Intracranial pressure monitoring in normal dogs using subdural and intraparenchymal miniature strain-gauge transducers.

BackgroundMonitoring of intracranial pressure (ICP) is a critical component in the management of intracranial hypertension. Safety, efficacy, and optimal location of microsensor devices have not been defined in dogs.Hypothesis/objectiveAssessment of ICP using a microsensor transducer is feasible in anesthetized and conscious animals and is independent of transducer location. Intraparenchymal transducer placement is associated with more adverse effects.AnimalsSeven adult, bred-for-research dogs.MethodsIn a prospective investigational study, microsensor ICP transducers were inserted into subdural and intraparenchymal locations at defined rostral or caudal locations within the rostrotentorial compartment under general anesthesia. Mean arterial pressure and ICP were measured continuously during physiological maneuvers, and for 20 hours after anesthesia.ResultsBaseline mean ± SD values for ICP and cerebral perfusion pressure were 7.2 ± 2.3 and 78.9 ± 7.6 mm Hg, respectively. Catheter position did not have a significant effect on ICP measurements. There was significant variation from baseline ICP accompanying physiological maneuvers (P < .001) and with normal activities, especially with changes in head position (P < .001). Pathological sequelae were more evident after intraparenchymal versus subdural placement.Conclusions and clinical importanceUse of a microsensor ICP transducer was technically straightforward and provided ICP measurements within previously reported reference ranges. Results support the use of an accessible dorsal location and subdural positioning. Transient fluctuations in ICP are normal events in conscious dogs and large variations associated with head position should be accounted for when evaluating animals with intracranial hypertension

Efficient B cell responses to Borrelia hermsii infection depend on BAFF and BAFFR but not TACI.

T cell-independent antibody responses develop rapidly, within 3 to 4 days, and are critical for preventing blood-borne pathogens from evolving into life-threatening infections. The interaction of BAFF, also known as BLyS, with its receptors BAFFR and TACI on B cells is critical for B cell homeostasis and function. Using a synthetic polysaccharide antigen, it has previously been shown that TACI is critical for T cell-independent antibody responses. To examine the role of BAFFR and TACI in T cell-independent antibody responses to an active infection, we utilized the Borrelia hermsii infection system. In this infection system, T cell-independent responses mediated by the B1b cell subset are critical for controlling bacteremia. We found that B1b cells express BAFFR and TACI and that the surface expression of both receptors is upregulated on B1b cells following exposure to whole B. hermsii cells. Surprisingly, we found that TACI(-/-) mice are not impaired either in specific antibody responses to B. hermsii or in controlling B. hermsii bacteremia. In contrast, TACI-deficient mice immunized with heat-killed type 3 serotype pneumococcus cells are impaired in generating pneumococcal polysaccharide-specific responses and succumb to challenge with live type 3 serotype pneumococcus, indicating that TACI is required for T cell-independent antibody responses to bacterial-associated polysaccharides. Although we have found that TACI is dispensable for controlling B. hermsii infection, mice deficient in BAFFR or BAFF exhibit impairment in B. hermsii-specific IgM responses and clearance of bacteremia. Collectively, these data indicate a disparity in the roles for TACI and BAFFR in primary T cell-independent antibody responses to bacterial pathogens

Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands

Sequence-specific DNA-binding small molecules that can permeate human cells potentially could regulate transcription of specific genes. Multiple cellular DNA-binding transcription factors are required by HIV type 1 for RNA synthesis. Two pyrrole-imidazole polyamides were designed to bind DNA sequences immediately adjacent to binding sites for the transcription factors Ets-l, lymphoid-enhancer binding factor 1, and TATA-box binding protein. These synthetic ligands specifically inhibit DNA-binding of each transcription factor and HIV type 1 transcription in cell-free assays. When used in combination, the polyamides inhibit virus replication by >99% in isolated human peripheral blood lymphocytes, with no detectable cell toxicity, The ability of small molecules to target predetermined DNA sequences located within RNA polymerase II promoters suggests a general approach for regulation of gene expression, as well as a mechanism for the inhibition of viral replication

