Intraepithelial γδ T Cells Remain Increased in the Duodenum of AIDS Patients Despite Antiretroviral Treatment

Intraepithelial lymphocytes (IELs) bearing the γδ T-cell receptor are a unique intestinal subset whose function remains elusive. Here, we examine how they behave in AIDS and during various regimens of antiretroviral treatment in order to obtain mechanistic insight into their adaptive or innate functional in vivo properties. IELs were studied by multimarker two-colour immunofluorescence in situ staining. Consecutive duodenal biopsies were obtained from advanced infection-prone HIV+ patients (n = 30). The systemic adaptive immune status was monitored by determining T-cell subsets and immunoglobulins in peripheral blood. The γδ IEL ratio (median 14.5%, range 1.5–56.3%) was significantly increased (p<0.02) compared with that in clinically healthy HIV− control subjects (n = 11, median 2.8%; range 0.3–38%), although the number of γδ IELs per mucosal length unit (U) only tended to be increased (4.0/U in HIV+ versus 3.2/U in HIV−subjects). Notably, the total number of CD3+ IELs was significantly reduced in AIDS (p<0.0001, 39.6/U in HIV+ versus 86.4/U in HIV− subjects). Almost 100% of the γδ IELs were CD8− and they often expressed the Vδ1/Jδ1-encoded epitope (median 65.2%). HIV+ patients on highly active antiretroviral therapy only tended to have a lower ratio of γδ IELs (median 12.8%) than those receiving no treatment (median 14.3%) or 1 nucleoside analogue (NA) (median 23.5%) or 2 NAs (median 13.0%). This minimal variation among therapy groups, contrasting the treatment response of systemic and local adaptive immunity, harmonizes with the novel idea derived from animal experiments that γδ T cells are largely innate cells in first-line microbial defence

The moose nose bot fly Cephenemyia ulrichii Brauer (Diptera: Oestridae) reported in Norway for the first time

Our conclusion is that C. ulrichii has reached the northeastern part of Norway (Pasvik). A further expansion of this parasite may be expected in Norway as well as in southern Sweden. This study shows that moose can be sampled for C. ulrichii with the described technique in the hunting season when the larvae are in their first instar

The timing and departure rate of larvae of the warble fly Hypoderma (= Oedemagena) tarandi (L.) and the nose bot fly Cephenemyia trompe (Modeer) (Diptera: Oestridae) from reindeer

The emergence of larvae of the reindeer warble fly Hypoderma (= Oedemagena) tarandi (L.) (n = 2205) from 4, 9, 3, 6 and 5 Norwegian semi-domestic reindeer yearlings (Rangifer tarandus tarandus (L.)) was registered in 1988, 1989, 1990, 1991 and 1992, respectively. Larvae of the reindeer nose bot fly Cephenemyia trompe (Moder) (n = 261) were recorded during the years 1990, 1991 and 1992 from the same reindeer. A collection cape technique (only H. tarandi) and a grating technique (both species) were used. In both species, dropping started around 20 Apr and ended 20 June. Peak emergence occurred from 10 May - 10 June, and was usually bimodal. The temperature during the larvae departure period had a slight effect (significant only in 1991) on the dropping rate of H. tarandi larvae, and temperature during infection in the preceding summer is therefore supposed to explain the uneven dropping rate. This appeared to be due to the occurrence of successive periods of infection caused by separate periods of weather that were favourable for mass attacks by the flies. As a result, the temporal pattern of maturation of larvae was divided into distinct pulses. Departure time of the larvae in relation to spring migration of the reindeer influences infection levels. Applied possibilities for biological control by separating the reindeer from the dropping sites are discussed

Thermodynamic Properties near the onset of Loop-Current Order in high-TcT_c superconducting cuprates

