, the whole sequence was most closely related to the chimpanzee AdV SAdV-35.1 and the human AdV HAdV-21. Phylogenetic trees were constructed for DPOL, pTP, penton base and hexon gene alignments, revealing a mixed clustering of GgorAdV-B7 with different AdVs in each phylogenetic tree. In the DPOL and the pTP gene, GgorAdV-B7 formed a tight clade with AdVs from chimpanzees and gorillas. In the hexon gene GgorAdV-B7 was most closely associated with one chimpanzee AdV SAdV- 35.1, one bonobo AdV SAdV-35.2 and three human AdVs (HAdV-11, -21, and -35). However, the penton base gene of GgorAdV-B7 showed a striking similarity to that of the chimpanzee AdV SAdV-29. Taken together, these observations cannot be explained by cospeciation of GgorAdV-B7 with its gorilla host. Rather, they are in line with recombination and host switching, and the striking similarity to SAdV-29 suggests that recombination events between AdVs of different host species might take place. In light of current knowledge, parent viruses could not be assigned, indicating a more ancient recombination event with subsequent genetic drift or recombination with an unknown AdV. The high variety of known and novel AdVs of NHPs calls for larger studies to understand the diversity of AdVs currently circulating in African NHPs as well as in local African human populations. This may answer the intriguing question of whether NHPs and humans have an intersected “adeno-virosphere” and may provide the basis for elucidating the potential pathological consequences of interspecies AdV transmission. Studies of this kind may help to establish a global early warning system for emerging diseases, given the need to protect both public health and endangered NHPs

A novel adenovirus of Western lowland gorillas (<it>Gorilla gorilla gorilla</it>)

Abstract Adenoviruses (AdV) broadly infect vertebrate hosts including a variety of primates. We identified a novel AdV in the feces of captive gorillas by isolation in cell culture, electron microscopy and PCR. From the supernatants of infected cultures we amplified DNA polymerase (DPOL), preterminal protein (pTP) and hexon gene sequences with generic pan primate AdV PCR assays. The sequences in-between were amplified by long-distance PCRs of 2 - 10 kb length, resulting in a final sequence of 15.6 kb. Phylogenetic analysis placed the novel gorilla AdV into a cluster of primate AdVs belonging to the species Human adenovirus B (HAdV-B). Depending on the analyzed gene, its position within the cluster was variable. To further elucidate its origin, feces samples of wild gorillas were analyzed. AdV hexon sequences were detected which are indicative for three distinct and novel gorilla HAdV-B viruses, among them a virus nearly identical to the novel AdV isolated from captive gorillas. This shows that the discovered virus is a member of a group of HAdV-B viruses that naturally infect gorillas. The mixed phylogenetic clusters of gorilla, chimpanzee, bonobo and human AdVs within the HAdV-B species indicate that host switches may have been a component of the evolution of human and non-human primate HAdV-B viruses.</p

Seroreactivity of German sera and Ivorian plasma samples against polyomaviruses by age group.

a<p>number of sera from Germany before, number of plasma samples from Côte d'Ivoire after the slash;</p><p>-, not available.</p

Reactivity of chimpanzee plasma samples to VP1 proteins of chimpanzee polyomaviruses.

<p>Antibody reactivity was assessed against the 4 chimpanzee polyomaviruses ChPyV, PtrovPyV3, PtrovPyV4 and PtrosPyV2 using plasma of 40 chimpanzees. Samples were analysed for seroreactivity with a capsomer-based IgG ELISA using the VP1 major capsid protein of the above polyomaviruses as antigens. The spread of absorbance measurement is shown with black dots, and cut-off values (COVs) are depicted with solid lines (PtrovPyV3: 0.028; PtrovPyV4: 0.023; PtrosPyV2: 0.013). A COV for ChPyV could not be calculated because all OD₄₅₀ values were >0.3.</p