Integration of G Protein α (Gα) Signaling by the Regulator of G Protein Signaling 14 (RGS14)

RGS14 contains distinct binding sites for both active (GTP-bound) and inactive (GDP-bound) forms of Gα subunits. The N-terminal regulator of G protein signaling (RGS) domain binds active Gα_i/o-GTP, whereas the C-terminal G protein regulatory (GPR) motif binds inactive Gα_i1/3-GDP. The molecular basis for how RGS14 binds different activation states of Gα proteins to integrate G protein signaling is unknown. Here we explored the intramolecular communication between the GPR motif and the RGS domain upon G protein binding and examined whether RGS14 can functionally interact with two distinct forms of Gα subunits simultaneously. Using complementary cellular and biochemical approaches, we demonstrate that RGS14 forms a stable complex with inactive Gα_i1-GDP at the plasma membrane and that free cytosolic RGS14 is recruited to the plasma membrane by activated Gα_o-AlF₄⁻. Bioluminescence resonance energy transfer studies showed that RGS14 adopts different conformations in live cells when bound to Gα in different activation states. Hydrogen/deuterium exchange mass spectrometry revealed that RGS14 is a very dynamic protein that undergoes allosteric conformational changes when inactive Gα_i1-GDP binds the GPR motif. Pure RGS14 forms a ternary complex with Gα_o-AlF₄⁻ and an AlF₄⁻-insensitive mutant (G42R) of Gα_i1-GDP, as observed by size exclusion chromatography and differential hydrogen/deuterium exchange. Finally, a preformed RGS14·Gα_i1-GDP complex exhibits full capacity to stimulate the GTPase activity of Gα_o-GTP, demonstrating that RGS14 can functionally engage two distinct forms of Gα subunits simultaneously. Based on these findings, we propose a working model for how RGS14 integrates multiple G protein signals in host CA2 hippocampal neurons to modulate synaptic plasticity.     

Early Miocene rodents of Gökler (Kazan Basin,Central Anatolia,Turkey)

Abstract

The rich and relatively diverse fossil mammalian assemblage from Gökler is of special importance for understanding of faunal evolution in Central Anatolia. Large mammals were not recovered, but insectivores and rodents are abundant. The assemblage of rodents is studied in detail and comprises mainly diversified cricetids. Dormice are abundant, but are represented by only one species. Squirrels are represented only by few specimens and also beaver remains were identified. Spanocricetodon sinuosus is referred to a new genus Latocricetodon nov. gen that is tentatively assigned to the Pseudocricetodontinae. Newly named species are Cricetodon goklerensis sp. nov., Democricetodon haltmari sp. nov., Eumyarion lukasi sp. nov. and Glirudinus matusi sp. nov. The rodent assemblage is assigned to local zone C which is correlated to the European biounit MN2 (early Miocene). Our biochronological assessment is supported by radiometric dating from two volcanic ash layers.

Latocricetodon

LSID http://zoobank.org/urn:lsid:zoobank.org:act:3414DB1E-0C5E-4154-BE5E-02A9ED183B1A

Cricetodon goklerensis

LSID http://zoobank.org/urn:lsid:zoobank.org:act:1B658872-6C10-4355-B87C-3E6277AF4EDA

Democricetodon haltmari

LSID http://zoobank.org/urn:lsid:zoobank.org:act:9B13F956-7F8C-406A-9970-1F5E999E54C6

Eumyarion lukasi

LSID http://zoobank.org/urn:lsid:zoobank.org:act:34DED87E-855F-4969-AB84-10BED5C572BF

Glirudinus matusi

LSID http://zoobank.org/urn:lsid:zoobank.org:act:798ECB9A-E3B5-4C38-B5B3-FEB17AF734FE     

Structure,Function, and Dynamics of the Gα Binding Domain of Ric-8A

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Genetic control of IgM responses to (T,G)-A — L

