A Phase III, multicenter, randomized, double-blind, active comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of V114 compared with PCV13 in healthy infants (PNEU-PED-EU-1).

Background: V114 (15-valent pneumococcal conjugate vaccine [PCV]) contains all serotypes in 13-valent PCV (PCV13) and additional serotypes 22F and 33F. This study evaluated safety and immunogenicity of V114 compared with PCV13 in healthy infants, and concomitant administration with DTPa-HBV-IPV/Hib and rotavirus RV1 vaccines.

Methods: V114 and PCV13 were administered in a 2+1 schedule at 2, 4, and 11-15 months of age.

Health-related quality of life following surgical attenuation of congenital portosystemic shunts versus healthy controls.

Objectives: To design a health-related quality of life questionnaire for dogs with congenital portosystemic shunts, use it in a cohort of dogs treated with suture attenuation and compare results with those obtained from a healthy control cohort.

Materials And Methods: Data were collected from the hospital records of dogs treated with suture ligation of an intrahepatic or extrahepatic congenital portosystemic shunt at two referral centres. Owners were asked to complete a questionnaire assessing their dog's health-related quality of life preoperatively (retrospectively) and at the time of follow-up.

Reversible infertility in a liver receptor homologue-1 (LRH-1)-knockdown mouse model.

Liver receptor homologue-1 (LRH-1) is an orphan nuclear receptor that has been implicated in steroid hormone biosynthesis and fertility. Herein we describe a transgenic inducible short hairpin (sh) RNA mouse model that was used to study the effect of transient LRH-1 knockdown in vivo. Induction of expression of the shRNA directed against LRH-1 for 2-6 weeks resulted in 80% knockdown of LRH-1 protein in the ovary and complete infertility.

Gender-specific increase of bone mass by CART peptide treatment is ovary-dependent.

Cocaine- and amphetamine-regulated transcript (CART) has emerged as a neurotransmitter and hormone that has been implicated in many processes including food intake, maintenance of body weight, and reward, but also in the regulation of bone mass. CART-deficient mice are characterized by an osteoporotic phenotype, whereas female transgenic mice overexpressing CART display an increase in bone mass. Here we describe experiments that show that peripheral subcutaneous sustained release of different CART peptide isoforms for a period up to 60 days increased bone mass by 80% in intact mice.

Lrp5 functions in bone to regulate bone mass.

The human skeleton is affected by mutations in low-density lipoprotein receptor-related protein 5 (LRP5). To understand how LRP5 influences bone properties, we generated mice with osteocyte-specific expression of inducible Lrp5 mutations that cause high and low bone mass phenotypes in humans. We found that bone properties in these mice were comparable to bone properties in mice with inherited mutations.

Liver receptor homolog-1 is critical for adequate up-regulation of Cyp7a1 gene transcription and bile salt synthesis during bile salt sequestration.

Unlabelled: Liver receptor homolog-1 (LRH-1) is a nuclear receptor that controls a variety of metabolic pathways. In cultured cells, LRH-1 induces the expression of CYP7A1 and CYP8B1, key enzymes in bile salt synthesis. However, hepatic Cyp7a1 mRNA levels were not reduced upon hepatocyte-specific Lrh-1 deletion in mice.

Early postnatal lethality and cardiovascular defects in CXCR7-deficient mice.

CXCR7 is a G-protein coupled receptor that was recently deorphanized and shown to have SDF1 and I-TAC as high affinity ligands. Here we describe the characterization of CXCR7-deficient mice that were generated to further investigate the function of this receptor in vivo. Expression analysis using a LacZ reporter knockin revealed that postnatally Cxcr7 was specifically expressed in cardiomyocytes, vascular endothelial cells of the lung and heart, the cerebral cortex and in osteocytes of the bone.

Factors affecting the level and localization of the transferrin receptor in Trypanosoma brucei.

