共查询到20条相似文献,搜索用时 46 毫秒
1.
Danielle F. Royer Charles A. Lockwood Jeremiah E. Scott Frederick E. Grine 《American journal of physical anthropology》2009,140(2):312-323
Previous studies of the Middle Stone Age human remains from Klasies River have concluded that they exhibited more sexual dimorphism than extant populations, but these claims have not been assessed statistically. We evaluate these claims by comparing size variation in the best‐represented elements at the site, namely the mandibular corpora and M2s, to that in samples from three recent human populations using resampling methods. We also examine size variation in these same elements from seven additional middle and late Pleistocene sites: Skhūl, Dolní Věstonice, Sima de los Huesos, Arago, Krapina, Shanidar, and Vindija. Our results demonstrate that size variation in the Klasies assemblage was greater than in recent humans, consistent with arguments that the Klasies people were more dimorphic than living humans. Variation in the Skhūl, Dolní Věstonice, and Sima de los Huesos mandibular samples is also higher than in the recent human samples, indicating that the Klasies sample was not unusual among middle and late Pleistocene hominins. In contrast, the Neandertal samples (Krapina, Shanidar, and Vindija) do not evince relatively high mandibular and molar variation, which may indicate that the level of dimorphism in Neandertals was similar to that observed in extant humans. These results suggest that the reduced levels of dimorphism in Neandertals and living humans may have developed independently, though larger fossil samples are needed to test this hypothesis. Am J Phys Anthropol, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
2.
CK Barrett D Guatelli-Steinberg PW Sciulli 《American journal of physical anthropology》2012,149(2):193-204
Previous studies have suggested that Neandertals experienced greater physiological stress and/or were less capable of mitigating stress than most prehistoric modern human populations. The current study compares estimates of dental fluctuating asymmetry (DFA) for prehistoric Inupiat from Point Hope Alaska, the Late Archaic, and Protohistoric periods from Ohio and West Virginia, and a modern sample from Ohio to Neandertals from Europe and Southwest Asia. DFA results from developmental perturbation during crown formation and is thus an indicator of developmental stress, which previous studies have found to be higher in Neandertals than in several modern human populations. Here, we use recent methodological improvements in the analysis of fluctuating asymmetry suggested by Palmer and Strobeck (Annu Rev Ecol Syst 17 ( 1986 ) 391–421, Developmental instability: causes and consequences ( 2003a ) v.1–v.36, Developmental instability: causes and consequences ( 2003b ) 279–319) and compare the fit of Neandertal DFA Index values with those of modern humans. DFA estimates for each of the modern population samples exceeded measurement error, with the Inupiat exhibiting the highest levels of DFA for most tooth positions. All significant Neandertal z‐scores were positive, exceeding the estimates for each of the modern prehistoric groups. Neandertals exhibited the fewest significant differences from the Inupiat (9.2% of values are significant at P < 0.05), while for the other modern prehistoric groups more than 10% of the Neandertal z‐scores are significant at P < 0.05, more than 90% of these significant scores at P < 0.01. These results suggest that the Inupiat experienced greater developmental stress than the other prehistoric population samples, and that Neandertals were under greater developmental stress than all other prehistoric modern human samples. Am J Phys Anthropol 149:193–204, 2012. © 2012 Wiley Periodicals, Inc. 相似文献
3.
Arsuaga JL Fernández Peris J Gracia-Téllez A Quam R Carretero JM Barciela González V Blasco R Cuartero F Sañudo P 《Journal of human evolution》2012,62(5):629-639
Systematic excavations carried out since 1989 at Bolomor Cave have led to the recovery of four Pleistocene human fossil remains, consisting of a fibular fragment, two isolated teeth, and a nearly complete adult parietal bone. All of these specimens date to the late Middle and early Late Pleistocene (MIS 7-5e). The fibular fragment shows thick cortical bone, an archaic feature found in non-modern (i.e. non-Homo sapiens) members of the genus Homo. Among the dental remains, the lack of a midtrigonid crest in the M1 represents a departure from the morphology reported for the majority of Neandertal specimens, while the large dimensions and pronounced shoveling of the marginal ridges in the C1 are similar to other European Middle and late Pleistocene fossils. The parietal bone is very thick, with dimensions that generally fall above Neandertal fossils and resemble more closely the Middle Pleistocene Atapuerca (SH) adult specimens. Based on the presence of archaic features, all the fossils from Bolomor are attributed to the Neandertal evolutionary lineage. 相似文献
4.