The primary antibody response to aqueous immunization with a low molecular-weight lot of (T,G)-A — L (#420) was studied in congenic pairs of inbred mouse strains. Two new genetic controls were identified, both of which quantitatively regulate the production of IgM anti-(T,G)-A — L antibody. Testing of F₁ and F₂ progeny demonstrated that one of these genes is linked to the major histocompatibility (H-2) complex, and that high response is dominant over low response. Whether this gene is identical toIr-1A is not yet known. The other gene, designatedIg-TGAL _M , is linked to the immunoglobulin heavy-chain allotype locus (Ig-1) and is expressed in a genedose dependent manner. Following secondary challenge with (T,G)-A — L 420, quantitative differences in IgG antibody response were observed inIr-1A high-responder congenics differing only at theIg-1 locus. Breeding studies, however, failed to demonstrate any linkage between this locus and the quantitative control of IgG anti-(T,G)-A — L antibody. These data demonstrate thatH-2-linked immune response genes can regulate IgM as well as IgG antibody responses, that genetic control of the IgM response to (T,G)-A — L is linked toIg-1, and that bothH-2-linked andIg-1-linked genes may simultaneously affect an IgM antibody response to the same antigen.Abbreviations used in this paper are (T,G)-A — L poly-l-(Tyr,Glu)-poly-d,l-Ala-poly-l-Lys - NMS normal mouse serum - SRBC sheep red blood cells - i.p. intraperitoneal - PBS phosphate-buffered saline - RAMG polyvalent rabbit anti-mouse globulin - 2-Me 2-Mercaptoethanol - 2-MeS 2-Me-sensitive - PFC plaque-forming cells - ABC antigen-binding cells     

Association of the TNF-α-308 (G→A) polymorphism with self-reported history of childhood asthma

Asthma is a complex disease involving genetic and environmental aetiology. The tumour necrosis factor-alpha (TNF-alpha) and angiotensin-converting enzyme (ACE) genes have been implicated in asthma pathogenesis. This study investigated the association of a G-308A variant of TNF-alpha and an insertion/deletion (I/D) variant of ACE with a self-reported history of childhood asthma, in two population groups. At Northwick Park Hospital, London, 1,811 pregnant women attending for antenatal care were recruited. Participants with a self-reported history of childhood asthma, determined by a researcher-administered questionnaire, and controls with no personal or family history of asthma, of UK/Irish (cases n=20; controls n=416) and South Asian (cases n=6; controls n=275) origin were used in this study. Participants were genotyped for the TNF-alpha-308 and ACE I/D variants by a PCR-RFLP and PCR approach. The TNF-alpha-308 allele 2 (-308A) was significantly associated with self-reported childhood asthma in the UK/Irish (Odds ratios (OR): 2.6; 95% confidence intervals (CI): 1.1-6.2; P=0.03) but not in the South Asian population. The ACE DD genotype was not associated with childhood asthma in either population group. Gametic phase disequilibrium between the TNF-alpha-308 and ACE I/D variants was significantly different from zero in UK/Irish cases (delta=0.09; P=0.034). The TNF-alpha308 allele 2 or a linked major histocompatibility complex (MHC) variant may be a genetic risk factor for childhood asthma in the UK/Irish sample.     

A systematic revision of Baconia Lewis (Coleoptera,?Histeridae,Exosternini)

