Variants in toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African-Americans, and West Africans

Tuberculosis (TB) is a global public health problem and a source of preventable deaths each year, with 8.8 million new cases of TB and 1.6 million deaths worldwide in 2005. Approximately, 10% of infected individuals develop pulmonary or extrapulmonary TB, suggesting that host defense factors influence development of active disease. Toll-like receptor’ (TLR) polymorphisms have been associated with regulation of TLR expression and development of active TB. In the present study, 71 polymorphisms in TLR1, TLR2, TLR4, TLR6, and TLR9 were examined from 474 (295 cases and 179 controls) African-Americans, 381 (237 cases and 144 controls) Caucasians, and from 667 (321 cases and 346 controls) Africans from Guinea-Bissau for association with pulmonary TB using generalized estimating equations and logistic regression. Statistically significant associations were observed across populations at TLR9 and TLR2. The strongest evidence for association came at an insertion (I)/deletion (D) polymorphism (?196 to ?174) in TLR2 that associated with TB in both Caucasians (II vs. ID&DD, OR = 0.41 [95% CI 0.24–0.68], p = 0.0007) and Africans (II vs. ID&DD, OR = 0.70 [95% CI 0.51–0.95], p = 0.023). Our findings in three independent population samples indicate that variations in TLR2 and TLR9 might play important roles in determining susceptibility to TB.     

Discriminative proprieties of Vary and Repeat contingencies

Pigeons were trained on an arbitrary matching-to-sample task in which Vary and Repeat contingencies served as sample stimuli. During the sample component, two keys were lit red and a four-peck sequence was reinforced if its frequency was less than a certain threshold (Vary sample) or if it comprised one of two target sequences (Repeat sample). During the comparison component, two keys were lit white and green, and correct choices depended on the previous sample contingency. Pigeons learned to emit high and low variability levels during the sample, and correct matching choices were obtained. In two discrimination testing phases, the requirement of variation (Vary sample) or of repetition (Repeat sample) was parametrically manipulated such that behavioral variability became undifferentiated between samples (low sample disparity) and then differentiated (high sample disparity) again. Accurate choices fell to chance under low sample disparity conditions, but improved under high disparity conditions. The results provide evidence that high and low variability levels can be produced in the absence of antecedent cues and that pigeons can accurately report whether they had experienced a Vary or a Repeat contingency, thus indicating that those contingencies may serve discriminative functions.     

N‐terminal interaction domain implicates PAK4 in translational regulation and reveals novel cellular localization signals

The serine/threonine kinase PAK4 is a Rho GTPases effector protein implicated in many critical biological processes, including regulation of cell morphology and motility, embryonic development, cell survival, response to infection, and oncogenic transformation. Consistently with its pro‐oncogenic features, PAK4 was found to be overexpressed in many cancer cell lines and tissues, and to be necessary to promote activation of survival pathways. PAK4, like other Paks, is now considered a promising target for specific therapy. Little is known on its modes of regulation, molecular partners, and substrates. Because the N‐terminal regulatory moiety plays important roles in PAK4 activity and functions, even independently of GTPase interactions, in this study we employed an affinity chromatography approach to identify N‐terminal domain binding partners. Within this protein region we identified a novel interaction domain involved in association with ribonucleoprotein (RNP) complexes, suggesting PAK4 implications in translational regulation. Indeed, we found that active PAK4 can affect (cap‐independent) translation from specific IRES sequences in vivo, and that the N‐terminal domain is critical for this regulation. Further, we could establish that within the RNP interacting sequence PAK4 regulatory domain contains targeting elements that drive cytoplasmic localization and act as nuclear export signal. Functional implication of endogenous PAK4 protein, which was found in both cytoplasmic and nuclear fractions, in IRES‐mediated translation further underlines the significance of the reported findings. Our data reveal novel means for PAK4 regulation of gene expression, and provide new elements to understand the molecular mechanisms that determine PAK4 cellular localization and functions. J. Cell. Physiol. 224: 722–733, 2010. © 2010 Wiley‐Liss, Inc.     

