L-selectin-negative CCR7- effector and memory CD8+ T cells enter reactive lymph nodes and kill dendritic cells

T lymphocytes lacking the lymph node-homing receptors L-selectin and CCR7 do not migrate to lymph nodes in the steady state. Instead, we found here that lymph nodes draining sites of mature dendritic cells or adjuvant inoculation recruited L-selectin-negative CCR7- effector and memory CD8+ T cells. This recruitment required CXCR3 expression on T cells and occurred through high endothelial venules in concert with lumenal expression of the CXCR3 ligand CXCL9. In reactive lymph nodes, recruited T cells established stable interactions with and killed antigen-bearing dendritic cells, limiting the ability of these dendritic cells to activate naive CD4+ and CD8+ T cells. The inducible recruitment of blood-borne effector and memory T cells to lymph nodes may represent a mechanism for terminating primary and limiting secondary immune responses.

High variability and non-neutral evolution of the mammalian avpr1a gene

BACKGROUND: The arginine-vasopressin 1a receptor has been identified as a key determinant for social behaviour in Microtus voles, humans and other mammals. Nevertheless, the genetic bases of complex phenotypic traits like differences in social and mating behaviour among species and individuals remain largely unknown. Contrary to previous studies focusing on differences in the promotor region of the gene, we investigate here the level of functional variation in the coding region (exon 1) of this locus. RESULTS: We detected high sequence diversity between higher mammalian taxa as well as between species of the genus Microtus. This includes length variation and radical amino acid changes, as well as the presence of distinct protein variants within individuals. Additionally, negative selection prevails on most parts of the first exon of the arginine-vasopressin receptor 1a (avpr1a) gene but it contains regions with higher rates of change that harbour positively selected sites. Synonymous and non-synonymous substitution rates in the avpr1a gene are not exceptional compared to other genes, but they exceed those found in related hormone receptors with similar functions. DISCUSSION: These results stress the importance of considering variation in the coding sequence of avpr1a in regards to associations with life history traits (e.g. social behaviour, mating system, habitat requirements) of voles, other mammals and humans in particular.

Toxicity in neuronal cells caused by cerebrospinal fluid from pneumococcal and gram-negative meningitis

To identify neurotoxic factors in meningitis, a neuronal cell line (HN33.1) was exposed to cerebrospinal fluid (CSF) obtained from rabbits with pneumococcal meningitis or Escherichia coli meningitis or 2 h and 6 h after meningitis was induced by proinflammatory bacterial products (pneumococcal cell walls, endotoxin). CSF from all types of meningitis induced similar degrees of cytotoxicity. When a soluble tumor necrosis factor (TNF) receptor that completely blocked TNF-mediated toxicity at 10(-7) M was used, all toxicity in meningitis caused by E. coli, endotoxin, or pneumococcal cell wall administration (2 h afterwards) was mediated by TNF. In contrast, CSF from animals with meningitis caused by live pneumococci or pneumococcal cell wall injection (6 h afterwards) retained cytotoxicity in the presence of the TNF receptor. Thus, in established pneumococcal meningitis, but not in the other forms of meningitis, TNF is not the only component toxic in this neuronal cell line.

Evaluation of the colorimetric VITEK 2 card for identification of gram-negative nonfermentative rods: comparison to 16S rRNA gene sequencing

Ninety strains of a collection of well-identified clinical isolates of gram-negative nonfermentative rods collected over a period of 5 years were evaluated using the new colorimetric VITEK 2 card. The VITEK 2 colorimetric system identified 53 (59%) of the isolates to the species level and 9 (10%) to the genus level; 28 (31%) isolates were misidentified. An algorithm combining the colorimetric VITEK 2 card and 16S rRNA gene sequencing for adequate identification of gram-negative nonfermentative rods was developed. According to this algorithm, any identification by the colorimetric VITEK 2 card other than Achromobacter xylosoxidans, Acinetobacter sp., Burkholderia cepacia complex, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia should be subjected to 16S rRNA gene sequencing when accurate identification of nonfermentative rods is of concern.