Here we present a complete revision of the species of Baconia. Up until now there have been 27 species assigned to the genus (Mazur, 2011), in two subgenera (Binhister Cooman and Baconia s. str.), with species in the Neotropical, Nearctic, Palaearctic, and Oriental regions. We recognize all these species as valid and correctly assigned to the genus, and redescribe all of them. We synonymize Binhister, previously used for a polyphyletic assemblage of species with varied relationships in the genus. We move four species into Baconia from other genera, and describe 85 species as new, bringing the total for the genus to 116 species. We divide these into 12 informal species groups, leaving 13 species unplaced to group. We present keys and diagnoses for all species, as well as habitus photos and illustrations of male genitalia for nearly all. The genus now contains the following species and species groups: Baconia loricata group [Baconia loricata Lewis, 1885, B. patula Lewis, 1885, Baconia gounellei (Marseul, 1887a), Baconia jubaris (Lewis, 1901), Baconia festiva (Lewis, 1891), Baconia foliosoma sp. n., Baconia sapphirina sp. n., Baconia furtiva sp. n., Baconia pernix sp. n., Baconia applanatis sp. n., Baconia disciformis sp. n., Baconia nebulosa sp. n., Baconia brunnea sp. n.], Baconia godmani group [Baconia godmani (Lewis, 1888), Baconia venusta (J. E. LeConte, 1845), Baconia riehli (Marseul, 1862), comb. n., Baconia scintillans sp. n., Baconia isthmia sp. n., Baconia rossi sp. n., Baconia navarretei sp. n., Baconia maculata sp. n., Baconia deliberata sp. n., Baconia excelsa sp. n., Baconia violacea (Marseul, 1853), Baconia varicolor (Marseul, 1887b), Baconia dives (Marseul, 1862), Baconia eximia (Lewis, 1888), Baconia splendida sp. n., Baconia jacinta sp. n., Baconia prasina sp. n., Baconia opulenta sp. n., Baconia illustris (Lewis, 1900), Baconia choaspites (Lewis, 1901), Baconia lewisi Mazur, 1984], Baconia salobrus group [Baconia salobrus (Marseul, 1887b), Baconia turgifrons sp. n., Baconia crassa sp. n., Baconia anthracina sp. n., Baconia emarginata sp. n., Baconia obsoleta sp. n.], Baconia ruficauda group [Baconia ruficauda sp. n., Baconia repens sp. n.], Baconia angusta group [Baconia angusta Schmidt, 1893a, Baconia incognita sp. n., Baconia guartela sp. n., Baconia bullifrons sp. n., Baconia cavei sp. n., Baconia subtilis sp. n., Baconia dentipes sp. n., Baconia rubripennis sp. n., Baconia lunatifrons sp. n.], Baconia aeneomicans group [Baconia aeneomicans (Horn, 1873), Baconia pulchella sp. n., Baconia quercea sp. n., Baconia stephani sp. n., Baconia irinae sp. n., Baconia fornix sp. n., Baconia slipinskii Mazur, 1981, Baconia submetallica sp. n., Baconia diminua sp. n., Baconia rufescens sp. n., Baconia punctiventer sp. n., Baconia aulaea sp. n., Baconia mustax sp. n., Baconia plebeia sp. n., Baconia castanea sp. n., Baconia lescheni sp. n., Baconia oblonga sp. n., Baconia animata sp. n., Baconia teredina sp. n., Baconia chujoi (Cooman, 1941), Baconia barbarus (Cooman, 1934), Baconia reposita sp. n., Baconia kubani sp. n., Baconia wallacea sp. n., Baconia bigemina sp. n., Baconia adebratti sp. n., Baconia silvestris sp. n.], Baconia cylindrica group [Baconia cylindrica sp. n., Baconia chatzimanolisi sp. n.], Baconia gibbifer group [Baconia gibbifer sp. n., B. piluliformis sp. n., Baconia maquipucunae sp. n., Baconia tenuipes sp. n., Baconia tuberculifer sp. n., Baconia globosa sp. n.], Baconia insolita group [Baconia insolita (Schmidt, 1893a), comb. n., Baconia burmeisteri (Marseul, 1870), Baconia tricolor sp. n., Baconia pilicauda sp. n.], Baconia riouka group [Baconia riouka (Marseul, 1861), Baconia azuripennis sp. n.], Baconia famelica group [Baconia famelica sp. n., Baconia grossii sp. n., Baconia redemptor sp. n., Baconia fortis sp. n., Baconia longipes sp. n., Baconia katieae sp. n., Baconia cavifrons (Lewis, 1893), comb. n., Baconia haeterioides sp. n.], Baconia micans group [Baconia micans (Schmidt, 1889a), Baconia carinifrons sp. n., Baconia fulgida (Schmidt, 1889c)], Baconia incertae sedis [Baconia chilense (Redtenbacher, 1867), Baconia glauca (Marseul, 1884), Baconia coerulea (Bickhardt, 1917), Baconia angulifrons sp. n., Baconia sanguinea sp. n., Baconia viridimicans (Schmidt, 1893b), Baconia nayarita sp. n., Baconia viridis sp. n., Baconia purpurata sp. n., Baconia aenea sp. n., Baconia clemens sp. n., Baconia leivasi sp. n., Baconia atricolor sp. n.]. We designate lectotypes for the following species: Baconia loricata Lewis, 1885,Phelister gounellei Marseul, 1887, Baconia jubaris Lewis, 1901, Baconia festiva Lewis, 1891, Platysoma venustum J.E. LeConte, 1845, Phelister riehli Marseul, 1862, Phelister violaceus Marseul, 1853, Phelister varicolor Marseul, 1887b, Phelister illustris Lewis, 1900, Baconia choaspites Lewis, 1901, Epierus festivus Lewis, 1898, Phelister salobrus Marseul, 1887, Baconia angusta Schmidt, 1893a, Phelister insolitus Schmidt, 1893a, Pachycraerus burmeisteri Marseul, 1870, Phelister riouka Marseul, 1861, Homalopygus cavifrons Lewis, 1893, Phelister micans Schmidt, 1889a, Phelister coeruleus Bickhardt, 1917, and Phelister viridimicans Schmidt, 1893b. We designate neotypes for Baconia patula Lewis, 1885 and Hister aeneomicans Horn, 1873, whose type specimens are lost.     

