Electroencephalographic studies of sleep

Various experimental studies on sleep are described. The following areas are discussed: (1) effect of altered day length on sleep, (2) effect of a partial loss of sleep on subsequent nocturnal sleep; (3) effect of rigid control over sleep-wake-up times; (4) sleep and wakefulness in a time-free environment; (5) distribution of spindles during a full night of sleep; and (6) effect on sleep and performance of swiftly changing shifts of work

Evaluation of Phage Display Discovered Peptides as Ligands for Prostate-Specific Membrane Antigen (PSMA)

The aim of this study was to identify potential ligands of PSMA suitable for further development as novel PSMA-targeted peptides using phage display technology. The human PSMA protein was immobilized as a target followed by incubation with a 15-mer phage display random peptide library. After one round of prescreening and two rounds of screening, high-stringency screening at the third round of panning was performed to identify the highest affinity binders. Phages which had a specific binding activity to PSMA in human prostate cancer cells were isolated and the DNA corresponding to the 15-mers were sequenced to provide three consensus sequences: GDHSPFT, SHFSVGS and EVPRLSLLAVFL as well as other sequences that did not display consensus. Two of the peptide sequences deduced from DNA sequencing of binding phages, SHSFSVGSGDHSPFT and GRFLTGGTGRLLRIS were labeled with 5-carboxyfluorescein and shown to bind and co-internalize with PSMA on human prostate cancer cells by fluorescence microscopy. The high stringency requirements yielded peptides with affinities KD∼1 μM or greater which are suitable starting points for affinity maturation. While these values were less than anticipated, the high stringency did yield peptide sequences that apparently bound to different surfaces on PSMA. These peptide sequences could be the basis for further development of peptides for prostate cancer tumor imaging and therapy. © 2013 Shen et al

Pathological and ecological host consequences of infection by an introduced fish parasite

The infection consequences of the introduced cestode fish parasite Bothriocephalus acheilognathi were studied in a cohort of wild, young-of-the-year common carp Cyprinus carpio that lacked co-evolution with the parasite. Within the cohort, parasite prevalence was 42% and parasite burdens were up to 12% body weight. Pathological changes within the intestinal tract of parasitized carp included distension of the gut wall, epithelial compression and degeneration, pressure necrosis and varied inflammatory changes. These were most pronounced in regions containing the largest proportion of mature proglottids. Although the body lengths of parasitized and non-parasitized fish were not significantly different, parasitized fish were of lower body condition and reduced weight compared to non-parasitized conspecifics. Stable isotope analysis (δ15N and δ13C) revealed trophic impacts associated with infection, particularly for δ15N where values for parasitized fish were significantly reduced as their parasite burden increased. In a controlled aquarium environment where the fish were fed ad libitum on an identical food source, there was no significant difference in values of δ15N and δ13C between parasitized and non-parasitized fish. The growth consequences remained, however, with parasitized fish growing significantly slower than non-parasitized fish, with their feeding rate (items s−1) also significantly lower. Thus, infection by an introduced parasite had multiple pathological, ecological and trophic impacts on a host with no experience of the parasite

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

Intraoperative electrocortical stimulation of Brodman area 4: a 10-year analysis of 255 cases

BACKGROUND: Brain tumor surgery is limited by the risk of postoperative neurological deficits. Intraoperative neurophysiological examination techniques, which are based on the electrical excitability of the human brain cortex, are thus still indispensable for surgery in eloquent areas such as the primary motor cortex (Brodman Area 4). METHODS: This study analyzed the data obtained from a total of 255 cerebral interventions for lesions with direct contact to (121) or immediately adjacent to (134) Brodman Area 4 in order to optimize stimulation parameters and to search for direct correlation between intraoperative potential changes and specific surgical maneuvers when using monopolar cortex stimulation (MCS) for electrocortical mapping and continuous intraoperative neurophysiological monitoring. RESULTS: Compound muscle action potentials (CMAPs) were recorded from the thenar muscles and forearm flexors in accordance with the large representational area of the hand and forearm in Brodman Area 4. By optimizing the stimulation parameters in two steps (step 1: stimulation frequency and step 2: train sequence) MCS was successful in 91% (232/255) of the cases. Statistical analysis of the parameters latency, potential width and amplitude showed spontaneous latency prolongations and abrupt amplitude reductions as a reliable warning signal for direct involvement of the motor cortex or motor pathways. CONCLUSION: MCS must be considered a stimulation technique that enables reliable qualitative analysis of the recorded potentials, which may thus be regarded as directly predictive. Nevertheless, like other intraoperative neurophysiological examination techniques, MCS has technical, anatomical and neurophysiological limitations. A variety of surgical and non-surgical influences can be reason for false positive or false negative measurements

