Ionic liquids in biotechnology: applications and perspectives for biotransformations

Ionic liquids are considered as an alternative to organic solvents for catalysis. The literature in this field is reviewed with focus on advantageous use of ionic liquids in biocatalysis and biotransformations. The overview reveals that the exploration and mapping of ionic liquids with respect to biocatalysis is still sketchy. It is apparent that advantages can be gained in view of activity, stability and selectivity. Furthermore, integration of reaction and separation has a high potential in the field. The review presents quantitative data on the productivities, space–time yields, as well as stability as far as they can be extracted from the literature. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Synergistic anti‐proliferative and pro‐apoptotic activity of combined therapy with bortezomib,a proteasome inhibitor,with anti‐epidermal growth factor receptor (EGFR) drugs in human cancer cells

The article to which this erratum refers was published in J Cell Physiol (2008) 216: 698–707. © 2008 Wiley‐Liss, Inc. DOI: 10.1002/jcp.21444     

Modeling balance control during sustained waking allows posturographic sleepiness testing

We develop a method to quantify sleepiness. Sleepiness is a major risk factor in traffic and occupational accidents, but lack of convenient tests precludes monitoring impending sleepiness. Posturographic balance testing could address this need because sleepiness increases postural sway. It is, however, unclear how sleepiness influences balance control. Our results, for 12 subjects, show that balance control is more susceptible to increasing time awake (TA) compared to neuromuscular processes. This conclusion is reached since during sustained waking the control process slows down by 3.4% per hour of increased TA. This slowdown accounts for 65% of the variance in diurnal balance. We quantified balance control by modeling the body as an inverted pendulum and by expressing the control as the critical time interval for open-loop control (Deltat(c)) of the center-of-mass movements of this pendulum. To estimate the subjects' TA, we regressed the Deltat(c) scores recorded during sustained waking against increasing TA, and equated separate Deltat(c) test scores with the diurnal Deltat(c) scores. We estimated TA with 68% positive predictive value. The results encourage implementing balance modeling into a device that performs clinical or industrial balance testing because the model-based Deltat(c) score responded to increasing TA.     

MAGE-A3<Subscript>161–175 </Subscript>contains an HLA-DRβ4 restricted natural epitope poorly formed through indirect presentation by dendritic cells

We report here that HLA-DRβ4*01 restricted MAGE-A3_161–175 specific CD4⁺ T cells from a healthy donor recognize a naturally processed epitope formed through the exogenous but not the endogenous pathway. However, the intensity of recognition of the native epitope by MAGE-A3_161–175 specific CD4⁺ T cells strongly depends on the antigen presenting cells and the amount of protein available for processing. EBV-transformed lymphoblastoid cells (LCLs) and melanoma cells engineered to express MAGE-A3 in the endosomal/lysosomal compartment were strongly recognized while autologous dendritic cells loaded with lysate from MAGE-A3 expressing cells were, although significantly, poorly recognized. To prove that the amount of antigen available for processing was a key factor determining the different response LCLs were sorted by MAGE-A3 expression. The response intensity correlated with the amount of MAGE-A3 expressed by the cells. Collectively, these results suggest that different antigen presenting cells with different amount of antigen available for processing as well as protease activity are important factors in determining the epitope repertoire produced in vivo, and therefore reliable tools should be used when testing recognition of native epitopes by peptide specific CD4⁺ T cells.     

Carcinoembryonic antigen-specific but not antiviral CD4+ T cell immunity is impaired in pancreatic carcinoma patients

Pancreatic carcinoma is a very aggressive disease with dismal prognosis. Although evidences for tumor-specific T cell immunity exist, factors related to tumor microenvironment and the presence of immunosuppressive cytokines in patients' sera have been related to its aggressive behavior. Carcinoembryonic Ag (CEA) is overexpressed in 80-90% of pancreatic carcinomas and contains epitopes recognized by CD4(+) T cells. The aim of this study was to evaluate the extent of cancer-immune surveillance and immune suppression in pancreatic carcinoma patients by comparing the anti-CEA and antiviral CD4(+) T cell immunity. CD4(+) T cells from 23 normal donors and 44 patients undergoing surgical resection were tested for recognition of peptides corresponding to CEA and viral naturally processed promiscuous epitopes by proliferation and cytokine release assays. Anti-CEA CD4(+) T cell immunity was present in a significantly higher number of normal donors than pancreatic cancer patients. Importantly, whereas CD4(+) T cells from normal donors produced mainly GM-CSF and IFN-gamma, CD4(+) T cells from the patients produced mainly IL-5, demonstrating a skew toward a Th2 type. On the contrary, the extent of antiviral CD4(+) T cell immunity was comparable between the two groups and showed a Th1 type. The immunohistochemical analysis of tumor-infiltrating lymphocytes showed a significantly higher number of GATA-3(+) compared with T-bet(+) lymphoid cells, supporting a Th2 skew also at the tumor site. Collectively, these results demonstrate that Th2-immune deviation in pancreatic cancer is not generalized but tumor related and suggests that the skew might be possibly due to factor(s) present at the tumor site.     