A new species of Alstroemeria (Alstroemeriaceae) from Pará, Brazil

A new species,Alstroemeria paraensis, from Pará, Brazil, is described and illustrated. This species is characterized by its robust floral stem, reduced leaves, congested inflorescence, and maculated inner and outer tepals.     

The hipparions (Mammalia,Equidae) from Gülpinar (Canakkale,Turkey)

The mammalian fauna from Gülpinar (Canakkale, Turkey), dated Turolian, comprises threeHipparion taxa:H. cf.matthewi, H. sp. medium-sized, andH. sp. large. Two metatarsals may represent a fourth taxon or may derive from a different locality. The hipparion material is described here.     

A new species of Anthodiscus (Caryocaraceae) from Chocó, Colombia

The first record ofAnthodiscus from the rain forest of Pacific coastal Colombia is the new speciesA. chocoensis which is described here. The distribution of the genus is discussed in relation to its recent discovery in both the Chocó and the coastal forests of eastern Brazil.     

A New Synthesis of (—)-exo-Brevicomin

Rubusoside derivatives by transgalactosylation of various β-galactosidases were isolated and their structures were analyzed. Escherichia coli β-galactosidase produced mainly 13-O-β-d-glucosyl-19-O-[β-d-galactosyl-(1→6)-β-d-glucosyl]-steviol (RGal-2). Bacillus circulans β-galactosidase produced mainly 13-O-β-d-glucosyl-19-O-[β-d-galactosyl-(1→4)-β-d-glucosyl]-steviol (RGal-1a) in the early stage of the reaction and then produced 13-O-[β-d-galactosyl-(1→4)-β-d-glucosyl]-19-O-β-d-glucosyl-steviol (RGal-1b). With decreasing the amount of these products (RGal-1a and RGal-1b), RGal-2 was produced.     

A Total Synthesis of (±)-Pachyrrhizone

We examined whether developing cotyledons of soybean seed had photosynthetic activities. The cotyledons evolved oxygen under illumination and the activity was inhibited by 3-(3′,4′-dichlorophenyl)-1,1-dimethylurea. The rate of oxygen evolution decreased during the development of seeds; about 30μ miol O₂ · mg chlorophyll^-1 · hr^-1 at the early developing stage and about 10μ miol O₂-mg chlorophyll^-1 · hr^-1 at the late developing stage. The rate of oxygen uptake remained at an almost constant level of 40^mol 0₂-mg chlorophyll^-1 · hr^-1 throughout the development. Photosynthetic ¹⁴CO₂-fixation by the cotyledon was observed. Ribulose bisphosphate carboxylase was immunochemically detected in the developing cotyledons. These results show that functional photosynthetic apparatus is present in the developing cotyledons of soybean seeds.     

