Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards

Myeloid-derived suppressor cells (MDSCs) have emerged as major regulators of immune responses in cancer and other pathological conditions. In recent years, ample evidence supports key contributions of MDSC to tumour progression through both immune-mediated mechanisms and those not directly associated with immune suppression. MDSC are the subject of intensive research with >500 papers published in 2015 alone. However, the phenotypic, morphological and functional heterogeneity of these cells generates confusion in investigation and analysis of their roles in inflammatory responses. The purpose of this communication is to suggest characterization standards in the burgeoning field of MDSC research

2-Phenyl-3-(trimethyl­sil­yl)propan-1-aminium chloride

The title compound, C12H22NSi+·Cl−, contains two formula units in the asymmetric unit and is a hydro­chloride salt in which the amine N atom is protonated and the NH3 + group forms hydrogen bonds with the Cl− anion, forming a ribbon in the c-axis direction

Circulating Biomarkers to Identify Responders in Cardiac Cell therapy.

Bone marrow mononuclear cell (BM-MNC) therapy in ST-elevation acute myocardial infarction (STEMI) has no biological inclusion criteria. Here, we analyzed 63 biomarkers and cytokines in baseline plasma samples from 77 STEMI patients treated with BM-MNCs in the TIME and Late-TIME trials as well as 61 STEMI patients treated with placebo. Response to cell therapy was defined by changes in left ventricular ejection fraction, systolic/diastolic volumes, and wall motion indexes. We investigated the clinical value of circulating proteins in outcome prediction using significance testing, partial least squares discriminant analysis, and receiver operating characteristic (ROC) analysis. Responders had higher biomarker levels (76-94% elevated) than non-responders. Several biomarkers had values that differed significantly (P < 0.05) between responders and non-responders including stem cell factor, platelet-derived growth factor, and interleukin-15. We then used these lead candidates for ROC analysis and found multiple biomarkers with values areas under the curve >0.70 including interleukin 15. These biomarkers were not involved in the placebo-treated subjects suggesting that they may have predictive power. We conclude that plasma profiling after STEMI may help identify patients with a greater likelihood of response to cell-based treatment. Prospective trials are needed to assess the predictive value of the circulating biomarkers

One-year outcomes after transcatheter insertion of an interatrial shunt device for the management of heart failure with preserved ejection fraction

Background—Heart failure with preserved ejection fraction has a complex pathophysiology and remains a therapeutic challenge. Elevated left atrial pressure, particularly during exercise, is a key contributor to morbidity and mortality. Preliminary analyses have demonstrated that a novel interatrial septal shunt device that allows shunting to reduce the left atrial pressure provides clinical and hemodynamic benefit at 6 months. Given the chronicity of heart failure with preserved ejection fraction, evidence of longer-term benefit is required. Methods and Results—Patients (n=64) with left ventricular ejection fraction ≥40%, New York Heart Association class II–IV, elevated pulmonary capillary wedge pressure (≥15 mm Hg at rest or ≥25 mm Hg during supine bicycle exercise) participated in the open-label study of the interatrial septal shunt device. One year after interatrial septal shunt device implantation, there were sustained improvements in New York Heart Association class (P<0.001), quality of life (Minnesota Living with Heart Failure score, P<0.001), and 6-minute walk distance (P<0.01). Echocardiography showed a small, stable reduction in left ventricular end-diastolic volume index (P<0.001), with a concomitant small stable increase in the right ventricular end-diastolic volume index (P<0.001). Invasive hemodynamic studies performed in a subset of patients demonstrated a sustained reduction in the workload corrected exercise pulmonary capillary wedge pressure (P<0.01). Survival at 1 year was 95%, and there was no evidence of device-related complications. Conclusions—These results provide evidence of safety and sustained clinical benefit in heart failure with preserved ejection fraction patients 1 year after interatrial septal shunt device implantation. Randomized, blinded studies are underway to confirm these observations

Spatially Resolved PAH Emission Features in Nearby, Low Metallicity, Star-Forming Galaxies

Low-resolution, mid-infrared Spitzer/IRS spectral maps are presented for three nearby, low-metallicity dwarf galaxies (NGC 55, NGC 3109 and IC 5152) for the purpose of examining the spatial distribution and variation of polycyclic aromatic hydrocarbon (PAH) emission. The sample straddles a metallicity of 12+log(O/H)~8.0, a transition point below which PAH intensity empirically drops and the character of the interstellar medium changes. We derive quantitative radiances of PAH features and atomic lines on both global and spatially-resolved scales. The Spitzer spectra, combined with extensive ancillary data from the UV through the mid-infrared, allow us to examine changes in the physical environments and in PAH feature radiances down to a physical scale of 50 pc. We discuss correlations between various PAH emission feature and atomic line radiances. The (6.2 micron)/(11.3 micron), (7.7 micron)/(11.3 micron), (8.6 micron)/(11.3 micron), (7.7 micron)/(6.2 micron), and (8.6 micron)/(6.2 micron) PAH radiance ratios are found to be independent of position across all three galaxies, although the ratios do vary from galaxy to galaxy. As seen in other galaxies, we find no variation in the grain size distribution as a function of local radiation field strength. Absolute PAH feature intensities as measured by a ratio of PAH/(24 micron) radiances are seen to vary both positionally within a given galaxy, and from one galaxy to another when integrated over the full observed extent of each system. We examine direct comparisons of CC mode PAH ratios (7.7 micron)/(6.2 micron) and (8.6 micron)/(6.2 micron) to the mixed (CC/CH) mode PAH ratio (7.7 micron)/(11.3 micron). We find little variation in either mode, and no difference in trends between modes. While the local conditions change markedly over the observed regions of these galaxies, the properties of PAH emission show a remarkable degree of uniformity.Comment: Astrophysical Journal, in pres

