Clinical Proteomics of Biofluids in Haematological Malignancies

Since the emergence of high-throughput proteomic techniques and advances in clinical technologies, there has been a steady rise in the number of cancer-associated diagnostic, prognostic, and predictive biomarkers being identified and translated into clinical use. The characterisation of biofluids has become a core objective for many proteomic researchers in order to detect disease-associated protein biomarkers in a minimally invasive manner. The proteomes of biofluids, including serum, saliva, cerebrospinal fluid, and urine, are highly dynamic with protein abundance fluctuating depending on the physiological and/or pathophysiological context. Improvements in mass-spectrometric technologies have facilitated the in-depth characterisation of biofluid proteomes which are now considered hosts of a wide array of clinically relevant biomarkers. Promising efforts are being made in the field of biomarker diagnostics for haematologic malignancies. Several serum and urine-based biomarkers such as free light chains, β-microglobulin, and lactate dehydrogenase are quantified as part of the clinical assessment of haematological malignancies. However, novel, minimally invasive proteomic markers are required to aid diagnosis and prognosis and to monitor therapeutic response and minimal residual disease. This review focuses on biofluids as a promising source of proteomic biomarkers in haematologic malignancies and a key component of future diagnostic, prognostic, and disease-monitoring applications.     

Food in an evolutionary context: insights from mother's milk

In the emergence of diverse animal life forms, food is the most insistent and pervasive of environmental pressures. As the life sciences begin to understand organisms in genomic detail, evolutionary perspectives provide compelling insights into the results of these dynamic interactions between food and consumer. Such an evolutionary perspective is particularly needed today in the face of unprecedented capabilities to alter the food supply. What should we change? Answering this question for food production, safety and sustainability will require a much more detailed understanding of the complex interplay between humans and their food. Many organisms that we grow, produce, process and consume as foods naturally evolved adaptations in part to avoid being eaten. Crop breeding and processing have been the tools to convert overtly toxic and antinutritious commodities into foods that are safe to eat. Now the challenge is to enhance the nutritional quality and thereby contribute to improving human health. We posit that the Rosetta stone of food and nourishment is mammalian lactation and ‘mother's milk’. The milk that a mammalian mother produces for her young is a complete and comprehensive diet. Moreover, the capacity of the mammary gland as a remarkable bioreactor to synthesise milk, and the infant to utilise milk, reflects 200 million years of symbiotic co‐evolution between producer and consumer. Here we present emerging transdisciplinary research ‘decoding’ mother's milk from humans and other mammals. We further discuss how insights from mother's milk have important implications for food science and human health. Copyright © 2012 Society of Chemical Industry     

Naturally suppressed apoptosis prevents follicular atresia and oocyte reserve decline in the adult ovary of Lagostomus maximus (Rodentia, Caviomorpha)

It has been widely accepted that mammalian females are born with a non-renewing, finite pool of oocytes that will be continuously cleared by atresia, with only a small proportion of them reaching ovulation. Apoptosis regulates this mass germ cell death, especially through the balance between pro- and anti-apoptotic proteins encoded by the BCL-2 gene family. The caviomorph rodent Lagostomus maximus, the South American plains viscacha, displays the highest ovulation rate known for a mammal releasing 400-800 eggs per cycle. We tested the hypothesis that in L. maximus massive polyovulation is a consequence of reduced apoptosis resulting in suppressed follicular atresia. We found that anti-apoptotic BCL-2 gene is markedly expressed in all kind of follicles from primordial to fully mature antral stages in the adult ovary of L. maximus. On the other hand, pro-apoptotic BAX gene showed weak signals or was undetectable by immunohistochemical examination. Western blot against both proteins confirmed immunohistochemical results. Screening for DNA fragmentation by TUNEL assay was conspicuously negative in ovaries from both pregnant and non-pregnant females. In addition, alpha-oestrogen receptor also showed an enhanced expression from primordial stage to fully mature antral follicles. Our results show that natural preferential expression of BCL-2 and restricted BAX expression greatly suppresses apoptosis in the ovary of L. maximus. This prevents the decline of the oocyte reserve by abolishing follicular atresia and enables the highest ovulation rate known for a mammal, 400-800 or more eggs per cycle.     

