The human microbiome has emerged as a major player in regulating human health and disease. Translational studies of the microbiome have the potential to indicate clinical applications such as fecal ...transplants and probiotics. However, one major issue is accurate identification of microbes constituting the microbiota. Studies of the microbiome have frequently utilized sequencing of the conserved 16S ribosomal RNA (rRNA) gene. We present a comparative study of an alternative approach using whole genome shotgun sequencing (WGS). In the present study, we analyzed the human fecal microbiome compiling a total of 194.1 × 106 reads from a single sample using multiple sequencing methods and platforms. Specifically, after establishing the reproducibility of our methods with extensive multiplexing, we compared: 1) The 16S rRNA amplicon versus the WGS method, 2) the Illumina HiSeq versus MiSeq platforms, 3) the analysis of reads versus de novo assembled contigs, and 4) the effect of shorter versus longer reads. Our study demonstrates that whole genome shotgun sequencing has multiple advantages compared with the 16S amplicon method including enhanced detection of bacterial species, increased detection of diversity and increased prediction of genes. In addition, increased length, either due to longer reads or the assembly of contigs, improved the accuracy of species detection.
•Human microbiome has emerged as a major player in regulating health and disease.•Accurate identification of microbes constituting the microbiome is major challenge.•We report comparative study of whole genome shotgun (WGS) and amplicon sequencing.•WGS enhances detection of bacterial species with high accuracy.•WGS increased detection of microbial diversity and prediction of putative genes.
ABSTRACT We present a study of the spatial distribution and kinematics of star-forming galaxies in 30 massive clusters at 0.15 < z < 0.30, combining wide-field Spitzer 24 m and GALEX near-ultraviolet ...imaging with highly complete spectroscopy of cluster members. The fraction (fSF) of star-forming cluster galaxies rises steadily with cluster-centric radius, increasing fivefold by 2r200, but remains well below field values even at 3r200. This suppression of star formation at large radii cannot be reproduced by models in which star formation is quenched in infalling field galaxies only once they pass within r200 of the cluster, but is consistent with some of them being first pre-processed within galaxy groups. Despite the increasing fSF-radius trend, the surface density of star-forming galaxies actually declines steadily with radius, falling ∼15× from the core to 2r200. This requires star formation to survive within recently accreted spirals for 2-3 Gyr to build up the apparent over-density of star-forming galaxies within clusters. The velocity dispersion profile of the star-forming galaxy population shows a sharp peak of 1.44 at 0.3r500, and is 10%-35% higher than that of the inactive cluster members at all cluster-centric radii, while their velocity distribution shows a flat, top-hat profile within r500. All of these results are consistent with star-forming cluster galaxies being an infalling population, but one that must also survive ∼0.5-2 Gyr beyond passing within r200. By comparing the observed distribution of star-forming galaxies in the stacked caustic diagram with predictions from the Millennium simulation, we obtain a best-fit model in which star formation rates decline exponentially on quenching timescales of 1.73 0.25 Gyr upon accretion into the cluster.
Abstract We report direct evidence of pre-processing of the galaxies residing in galaxy groups falling into galaxy clusters drawn from the Local Cluster Substructure Survey (LoCuSS). 34 groups have ...been identified via their X-ray emission in the infall regions of 23 massive (〈M200〉 = 1015 M⊙) clusters at 0.15 < z < 0.3. Highly complete spectroscopic coverage combined with 24 μm imaging from Spitzer allows us to make a consistent and robust selection of cluster and group members including star-forming galaxies down to a stellar mass limit of M⋆ = 2 × 1010 M⊙. The fraction fSF of star-forming galaxies in infalling groups is lower and with a flatter trend with respect to clustercentric radius when compared to the rest of the cluster galaxy population. At R ≈ 1.3 r200, the fraction of star-forming galaxies in infalling groups is half that in the cluster galaxy population. This is direct evidence that star-formation quenching is effective in galaxies already prior to them settling in the cluster potential, and that groups are favourable locations for this process.