Yeast mother cell-specific ageing, genetic (in)stability, and the somatic mutation theory of ageing

Yeast mother cell-specific ageing is characterized by a limited capacity to produce daughter cells. The replicative lifespan is determined by the number of cell cycles a mother cell has undergone, not by calendar time, and in a population of cells its distribution follows the Gompertz law. Daughter cells reset their clock to zero and enjoy the full lifespan characteristic for the strain. This kind of replicative ageing of a cell population based on asymmetric cell divisions is investigated as a model for the ageing of a stem cell population in higher organisms. The simple fact that the daughter cells can reset their clock to zero precludes the accumulation of chromosomal mutations as the cause of ageing, because semiconservative replication would lead to the same mutations in the daughters. However, nature is more complicated than that because, (i) the very last daughters of old mothers do not reset the clock; and (ii) mutations in mitochondrial DNA could play a role in ageing due to the large copy number in the cell and a possible asymmetric distribution of damaged mitochondrial DNA between mother and daughter cell. Investigation of the loss of heterozygosity in diploid cells at the end of their mother cell-specific lifespan has shown that genomic rearrangements do occur in old mother cells. However, it is not clear if this kind of genomic instability is causative for the ageing process. Damaged material other than DNA, for instance misfolded, oxidized or otherwise damaged proteins, seem to play a major role in ageing, depending on the balance between production and removal through various repair processes, for instance several kinds of proteolysis and autophagy. We are reviewing here the evidence for genetic change and its causality in the mother cell-specific ageing process of yeast

Vision as a compensatory mechanism for disturbance rejection in upwind flight

Recent experimental results demonstrate that flies possess a robust tendency to orient towards the frontally-centered focus of the visual motion field that typically occurs during upwind flight. We present a closed loop flight model, with a control algorithm based on feedback of the location of the visual focus of contraction, which is affected by changes in wind direction. The feasibility of visually guided upwind orientation is demonstrated with a model derived from current understanding of the biomechanics and sensorimotor computation of insects. The matched filter approach used to model the visual system computations compares extremely well with open-loop experimental data

Fluctuating Motor Forces Bend Growing Microtubules

Despite their rigidity, microtubules in living cells bend significantly during polymerization resulting in greater curvature than can be explained by thermal forces alone. However, the source of the non-thermal forces that bend growing microtubules remains obscure. We analyzed the motion of microtubule tips in NIH-3T3 fibroblasts expressing EGFP-EB1, a fluorescent +TIP protein that specifically binds to the growing ends of microtubules. We found that dynein inhibition significantly reduced the deviation of the growing tip from its initial trajectory. Inhibiting myosin modestly reduced tip fluctuations, while simultaneous myosin and dynein inhibition caused no further decrease in fluctuations compared to dynein inhibition alone. Our results can be interpreted with a model in which dynein linkages play a key role in generating and transmitting fluctuating forces that bend growing microtubules.National Institutes of Health (U.S.) (NIH GM102486)National Science Foundation (U.S.) (NSF CMMI 0954302, NSF CMMI 0927945, and NSF CTS-0505929

Liver and brain abscess caused by Aggregatibacter paraphrophilus in association with a large patent foramen ovale: a case report

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Introduction Aggregatibacter paraphrophilus (former name Haemophilus paraphrophilus) is a normal commensal of the oral flora. It is a rare cause of hepatobiliary or intracerebral abscesses. Case presentation We report a case of a 53-year-old Caucasian man with a liver abscess and subsequent brain abscesses caused by Aggregatibacter paraphrophilus. The probable source of the infection was the oral flora of our patient following ingestion of a dental filling. The presence of a large patent foramen ovale was a predisposing factor for multifocal abscesses. Conclusion In this case report, we describe an unusual case of a patient with both liver and brain abscesses caused by an oral commensal Aggregatibacter paraphrophilus that can occasionally show significant pathogenic potential.Published versio