Transfer of bloodstream-form Trypanosoma brucei variant 221a from calf serum to dog serum-based medium induces acute iron starvation, as the transferrin receptor (Tf-R) of variant 221a binds dog Tf poorly. We show here that transfer to dog serum induces a 3-5-fold increase in Tf-R mRNA and protein within one doubling time (8 h). Because iron stores are still high 8 h after transfer, we infer that the signal for Tf-R overproduction is the decreased availability of cytosolic iron when cellular iron import drops.

Metabolically assessed muscle fibre recruitment in brief isometric contractions at different intensities.

This study investigated the recruitment of type I, IIA and IIAX fibres after seven isometric contractions at 40, 70 and 100% maximal voluntary knee extension torque (MVC, 1 s on/1 s off). Biopsies of the vastus lateralis muscle were collected from seven subjects at rest and immediately post-exercise. Fibre fragments were dissected from the freeze-dried samples and characterized as type I, IIA and IIAX using mATPase staining.

Variability in fibre properties in paralysed human quadriceps muscles and effects of training.

A spinal cord injury usually leads to an increase in contractile speed and fatigability of the paralysed quadriceps muscles, which is probably due to an increased expression of fast myosin heavy chain (MHC) isoforms and reduced oxidative capacity. Sometimes, however, fatigue resistance is maintained in these muscles and also contractile speed is slower than expected. To obtain a better understanding of the diversity of these quadriceps muscles and to determine the effects of training on characteristics of paralysed muscles, fibre characteristics and whole muscle function were assessed in six subjects with spinal cord lesions before and after a 12-week period of daily low-frequency electrical stimulation.

Effects of training on contractile properties of paralyzed quadriceps muscle.

Effects of two different training regimens on the contractile properties of the quadriceps muscle were studied in six individuals with spinal cord injury. Each subject had both limbs trained with the two regimens, consisting of stimulation with low frequencies (LF) at 10 HZ or high frequencies (HF) at 50 HZ; one limb of each subject was stimulated with the LF protocol and the other with the HF regimen. Twelve weeks of daily training increased tetanic tension by approximately 20%, which was not significantly different between training regimens.

The physiological significance of transferrin receptor variations in Trypanosoma brucei.

Trypanosoma brucei escapes destruction by the host immune system by regularly replacing its Variant Surface Glycoprotein (VSG) coat. The VSG is expressed in a VSG expression site, together with expression site associated gene (ESAG) 6 and 7, encoding the heterodimeric transferrin receptor (Tf-R). There are around 20 VSG expression sites, and trypanosomes can change the site that is active.

Peripheral vascular changes after electrically stimulated cycle training in people with spinal cord injury.

Objective: To test whether a short period of training leads to adaptations in the cross-sectional area of large conduit arteries and improved blood flow to the paralyzed legs of individuals with spinal cord injury (SCI).

Design: Before-after trial.

Setting: Rehabilitation center, academic medical center.

Reproducibility of contractile properties of the human paralysed and non-paralysed quadriceps muscle.

This study assessed the reproducibility of electrically evoked, isometric quadriceps contractile properties in eight people with spinal cord injury (SCI) and eight able-bodied (AB) individuals. Over all, the pooled coefficients of variation (CVps) in the SCI group were significantly lower (ranging from 0.03 to 0.

Characteristics of the transactivator gene ie1 of Spodoptera exigua multiple nucleopolyhedrovirus.

The genomic position and nucleotide sequence of the immediate early gene ie1 of Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) were determined. The SeMNPV ie1 gene had the potential to encode a protein of 714 amino acids with a predicted molecular mass of 82.0 kDa, representing the largest baculovirus IE1 known to date.

Altered contractile properties of the quadriceps muscle in people with spinal cord injury following functional electrical stimulated cycle training.

Study Design: A longitudinal training study.

Objectives: To assess if contractile speed and fatigability of paralysed quadriceps muscles in individuals with spinal cord injury (SCI) can be altered by functional electrical stimulation leg cycle ergometry (FES-LCE) training.