We have performed large-scale Monte Carlo simulations on a two-dimensional generalized Ashkin-Teller model to calculate the thermodynamic properties in the critical region near its transitions. The Ashkin-Teller model has a pair of Ising spins at each site which interact with neighboring spins through pair-wise and 4-spin interactions. The model represents the interactions between orbital current loops in $Cu O_2$-plaquettes of high-$T_c$ cuprates, which order with a staggered magnetization \Mso inside each unit-cell in the underdoped region of the phase diagram below a temperature $T^*(x)$ which depends on doping. The pair of Ising spins per unit-cell represent the directions of the currents in the links of the current loops. The generalizations are the inclusion of anisotropy in the pair-wise nearest neighbor current-current couplings consistent with the symmetries of a square lattice and the next nearest neighbor pair-wise couplings. We use the Binder cumulant to estimate the correlation length exponent $\nu$ and the order parameter exponent $\beta$. Our principal results are that in a range of parameters, the Ashkin-Teller model as well as its generalization has an order parameter susceptibility which diverges as $T \to T^*$ and an order parameter below $T^*$. Importantly, however, there is no divergence in the specific heat. This puts the properties of the model in accord with the experimental results in the underdoped cuprates. We also calculate the magnitude of the "bump" in the specific heat in the critical region to put limits on its observability. Finally, we show that the staggered magnetization couples to the uniform magnetization $M_0$ such that the latter has a weak singularity at $T^*$ and also displays a wide critical region, also in accord with recent experiments.Comment: 14 pages, 19 figures, to appear in Physical Review

Coffee bean extracts rich and poor in kahweol both give rise to elevation of liver enzymes in healthy volunteers

BACKGROUND: Coffee oil potently raises serum cholesterol levels in humans. The diterpenes cafestol and kahweol are responsible for this elevation. Coffee oil also causes elevation of liver enzyme levels in serum. It has been suggested that cafestol is mainly responsible for the effect on serum cholesterol levels and that kahweol is mainly responsible for the effect on liver enzyme levels. The objective of this study was to investigate whether coffee oil that only contains a minute amount of kahweol indeed does not cause elevation of liver enzyme levels. METHODS: The response of serum alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) to Robusta coffee oil (62 mg/day cafestol, 1.6 mg/day kahweol) was measured in 18 healthy volunteers. RESULTS: After nine days one subject was taken off Robusta oil treatment due to an ALAT level of 3.6 times the upper limit of normal (ULN). Another two subjects stopped treatment due to other reasons. After 16 days another two subjects were taken off Robusta oil treatment. One of those subjects had levels of 5.8 ULN for ALAT and 2.0 ULN for ASAT; the other subject had an ALAT level of 12.4 ULN and an ASAT level of 4.7 ULN. It was then decided to terminate the study. The median response of subjects to Robusta oil after 16 days was 0.27 ULN (n = 15, 25(th),75(th )percentile: 0.09;0.53) for ALAT and 0.06 ULN (25(th),75(th )percentile -0.06;0.22) for ASAT. CONCLUSIONS: We conclude that the effect on liver enzyme levels of coffee oil containing hardly any kahweol is similar to that of coffee oil containing high amounts of kahweol. Therefore it is unlikely that kahweol is the component of coffee oil that is responsible for the effect. Furthermore, we conclude that otherwise unexplained elevation of liver enzyme levels observed in patients might be caused by a switch from consumption of filtered coffee to unfiltered coffee

Study protocol: differential effects of diet and physical activity based interventions in pregnancy on maternal and fetal outcomes--individual patient data (IPD) meta-analysis and health economic evaluation.

© 2014 Ruifrok et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.BACKGROUND: Pregnant women who gain excess weight are at risk of complications during pregnancy and in the long term. Interventions based on diet and physical activity minimise gestational weight gain with varied effect on clinical outcomes. The effect of interventions on varied groups of women based on body mass index, age, ethnicity, socioeconomic status, parity, and underlying medical conditions is not clear. Our individual patient data (IPD) meta-analysis of randomised trials will assess the differential effect of diet- and physical activity-based interventions on maternal weight gain and pregnancy outcomes in clinically relevant subgroups of women. METHODS/DESIGN: Randomised trials on diet and physical activity in pregnancy will be identified by searching the following databases: MEDLINE, EMBASE, BIOSIS, LILACS, Pascal, Science Citation Index, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Health Technology Assessment Database. Primary researchers of the identified trials are invited to join the International Weight Management in Pregnancy Collaborative Network and share their individual patient data. We will reanalyse each study separately and confirm the findings with the original authors. Then, for each intervention type and outcome, we will perform as appropriate either a one-step or a two-step IPD meta-analysis to obtain summary estimates of effects and 95% confidence intervals, for all women combined and for each subgroup of interest. The primary outcomes are gestational weight gain and composite adverse maternal and fetal outcomes. The difference in effects between subgroups will be estimated and between-study heterogeneity suitably quantified and explored. The potential for publication bias and availability bias in the IPD obtained will be investigated. We will conduct a model-based economic evaluation to assess the cost effectiveness of the interventions to manage weight gain in pregnancy and undertake a value of information analysis to inform future research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2013: CRD42013003804.This study was funded by the National Institute for Health Research (NIHR) HTA (Health Technology Assessment) UK programme 12/01

