Isolation of a primate embryonic stem cell line.

Embryonic stem cells have the ability to remain undifferentiated and proliferate indefinitely in vitro while maintaining the potential to differentiate into derivatives of all three embryonic germ layers. Here we report the derivation of a cloned cell line (R278.5) from a rhesus monkey blastocyst that remains undifferentiated in continuous passage for > 1 year, maintains a normal XY karyotype, and expresses the cell surface markers (alkaline phosphatase, stage-specific embryonic antigen 3, stage-specific embryonic antigen 4, TRA-1-60, and TRA-1-81) that are characteristic of human embryonal carcinoma cells. R278.5 cells remain undifferentiated when grown on mouse embryonic fibroblast feeder layers but differentiate or die in the absence of fibroblasts, despite the presence of recombinant human leukemia inhibitory factor. R278.5 cells allowed to differentiate in vitro secrete bioactive chorionic gonadotropin into the medium, express chorionic gonadotropin alpha- and beta-subunit mRNAs, and express alpha-fetoprotein mRNA, indicating trophoblast and endoderm differentiation. When injected into severe combined immunodeficient mice, R278.5 cells consistently differentiate into derivatives of all three embryonic germ layers. These results define R278.5 cells as an embryonic stem cell line, to our knowledge, the first to be derived from any primate species.

Robotic Outcome Assessment in a Non-Human Primate Model of Middle Cerebral Artery Stroke

Stroke is a prevalent disorder with immense socioeconomic impact. A variety of chronic neurological deficits result from stroke. In particular, sensorimotor deficits are a significant barrier to achieving post-stroke independence. Unfortunately, the majority of pre-clinical studies that show improved outcomes in animal stroke models have failed in clinical trials. Pre-clinical studies using non-human primate (NHP) stroke models prior to initiating human trials are a potential step to improving translation from animal studies to clinical trials. Robotic assessment tools represent a quantitative, reliable, and reproducible means to assess reaching behaviour following stroke in both humans and NHPs. We investigated the use of robotic technology to assess sensorimotor impairments in NHPs following middle cerebral artery occlusion (MCAO). Two cynomolgus macaques underwent transient MCAO for 90 minutes. Approximately 1.5 years following the procedure these NHPs and two non-stroke control monkeys were trained in a reaching task with both arms in the KINARM exoskeleton. This robot permits elbow and shoulder movements in the horizontal plane. The task required NHPs to make reaching movements from a centrally positioned start target to 1 of 8 peripheral targets uniformly distributed around the first target. We analyzed four movement parameters: reaction time, movement time (MT), initial direction error (IDE), and number of speed maxima to characterize sensorimotor deficiencies. We hypothesized reduced performance in these attributes during a neurobehavioural task with the paretic limb of NHPs following MCAO compared to controls. Reaching movements in the non-affected limbs of control and experimental NHPs showed bell-shaped velocity profiles. In contrast, the reaching movements with the affected limbs were highly variable. We found distinctive patterns in MT, IDE, and number of speed peaks between control and experimental monkeys and between limbs of NHPs with MCAO. NHPs with MCAO demonstrated more speed peaks, longer MTs, and greater IDE in their paretic limb compared to controls. These initial results qualitatively match human stroke subjects’ performance, suggesting that robotic neurobehavioural assessment in NHPs with stroke is feasible and could have translational relevance in subsequent human studies. Further studies will be necessary to replicate and expand on these preliminary findings.

Euripidis Tragoediae.

t. 1. Hecuba ; Orestes ; Phoenissae ; Medea -- t. 2. Hippolytus ; Alcestis ; Andromache ; Supplices ; Iphigenia Aulidensis -- t. 3. Iphigenia Tavrica ; Rhesus ; Troades ; Bacchae ; Cyclops -- t. 4. Heraclidae ; Helena ; Ion ; Hercules furens ; Electra.

Euripides.

--I. Biographical sketch of Euripides. The Bacchae. Ion. Alcestis. Medea. Hippolytus. The Phoenician virgins.--II. The Supplicants. Hercules. The Heraclidae. Iphigenia in Aulis. Rhesus. The Trojan dames.--III. Hecuba. Helena. Electra Orestes. Iphigenia in Tauris. Andromache.

Euripides /

I. Biographical sketch. The Bacchæ. Ion. Alcestis. Medea. Hippolytus. The Phoenician virgins.--II. The Supplicants. Hercules. The Heraclidæ. Iphigenia in Aulis. Rhesus. The Trojan dames.--III. Hecuba. Helena. Electra. Orestes. Iphigenia in Tauris. Andromache.

Euripidis Tragoediae : ad optimorum librorum fidem accurate editae.

Greek text; Latin t.p.

Euripides.

I. Biographical sketch of Euripides. The Bacchae. Ion. Alcestis. Medea. Hippolytus. The Phœnician virgins.--II. The Supplicants. Hercules. The Heraclidæ. Iphigenia in Aulis. Rhesus. The Trojan dames.--III. Hecuba. Helena. Electra. Orestes. Iphigenia in Tauris. Andromache.