Settings: The Sint Maartenskliniek rehabilitation centre and the University of Nijmegen, Nijmegen, the Netherlands.

Influence of muscle temperature on the contractile properties of the quadriceps muscle in humans with spinal cord injury.

Low muscle temperature in paralysed muscles of individuals with spinal cord injury may affect the contractile properties of these muscles. The present study was therefore undertaken to assess the effects of increased muscle temperature on the isometric contractile properties of electrically stimulated paralysed quadriceps muscles. When muscle temperature at a depth of 3 cm was increased from approximately 32 degrees C to approximately 36 degrees C by ultra-short-wave application, the half-relaxation time shortened and low-frequency force responses became less fused, but the maximal rate of increase in force remained unchanged.

Contractile properties of the quadriceps muscle in individuals with spinal cord injury.

Selected contractile properties and fatigability of the quadriceps muscle were studied in seven spinal cord-injured (SCI) and 13 able-bodied control (control) individuals. The SCI muscles demonstrated faster rates of contraction and relaxation than did control muscles and extremely large force oscillation amplitudes in the 10-Hz signal (65 +/- 22% in SCI versus 23 +/- 8% in controls). In addition, force loss and slowing of relaxation following repeated fatiguing contractions were greater in SCI compared with controls.

A novel signaling pathway controlling induced systemic resistance in Arabidopsis.

Plants have the ability to acquire an enhanced level of resistance to pathogen attack after being exposed to specific biotic stimuli. In Arabidopsis, nonpathogenic, root-colonizing Pseudomonas fluorescens bacteria trigger an induced systemic resistance (ISR) response against infection by the bacterial leaf pathogen P. syringae pv tomato.

Control of VSG gene expression sites in Trypanosoma brucei.

Antigenic variation in African trypanosomes continues to be one of the most elaborate and intriguing strategies ever devised by a protozoan parasite to avoid complete destruction by the immune defense of its mammalian host. Here we review some of the recent advances in our understanding of this strategy, concentrating on (unpublished) work from our laboratory.

PDZ motifs in PTP-BL and RIL bind to internal protein segments in the LIM domain protein RIL.

The specificity of protein-protein interactions in cellular signaling cascades is dependent on the sequence and intramolecular location of distinct amino acid motifs. We used the two-hybrid interaction trap to identify proteins that can associate with the PDZ motif-rich segment in the protein tyrosine phosphatase PTP-BL. A specific interaction was found with the Lin-11, Isl-1, Mec-3 (LIM) domain containing protein RIL.

The role of transferrin-receptor variation in the host range of Trypanosoma brucei.

Trypanosoma brucei is a unicellular parasite transmitted between African mammals by tsetse flies. T. brucei multiplies freely in the bloodstream of many different mammals, and survives by antigenic variation of the main component of its surface coat, variant surface glycoprotein (VSG).

Mechanisms of antigenic variation in African trypanosomes.

African trypanosomes can escape destruction by the immune system of their mammalian host by antigenic variation of the trypanosome surface coat. This coat is mainly composed of a single protein species, the Variant Surface Glycoprotein or VSG. The genes for VSGs are expressed in a polycistronic telomeric expression site together with at least eight expression site-associated genes (ESAGs).

Continuous infusions of alfentanil and propofol for coronary artery surgery.

Objective: To study the anesthetic efficacy of two different background infusion rates for alfentanil in a total intravenous anesthesia (TIVA) technique using propofol. Therefore, the effects of these infusions on hemodynamic stability and on the suppression of hemodynamic and somatic responses to noxious stimuli were compared.

Design: Prospective and randomized.

Afterimages: a collective term for percepts of different origin.

Exposure of the eye to a strong photoflash results in a so-called "afterimage", which may last for 20 min or longer. In contrast, the true afterimage, which fluctuates in brightness and is best seen in complete darkness, lasts only a few minutes. This true afterimage can be attributed to the strong oscillatory neuronal responses immediately initiated by the flash.