An approach to remote monitoring of heart rate variability (HRV) using microwave radar during a calculation task

Recently, nonrestrictive and noninvasive sensing techniques to measure vital signs have been actively researched and developed. This study aimed to develop a prototype system to monitor cardiac activity using microwave radar without making contact with the body and without removing clothing--namely, a completely noncontact, remote monitoring system. In addition, heart rate and changes in heart rate variability (HRV) during simple mental arithmetic tasks were observed with the prototype system. The prototype system has a microwave Doppler radar antenna with 24 GHz frequency and approximately 7 mW output power. The experiments were conducted with seven subjects (23.00±0.82 years). We found that the prototype system captured heart rate and HRV precisely. The strong relationship between the heart rates during tasks (r=0.96), LF (cross-correlation=0.76), and LF/HF (cross-correlation=0.73) of HRV calculated from the prototype system and from electrocardiograph (ECG) measurements were confirmed. The proposed completely noncontact, remote method appears promising for future monitoring of cardiac activity as an indicator of changes in mental workload in workplaces.     

Complex sequencing rules of birdsong can be explained by simple hidden Markov processes

Complex sequencing rules observed in birdsongs provide an opportunity to investigate the neural mechanism for generating complex sequential behaviors. To relate the findings from studying birdsongs to other sequential behaviors such as human speech and musical performance, it is crucial to characterize the statistical properties of the sequencing rules in birdsongs. However, the properties of the sequencing rules in birdsongs have not yet been fully addressed. In this study, we investigate the statistical properties of the complex birdsong of the Bengalese finch (Lonchura striata var. domestica). Based on manual-annotated syllable labeles, we first show that there are significant higher-order context dependencies in Bengalese finch songs, that is, which syllable appears next depends on more than one previous syllable. We then analyze acoustic features of the song and show that higher-order context dependencies can be explained using first-order hidden state transition dynamics with redundant hidden states. This model corresponds to hidden Markov models (HMMs), well known statistical models with a large range of application for time series modeling. The song annotation with these models with first-order hidden state dynamics agreed well with manual annotation, the score was comparable to that of a second-order HMM, and surpassed the zeroth-order model (the Gaussian mixture model; GMM), which does not use context information. Our results imply that the hierarchical representation with hidden state dynamics may underlie the neural implementation for generating complex behavioral sequences with higher-order dependencies.     

Unfolding mechanism of a hyperthermophilic protein O(6)-methylguanine-DNA methyltransferase

Unfolding intermediates have been found only rarely in earlier studies, and how a protein unfolds is therefore poorly understood. In this paper, we show experimental evidence for multiple pathways and multiple intermediates during unfolding reaction of O(6)-methylguanine-DNA methyltransferase from hyperthermophile Thermococcus kodakaraensis (Tk-MGMT). The unfolding profiles monitored by far-UV CD and tryptophan fluorescence were both biphasic, and unfolding monitored by fluorescence was faster than that monitored by CD. GdnHCl-induced titration curves indicate that the intermediates with significant alpha-helical structure accumulate during unfolding. Dependence of kinetic phases on initial GdnHCl concentrations and cysteine reactivity of Tk-MGMT were investigated, suggesting that the heterogeneity of native conformations and parallel unfolding pathways.     

Functional changes in adenylyl cyclases and associated decreases in relaxation responses in mesenteric arteries from diabetic rats

To assess the functional change in adenylyl cyclases (AC) associated with the diabetic state, we investigated AC-mediated relaxations and cAMP production in mesenteric arteries from rats with streptozotocin (STZ)-induced diabetes. The relaxations induced by the water-soluble forskolin (FSK) analog NKH477, which is a putative AC5 activator, but not by the beta-adrenoceptor agonist isoproterenol (Iso) and the AC activator FSK, were reduced in intact diabetic mesenteric artery. In diabetic rats, however, Iso-, FSK-, and NKH477-induced relaxations were attenuated in the presence of inhibitors of nitric oxide synthase and cyclooxygenase. To exclude the influence of phosphodiesterase (PDE), we also examined the relaxations induced by several AC activators in the presence of 3-isobutyl-1-methylxanthine (IBMX; a PDE inhibitor). Under these conditions, the relaxation induced by Iso was greatly impaired in STZ-diabetic rats. This Iso-induced relaxation was significantly attenuated by pretreatment with SQ-22536, an AC inhibitor, in mesenteric rings from age-matched controls but not in those from STZ-diabetic rats. Under the same conditions, the relaxations induced by FSK or NKH477 were impaired in STZ-diabetic rats. Neither FSK- nor A-23187 (a Ca2+ ionophore)-induced cAMP production was significantly different between diabetics and controls. However, cAMP production induced by Iso or NKH477 was significantly impaired in diabetic mesenteric arteries. Expression of mRNAs and proteins for AC5/6 was lower in diabetic mesenteric arteries than in controls. These results suggest that AC-mediated relaxation is impaired in the STZ-diabetic rat mesenteric artery, perhaps reflecting a reduction in AC5/6 activity.     

