Copulatory function and development shape modular architecture of genitalia differently in males and females

Genitalia are multitasking structures whose development is mediated by numerous regulatory pathways. This multifactorial nature provides an avenue for multiple sources of selection. As a result, genitalia tend to evolve as modular systems comprising semi-independent subsets of structures, yet the processes that give rise to those patterns are still poorly understood. Here, we ask what are the relative roles of development and function in shaping modular patterns of genitalia within populations and across species of stink-bugs. We found that male genitalia are less integrated, more modular, and primarily shaped by functional demands. In contrast, females show higher integration, lower modularity, and a predominant role of developmental processes. Further, interactions among parts of each sex are more determinant to modularity than those between the sexes, and patterns of modularity are equivalent between and within species. Our results strongly indicate that genitalia have been subjected to sex-specific selection, although male and female genitalia are homologous and functionally associated. Moreover, modular patterns are seemingly constant in the evolutionary history of stink-bugs, suggesting a scenario of multivariate stabilizing selection within each sex. Our study demonstrates that interactions among genital parts of the same sex may be more fundamental to genital evolution than previously thought.     

Inhibition of early murine hemopoietic progenitor cell proliferation after in vivo locoregional administration of transforming growth factor-beta 1

Transforming growth factor-beta 1 (TGF beta 1) has been shown in vitro to be a potent negative regulator of growth and differentiation of early hemopoietic progenitor cells, but not of more mature progenitors. However, little information is yet available regarding similar effects in vivo. We have developed an approach whereby TGF beta 1 can be administered locoregionally to the bone marrow via direct injection into the femoral artery. Our studies show that intrafemoral administration of a single bolus dose of TGF beta 1 potently inhibits the baseline and IL-3-driven proliferation of bone marrow cells. This inhibition is relatively selective for the earlier multipotential granulocyte, erythroid, megakaryocyte, and macrophage CFU progenitor cells since these are completely inhibited while the more differentiated CFU assayed in culture colonies are inhibited by about 50%. The inhibition of hemopoietic progenitor growth and differentiation is both time and dose dependent with the maximal effect on the marrow observed at 24 h with doses greater than or equal to 5 micrograms/mouse, and the effect is reversed at later times. A possible practical implication of these in vivo results could be the use of TGF beta 1 to protect stem cells in the bone marrow from the myelotoxic effects of chemotherapeutic drugs.     

Longevity mutation in SCH9 prevents recombination errors and premature genomic instability in a Werner/Bloom model system

Werner and Bloom syndromes are human diseases characterized by premature age-related defects including elevated cancer incidence. Using a novel Saccharomyces cerevisiae model system for aging and cancer, we show that cells lacking the RecQ helicase SGS1 (WRN and BLM homologue) undergo premature age-related changes, including reduced life span under stress and calorie restriction (CR), G1 arrest defects, dedifferentiation, elevated recombination errors, and age-dependent increase in DNA mutations. Lack of SGS1 results in a 110-fold increase in gross chromosomal rearrangement frequency during aging of nondividing cells compared with that generated during the initial population expansion. This underscores the central role of aging in genomic instability. The deletion of SCH9 (homologous to AKT and S6K), but not CR, protects against the age-dependent defects in sgs1Δ by inhibiting error-prone recombination and preventing DNA damage and dedifferentiation. The conserved function of Akt/S6k homologues in lifespan regulation raises the possibility that modulation of the IGF-I–Akt–56K pathway can protect against premature aging syndromes in mammals.     

The NF-kappaB canonical pathway is involved in the control of the exonucleolytic processing of coding ends during V(D)J recombination

V(D)J recombination is essential to produce an Ig repertoire with a large range of Ag specificities. Although NF-kappaB-binding sites are present in the human and mouse IgH, Igkappa, and Iglambda enhancer modules and RAG expression is controlled by NF-kappaB, it is not known whether NF-kappaB regulates V(D)J recombination mechanisms after RAG-mediated dsDNA breaks. To clarify the involvement of NF-kappaB in human V(D)J recombination, we amplified Ig gene rearrangements from individual peripheral B cells of patients with X-linked anhidrotic ectodermal dysplasia with hyper-IgM syndrome (HED-ID) who have deficient expression of the NF-kappaB essential modulator (NEMO/Ikkgamma). The amplification of nonproductive Ig gene rearrangements from HED-ID B cells reflects the influence of the Ikkgamma-mediated canonical NF-kappaB pathway on specific molecular mechanisms involved in V(D)J recombination. We found that the CDR3(H) from HED-ID B cells were abnormally long, as a result of a marked reduction in the exonuclease activity on the V, D, and J germline coding ends, whereas random N-nucleotide addition and palindromic overhangs (P nucleotides) were comparable to controls. This suggests that an intact canonical NF-kappaB pathway is essential for normal exonucleolytic activity during human V(D)J recombination, whereas terminal deoxynucleotide transferase, Artemis, and DNA-dependent protein kinase catalytic subunit activity are not affected. The generation of memory B cells and somatic hypermutation were markedly deficient confirming a role for NF-kappaB in these events of B cell maturation. However, selection of the primary B cell repertoire appeared to be intact and was partially able to correct the defects generated by abnormal V(D)J recombination.     