Keratinocyte stem cells: Friends and foes

Skin and its appendages provide a protective barrier against the assaults of the environment. To perform its role, epidermis undergoes an ongoing renewal through a balance of proliferation and differentiation/apoptosis called homeostasis. Keratinocyte stem cells reside in a special microenvironment called niche in basal epidermis, adult hair follicle, and sebaceous glands. While a definite marker has yet to be detected, data raised part in humans and part in the mouse system point to a critical role of stem and its progeny transit amplifying cells in epidermal homeostasis. Stem cells are protected from apoptosis and are long resident in adult epidermis. This renders them more prone to be the origin of skin cancer. In this review, we will outline the main features of adult stem cells in mouse and humans and discuss their fate in relation to differentiation, apoptosis, and cancer. J. Cell. Physiol. 225: 310–315, 2010. © 2010 Wiley‐Liss, Inc.     

Multilocus phylogenetic and coalescent analyses identify two cryptic species in the Italian bianchetto truffle, <Emphasis Type="Italic">Tuber borchii</Emphasis> Vittad.

Tuber borchii (Ascomycota, Pezizales) is a highly valued truffle sold in local markets in Italy. Despite its economic importance, knowledge on its distribution and genetic structure is scarce. The objective of this work was to investigate the factors shaping the genetic structure of T. borchii using 61 representative specimens with a broad distribution throughout Italy. In spite of the lack of morphological differences, phylogenetic and coalescent-based analyses using four loci identified two genetically isolated groups sympatrically distributed. The low levels of divergence between the two clades may be the result of recent range expansions from geographically distinct refugia, potentially mediated by reforestation using coniferous species that are common ectomycorrhizal symbionts for both groups.     

Maté Tea Inhibits In Vitro Pancreatic Lipase Activity and Has Hypolipidemic Effect on High‐fat Diet‐induced Obese Mice

The inhibitory effects of maté tea (MT), a beverage produced with leaves from Ilex paraguariensis, in vitro lipase activity and on obesity in obese mice models were examined. For the in vitro experiment, porcine and human pancreatic lipase (PL) activities were determined by measuring the rate of release of oleic acid from hydrolysis of olive oil emulsified with taurocholate, phospholipids, gum arabic, or polyvinyl alcohol. For the in vivo experiments, animals were fed with a standard diet (SD, n = 10) or high‐fat diet (HFD, n = 30) for 16 weeks. After the first 8 weeks on the HFD, the animals were treated with 1 and 2 g/kg of body weight of MT. The time course of the body weight and obesity‐related biochemical parameters were evaluated. The results showed that MT inhibited both porcine and human PL (half‐maximal inhibitory concentration = 1.5 mg MT/ml) and induced a strong inhibition of the porcine lipase activity in the hydrolysis of substrate emulsified with taurocholate + phosphatidylcholine (PC) (83 ± 3.8%) or PC alone (62 ± 4.3%). MT suppressed the increases in body weight (P < 0.05) and decreased the serum triglycerides and low‐density lipoprotein (LDL)‐cholesterol concentrations at both doses (from 190.3 ± 5.7 to 135.0 ± 8.9 mg/dl, from 189.1 ± 7.3 to 129.3 ± 17.6 mg/dl; P < 0.05, respectively) after they had been increased by the HFD. The liver lipid content was also decreased by the diet containing MT (from 132.6 ± 3.9 to 95.6 ± 6.1 mg/g of tissue; P < 0.05). These results suggest that MT could be a potentially therapeutic alternative in the treatment of obesity caused by a HFD.     

Proteins pattern alteration in AZT-treated K562 cells detected by two-dimensional gel electrophoresis and peptide mass fingerprinting

In this study we report the effect of AZT on the whole protein expression profile both in the control and the AZT-treated K562 cells, evidenced by two-dimensional gel electrophoresis and peptide mass fingerprinting analysis. Two-dimensional gels computer digital image analysis showed two spots that appeared up-regulated in AZT-treated cells and one spot present only in the drug exposed samples. Upon extraction and analysis by peptide mass fingerprinting, the first two spots were identified as PDI-A3 and stathmin, while the third one was proved to be NDPK-A. Conversely, two protein spots were present only in the untreated K562 cells, and were identified as SOD1 and HSP-60, respectively.