We present a new catalogue of 55 121 groups and clusters centred on luminous red galaxies from Sloan Digital Sky Survey Data Release 7 in the redshift range 0.15 ≤z≤ 0.4. We provide halo mass (M
500) ...estimates for each of these groups derived from a calibration between the optical richness of bright galaxies (M
r
≤−20.5) within 1 Mpc and X-ray-derived mass for a small subset of 129 groups and clusters with X-ray measurements. For 20 157 high-mass groups and clusters with M
500 > 1013.7 M⊙, we find that the catalogue has a purity of >97 per cent and a completeness of ∼90 per cent. We derive the mean (stacked) surface number density profiles of galaxies as a function of total halo mass in different mass bins. We find that derived profiles can be well described by a projected Navarro-Frenk-White profile with a concentration parameter (〈c〉≡〈r
200/r
s〉≈ 2.6) that is approximately a factor of 2 lower than that of the dark matter (as predicted by N-body cosmological simulations) and nearly independent of halo mass. Interestingly, in spite of the difference in shape between the galaxy and dark matter radial distributions, both exhibit a high degree of self-similarity. We also stack the satellite profiles based on other observables, namely redshift, brightest cluster galaxy (BCG) luminosity and satellite luminosity and colour. We see no evidence for strong variation in profile shape with redshift over the range we probe or with BCG luminosity (or BCG luminosity fraction), but we do find a strong dependence on satellite luminosity and colours, in agreement with previous studies. A self-consistent comparison to several recent semi-analytic models of galaxy formation indicates that (1) beyond ≈0.3r
500 current models are able to reproduce both the shape and normalization of the satellite profiles, and (2) within ≈0.3r
500 the predicted profiles are sensitive to the details of the satellite-BCG merger time-scale calculation. The former is a direct result of the models being tuned to match the global galaxy luminosity function combined with the assumption that the satellite galaxies do not suffer significant tidal stripping, even though their surrounding dark matter haloes can be removed through this process. Combining our results with measurements of the intracluster light should provide a way to inform theoretical models on the efficacy of the tidal stripping and merging processes.
Dichloroacetate (DCA), through the inhibition of aerobic glycolysis (the 'Warburg effect') and promotion of pyruvate oxidation, induces growth reduction in many tumours and is now undergoing several ...clinical trials. If aerobic glycolysis is active in multiple myeloma (MM) cells, it can be potentially targeted by DCA to induce myeloma growth inhibition.
Representative multiple myeloma cell lines and a myeloma-bearing mice were treated with DCA, alone and in combination with bortezomib.
We found that aerobic glycolysis occurs in approximately half of MM cell lines examined, producing on average 1.86-fold more lactate than phorbol myristate acetate stimulated-peripheral blood mononuclear cells and is associated with low-oxidative capacity. Lower doses of DCA (5-10 mM) suppressed aerobic glycolysis and improved cellular respiration that was associated with activation of the pyruvate dehydrogenase complex. Higher doses of DCA (10-25 mM) induced superoxide production, apoptosis, suppressed proliferation with a G0/1 and G2M phase arrest in MM cell lines. In addition, DCA increased MM cell line sensitivity to bortezomib, and combinatorial treatment of both agents improved the survival of myeloma-bearing mice.
Myeloma cells display aerobic glycolysis and DCA may complement clinically used MM therapies to inhibit disease progression.
This paper presents a spatially resolved kinematic study of the jellyfish galaxy JO201, one of the most spectacular cases of ram-pressure stripping (RPS) in the GAs Stripping Phenomena in galaxies ...with MUSE (GASP) survey. By studying the environment of JO201, we find that it is moving through the dense intracluster medium of Abell 85 at supersonic speeds along our line of sight, and that it is likely accompanied by a small group of galaxies. Given the density of the intracluster medium and the galaxy's mass, projected position, and velocity within the cluster, we estimate that JO201 must so far have lost ∼50% of its gas during infall via RPS. The MUSE data indeed reveal a smooth stellar disk accompanied by large projected tails of ionized ( ) gas, composed of kinematically cold (velocity dispersion <40 km s−1) star-forming knots and very warm (>100 km s−1) diffuse emission, that extend out to at least from the galaxy center. The ionized -emitting gas in the disk rotates with the stars out to ∼6 kpc; but, in the disk outskirts, it becomes increasingly redshifted with respect to the (undisturbed) stellar disk. The observed disturbances are consistent with the presence of gas trailing behind the stellar component resulting from intense face-on RPS along the line of sight. Our kinematic analysis is consistent with the estimated fraction of lost gas and reveals that stripping of the disk happens outside-in, causing shock heating and gas compression in the stripped tails.
