Proliferation response of leukemic cells to CD70 ligation oscillates with recurrent remission and relapse in a low-grade lymphoma

Interactions of the TNF-related cell surface ligand CD70 with its receptor CD27 provide a costimulatory signal in B and T cell activation. Functional CD70-CD27 interactions could contribute to lymphoma and leukemia progression. This possibility was studied using DNA microarrays on a unique case of low-grade lymphoma/leukemia characterized by recurrent cycles of acute leukemic phase alternating with spontaneous remission. Upon induction of the acute phase expression of CD70 and CD27 in the leukemic cells increased 38- and 25-fold, respectively. Coexpression of membrane CD70 and CD27 on the leukemic (CD5+CD19+) cells was maximal 2-3 days following initiation of the attack. Soluble CD27 in the patient's serum was elevated during remission and further increased in the attack. Functional tests showed that neither anti-CD70 nor anti-CD27 Abs affect the rate of apoptosis. However, the anti-CD70 Ab specifically enhanced proliferation of the remission phase leukemic cells, whereas proliferation of the acute-phase counterparts that express higher level of membrane CD70 was unaffected. Hence, in this lymphoma/leukemia, membrane CD70 is presented on the leukemic cells in a responsive state during the remission and a nonresponsive state during the attack. Presumably, CD70 in its responsive state provides a costimulatory receptor for initiating the next acute phase while its nonresponsive state enables the remission.     

miRNA Signature of Mouse Helper T Cell Hyper-Proliferation

Helper T cells from a mutant mouse model, LAT Y136F, hyper-proliferate and cause a severe lymphoproliferative disease that kills the mice by six months of age. LAT Y136F mice carry a tyrosine to phenylalanine mutation in the Linker for Activation of T cells (LAT) gene. This mutation leads to a number of changes in T cells that result in altered cytokine production including increased IL-4 production, increased proliferation, and decreased apoptosis. Hyper-proliferation of the mutant T cells contributes to lymphadenopathy, splenomegaly, and multi-organ T cell infiltration. miRNAs are short non-coding RNAs that regulate expression of cohorts of genes. This study investigates which miRNAs are expressed in LAT Y136F T cells and compares these to miRNAs expressed in wild type T cells that are undergoing proliferation in two other settings. The first setting is homeostatic proliferation, which was modeled by adoptive transfer of wild type T cells into T cell-deficient mice. The second setting is proliferation in response to infection, which was modeled by infection of wild type mice with the nematode H. polygyrus. By comparing miRNA expression in these three proliferative states (LAT Y136F hyper-proliferation, homeostatic proliferation and proliferation in response to H. polygyrus infection) to expression in wild type naïve CD4⁺ T cells, we found miRNAs that were highly regulated in all three proliferative states (miR-21 and miR-146a) and some that were more specific to individual settings of proliferation such as those more specific for LAT Y136F lymphoproliferative disease (miR-669f, miR-155 and miR-466a/b). Future experiments that modulate levels of the miRNAs identified in this study may reveal the roles of these miRNAs in T cell proliferation and/or lymphoproliferative disease.     

Synthesis of eco-friendly silver nanoparticles using Allium sp. and their antimicrobial potential on selected vaginal bacteria

Allium cepa and garlic Allium sativa plants were used to evaluate their potential synthesis of silver nanoparticles and their antibacterial effect on Streptococcus pneumoniae and Pseudomonas aeruginosa. Transmission electron microscopy (SEM) was used to distinguish the morphology of the nanoparticles attained from plant extracts. Energy dispersive X-ray (EDX) spectrometer established the existence of elemental sign of the silver and homogenous allocation of silver nanoparticles. Diffraction by using X ray (XRD) analysis for the formed AgNPs revealed spherical plus cubical shapes structure with different planes ranged between 111 and 311 planes. The antibacterial action of AgNPs against vaginal pathogens, Streptococcus pneumoniae and Pseudomonas aeruginosa was recognized. Our work showed a rapid, eco-safety and suitable method for the synthesis of AgNPs from Allium cepa and garlic Allium sativa extracts and can be used in biomedical applications.     

Crucial role of the Rcl1p–Bms1p interaction for yeast pre-ribosomal RNA processing

The essential Rcl1p and Bms1p proteins form a complex required for 40S ribosomal subunit maturation. Bms1p is a GTPase and Rcl1p has been proposed to catalyse the endonucleolytic cleavage at site A₂ separating the pre-40S and pre-60S maturation pathways. We determined the 2.0 Å crystal structure of Bms1p associated with Rcl1p. We demonstrate that Rcl1p nuclear import depends on Bms1p and that the two proteins are loaded into pre-ribosomes at a similar stage of the maturation pathway and remain present within pre-ribosomes after cleavage at A₂. Importantly, GTP binding to Bms1p is not required for the import in the nucleus nor for the incorporation of Rcl1p into pre-ribosomes, but is essential for early pre-rRNA processing. We propose that GTP binding to Bms1p and/or GTP hydrolysis may induce conformational rearrangements within the Bms1p-Rcl1p complex allowing the interaction of Rcl1p with its RNA substrate.     

