ldne: a program for estimating effective population size from data on linkage disequilibrium

ldne is a program with a Visual Basic interface that implements a recently developed bias correction for estimates of effective population size (N(e) ) based on linkage disequilibrium data. The program reads genotypic data in standard formats and can accommodate an arbitrary number of samples, individuals, loci, and alleles, as well as two mating systems: random and lifetime monogamy. ldne calculates separate estimates using different criteria for excluding rare alleles, which facilitates evaluation of data for highly polymorphic markers such as microsatellites. The program also introduces a jackknife method for obtaining confidence intervals that appears to perform better than parametric methods currently in use.     

金喜楼梯草(荨麻科),越南楼梯草属植物一新种

对产自越南的荨麻科楼梯草属植物一新种金喜楼梯草（Elatostema kimhyense Y.G.Wei & V.T.Do）作了描述和绘图。该种生长于海拔350~400和1 100~1 200 m的石灰岩山地林下。该新种与越南楼梯草（E.vietnamense Q.Lin & L.D.Duan）接近,区别在于其拥有肉质茎,羽状脉,叶背面、苞片和小苞片被微硬毛。     

中国苦苣苔科一新记录属——四轮苣苔属

该文报道了中国苦苣苔科(Gesneriaceae)一新记录属——四轮苣苔属(Tetraphyllum Griff. ex C. B. Clarke)。该新记录属,即四轮苣苔属仅有3种,其中密花四轮苣苔[T. confertiflorum(Drake)B. L. Burtt]在我国首次记录。该研究提供了该属的形态描述和分种区别特征,并提供了该种的详细形态描述及彩色照片。凭证标本馆藏于广西植物研究所标本馆(IBK)和上海辰山植物标本馆(CSH)。     

Vertical transmission in feather mites: insights into its adaptive value

1. The consequences of symbiont transmission strategies are better understood than their adaptive causes. 2. Feather mites are permanent ectosymbionts of birds assumed to be transmitted mainly vertically from parents to offspring. The transmission of Proctophyllodes doleophyes Gaud (Astigmata, Proctophyllodidae) was studied in two European populations of pied flycatchers, Ficedula hypoleuca Pallas (Passeriformes, Muscicapidae). 3. The vertical transmission of this mite species is demonstrated here with an acaricide experiment. This study also compared (for two distant populations during 4 years) patterns in reductions in mite intensity in adult birds, from egg incubation to chick‐rearing periods, with the predictions of three hypotheses on how host survival prospects and mite intraspecific competition might drive feather mites' transmission strategy. 4. The results are in agreement with previous studies and show that feather mites transmit massively from parents to chicks. 5. The magnitude of the transmission was closer to that predicted by the hypothesis based on intraspecific competition, while a bet‐hedging strategy is also partially supported.     

On the G Protein-Coupled Receptor Neuromodulation of the Claustrum

Neurochemical Research - G protein-coupled receptors modulate the synaptic glutamate and GABA transmission of the claustrum. The work focused on the transmitter–receptor relationships in the...     

Characterization of the A2AR-D2R interface: focus on the role of the C-terminal tail and the transmembrane helices

A single serine point mutation (S374A) in the adenosine A_2A receptor (A_2AR) C-terminal tail reduces A_2AR-D₂R heteromerization and prevents its allosteric modulation of the dopamine D₂ receptor (D₂R). By means of site directed mutagenesis of the A_2AR and synthetic transmembrane (TM) α-helix peptides of the D₂R we further explored the role of electrostatic interactions and TM helix interactions of the A_2AR-D₂R heteromer interface. We found evidence that the TM domains IV and V of the D₂R play a major role in the A_2AR-D₂R heteromer interface since the incubation with peptides corresponding to these domains significantly reduced the ability of A_2AR and D₂R to heteromerize. In addition, the incubation with TM-IV or TM-V blocked the allosteric modulation normally found in A_2AR-D₂R heteromers. The mutation of two negatively charged aspartates in the A_2AR C-terminal tail (D401A/D402A) in combination with the S374A mutation drastically reduced the physical A_2AR-D₂R interaction and lost the ability of antagonistic allosteric modulation over the A_2AR-D₂R interface, suggesting further evidence for the existence of an electrostatic interaction between the C-terminal tail of A_2AR and the intracellular loop 3 (IL3) of D₂R. On the other hand, molecular dynamic model and bioinformatic analysis propose that specific AAR, AQE, and VLS protriplets as an important motive in the A_2AR-D_2LR heteromer interface together with D_2LR TM segments IV/V interacting with A_2AR TM-IV/V or TM-I/VII.     

