T-cell therapies for T-cell lymphoma

T-cell lymphomas represent a subpopulation of non-Hodgkin lymphomas with poor outcomes when treated with conventional chemotherapy. A variety of novel agents have been introduced as new treatment strategies either as first-line treatment or in conjunction with chemotherapy. Immunotherapy has been demonstrated to be a promising area for new therapeutics, including monoclonal antibodies and adoptive cellular therapeutics. T-cell therapeutics have been shown to have significant success in the treatment of B-cell malignancies and are rapidly expanding as potential treatment options for other cancers including T-cell lymphomas. Although treating T-cell lymphomas with T-cell therapeutics has unique challenges, multiple targets are currently being studied both preclinically and in clinical trials.     

Big cats at large: Density,structure, and spatio-temporal patterns of a leopard population free of anthropogenic mortality

Human impact is near pervasive across the planet and studies of wildlife populations free of anthropogenic mortality are increasingly scarce. This is particularly true for large carnivores that often compete with and, in turn, are killed by humans. Accordingly, the densities at which carnivore populations occur naturally, and their role in shaping and/or being shaped by natural processes, are frequently unknown. We undertook a camera-trap survey in the Sabi Sand Game Reserve (SSGR), South Africa, to examine the density, structure and spatio-temporal patterns of a leopard Panthera pardus population largely unaffected by anthropogenic mortality. Estimated population density based on spatial capture–recapture models was 11.8 ± 2.6 leopards/100 km². This is likely close to the upper density limit attainable by leopards, and can be attributed to high levels of protection (particularly, an absence of detrimental edge effects) and optimal habitat (in terms of prey availability and cover for hunting) within the SSGR. Although our spatio-temporal analyses indicated that leopard space use was modulated primarily by “bottom-up” forces, the population appeared to be self-regulating and at a threshold that is unlikely to change, irrespective of increases in prey abundance. Our study provides unique insight into a naturally-functioning carnivore population at its ecological carrying capacity. Such insight can potentially be used to assess the health of other leopard populations, inform conservation targets, and anticipate the outcomes of population recovery attempts.     

TLR- and NOD2-dependent regulation of human phagocyte-specific chitotriosidase

Human chitotriosidase is specifically expressed by phagocytes, has anti-fungal activity towards chitin-containing fungi in vitro and in vivo, and is part of innate immunity. We studied the effect of toll-like receptor (TLR)- and nucleotide-binding oligomerization domain (NOD)-2 triggering on chitotriosidase expression and release by phagocytes. We find that TLR, but not NOD2 activation, regulates chitotriosidase release by neutrophils. Furthermore, both TLR and NOD2 activation resulted in diminished induction by monocytes. Lastly, NOD2 activation, but not TLR stimulation, induces chitinase expression in macrophages. We conclude that phagocyte-specific regulation is important for efficient eradication of chitin-containing pathogens.     

Eat now,pay later? Evidence of deferred food-processing costs in diving seals

Seals may delay costly physiological processes (e.g. digestion) that are incompatible with the physiological adjustments to diving until after periods of active foraging. We present unusual profiles of metabolic rate (MR) in grey seals measured during long-term simulation of foraging trips (4-5 days) that provide evidence for this. We measured extremely high MRs (up to almost seven times the baseline levels) and high heart rates during extended surface intervals, where the seals were motionless at the surface. These occurred most often during the night and occurred frequently many hours after the end of feeding bouts. The duration and amount of oxygen consumed above baseline levels during these events was correlated with the amount of food eaten, confirming that these metabolic peaks were related to the processing of food eaten during foraging periods earlier in the day. We suggest that these periods of high MR represent a payback of costs deferred during foraging.     