Impact of interferometer optical path difference speed profile on the Fourier-transform-spectrometry-derived spectrum of a telecommunications signal

The impact of the interferometer optical path difference (OPD) speed profile on the spectrum, derived through the use of Fourier-transform spectrometry (FTS), of a synchronous optical network (SONET) signal is found. The SONET signal carries high-speed data traffic. It also may be modulated by low-frequency intensity or frequency modulation. It is found that the SONET header, high-speed data traffic and low-frequency modulation all manifest themselves as artifacts in the FTS-derived spectrum of the SONET signal. It is shown that a nonconstant OPD speed profile can smooth out these artifacts, making it unlikely that they will be mistaken for carrier signal peaks. However, it is found that smoothing out these artifacts lessens the achievable dynamic range of the FTS instrument in the frequency range of interest, the International Telecommunications Union common (C) and long (L) bands.     

Synergetic effect between photocatalytic degradation and adsorption processes on the removal of phenolic compounds from olive mill wastewater

The photocatalytic degradation of two phenolic compounds, p-coumaric acid and caffeic acid, was performed with a suspended mixture of TiO₂ and powdered activated carbon (PAC) (at pH = 3.4 and 8). Adsorption, direct photolysis and photocatalytic degradation were studied under different pH and UV light sources (sunlight vs. 365 nm UV lamps). The potential for reusing this catalyst mixture in sequential photocatalytic runs was examined as well. Quantum yields for the direct photolysis of caffeic acid under solar and artificial 365 nm light were calculated (for the first time) as 0.005 and 0.011, respectively.A higher removal rate of contaminants by either adsorption or photocatalysis was obtained at a low pH (pH 4). Furthermore, the addition of PAC increased the removal efficiency of the phenolic compounds. Fast removal of the pollutants from the solution over three sequential runs was achieved only when both TiO₂ and PAC were present. This suggests that at medium phenolic concentrations, the presence of PAC as a co-sorbent reduces surface poisoning of the TiO₂ catalyst and hence improves photocatalysis degradation of phenolic pollutants.The adsorption equilibrium of caffeic acid or p-coumaric acid on TiO₂, PAC and the combined mixture of TiO₂ and PAC follows the Langmuir isotherm model. Experiments with PAC TiO₂ mixture and olive mill wastewater (anaerobically treated and diluted by a factor of 10) showed higher removal of polyphenols than of chemical oxygen demand (COD). 87% removal of total polyphenols, compared to 58% of COD, was achieved after 24 h of exposure to 365 nm irradiation (7.6 W/m²) in the presence of a suspended mixture of TiO₂ and PAC, indicating “self-selectivity” of polyphenols.     

Inulin‐type fructans and whey protein both modulate appetite but only fructans alter gut microbiota in adults with overweight/obesity: A randomized controlled trial

Scope

Independently, prebiotics and dietary protein have been shown to improve weight loss and/or alter appetite. Our objective was to determine the effect of combined prebiotic and whey protein on appetite, body composition and gut microbiota in adults with overweight/obesity.

Methods and results

In a 12 week, placebo‐controlled, double‐blind study, 125 adults with overweight/obesity were randomly assigned to receive isocaloric snack bars of: (1) Control; (2) Inulin‐type fructans (ITF); (3) Whey protein; (4) ITF + Whey protein. Appetite, body composition and gut microbiota composition/genetic potential were assessed. Compared to Control, body fat was significantly reduced in the Whey protein group at 12 wks. Hunger, desire to eat and prospective food consumption were all lower with ITF, Whey protein and ITF + Whey protein compared to Control at 12 wks. Microbial community structure differed from 0 to 12 wks in the ITF and ITF +Whey Protein groups (i.e. increased Bifidobacterium ) but not Whey Protein or Control. Changes in microbial genetic potential were seen between Control and ITF‐containing treatments.