Ultrafast switch-on dynamics of frequency-tuneable semiconductor lasers

Single-mode frequency-tuneable semiconductor lasers based on monolithic integration of multiple cavity sections are important components, widely used in optical communications, photonic integrated circuits and other optical technologies. To date, investigations of the ultrafast switching processes in such lasers, essential to reduce frequency cross-talk, have been restricted to the observation of intensity switching over nanosecond-timescales. Here, we report coherent measurements of the ultrafast switch-on dynamics, mode competition and frequency selection in a monolithic frequency-tuneable laser using coherent time-domain sampling of the laser emission. This approach allows us to observe hopping between lasing modes on picosecond-timescales and the temporal evolution of transient multi-mode emission into steady-state single mode emission. The underlying physics is explained through a full multi-mode, temperature-dependent carrier and photon transport model. Our results show that the fundamental limit on the timescales of frequency-switching between competing modes varies with the underlying Vernier alignment of the laser cavity

Author Correction: Ultrafast switch-on dynamics of frequency-tuneable semiconductor lasers

The original version of this Article contained an error in the Acknowledgements, which incorrectly omitted the following: 'We also acknowledge support from the Australian Research Council's Discovery Projects Funding Scheme (Grant DP 160 103910).' This has been corrected in both the PDF and HTML versions of the Article

Evaluation of Urine CCA Assays for Detection of Schistosoma mansoni Infection in Western Kenya

Although accurate assessment of the prevalence of Schistosoma mansoni is important for the design and evaluation of control programs, the most widely used tools for diagnosis are limited by suboptimal sensitivity, slow turn-around-time, or inability to distinguish current from former infections. Recently, two tests that detect circulating cathodic antigen (CCA) in urine of patients with schistosomiasis became commercially available. As part of a larger study on schistosomiasis prevalence in young children, we evaluated the performance and diagnostic accuracy of these tests—the carbon test strip designed for use in the laboratory and the cassette format test intended for field use. In comparison to 6 Kato-Katz exams, the carbon and cassette CCA tests had sensitivities of 88.4% and 94.2% and specificities of 70.9% and 59.4%, respectively. However, because of the known limitations of the Kato-Katz assay, we also utilized latent class analysis (LCA) incorporating the CCA, Kato-Katz, and schistosome-specific antibody results to determine their sensitivities and specificities. The laboratory-based CCA test had a sensitivity of 91.7% and a specificity of 89.4% by LCA while the cassette test had a sensitivity of 96.3% and a specificity of 74.7%. The intensity of the reaction in both urine CCA tests reflected stool egg burden and their performance was not affected by the presence of soil transmitted helminth infections. Our results suggest that urine-based assays for CCA may be valuable in screening for S. mansoni infections

The morphology and biochemistry of nanostructures provide evidence for synthesis and signaling functions in human cerebrospinal fluid

<p>Abstract</p> <p>Background</p> <p>Cerebrospinal fluid (CSF) contacts many brain regions and may mediate humoral signaling distinct from synaptic neurotransmission. However, synthesis and transport mechanisms for such signaling are not defined. The purpose of this study was to investigate whether human CSF contains discrete structures that may enable the regulation of humoral transmission.</p> <p>Methods</p> <p>Lumbar CSF was collected prospectively from 17 participants: with no neurological or psychiatric disease, with Alzheimer's disease, multiple sclerosis, or migraine; and ventricular CSF from two cognitively healthy participants with long-standing shunts for congenital hydrocephalus. Cell-free CSF was subjected to ultracentrifugation to yield supernatants and pellets that were examined by transmission electron microscopy, shotgun protein sequencing, electrophoresis, western blotting, lipid analysis, enzymatic activity assay, and immuno-electron microscopy.</p> <p>Results</p> <p>Over 3,600 CSF proteins were identified from repeated shotgun sequencing of cell-free CSF from two individuals with Alzheimer's disease: 25% of these proteins are normally present in membranes. Abundant nanometer-scaled structures were observed in ultracentrifuged pellets of CSF from all 16 participants examined. The most common structures included synaptic vesicle and exosome components in 30-200 nm spheres and irregular blobs. Much less abundant nanostructures were present that derived from cellular debris. Nanostructure fractions had a unique composition compared to CSF supernatant, richer in omega-3 and phosphoinositide lipids, active prostanoid enzymes, and fibronectin.</p> <p>Conclusion</p> <p>Unique morphology and biochemistry features of abundant and discrete membrane-bound CSF nanostructures are described. Prostaglandin H synthase activity, essential for prostanoid production and previously unknown in CSF, is localized to nanospheres. Considering CSF bulk flow and its circulatory dynamics, we propose that these nanostructures provide signaling mechanisms <it>via </it>volume transmission within the nervous system that are for slower, more diffuse, and of longer duration than synaptic transmission.</p