Protective efficacy of nonpathogenic nef-deleted SHIV vaccination combined with recombinant IFN-gamma administration against a pathogenic SHIV challenge in rhesus monkeys

We previously reported that a nef-deleted SHIV (SHIV-NI) is nonpathogenic and gave macaques protection from challenge infection with pathogenic SHIV-C2/1. To investigate whether IFN-gamma augments the immune response induced by this vaccination, we examined the antiviral and adjuvant effect of recombinant human IFN-gamma (rIFN-gamma) in vaccinated and unvaccinated monkeys. Nine monkeys were vaccinated with nef-deleted nonpathogenic SHIV-NI. Four of them were administered with rIFN-gamma and the other five monkeys were administered with placebo. After the challenge with pathogenic SHIV-C2/1, CD4(+) T-cell counts were maintained similarly in monkeys of both groups, while those of the unvaccinated monkeys decreased dramatically at 2 weeks after challenge. However, the peaks of plasma viral load were reduced to 100-fold in SHIV-NI vaccinated monkeys combined with rIFN-gamma compared with those in SHIV-NI vaccinated monkeys without rIFN-gamma. The peaks of plasma viral load were inversely correlated with the number of SIV Gag-specific IFN-gamma-producing cells. In SHIV-NI-vaccinated monkeys with rIFN-gamma, the number of SIV Gag-specific IFN-gamma-producing cells of PBMCs increased 2-fold compared with those in SHIV-NI-vaccinated monkeys without rIFN-gamma, and the NK activity and MIP-1alpha production of PBMCs were also enhanced. Thus, vaccination of SHIV-NI in combination with rIFN-gamma was more effective in modulating the antiviral immune system into a Th1 type response than SHIV-NI vaccination alone. These results suggest that IFN-gamma augmented the anti-viral effect by enhancing innate immunity and shifting the immune response to Th1.     

HIV-Tat protein induces P-glycoprotein expression in brain microvascular endothelial cells

Among the different factors which can contribute to CNS alterations associated with HIV infection, Tat protein is considered to play a critical role. Evidence indicates that Tat can contribute to brain vascular pathology through induction of endothelial cell activation. In the present study, we hypothesized that Tat can affect expression of P-glycoprotein (P-gp) in brain microvascular endothelial cells (BMEC). P-gp is an ATP-dependent cellular efflux transporter which is involved in the removal of specific non-polar molecules, including drugs used for highly active antiretroviral therapy (HAART). Treatment of BMEC with Tat(1-72) resulted in P-gp overexpression both at mRNA and protein levels. These alterations were confirmed in vivo in brain vessels of mice injected with Tat(1-72) into the hippocampus. Furthermore, pre-treatment of BMEC with SN50, a specific NF-kappaB inhibitor, protected against Tat(1-72)-stimulated expression of mdr1a gene, i.e. the gene which encodes for P-gp in rodents. Tat(1-72)-mediated changes in P-gp expression were correlated with increased rhodamine 123 efflux, indicating the up-regulation of transporter functions of P-gp. These results suggest that Tat-induced overexpression of P-gp in brain microvessels may have significant implications for the development of resistance to HAART and may be a contributing factor for low efficacy of HAART in the CNS.     

Unprecedented intraspecific diversity of the MHC class I region of a teleost medaka, Oryzias latipes

The major histocompatibility complex (MHC) is present at a single chromosomal locus of all jawed vertebrate analyzed so far, from sharks to mammals, except for teleosts whose orthologs of the mammalian MHC-encoded genes are dispersed at several chromosomal loci. Even in teleosts, several class IA genes and those genes directly involved in class I antigen presentation preserve their linkage, defining the teleost MHC class I region. We determined the complete nucleotide sequence of the MHC class I region of the inbred HNI strain of medaka, Oryzias latipes (northern Japan population-derived), from four overlapping bacterial artificial chromosome (BAC) clones spanning 540,982 bp, and compared it with the published sequence of the corresponding region of the inbred Hd-rR strain of medaka (425,935 bp, southern Japan population-derived) as the first extensive study of intraspecies polymorphisms of the ectotherm MHC regions. A segment of about 100 kb in the middle of the compared sequences encompassing two class Ia genes and two immunoproteasome subunit genes, PSMB8 and PSMB10, was so divergent between these two inbred strains that a reliable sequence alignment could not be made. The rest of the compared region (about 320 kb) showed a fair correspondence, and an approximately 96% nucleotide identity was observed upon gap-free segmental alignment. These results indicate that the medaka MHC class I region contains an ∼100-kb polymorphic core, which is most probably evolving adaptively by accumulation of point mutations and extensive genetic rearrangements such as insertions, deletions and duplications. The nucleotide sequence data of HNI MHC class I region reported in this paper have been submitted to the DDBJ/EMBL/GenBank and were assigned the accession number AB183488.     

KATAMARI1/MURUS3 Is a novel golgi membrane protein that is required for endomembrane organization in Arabidopsis

In plant cells, unlike animal and yeast cells, endomembrane dynamics appear to depend more on actin filaments than on microtubules. However, the molecular mechanisms of endomembrane-actin filament interactions are unknown. In this study, we isolated and characterized an Arabidopsis thaliana mutant, katamari1 (kam1), which has a defect in the organization of endomembranes and actin filaments. The kam1 plants form abnormally large aggregates that consist of endoplasmic reticulum with actin filaments in the perinuclear region within the cells and are defective in normal cell elongation. Map-based cloning revealed that the KAM1 gene is allelic to the MUR3 gene. We demonstrate that the KAM1/MUR3 protein is a type II membrane protein composed of a short cytosolic N-terminal domain and a transmembrane domain followed by a large lumenal domain and is localized specifically on Golgi membranes. We further show that actin filaments interact with Golgi stacks via KAM1/MUR3 to maintain the proper organization of endomembranes. Our results provide functional evidence that KAM1/MUR3 is a novel component of the Golgi-mediated organization of actin functioning in proper endomembrane organization and cell elongation.