Methylenetetrahydrofolate reductase,MTHFR, polymorphisms and predisposition to different multifactorial disorders

Gene polymorphisms involved in homocysteine-methionine pathway result in hyperhomocysteinemia, a predisposing condition to several diseases. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate and homocysteine metabolism. The two known functional polymorphisms of MTHFR gene, 677C>T and 1298A>C have been implicated in a variety of multifactorial diseases: cardio-cerebrovascular and neurodegenerative disorders, autoimmune diseases, birth defects, diabetes, neuropsychiatric disorders, cancer and renal disease. C667T, and to a lesser extent A1298C polymorphisms, have been also reported to have a pharmacogenetic role in predicting drug toxicity in cancer and rheumatoid arthritis treatment. We review here the principal effects of the MTHFR gene variations in different clinical conditions.     

Does selection on horn length of males and females differ in protected and hunted populations of a weakly dimorphic ungulate?

Weaponry in ungulates may be costly to grow and maintain, and different selective pressures in males and females may lead to sex‐biased natural survival. Sexual differences in the relationship between weapon growth and survival may increase under anthropogenic selection through culling, for example because of trophy hunting. Selection on weaponry growth under different scenarios has been largely investigated in males of highly dimorphic ungulates, for which survival costs (either natural or hunting related) are thought to be greatest. Little is known, however, about the survival costs of weaponry in males and females of weakly dimorphic species. We collected information on horn length and age at death/shooting of 407 chamois Rupicapra rupicapra in a protected population and in two hunted populations with different hunting regimes, to explore sexual differences in the selection on early horn growth under contrasting selective pressures. We also investigated the variation of horn growth and body mass in yearling males (n = 688) and females (n = 539) culled in one of the hunted populations over 14 years. The relationship between horn growth and survival showed remarkable sexual differences under different evolutionary scenarios. Within the protected population, under natural selection, we found no significant trade‐off in either males or females. Under anthropogenic pressure, selection on early horn growth of culled individuals showed diametrically opposed sex‐biased patterns, depending on the culling regime and hunters’ preferences. Despite the selective bias between males and females in one of the hunted populations, we did not detect significant sex‐specific differences in the long‐term pattern of early growth. The relationship between early horn growth and natural survival in either sex might suggest stabilizing selection on horn size in chamois. Selection through culling can be strongly sex‐biased also in weakly dimorphic species, depending on hunters’ preferences and hunting regulations, and long‐term data are needed to reveal potential undesirable evolutionary consequences.     

Tetracycline derivatives and ceftriaxone, a cephalosporin antibiotic, protect neurons against apoptosis induced by ionizing radiation

DNA damage induced by low doses of ionizing radiation causes apoptosis, which is partially mediated via the generation of free radicals. Both free radicals and apoptosis are involved in the majority of brain diseases, including stroke, Alzheimer's disease and amyotrophic lateral sclerosis. Because previous studies have shown that tetracycline derivatives doxycycline and minocycline have anti-inflammatory effects and are protective against brain ischemia, we studied whether minocycline and doxycycline or ceftriaxone, a cephalosporin antibiotic with the potential to inhibit excitotoxicity, protect neurons against ionizing radiation in primary cortical cultures. A single dose of 1 Gy significantly increased lactate dehydrogenase release, induced DNA fragmentation in neurons and triggered microglial proliferation. Treatment with minocycline (20 nM), doxycycline (20 nM) and ceftriaxone (1 microM) significantly reduced irradiation-induced lactate dehydrogenase release and DNA fragmentation. The most efficient protection was achieved by minocycline treatment, which also inhibited the irradiation-induced increase in microglial cell number. Our results suggest that some tetracycline derivatives, such as doxycycline and minocycline, and ceftriaxone, a cephalosporin derivative, protect neurons against apoptotic death.