Belowground organism activities affect plant aboveground phenotype, inducing plant tolerance to parasites

Soil fauna activities are probably more important than currently acknowledged in determining individual plant response to stresses and overall plant diversity. Here we demonstrate that the positive effect of earthworms on rice could be the result of a systemic effect on plant physiology. Moreover, this effect could improve tolerance to stressors such as parasitic nematodes. In a controlled experiment, an 82% decrease in the production of infested plants was suppressed when earthworms were present. Earthworms had no direct effect on nematode population size. In their presence, however, root biomass was not affected by nematodes and the expected inhibition of photosynthesis was suppressed. In the leaves, the expression of three stress‐responsive genes (coding for lipoxygenase, phospholipase D and cysteine protease) was modulated by the presence of belowground invertebrate activities. We document conflicting systemic effects of parasitic nematodes and beneficial earthworms, although we cannot precisely identify the mechanism involved. These results reveal the importance of non‐trophic belowground/aboveground interactions for plant health and response to stresses.     

IL-10 from CD4CD25Foxp3CD127 adaptive regulatory T cells modulates parasite clearance and pathology during malaria infection

The outcome of malaria infection is determined, in part, by the balance of pro-inflammatory and regulatory immune responses. Failure to develop an effective pro-inflammatory response can lead to unrestricted parasite replication, whilst failure to regulate this response leads to the development of severe immunopathology. IL-10 and TGF-beta are known to be important components of the regulatory response, but the cellular source of these cytokines is still unknown. Here we have examined the role of natural and adaptive regulatory T cells in the control of malaria infection and find that classical CD4+CD25(hi) (and Foxp3+) regulatory T cells do not significantly influence the outcome of infections with the lethal (17XL) strain of Plasmodium yoelii (PyL). In contrast, we find that adaptive IL-10-producing, CD4+ T cells (which are CD25-, Foxp3-, and CD127- and do not produce Th1, Th2, or Th17 associated cytokines) that are generated during both PyL and non-lethal P. yoelii 17X (PyNL) infections are able to down-regulate pro-inflammatory responses and impede parasite clearance. In summary, we have identified a population of induced Foxp3- regulatory (Tr1) T cells, characterised by production of IL-10 and down regulation of IL-7Ralpha, that modulates the inflammatory response to malaria.     

Chromatin stiffening underlies enhanced locus mobility after DNA damage in budding yeast

DNA double‐strand breaks (DSBs) induce a cellular response that involves histone modifications and chromatin remodeling at the damaged site and increases chromosome dynamics both locally at the damaged site and globally in the nucleus. In parallel, it has become clear that the spatial organization and dynamics of chromosomes can be largely explained by the statistical properties of tethered, but randomly moving, polymer chains, characterized mainly by their rigidity and compaction. How these properties of chromatin are affected during DNA damage remains, however, unclear. Here, we use live cell microscopy to track chromatin loci and measure distances between loci on yeast chromosome IV in thousands of cells, in the presence or absence of genotoxic stress. We confirm that DSBs result in enhanced chromatin subdiffusion and show that intrachromosomal distances increase with DNA damage all along the chromosome. Our data can be explained by an increase in chromatin rigidity, but not by chromatin decondensation or centromeric untethering only. We provide evidence that chromatin stiffening is mediated in part by histone H2A phosphorylation. Our results support a genome‐wide stiffening of the chromatin fiber as a consequence of DNA damage and as a novel mechanism underlying increased chromatin mobility.     

Children Love Their Pets: Do Relationships between Children and Pets Co-vary with Taxonomic Order,Gender, and Age?

Generally, children love their pets. However, a deeper insight into the beneficial effects of pets on the physical, psychological, and social wellbeing and development of children is needed. This study investigated whether children have more intense relationships with animals which are behaviorally similar to humans (according to the scala naturae), and whether the relationship patterns between 11- to 14-year-old children (n = 72) and their pets differ from those in prepubescent children, between 6 and 10 years of age (n = 84). We also investigated whether pet-relationship quality is associated with children’s age, gender, and number of siblings. Data about individual bonding type and attachment quality between the children and their pet were collected using a questionnaire. The results indicate that the younger children’s relationships clearly co-varied with taxonomic order of the pet. In contrast, 11- to 14-year-old children reported similarly high scores of attachment with their mouse or iguana as with their dog or cat, and the relationship patterns did not co-vary with taxonomic order. Gender effects on relationship quality were found in both age groups; especially girls reported intense relationships with their pets. In addition to gender, children without siblings had stronger attachment to their pet than children who had siblings. Our data suggest that young children develop high-quality relationships with pets, particularly those which are taxonomically closely related, such as dogs and cats, and less so with other pet species, such as birds or fish. Older children were also able to strongly attach to other pet species. We argue that mental relationship representations change during puberty and that older (11- to 14-year-old) children may no longer make attachments to pets based on them being behaviorally similar to people.     

The apical ectodermal ridge is a timer for generating distal limb progenitors

The apical ectodermal ridge (AER) is a transient embryonic structure essential for the induction, patterning and outgrowth of the vertebrate limb. However, the mechanism of AER function in limb skeletal patterning has remained unclear. In this study, we genetically ablated the AER by conditionally removing FGFR2 function and found that distal limb development failed in mutant mice. We showed that FGFR2 promotes survival of AER cells and interacts with Wnt/beta-catenin signaling during AER maintenance. Interestingly, cell proliferation and survival were not significantly reduced in the distal mesenchyme of mutant limb buds. We established Hoxa13 expression as an early marker of distal limb progenitors and discovered a dynamic morphogenetic process of distal limb development. We found that premature AER loss in mutant limb buds delayed generation of autopod progenitors, which in turn failed to reach a threshold number required to form a normal autopod. Taken together, we have uncovered a novel mechanism, whereby the AER regulates the number of autopod progenitors by determining the onset of their generation.