Proposed minimum reporting standards for chemical analysis

There is a general consensus that supports the need for standardized reporting of metadata or information describing large-scale metabolomics and other functional genomics data sets. Reporting of standard metadata provides a biological and empirical context for the data, facilitates experimental replication, and enables the re-interrogation and comparison of data by others. Accordingly, the Metabolomics Standards Initiative is building a general consensus concerning the minimum reporting standards for metabolomics experiments of which the Chemical Analysis Working Group (CAWG) is a member of this community effort. This article proposes the minimum reporting standards related to the chemical analysis aspects of metabolomics experiments including: sample preparation, experimental analysis, quality control, metabolite identification, and data pre-processing. These minimum standards currently focus mostly upon mass spectrometry and nuclear magnetic resonance spectroscopy due to the popularity of these techniques in metabolomics. However, additional input concerning other techniques is welcomed and can be provided via the CAWG on-line discussion forum at or . Further, community input related to this document can also be provided via this electronic forum. The contents of this paper do not necessarily reflect any position of the Government or the opinion of the Food and Drug Administration Sponsor: Metabolomics Society http://www.metabolomicssociety.org/ Reference: http://msi-workgroups.sourceforge.net/bio-metadata/reporting/pbc/ http://msi-workgroups.sourceforge.net/chemical-analysis/ Version: Revision: 5.1 Date: 09 January, 2007     

Assessment of methylation events during colorectal tumor progression by absolute quantitative analysis of methylated alleles

To date, the epigenetic events involved in the progression of colorectal cancer are not well described. To study, in detail, methylation during colorectal cancer development in high-risk adenomas, we developed an assay combining in situ (on-slide) sodium bisulfite modification (SBM) of paraffin-embedded archival tissue sections with absolute quantitative assessment of methylated alleles (AQAMA). We tested the performance of the assay to detect methylation level differences between paired pre-malignant and malignant colorectal cancer stages. AQAMA assays were used to measure methylation levels at MINT (methylated in tumor) loci MINT1, MINT2, MINT12, and MINT31. Assay performance was verified on cell line DNA and standard cDNA. On-slide SBM, allowing DNA methylation assessment of 1 to 2 mm(2) of paraffin-embedded archival tissue, was employed. Methylation levels of adenomatous and cancerous components within a single tissue section in 72 colorectal cancer patients were analyzed. AQAMA was verified as accurately assessing CpG island methylation status in cell lines. The correlation between expected and measured cDNA methylation levels was high for all four MINT AQAMA assays (R >or= 0.966, P<0.001). Methylation levels at the four loci increased in 11% and decreased in 36% of specimens comparing paired adenoma and cancer tissues (P<0.0001 by Kolmogorov-Smirnov test). Single-PCR AQAMA provided accurate methylation level measurement. Variable MINT locus methylation level changes occur during malignant progression of colorectal adenoma. Combining AQAMA with on-slide SBM provides a sensitive assay that allows detailed histology-oriented analysis of DNA methylation levels and may give new, accurate insights into understanding development of epigenetic aberrancies in colorectal cancer progression.     

Alanine dehydrogenase and its applications – A review

Alanine dehydrogenase (AlaDH) (E.C.1.4.1.1) is a microbial enzyme that catalyzes a reversible conversion of L-alanine to pyruvate. Inter-conversion of alanine and pyruvate by AlaDH is central to metabolism in microorganisms. Its oxidative deamination reaction produces pyruvate which plays a pivotal role in the generation of energy through the tricarboxylic acid cycle for sporulation in the microorganisms. Its reductive amination reaction provides a route for the incorporation of ammonia and produces L-alanine which is required for synthesis of the peptidoglycan layer, proteins, and other amino acids. Also, AlaDH helps in redox balancing as its deamination/amination reaction is linked to the reduction/oxidation of NAD⁺/NADH in microorganisms. AlaDH from a few microorganisms can also reduce glyoxylate into glycine (aminoacetate) in a nonreversible reaction. Both its oxidative and reductive reactions exhibit remarkable applications in the pharmaceutical, environmental, and food industries. The literature addressing the characteristics and applications of AlaDH from a wide range of microorganisms is summarized in the current review.