Conclusion

Adding ITF, whey protein or both to snack bars improved several aspects of appetite control. Changes in gut microbiota may explain in part the effects of ITF but likely not whey protein.

     

18F Site-Specific Labelling of a Single-Chain Antibody against Activated Platelets for the Detection of Acute Thrombosis in Positron Emission Tomography

Positron emission tomography is the imaging modality of choice when it comes to the high sensitivity detection of key markers of thrombosis and inflammation, such as activated platelets. We, previously, generated a fluorine-18 labelled single-chain antibody (scFv) against ligand-induced binding sites (LIBS) on activated platelets, binding it to the highly abundant platelet glycoprotein integrin receptor IIb/IIIa. We used a non-site-specific bio conjugation approach with N-succinimidyl-4-[¹⁸F]fluorobenzoate (S[¹⁸F]FB), leading to a mixture of products with reduced antigen binding. In the present study, we have developed and characterised a novel fluorine-18 PET radiotracer, based on this antibody, using site-specific bio conjugation to engineer cysteine residues with N-[2-(4-[¹⁸F]fluorobenzamido)ethyl]maleimide ([¹⁸F]FBEM). ScFv_anti-LIBS and control antibody mut-scFv, with engineered C-terminal cysteine, were reduced, and then, they reacted with N-[2-(4-[¹⁸F]fluorobenzamido)ethyl]maleimide ([¹⁸F]FBEM). Radiolabelled scFv was injected into mice with FeCl₃-induced thrombus in the left carotid artery. Clots were imaged in a PET MR imaging system, and the amount of radioactivity in major organs was measured using an ionisation chamber and image analysis. Assessment of vessel injury, as well as the biodistribution of the radiolabelled scFv, was studied. In the in vivo experiments, we found uptake of the targeted tracer in the injured vessel, compared with the non-injured vessel, as well as a high uptake of both tracers in the kidney, lung, and muscle. As expected, both tracers cleared rapidly via the kidney. Surprisingly, a large quantity of both tracers was taken up by organs with a high glutathione content, such as the muscle and lung, due to the instability of the maleimide cysteine bond in vivo, which warrants further investigations. This limits the ability of the novel antibody radiotracer ¹⁸F-scFv_anti-LIBS to bind to the target in vivo and, therefore, as a useful agent for the sensitive detection of activated platelets. We describe the first fluorine-18 variant of the scFv_anti-LIBS against activated platelets using site-specific bio conjugation.     

Self-efficacy change as a mediator of associations between therapeutic bond and one-year outcomes in treatments for alcohol dependence.

Empirically-supported treatments for alcohol dependence exist, yet understanding of influences contributing to the intended behavior change is limited. The current study, a secondary analysis of the recent multisite COMBINE trial (The COMBINE Study Research Group, 2003), tested a mediational model wherein change in client self-efficacy for abstinence was examined as a potential mediator of associations between client report of the therapeutic bond and one-year outcomes of drinking frequency, drinking consequences, and psychiatric functioning. For analyses, the 1383 COMBINE trial participants were grouped as follows: 1) those receiving study medications (naltrexone, acamprosate, naltrexone + acamprosate, placebo) and enrolled in medication management (MM) only (n = 607), 2) those receiving study medications/MM and also enrolled in a combination behavioral intervention (CBI) as well (n = 619), and 3) those enrolled in CBI only (n = 157). Mediation analyses using the product-of-coefficients approach indicated self-efficacy change during treatment significantly mediated associations between the therapeutic bond with the CBI therapist and each of the three one-year outcomes among those exclusively receiving CBI, but failed to do so among those receiving pills/MM (with or without CBI). Effect sizes were small, but indicated that variance in bond-outcome associations was partially mediated by self-efficacy change for trial participants. Findings advance understanding of proximal client change processes during delivery of treatments for alcohol dependence. (PsycINFO Database Record (c) 2011 APA, all rights reserved)