A missense mutation (G197→A) in theα-l-fucosidase gene of fucosidosis patients leads to loss ofα-l-fucosidase

Fucosidosis is an autosomal recessive lysosomal storage disease resulting from the absence of -l-fucosidase activity. Two natural missense mutations (G¹⁹⁷A) and (A⁸⁶⁰G) within the -l-fucosidase gene have been reported to be homozygous in four patients with fucosidosis. Expression of wild-type and mutated -l-fucosidase cDNAs in COS-1 cells revealed complete deficiency of -l-fucosidase for the G¹⁹⁷A transition and a normal level of enzyme for A⁸⁶⁰G. We therefore conclude that the change of G¹⁹⁷A is responsible for fucosidosis in the patients while A⁸⁶⁰G is a normal polymorphic variant of -l-fucosidase.     

A new species of fossorial natricid snakes of the genus Trachischium Günther, 1858 (Serpentes: Natricidae) from the Himalayas of northeastern India

A new species of natricid snakes, Trachischium apteii sp. nov. is described from the northeastern Indian State of Arunachal Pradesh. The new species differs from its congeners in the following suite of characters: dorsal scales in 15:15:15 rows, SVL 293–299 mm, higher ventral count 143–150, very faint dorsal longitudinal lines, absence of yellow patch on the neck and the belly being pale yellow. Preliminary discussion on the phylogenetic position of the members of the genus Trachischium is presented. This discovery of a new snake species advocates the need for dedicated surveys to document biodiversity across Arunachal Pradesh and the neighbouring States of northeastern India.     

A euryhaline fish,lost in the desert: The unexpected metapopulation structure of Coptodon guineensis (Günther, 1862) in the Sebkha of Imlili

Euryhaline Cichlid fish of the species Coptodon guineensis are present in different water holes situated in a dried depression in the desert in the extreme South of Morocco, the Sebkha of Imlili. A genetic survey of this population, using complete sequences of the ND2 gene (mtDNA) and sixteen microsatellite loci, revealed that the fish in the sebkha did not form a single population, but rather a metapopulation. This metapopulational structure may be regarded as good news from the point of view of the conservation of fish in the sebkha. Although small individual populations may have short, finite life spans, the metapopulation as a whole is more stable, because immigrants from one population are likely to re-colonize the habitat, left open by the extinction of another.     

Leptin rs2167270 G > A (G19A) polymorphism may decrease the risk of cancer: A case-control study and meta-analysis involving 19 989 subjects

Accumulating evidence has suggested that leptin (LEP) is very important for the development of cancer. Recently, a number of case-control studies about the relationship of the rs2167270 G > A (G19A) variants in the LEP gene with the risk of cancer have yielded inconsistent results. In this study, we have carried out a case-control study [1063 esophagogastric junction adenocarcinoma (EGJA) cases and 1677 controls] in a Chinese population. Furthermore, we carried out a pooled-analysis of 13 studies involving 8059 cancer patients and 11 930 controls to assess whether the LEP G19A locus was associated with overall cancer susceptibility. Odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were harnessed to evaluate the potential association. In our case-control study, we found an association between the carriers of LEP 19A allele and EGJA risk. In addition, the results of meta-analysis also suggested significant associations with cancer risk (A vs G: OR = 0.92, 95% CI = 0.88–0.97, P = 0.001; AA vs GG: OR = 0.83, 95% CI = 0.74–0.93, P = 0.001, GA/AA vs GG: OR = 0.93, 95% CI = 0.88–0.99, P = 0.023 and AA vs GG/GA: OR = 0.83, 95% CI = 0.74–0.92, P < 0.001). Upon conducting a stratified analysis, we found that LEP 19A allele might decrease the susceptibility of non-Hodgkin lymphoma (NHL) and colorectal cancer (CRC). In a stratified-by-ethnicity analysis, significant associations were also found in Asians, Caucasians, and mixed populations. We can conclude that the LEP G19A polymorphism constitutes a decreased risk of cancer.     

A new species of Apechoneura Kriechbaumer (Hymenoptera, Ichneumonidae, Labeninae) from Colombia

A new species of the ichneumonid subfamily Labeninae, Apechoneura seminigrasp. n., is described. Specimens were collected from the Amazon Rainforest of Colombia.