2-(4-Hy­droxy­phen­yl)-3-(trimethyl­sil­yl)propanaminium chloride

In the title crystal structure, C12H22NOSi+·Cl−, anions and cations are linked via O—H⋯Cl, N—H⋯Cl and N—H⋯O hydrogen bonds to form a two-dimensional network parallel to (101). Within the hydrogen-bonded network, R 4 2(22) ring motifs are stacked along [010]

Conformational changes in alpha 7 acetylcholine receptors underlying allosteric modulation by divalent cations

Abstract Allosteric modulation of membrane receptors is a widespread mechanism by which endogenous and exogenous agents regulate receptor function. For example, several members of the nicotinic receptor family are modulated by physiological concentrations of extracellular calcium ions. In this paper, we examined conformational changes underlying this modulation and compare these with changes evoked by ACh. Two sets of residues in the α7 acetylcholine receptor extracellular domain were mutated to cysteine and analyzed by measuring the rates of modification by the thiol-specific reagent 2-aminoethylmethane thiosulfonate. Using Ba2+ as a surrogate for Ca2+, we found a divalent-dependent decrease the modification rates of cysteine substitutions at M37 and M40, residues at which rates were also slowed by ACh. In contrast, Ba2+ had no significant effect at N52C, a residue where ACh increased the rate of modification. Thus divalent modulators cause some but not all of the conformational effects elicited by agonist. Cysteine substitution of either of two glutamates (E44 or E172), thought to participate in the divalent cation binding site, caused a loss of allosteric modulation, yet Ba2+ still had a significant effect on modification rates of these residues. In addition, the effect of Ba2+ at these residues did not appear to be due to direct occlusion. Our data demonstrate that modulation by divalent cations involves substantial conformational changes in the receptor extracellular domain. Our evidence also suggests the modulation occurs via a binding site distinct from one which includes either (or both) of the conserved glutamates at E44 or E172

Risk factors for common cancers among patients at Kamuzu Central Hospital in Lilongwe, Malawi: A retrospective cohort study

Little is known about risk factors for different cancers in Malawi. This study aimed to assess risk factors for and epidemiologic patterns of common cancers among patients treated at Kamuzu Central Hospital (KCH) in Lilongwe, and to determine the prevalence of Human Immunodeficiency Virus (HIV) infection in the same population

Risk factors for common cancers among patients at Kamuzu Central Hospital in Lilongwe, Malawi: A retrospective cohort study

Background: Little is known about risk factors for different cancers in Malawi. This study aimed to assess risk factors for and epidemiologic patterns of common cancers among patients treated at Kamuzu Central Hospital (KCH) in Lilongwe, and to determine the prevalence of Human Immunodeficiency Virus (HIV) infection in the same population.Methods: We analysed data from the hospital-based KCH cancer registry, from June 2009 to September 2012, including data from a nested substudy on coinfections among cancer patients. Demographics and behavioural variables, including smoking and alcohol use, were collected through personal interviews with patients. We assessed HIV prevalence across cancer types. The distribution of cancer types was reported overall and by gender. Logistic regression was used to assess risk factors associated with common cancer types.Results: Data from 504 registered cancer patients were included—300 (59.5%) were female and 204 (40.5%) were male. Mean age was 49 years (standard deviation, SD = 16). There were 343 HIV-negative patients (71.2%), and 139 (28.8%) were HIV-positive. The commonest cancers were oesophageal (n = 172; 34.5%), cervical (n = 109; 21.9%), and Kaposi’s sarcoma (KS) (n = 52; 10.4%). Only 18% of cancer cases were histologically confirmed. Patients with oesophageal cancer were likely to be older than 50 years (odds ratio, OR = 2.22), male (OR = 1.47), and smokers (OR = 2.02). Kaposi’s sarcoma patients had the highest odds (OR = 54.4) of being HIV-positive and were also more likely to be male (OR = 6.02) and smokers. Cervical cancer patients were more likely to be HIV-positive (OR = 2.2) and less than 50 years of age.Conclusions: Age, smoking, and HIV are important risk factors for the 3 commonest cancer types (oesophageal, KS, and cervical) at this teaching hospital in Malawi. HIV is the single most important risk factor for Kaposi’s sarcoma and cervical cancer