Agonist-induced formation of FGFR1 homodimers and signaling differ among members of the FGF family

Fibroblast growth factor receptor 1 (FGFR1) is known to be activated by homodimerization in the presence of both the FGF agonist ligand and heparan sulfate glycosaminoglycan. FGFR1 homodimers in turn trigger a variety of downstream signaling cascades via autophosphorylation of tyrosine residues in the cytoplasmic domain of FGFR1. By means of Bioluminescence Energy Resonance Transfer (BRET) as a sign of FGFR1 homodimerization, we evaluated in HEK293T cells the effects of all known FGF agonist ligands on homodimer formation. A significant correlation between BRET² signaling and ERK1/2 phosphorylation was observed, leading to a further characterization of the binding and signaling properties of the FGF subfamilies. FGF agonist ligand-FGFR1 binding interactions appear as the main mechanism for the control of FGFR1 homodimerization and MAPK signaling which demonstrated a high correlation. The bioinformatic analysis demonstrates the interface of the two pro-triplets SSS (Ser–Ser–Ser) and YGS (Tyr–Gly–Ser) located in the extracellular and intracellular domain of the FGFR1. These pro-triplets are postulated participate in the FGFR1 homodimerization interface interaction. The findings also reveal that FGF agonist ligands within the same subfamily of the FGF gene family produced similar increases in FGFR1 homodimer formation and MAPK signaling. Thus, the evolutionary relationship within this gene family appears to have a distinct functional relevance.     

Dopamine D2 and D4 receptor heteromerization and its allosteric receptor-receptor interactions

Dopamine D₂ and D₄ receptors partially codistribute in the dorsal striatum and appear to play a fundamental role in complex behaviors and motor function. The discovery of D₂R–D_4.xR (D_4.2R, D_4.4R or D_4.7R) heteromers has been made in cellular models using co-immunoprecipitation, in situ Proximity Ligation Assays and BRET¹ techniques with the D₂R and D_4.7R receptors being the least effective in forming heteromers. Allosteric receptor–receptor interactions in D₂R–D_4.2R and D₂R–D_4.4 R heteromers were observed using the MAPK assays indicating the existence of an enhancing allosteric receptor–receptor interaction in the corresponding heteromers between the two orthosteric binding sites. The bioinformatic predictions suggest the existence of a basic set of common triplets (ALQ and LRA) in the two participating receptors that may contribute to the receptor–receptor interaction interfaces.     

On the Existence of a Possible A2A-D2-β-Arrestin2 Complex: A2A Agonist Modulation of D2 Agonist-Induced β-Arrestin2 Recruitment

Given that coactivation of adenosine A_2A (A_2AR) and dopamine D₂ (D₂R) receptors results in the coaggregation, cointernalization, and codesensitization of the A_2AR and D₂R and the role of scaffolding protein β-arrestin2 in the desensitization, internalization, and signaling of G-protein-coupled receptors, in this study we explored the ability of the A_2AR agonist CGS21680 in A_2AR-D₂R-coexpressing cells to modulate the D₂R agonist-induced recruitment of β-arrestin2 to the D₂R by means of proximity-based bioluminescence resonance energy transfer (BRET²) and co-trafficking analysis. We found evidence that CGS21680 can increase the maximal BRET² signal between β-arrestin2^RLuc and D_2LR^GFP2 upon D₂R activation, by increasing the potency of the D₂R agonist to exert this action. In addition, this change was associated with an increased formation of cytoplasmic clusters containing β-arrestin2^GFP2 and D_2LR^YFP as seen from the co-trafficking analysis. Furthermore, the A_2AR agonist advanced the time for the increase in Akt phosphorylation obtained with the D₂R agonist. Finally, using a novel bioinformatics approach to predict the protein-protein interface, we have also found that amino acid pro-triplets TNY, LLS, RAF, and VSR may be crucial for the -induced β-arrestin2 recruitment by A_2AR-D₂R heteromers. Taken together, the results indicate that the antagonistic A_2AR-D₂R allosteric receptor-receptor interaction in A_2AR-D₂R heteromers favors β-arrestin2 recruitment to the D_2LR protomer with subsequent cointernalization associated with a reduced time onset of Akt phosphorylation followed by a rapid dephosphorylation. Thus, β-arrestin2 action becomes more rapid and short-lasting and, in this way, mimics G-protein-mediated signaling.     

Dopamine D4 receptor oligomerization--contribution to receptor biogenesis

Dopamine D(4) receptors (D(4) Rs) are G protein-coupled receptors that play a role in attention and cognition. In the present study, we investigated the dimerization properties of this receptor. Western blot analysis of the human D(4.2)R, D(4.4)R and D(4.7)R revealed the presence of higher molecular weight immunoreactive bands, which might indicate the formation of receptor dimers and multimers. Homo- and heterodimerization of the receptors was confirmed by co-immunoprecipitation and bioluminescence resonance energy transfer studies. Although dimerization of a large number of G protein-coupled receptors has been described, the functional importance often remains to be elucidated. Folding efficiency is rate-limiting for D(4)R biogenesis and quality control in the endoplasmic reticulum plays an important role for D(4)R maturation. Co-immunoprecipitation and immunofluorescence microscopy studies using wild-type and a nonfunctional D(4.4)R folding mutant show that oligomerization occurs in the endoplasmic reticulum and that this plays a role in the biogenesis and cell surface targeting of the D(4)R. The different polymorphic repeat variants of the D(4)R display differential sensitivity to the chaperone effect. In the present study, we show that this is also reflected by bioluminescence resonance energy transfer saturation assays, suggesting that the polymorphic repeat variants have different relative affinities to form homo- and heterodimers. In summary, we conclude that D(4)Rs form oligomers with different affinities and that dimerization plays a role in receptor biogenesis.