SUMOylation and PARylation cooperate to recruit and stabilize SLX4 at DNA damage sites

SUMOylation plays important roles in the DNA damage response. However, whether it is important for interstrand crosslink repair remains unknown. We report that the SLX4 nuclease scaffold protein is regulated by SUMOylation. We have identified three SUMO interaction motifs (SIMs) in SLX4, mutating all of which abrogated the binding of SLX4 to SUMO-2 and covalent SLX4 SUMOylation. An SLX4 mutant lacking functional SIMs is not recruited to PML nuclear bodies nor stabilized at laser-induced DNA damage sites. Additionally, we elucidated a novel role for PARylation in the recruitment of SLX4 to sites of DNA damage. Combined, our results uncover how SLX4 is regulated by post-translational modifications.     

Activating and inhibitory Fcγ receptors in rheumatoid arthritis: from treatment to targeted therapies

Fcγ receptors (FcγRs) bind the constant Fc region of IgG molecules. IgG/antigen-containing immune complexes elicit a variety of effector functions in cells that express activating FcγRs. Because activating FcγRs are present on cells from the innate immune system, such as dendritic cells, monocytes/macrophages and granulocytes, these IgG receptors form a crucial link between the innate and the acquired immune systems. Recently, the ability to detect the inhibitory FcγRIIb on cells has indicated an imbalance between activating and inhibitory FcγRs in rheumatoid arthritis. This progress offers an opportunity to study modulation of FcγR balance and could stimulate development of FcγR-directed immunotherapy.     

The expression of the Ig H chain repertoire in developing bone marrow B lineage cells

Analyses of rearranged Ig H chain V region genes of bone marrow pre-B cells demonstrate extensive sequence diversity, particularly within the third hypervariable region (HCDR3). This diversity is constrained, however, through preferential utilization of certain D gene segments and possibly VH gene segments and a preponderance of productive rearrangements, primarily those expressing D gene segments in a preferred reading frame. The predominance of productively rearranged V genes with D regions translated in a preferred frame, is, at least in part, the consequence of selective clonal expansion encompassing at least five to six divisions subsequent to VH-D-JH rearrangement. Selection for clonal expansion appears to be dependent on recognition of the nascent H chain product of certain productively rearranged genes.     

Rare phenotypes of the phosphoglucomutase locus 1 detectable by isoelectric focusing on Cellogel

Summary The rare phenotypes PGM₁, determined by alleles PGM ₃ ¹ , PGM ₄ ¹ , PGM ₆ ¹ , and PGM ₇ ¹ were examined by starch gel electrophoresis and cellulose acetate gel isoelectric focusing and were compared with the commonest phenotypes of PGM₁.The frequencies of the rare genes found in the Polish populations were as follows: in Lublin, PGM ₃ ¹ =0.0002, PGM ₄ ¹ =0.0005, PGM ₆ ¹ =0.0010, and PGM ₇ ¹ =0.0005; in Wroclaw, PGM ₃ ¹ =0.0000, PGM ₄ ¹ =0.0005, PGM ₆ ¹ =0.0007, and PGM ₇ ¹ =0.0002.The results suggest that the F and S type variants of the genes PGM ₄ ¹ and PGM ₇ ¹ probably do not occur. It is still possibile that F and S variants exist for the genes PGM ₃ ¹ and PGM ₆ ¹ .     

Phytelephas aequatorialis (arecaceae) in human and animal nutrition

Field observations revealed the consumption of several parts of the vegetable ivory (“tagua”) palm not previously reported to be eaten by humans or animals. The whole male inflorescence provides cattle with a fodder nutritionally similar to ryegrass, while the flower clusters provide humans with 102 Kcal/100 g, about four times the caloric density of cauliflower or broccoli. The central mesocarp is similar in composition and caloric density to other fruits and is a comparatively rich source of calcium (116 mg/100 g), potassium (841 mg/100 g), and zinc (1.3 mg/100 g). The interior mesocarp, with 22% fat, is a high caloric density (288 Kcal/100 g) fodder for chickens and is rich in linoleic acid (21%). The immature endosperm, eaten as a snack, is of negligible importance in human nutrition.     

Conservation of alternative splicing and genomic organization of the myosin alkali light-chain (Mlc1) gene among Drosophila species

The Mlc1 gene of Drosophila melanogaster encodes two MLC1 isoforms via developmentally regulated alternative pre-mRNA splicing. In larval muscle and tubular and abdominal muscles of adults, all of the six exons are included in the spliced mRNA, whereas, in the fibrillar indirect flight muscle of adult, exon 5 is excluded from the mRNA. We show that this tissue-specific pattern of alternative splicing of the Mlc1 pre-mRNA is conserved in D. simulans, D. pseudoobscura, and D. virilis. Isolation and sequencing of the Mlc1 genes from these three other Drosophila species have revealed that the overall organization of the genes is identical and that the genes have maintained a very high level of sequence identity within the coding region. Pairwise amino acid identities are 94%-99%, and there are no charge changes among the proteins. Total nucleotide divergence within the coding region of the four genes supports the accepted genealogy of these species, but the data indicate a significantly higher rate of amino acid replacement in the branch leading to D. pseudoobscura. A comparison of nucleotide substitutions in the coding portions of exon 5 and exon 6, which encode the alternative carboxyl termini of the two MLC1 isoforms, suggests that exon 5 is subject to greater evolutionary constraints than is exon 6. In addition to the coding sequences, there is significant sequence conservation within the 5' and 3' noncoding DNA and two of the introns, including one that flanks exon 5. These regions are candidates for cis- regulatory elements. Our results suggest that evolutionary constraints are acting on both the coding and noncoding sequences of the Mlc1 gene to maintain proper expression and function of the two MLC1 polypeptides.      

Role of interleukin-7 in degenerative and inflammatory joint diseases

IL-7 is known foremost for its immunostimulatory capacities, including potent T cell-dependent catabolic effects on bone. In joint diseases like rheumatoid arthritis and osteoarthritis, IL-7, via immune activation, can induce joint destruction. Now it has been demonstrated that increased IL-7 levels are produced by human articular chondrocytes of older individuals and osteoarthritis patients. IL-7 stimulates production of proteases by IL-7 receptor-expressing chondrocytes and enhances cartilage matrix degradation. This indicates that IL-7, indirectly via immune activation, but also by a direct action on cartilage, contributes to joint destruction in rheumatic diseases.     

A novel test for identifying genes involved in aldehyde detoxification in the yeast. Increased sensitivity of superoxide-deficient yeast to aldehydes and their metabolic precursors

A novel test for the identification of genes involved in aldehyde metabolism is proposed, based on detection of altered sensitivity of the yeast to corresponding alcohols, metabolic precursors of the aldehydes. This attitude enabled to an unexpected detection increased sensitivity of mutants devoid of CuZn-superoxide dismutase (CuZnSOD) to allyl alcohol (precursor of acrolein) and nonenol. We interpret this finding as due to inactivation of some important element of aldehyde detoxification by increased flux of superoxide in DeltaCuZnSOD mutants.