Combined endurance/resistance training early on, after a first myocardial infarction, does not induce negative left ventricular remodelling

BACKGROUND: Resistance training (RT) is safe and practicable in low-risk populations with coronary artery disease. In patients with left ventricular (LV) dysfunction after an acute ischaemic event, few data exist about the impact of RT on LV remodelling. METHODS: In this prospective, randomized, controlled study, 38 patients, after a first myocardial infarction and a maximum ejection fraction (EF) of 45%, were assigned either to combined endurance training (ET)/RT (n=17; 15 men; 54.7+/-9.4 years and EF: 40.3+/-4.5%) or to ET alone (n=21; 17 men; 57.0+/-9.6 years and EF: 41.9+/-4.9%) for 12 weeks. ET was effectuated at an intensity of 70-85% of peak heart rate; RT, between 40 and 60% of the one-repetition maximum. LV remodelling was assessed by MRI. RESULTS: No statistically significant differences between the groups in the changes of end-diastolic volume (P=0.914), LV mass (P=0.885) and EF (P=0.763) were observed. Over 1 year, the end-diastolic volume increased from 206+/-41 to 210+/-48 ml (P=0.379) vs. 183+/-44 to 186+/-52 ml (P=0.586); LV mass from 149+/-28 to 155+/-31 g (P=0.408) vs. 144+/-36 to 149+/-42 g (P=0.227) and EF from 49.1+/-12.3 to 49.3+/-12.0% (P=0.959) vs. 51.5+/-13.1 to 54.1% (P=0.463), in the ET/RT and ET groups, respectively. Peak VO2 and muscle strength increased significantly in both groups, but no difference between the groups was noticed. CONCLUSION: RT with an intensity of up to 60% of the one-repetition maximum, after an acute myocardial infarction, does not lead to a more pronounced LV dilatation than ET alone. A combined ET/RT, or ET alone, for 3 months can both increase the peak VO2 and muscle strength significantly.

Negative impact of the noseclip on high-frequency respiratory impedance measurements

The noseclip is conventionally used in lung function testing to prevent leakage via the nasal compartments. However, some subjects exhibit a velum-opening reflex which may affect results. We performed forced oscillation measurements at frequencies (8-256 Hz) that include the first antiresonance, comparing the noseclip with a cotton wool nose plug to eliminate upper airway contribution. Three sets of measurements were made in 18 adults: with and without noseclip, and with cotton wool. Velum opening during noseclip measurements was monitored using a nasal pressure transducer. A significantly greater proportion of subjects produced a characteristic distortion to the first antiresonance with the noseclip than with either no noseclip or with cotton wool. Distortion of the spectrum coincided with the transmission of oscillations into the nasal cavity. Thus, the noseclip cannot be used in high-frequency forced oscillation measurements because of the velum reflex. The cotton wool plug offers a simple alternative. This effect has unknown impact in other lung function tests.

Negative index metamaterials and metaspacers for optical frequencies

Metamaterials are artificial materials that exhibit properties, such as negative index of refraction, that are not possible through natural materials. Due to many potential applications of negative index metamaterials, significant progress in the field has been observed in the last decade. However, achieving negative index at visible frequencies is a challenging task. Generally, fishnet metamaterials are considered as a possible route to achieve negative index in the visible spectrum. However, so far no metamaterial has been demonstrated to exhibit simultaneously negative permittivity and permeability (double-negative) beyond the red region of the visible spectrum. This study is mainly focused on achieving higher operating frequency for low-loss, double-negative metamaterials. Two double-negative metamaterials have been proposed to operate at highest reported frequencies. The first proposed metamaterial is based on the interaction of surface plasmon polaritons of a thin metal film with localized surface plasmons of a metallic array placed close to the thin film. It is demonstrated that the metamaterial can easily be scaled to operate at any frequency in the visible spectrum as well as possibly to the ultraviolet spectrum. Furthermore, the underlying physical phenomena and possible future extensions of the metamaterial are also investigated. The second proposed metamaterial is a modification to the so-called fishnet metamaterial. It has been demonstrated that this ‘modified fishnet’ exhibits two double-negative bands in the visible spectrum with highest operating frequency in the green region with considerably high figure of merit. In contrast to most of the fishnet metamaterials proposed in the past, behavior of this modified fishnet is independent of polarization of the incident field. In addition to the two negative index metamaterials proposed in this study, the use of metamaterial as a spacer, named as metaspacer, is also investigated. In contrast to naturally available dielectric spacers used in microfabrication, metaspacers can be realized with any (positive or negative) permittivity and permeability. As an example, the use of a negative index metaspacer in place of the dielectric layer in a fishnet metamaterial is investigated. It is shown that fishnet based on negative index metaspacer gives many improved optical properties over the conventional fishnet such as wider negative index band, higher figure of merit, higher optical transmission and stronger magnetic response. In addition to the improved properties, following interesting features were observed in the metaspacer based fishnet metamaterial. At the resonance frequency, the shape of the permeability curve was ‘inverted’ as compared to that for conventional fishnet metamaterial. Furthermore, dependence of the resonance frequency on the fishnet geometry was also reversed. Moreover, simultaneously negative group and phase velocities were observed in the low-loss region of the metaspacer based fishnet metamaterial. Due to interesting features observed using metaspacer, this study will open a new horizon for the metamaterial research.

