Antibody responses against xenotropic murine leukemia virus-related virus envelope in a murine model

Background

Xenotropic murine leukemia virus-related virus (XMRV) was recently discovered to be the first human gammaretrovirus that is associated with chronic fatigue syndrome and prostate cancer (PC). Although a mechanism for XMRV carcinogenesis is yet to be established, this virus belongs to the family of gammaretroviruses well known for their ability to induce cancer in the infected hosts. Since its original identification XMRV has been detected in several independent investigations; however, at this time significant controversy remains regarding reports of XMRV detection/prevalence in other cohorts and cell type/tissue distribution. The potential risk of human infection, coupled with the lack of knowledge about the basic biology of XMRV, warrants further research, including investigation of adaptive immune responses. To study immunogenicity in vivo, we vaccinated mice with a combination of recombinant vectors expressing codon-optimized sequences of XMRV gag and env genes and virus-like particles (VLP) that had the size and morphology of live infectious XMRV.

Results

Immunization elicited Env-specific binding and neutralizing antibodies (NAb) against XMRV in mice. The peak titers for ELISA-binding antibodies and NAb were 1∶1024 and 1∶464, respectively; however, high ELISA-binding and NAb titers were not sustained and persisted for less than three weeks after immunizations.

Conclusions

Vaccine-induced XMRV Env antibody titers were transiently high, but their duration was short. The relatively rapid diminution in antibody levels may in part explain the differing prevalences reported for XMRV in various prostate cancer and chronic fatigue syndrome cohorts. The low level of immunogenicity observed in the present study may be characteristic of a natural XMRV infection in humans.     

Isolation and Characterization of Antimicrobial Compounds in Plant Extracts against Multidrug-Resistant Acinetobacter baumannii

The number of fully active antibiotic options that treat nosocomial infections due to multidrug-resistant Acinetobacter baumannii (A. baumannii) is extremely limited. Magnolia officinalis, Mahonia bealei, Rabdosia rubescens, Rosa rugosa, Rubus chingii, Scutellaria baicalensis, and Terminalia chebula plant extracts were previously shown to have growth inhibitory activity against a multidrug-resistant clinical strain of A. baumannii. In this study, the compounds responsible for their antimicrobial activity were identified by fractionating each plant extract using high performance liquid chromatography, and determining the antimicrobial activity of each fraction against A. baumannii. The chemical structures of the fractions inhibiting >40% of the bacterial growth were elucidated by liquid chromatography/mass spectrometry analysis and nuclear magnetic resonance spectroscopy. The six most active compounds were identified as: ellagic acid in Rosa rugosa; norwogonin in Scutellaria baicalensis; and chebulagic acid, chebulinic acid, corilagin, and terchebulin in Terminalia chebula. The most potent compound was identified as norwogonin with a minimum inhibitory concentration of 128 µg/mL, and minimum bactericidal concentration of 256 µg/mL against clinically relevant strains of A. baumannii. Combination studies of norwogonin with ten anti-Gram negative bacterial agents demonstrated that norwogonin did not enhance the antimicrobial activity of the synthetic antibiotics chosen for this study. In conclusion, of all identified antimicrobial compounds, norwogonin was the most potent against multidrug-resistant A. baumannii strains. Further studies are warranted to ascertain the prophylactic and therapeutic potential of norwogonin for infections due to multidrug-resistant A. baumannii.     

Three-dimensional Nuclear Telomere Organization in Multiple Myeloma

Multiple myeloma (MM) is preceded by monoclonal gammopathy of undetermined significance (MGUS). Up to date, it is difficult to predict an individual's time to disease progression and the treatment response. To examine whether the nuclear telomeric architecture will unravel some of these questions, we carried out. Three-dimensional (3D) telomere analysis on samples from patients diagnosed with MGUS and MM, as well as from patients who went into relapse. Telomere signal intensity, number of telomere aggregates, nuclear volume, and the overall nuclear telomere distribution (a/c ratio) were analyzed. The telomeric profiles allowed for the differentiation of the disease stages. The telomeric profiles of myeloma cells obtained from blood and bone marrow aspirates were identical. Based on this study, we discuss the use of 3D telomere profiling as a potential future tool for risk stratification and personalized treatment decisions.     

Does aerobic and strength exercise sequence in the same session affect the oxygen uptake during and postexercise?