A logical OR redundancy within the Asx-Pro-Asx-Gly type I beta-turn motif

Turn secondary structure is essential to the formation of globular protein architecture. Turn structures are, however, much more complex than either α-helix or β-sheet, and the thermodynamics and folding kinetics are poorly understood. Type I β-turns are the most common type of reverse turn, and they exhibit a statistical consensus sequence of Asx-Pro-Asx-Gly (where Asx is Asp or Asn). A comprehensive series of individual and combined Asx mutations has been constructed within three separate type I 3:5 G1 bulge β-turns in human fibroblast growth factor-1, and their effects on structure, stability, and folding have been determined. The results show a fundamental logical OR relationship between the Asx residues in the motif, involving H-bond interactions with main-chain amides within the turn. These interactions can be modulated by additional interactions with residues adjacent to the turn at positions i + 4 and i + 6. The results show that the Asx residues in the turn motif make a substantial contribution to the overall stability of the protein, and the Asx logical OR relationship defines a redundant system that can compensate for deleterious point mutations. The results also show that the stability of the turn is unlikely to be the prime determinant of formation of turn structure in the folding transition state.     

Solution structure investigations of olefin Pd(II) and Pt(II) complex ion pairs bearing α-diimine ligands by F, H-HOESY NMR

Complexes [M(η¹,η²-C₈H₁₂OMe)((2,6-(R)₂---C₆H₃)N=C(R′)---C(R′)=N((2,6-(R)₂---C₆H₃))]PF₆ (where M=Pd, R=H and R′₂=Me₂ (1), M=Pd, R=Me and R′₂=Me₂ (2), M=Pd, R=Et and R′₂=Me₂ (3), M=Pd, R=iPr and R′₂=Me₂ (4), M=Pd, R=iPr and R′₂=An (5), M=Pt, R=iPr and R′₂=An (6)) were synthesized by the reaction of [M(η¹,η²-C₈H₁₂OMe)Cl]₂ with the appropriate α-diimine ligand in the presence of NH₄PF₆. Their ion pair structure in solution was investigated by detecting dipolar interactions between protons belonging to the cation and fluorine nuclei of the anion (interionic contacts) in the ¹⁹F, ¹H-HOESY NMR spectra. In complexes 1–4, the anion in solution is located close to the peripheral protons of the α-diimine ligand and it interacts with the R′ protons and with the R protons that point toward the R′ groups. The steric protection of apical position exerted by the R substituents is clearly illustrated by the absence of interionic contacts between any protons of the cycloctenylmethoxy-moiety and the anion for R≥Me in 1–4. In complexes 5 and 6 the interactions between the anion and the peripheral N,N protons also predominate but other anion–cation orientations are significantly present and, consequently, the interionic structure is less specific.     

Preparation and evaluation of the in vitro erythroid differentiation induction properties of some esters of methyl 3,4-O-isopropylidene-beta-D-galactopyranoside and 2,3-O-isopropylidene-D-mannofuranose.

Two series of glycide esters of short fatty acids, designed for avoiding intramolecular transesterification, were prepared and tested for in vitro erythroid differentiation induction activities using the K562 cell line as experimental system. The 6-O-isobutiryl and pivaloyl derivatives of methyl 3,4-O-isopropylidene-beta-D-galactopyranosides as well the same 1-O-esters of 2,3-O-isopropylidene-alpha- and beta-D-mannofuranose exhibit biological activities much higher that the corresponding acids and could be proposed as possible agents to modulate production of embryo-fetal hemoglobins by human erythroid cells.     

Bioremediation of a polyaromatic hydrocarbon contaminated soil by native soil microbiota and bioaugmentation with isolated microbial consortia

Biodegradation of a mixture of PAHs was assessed in forest soil microcosms performed either without or with bioaugmentation using individual fungi and bacterial and a fungal consortia. Respiratory activity, metabolic intermediates and extent of PAH degradation were determined. In all microcosms the low molecular weight PAH’s naphthalene, phenanthrene and anthracene, showed a rapid initial rate of removal. However, bioaugmentation did not significantly affect the biodegradation efficiency for these compounds. Significantly slower degradation rates were demonstrated for the high molecular weight PAH’s pyrene, benz[a]anthracene and benz[a]pyrene. Bioaugmentation did not improve the rate or extent of PAH degradation, except in the case of Aspergillus sp. Respiratory activity was determined by CO₂ evolution and correlated roughly with the rate and timing of PAH removal. This indicated that the PAHs were being used as an energy source. The native microbiota responded rapidly to the addition of the PAHs and demonstrated the ability to degrade all of the PAHs added to the soil, indicating their ability to remediate PAH-contaminated soils.