ADVENTURES IN FRIEDMANN COSMOLOGIES---INTERACTION OF POSITIVE ENERGY DENSITIES WITH NEGATIVE ENERGY DENSITIES AND CURVATURE OF THE UNIVERSE

In this report we will investigate the effect of negative energy density in a classic Friedmann cosmology. Although never measured and possibly unphysical, the evolution of a Universe containing a significant cosmological abundance of any of a number of hypothetical stable negative energy components is explored. These negative energy (Ω < 0) forms include negative phantom energy (w<-1), negative cosmological constant (w=-1), negative domain walls (w=-2/3), negative cosmic strings (w= -1/3), negative mass (w=0), negative radiation (w=1/3), and negative ultra-light (w > 1/3). Assuming that such universe components generate pressures as perfect fluids, the attractive or repulsive nature of each negative energy component is reviewed. The Friedmann equations can only be balanced when negative energies are coupled to a greater magnitude of positive energy or positive curvature, and minimal cases of both of these are reviewed. The future and fate of such universes in terms of curvature, temperature, acceleration, and energy density are reviewed including endings categorized as a Big Crunch, Big Void, or Big Rip and further qualified as "Warped", "Curved", or "Flat", "Hot" versus "Cold", "Accelerating" versus" Decelerating" versus "Coasting". A universe that ends by contracting to zero energy density is termed a Big Poof. Which contracting universes ``bounce" in expansion and which expanding universes ``turnover" into contraction are also reviewed. The name by which the ending of the Universe is mentioned is our own nomenclature.

Multiparameter flow cytometry characterization of MHC class I negative mouse bone marrow cells

BACKGROUND: MHC-I down-regulation was described in foetal liver progenitors, and two different subsets of adult bone marrow derived stem cells. These cells, namely, MHC-I-/Thy1+ bone marrow derived liver stem cells (BMDLSC) and the multipotent adult progenitors (MAPC) differentiated into functioning hepatocytes. The aim of this paper was to characterize the MHC-I negative bone marrow compartment as it pertains to BMDLSC and MAPC. MATERIAL/METHODS: We performed multiparameter flow-cytometry analyses of the MHC-I negative compartment using hematopoietic (CD45, Ter119), and stem cell markers (Thy1.2, c-Kit, IL-3R, CD34) in adult mice. RESULTS: When analysing CD45 and Ter119 expression, the MHC-I negative bone marrow compartment divides into four sub-populations: 1. CD45-/Ter119+: 86.0+/-4.4%; 2. CD45+/Ter119+: 0.2+/-0.1%; 3. CD45+/Ter119-: 11.6+/-3.0%; 4. CD45-/Ter119-: 2.0+/-2.1%. Stem cells markers were only expressed on MHC-I negative/ CD45+/Ter119- cells. In vivo, MAPC (Ter119-/CD45- cells) are composed of MHC-I negative (24%) and MHC-I positive cells and do not express any of the stem cell markers tested. CONCLUSIONS: In conclusion, mouse BMDLSC and MAPC are two distinct stem cell populations. Down-regulation of MHC-I was the only common characteristic found between BMDLSC and MAPC suggesting that selection of MHC-I negative cells might represent an efficient strategy to enrich for bone marrow stem cells with liver developmental potential.

Screening for carriage of methicillin-resistant Staphylococcus aureus shortly after exposure may lead to false-negative results

We evaluated a double screening strategy for carriage of methicillin-resistant Staphylococcus aureus (MRSA) in patients exposed to a newly detected MRSA carrier. If the first screening of the exposed patient yielded negative results, screening was repeated 4 days later. This strategy detected 12 (28%) of the 43 new MRSA carriers identified during the study period. The results suggest that there is an incubation period before MRSA carriage is detectable.