Differences in Walking Pattern during 6-Min Walk Test between Patients with COPD and Healthy Subjects

BACKGROUND: To date, detailed analyses of walking patterns using accelerometers during the 6-min walk test (6MWT) have not been performed in patients with chronic obstructive pulmonary disease (COPD). Therefore, it remains unclear whether and to what extent COPD patients have an altered walking pattern during the 6MWT compared to healthy elderly subjects. METHODOLOGY/PRINCIPAL FINDINGS: 79 COPD patients and 24 healthy elderly subjects performed the 6MWT wearing an accelerometer attached to the trunk. The accelerometer features (walking intensity, cadence, and walking variability) and subject characteristics were assessed and compared between groups. Moreover, associations were sought with 6-min walk distance (6MWD) using multiple ordinary least squares (OLS) regression models. COPD patients walked with a significantly lower walking intensity, lower cadence and increased walking variability compared to healthy subjects. Walking intensity and height were the only two significant determinants of 6MWD in healthy subjects, explaining 85% of the variance in 6MWD. In COPD patients also age, cadence, walking variability measures and their interactions were included were significant determinants of 6MWD (total variance in 6MWD explained: 88%). CONCLUSIONS/SIGNIFICANCE: COPD patients have an altered walking pattern during 6MWT compared to healthy subjects. These differences in walking pattern partially explain the lower 6MWD in patients with COPD

Six pelagic seabird species of the North Atlantic engage in a fly-and-forage strategy during their migratory movements

Funding Information: We thank all the fieldworkers for their hard work collecting data. Funding for this study was provided by the Norwegian Ministry for Climate and the Environment, the Norwegian Ministry of Foreign Affairs and the Norwegian Oil and Gas Association along with 8 oil companies through the SEATRACK project (www. seapop. no/ en/ seatrack). Fieldwork in Norwegian colonies (incl. Svalbard and Jan Mayen) was supported by the SEAPOP program (www.seapop.no, grant no. 192141). The French Polar Institute (IPEV project 330 to O.C.) supported field operation for Kongsfjord kittiwakes. The work on the Isle of May was also supported by the Natural Environment Research Council (Award NE/R016429/1 as part of the UK-SCaPE programme delivering National Capability). We thank Maria Bogdanova for field support and data processing. Finally, we thank 3 anonymous reviewers for their help improving the first version of the manuscript.Peer reviewedPublisher PD

Cdt1 proteolysis is promoted by dual PIP degrons and is modulated by PCNA ubiquitylation

Cdt1 plays a critical role in DNA replication regulation by controlling licensing. In Metazoa, Cdt1 is regulated by CRL4Cdt2-mediated ubiquitylation, which is triggered by DNA binding of proliferating cell nuclear antigen (PCNA). We show here that fission yeast Cdt1 interacts with PCNA in vivo and that DNA loading of PCNA is needed for Cdt1 proteolysis after DNA damage and in S phase. Activation of this pathway by ultraviolet (UV)-induced DNA damage requires upstream involvement of nucleotide excision repair or UVDE repair enzymes. Unexpectedly, two non-canonical PCNA-interacting peptide (PIP) motifs, which both have basic residues downstream, function redundantly in Cdt1 proteolysis. Finally, we show that poly-ubiquitylation of PCNA, which occurs after DNA damage, reduces Cdt1 proteolysis. This provides a mechanism for fine-tuning the activity of the CRL4Cdt2 pathway towards Cdt1, allowing Cdt1 proteolysis to be more efficient in S phase than after DNA damage

Changing climate and outbreaks of forest pest insects in a cold northern country, Finland

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