Euripides, with an English translation,

Bibliography: v. 1, p. xv.

Euripides' Werke,

1 Bd. Medea. Die Fönikerinnen. Hekabe. Orestes.--2 Bd. Der Cyklop. Ifigenia in Aulis. Ion. Helena.--3 Bd. Die Herakliden. Hippolytus oder fädra. Die Bacchantinnen. Der Wütende.--4. Bd. Medea. Die Fönikerinnen. Hekabe. Orestes.--5. Bd. Andromache. Nachricht von einer Handschrift aus Wolfenbüttel. Ifigenia in Tauris. Rhesus. Danae. Fragmente. Nachträge und Berichtigungen. Herkules.--4 Bd. Die Flehenden. Elektra. Alceste. Die Trojanerinnen.--5 Bd. Andromache. Nachricht von einer handschrift aus Wolfenbüttel. Ifigenia in Tauris. Rhesus. Danae. Fragmente. Nachträge und Berichtigingen.

Hecuba and other plays

With no. 54 and 58 of the series, completes the English versions of Euripides.

Fabulae /

Text in Greek ; introduction and notes in Latin.

Event-related potential correlates of impaired visuospatial working memory in schizophrenia

Previous studies have reported that patients with schizophrenia demonstrate impaired performance during working memory (WM) tasks. The current study aimed to determine whether WM impairments in schizophrenia are accompanied by reduced slow wave (SW) activity during on-line maintenance of mnemonic information. Event-related potentials were obtained from patients with schizophrenia and well controls as they performed a visuospatial delayed response task. On 50% of trials, a distractor stimulus was introduced during the delay. Compared with controls, patients with schizophrenia produced less SW memory negativity, particularly over the right hemisphere, together with reduced frontal enhancement of SW memory negativity in response to distraction. The results indicate that patients with schizophrenia generate less maintenance phase neuronal activity during WM performance, especially under conditions of distraction.

Twists, knots, and rings in proteins: Structural definition of the cyclotide framework

In recent years an increasing number of miniproteins containing an amide-cyclized backbone have been discovered. The cyclotide family is the largest group of such proteins and is characterized by a circular protein backbone and six conserved cysteine residues linked by disulfide bonds in a tight core of the molecule. These form a cystine knot in which an embedded ring formed by two of the disulfide bonds and the connecting backbone segment is threaded by a third disulfide bond. In the current study we have undertaken high resolution structural analysis of two prototypic cyclotides, kalata B1 and cycloviolacin O1, to define the role of the conserved residues in the sequence. We provide the first comprehensive analysis of the topological features in this unique family of proteins, namely rings (a circular backbone), twists (a cis-peptide bond in the Mobius cyclotides) and knots (a knotted arrangement of the disulfide bonds).

Human brain regions required for the dividing and switching of attention between two features of a single object

This combined PET and ERP study was designed to identify the brain regions activated in switching and divided attention between different features of a single object using matched sensory stimuli and motor response. The ERP data have previously been reported in this journal [64]. We now present the corresponding PET data. We identified partially overlapping neural networks with paradigms requiring the switching or dividing of attention between the elements of complex visual stimuli. Regions of activation were found in the prefrontal and temporal cortices and cerebellum. Each task resulted in different prefrontal cortical regions of activation lending support to the functional subspecialisation of the prefrontal and temporal cortices being based on the cognitive operations required rather than the stimuli themselves. (C) 2003 Elsevier Science B.V. All rights reserved.

Cross-reactive recognition of human and primate cytomegalovirus sequences by human CD4 cytotoxic T lymphocytes specific for glycoprotein B and H

Although the importance of CD4(+) T cell responses to human cytonnegalovirus (HCMV) has recently been recognized in transplant and immunosuppressed patients, the precise specificity and nature of this response has remained largely unresolved. In the present study we have isolated CD4(+) CTL which recognize epitopes from HCMV glycoproteins gB and gH in association with two different HLA-DR antigens, DRA1*0101/DRB1*0701 (DR7) and DRA1*0101/DRB1*1101 (DR11). Comparison of amino acid sequences of HICMV isolates revealed that the gB and gH epitope sequences recognized by human CD4(+) T cells were not only conserved in clinical isolates from HCMV but also in CMV isolates from higher primates (chimpanzee, rhesus and baboon). Interestingly, these epitope sequences from chimpanzee, rhesus and baboon CMV are efficiently recognized by human CD4(+) CTL. More importantly, we show that gB-specific T cells from humans can also efficiently lyse pepticle-sensitized Patr-DR7(+) cells from chimpanzees. These findings suggest that conserved gB and gH epitopes should be considered while designing a prophylactic vaccine against HCMV. In addition, they also provide a functional basis for the conservation of MHC class 11 lineages between humans and Old World primates and open the possibility for the use of such primate models in vaccine development against HCMV.