BACKGROUNDCultural ideals for a slimmer face have led to an upsurge in interest in facial contouring among East Asians. Although surgical resection has traditionally been the main treatment option, ...botulinum toxin injection is becoming a popular, noninvasive alternative.
OBJECTIVETo describe the use of botulinum toxin injection for masseter reduction in East Asians.
METHODSAn electronic search of the PubMed database was performed for studies published from 2000 to 2017 that meet the word combination of botulinum toxin, masseter, hypertrophy, and/or lower face contouring. Only the studies conducted in East Asian countries were analyzed in this review, exception of one study from Thailand.
RESULTSA total of 12 publications were identified. Each study was reviewed to extract relevant information on patient selection, injection techniques, efficacy, dosage, frequency, and main side effects of treating masseters with botulinum toxin.
CONCLUSIONBotulinum toxin injection for masseter reduction in East Asians is efficacious and generally considered safe with no significant side effects. Future areas for investigation include defining the criteria for benign masseteric hypertrophy, minimum effective dosage of botulinum toxin, and the potential long-term effects of the injection.
Core 1- and 3-derived mucin-type O-glycans are primary components of the mucus layer in the colon. Reduced mucus thickness and impaired O-glycosylation are observed in human ulcerative colitis. ...However, how both types of O-glycans maintain mucus barrier function in the colon is unclear. We found that C1galt1 expression, which synthesizes core 1 O-glycans, was detected throughout the colon, whereas C3GnT, which controls core 3 O-glycan formation, was most highly expressed in the proximal colon. Consistent with this, mice lacking intestinal core 1-derived O-glycans (IEC C1galt1
) developed spontaneous colitis primarily in the distal colon, whereas mice lacking both intestinal core 1- and 3-derived O-glycans (DKO) developed spontaneous colitis in both the distal and proximal colon. DKO mice showed an early onset and more severe colitis than IEC C1galt1
mice. Antibiotic treatment restored the mucus layer and attenuated colitis in DKO mice. Mucins from DKO mice were more susceptible to proteolysis than wild-type mucins. This study indicates that core 1- and 3-derived O-glycans collectively contribute to the mucus barrier by protecting it from bacterial protease degradation and suggests new therapeutic targets to promote mucus barrier function in colitis patients.
Purpose
Despite previous studies proposing shorter durations of anti-HER2 therapy for selected patients with HER2-positive early breast cancer (EBC), 12-months remains standard of care. A survey was ...performed to assess patient perspectives and willingness to participate in studies evaluating shorter durations of anti-HER2 therapy.
Methods
Patients with HER2-positive EBC completing or having previously completed anti-HER2 therapy, were recruited by healthcare professionals at The Ottawa Hospital Cancer Centre to participate in an anonymous online survey. The primary objective was to learn about patients’ perspectives on shorter durations (less than 12-months) of anti-HER2 therapy. Secondary objectives were to explore patients’ interest in clinical trials of shorter durations of anti-HER2 therapy and the degree of increased breast cancer risk they would accept with a shorter treatment duration.
Results
Responses were received from 94 eligible patients. Most patients received Trastuzumab alone (78%, 73/94), while 13% (12/94) received trastuzumab and pertuzumab. Side effects were experienced by 52% (46/89), the most common being; fatigue (61%, 28/46), myalgia (37%, 17/46), and diarrhea (24%, 11/46). Most patients (88%, 78/89) did not find treatment bothersome. Regarding perspectives on shorter durations of anti-HER2 therapy, most (79%, 74/94) respondents stated they would agree to less treatment if it were possible to receive fewer treatments with the same cancer benefits. 56% of patients were interested in clinical trials, however, about half stated they would not be accepting of any increase in breast cancer recurrence risk.
Conclusion
Trials to investigate who can safely and effectively be treated with shorter durations of anti-HER2 therapy are needed. This study provides important insights to patients’ perspectives on shorter durations of anti-HER2 treatment, and their concerns regarding potential increased cancer risk with less treatment.
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