Concurrent training is a strategy employed in both general fitness and sports conditioning. The purpose of this study was to compare the responses of VO2 in different combinations of strength exercise with aerobic interval exercise. Eight men (23.6 ± 4.2 years, 178 ± 6.3 cm, 77 ± 7.9 kg, 7.67 ± 1.95% body fat) completed 3 combinations of strength training (ST) and aerobic training (AT) in a randomized order with a 7-day recovery period: AT before ST exercises, AT between 2 blocks of ST exercises, and AT after ST exercises. The ST comprised 4 exercises performed in 3 sets of 10 reps and 2 exercises, abdominal crunch and lumbar extension, performed in 3 sets of 30 and 20 reps, respectively. The AT consisted of a 20-minute interval cycling. There were no significant differences in the values of absolute or relative VO2, in the heart rate (HR) and in the respiratory exchange ratio (RER) when the 3 sessions (during + postexercise measurements) were compared (values are mean ± SD). Analyzing only ST in each session, differences were detected in the RER values (F = 4.714; p < 0.05; η2 = 0.308) between AT before ST and AT in the middle of ST (1.01 ± 0.97 vs. 1.11 ± 0.07, respectively). In all sequences, there was a significant increase (p < 0.05) in the values of relative and absolute VO2 and HR, and a significant decrease in RER values (p < 0.05) from the first to the second part of the ST session. The values of absolute or relative VO2, HR, and RER did not vary significantly among the 3 sessions as compared with the AT after ST. These data support the hypothesis that ST and AT, when performed in sequence in the same session, do not seem to affect the overall oxygen consumption during the exercise session. Therefore, training sessions may incorporate both modalities without apparent impact on aerobic exercise.     

Differential antibacterial activity of moenomycin analogues on gram-positive bacteria

The moenomycin trisaccharide degradation product and synthetic disaccharide analogues based on the disaccharide core were bactericidal to gram-positive bacteria, inhibited lipid II polymerization, and inhibited cell wall synthesis in Enterococcus faecalis. Truncating moenomycin to the trisaccharide, and building upon the core disaccharide have both led to molecules possessing properties not shared with their respective parent structures.     

An examination of training on the VertiMax resisted jumping device for improvements in lower body power in highly trained college athletes

Training to develop superior muscular power has become a key component to most progressive sport conditioning programs. Conventional resistance training, plyometrics, and speed/agility modalities have all been employed in an effort to realize superlative combinations of training stimuli. New training devices such as the VertiMax resisted jump trainer are marketed as a means of improving lower body reactive power. The purpose of this study was to evaluate the effectiveness of the VertiMax, in combination with traditional training modalities, for improvements in lower body power among highly trained athletes. Forty men and women Division I collegiate athletes representing the sports of baseball, basketball, soccer, gymnastics, and track completed a 12-week mixed-methods training program. Two groups were constructed with both groups performing the same conventional resistance training and strength training exercises. The training control group performed traditional plyometric exercises while the experimental group performed similar loaded jump training on the VertiMax. Lower body power was measured before and after the training program by the TENDO FiTROdyne Powerlizer and statistically compared for differences between groups. Data analyses identified a significant (p < 0.05) and meaningful difference between power development among the 2 groups, with the VertiMax eliciting a greater treatment effect (effect size = 0.54) over conventional resistance and plyometric training alone (effect size = 0.09). These data convincingly demonstrate that the VertiMax represents an effective strategy for developing lower body power among trained college athletes, when combined with traditional strength and conditioning approaches.     

An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution

Cancer cells’ ability to inhibit apoptosis is key to malignant transformation and limits response to therapy. Here, we performed multiplexed immunofluorescence analysis on tissue microarrays with 373 cores from 168 patients, segmentation of 2.4 million individual cells, and quantification of 18 cell lineage and apoptosis proteins. We identified an enrichment for BCL2 in immune, and BAK, SMAC, and XIAP in cancer cells. Ordinary differential equation-based modeling of apoptosis sensitivity at single-cell resolution was conducted and an atlas of inter- and intra-tumor heterogeneity in apoptosis susceptibility generated. Systems modeling at single-cell resolution identified an enhanced sensitivity of cancer cells to mitochondrial permeabilization and executioner caspase activation compared to immune and stromal cells, but showed significant inter- and intra-tumor heterogeneity.Subject terms: Cancer microenvironment, Tumour heterogeneity