Stefano Benazzi Shara E. Bailey Francesco Mallegni 《American journal of physical anthropology》2013,152(2):300-305
The scarcity of Neandertal remains from Southern Europe hampers our understanding of Neandertal variability, and can bias interpretations about Neandertal geographic variation. To address this issue, it is often important to reassess human remains that, while discovered decades ago, remain relatively unknown to the scientific community. In this contribution, we provide a complete state‐of‐the‐art comparative morphometric analysis of Leuca I, an unworn left second upper molar (LM2) discovered in 1958 in Bambino's Cave (near Santa Maria di Leuca, Apulia, Italy) and attributed to Homo neanderthalensis. Our study includes comparisons of standard metric and nonmetric data, a 2D image analysis of the occlusal surface and measurements of both 2D and 3D enamel thickness and dental tissue proportions. Although Leuca I follows the Neandertal M2s trend in some morphometric aspects (i.e., small relative occlusal polygon area), in other cases it falls to the higher end (for 3D average enamel thickness) or even outside (for 3D‐relative enamel thickness) the Neandertal M2 variability, thus increasing the known Neandertal range of variation. Am J Phys Anthropol 152:300–305, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
5.
J P Shoemaker 《Experimental parasitology》1974,36(2):261-264
Plasmodium berghei infected C3H mice had lower parasitemias than the control mice on 4 (Days 4, 5, 7, and 8; P < 0.001, 0.02, 0.001, and 0.02, respectively) out of 7 check days when treated with 0.1% 6-propylthiouracil (6-PT) in water ad lib. The 6-PT-treated mice also survived longer than the control mice in 2 experiments: 11.8 (8–13) days vs 10.7 (8–13) days (P < 0.001); and 10.4 (9–11) days vs 9.4 (9–10) days (P < 0.001). Parasitemias of mice treated with 0.1% 6-PT + D-thyroxine (T4) were consistently higher on 6 of 7 check days than the 6-PT-treated group, with the 9th day count of 69.0 ± 11.6 for the 6-PT + T4 group being significantly higher (P < 0.05) than the count of 52.9 ± 19.9 for the 6-PT only group. Reduced T4 production, due to the 6-PT-induced hypothyroidism (lower 131I uptakes), may have caused the parasitemia reduction. Differences in temperature and metabolism do not appear to be involved. More experiments (in vitro) are necessary in order to determine definitely whether T4 is involved in the growth and metabolism of malaria parasites. 相似文献
6.
The Pech-de-l'Azé I skull and mandible are included in the juvenile Neandertal remains from Europe. However, some preserved features in the cranial skeleton seem to distinguish the specimen from other Neandertal children. Unfortunately, the stratigraphic position and dating of this child has never been clear. Our recent work on unpublished archives show that the Pech-de-l'Azé I Neandertal child was discovered at the bottom of layer 6, attributed to the Mousterian of Acheulean tradition type B. These skull and mandible are the first diagnostic human remains (aside from an isolated tooth) attributed to the Mousterian of Acheulian tradition (MTA) type B. Consequently, we confirm that Neandertals were the makers of this Mousterian industry, which is characterized by unusual high frequencies of Upper Paleolithic type tools, elongated blanks and blades. We were able to date the context of the hominid remains by dating layer 6 and the layers above and beneath it using ESR, coupled ESR/(230)Th/(234)U (coupled ESR/U-series), and AMS (14)C. Coupled ESR/U-series results on 16 mammalian teeth constrain the age of the uppermost layer 7 to 41-58ka, and layer 6 to 37-51ka. The wide spread in each age estimate results mainly from uncertainties in the gamma-dose rate. These ages are concordant with AMS (14)C ages of two bones coming from the top of layer 6, which provide dates of about 41.7-43.6ka cal BP. A combination of stratigraphic arguments and dating results for layers 6 and 7 show that the Neandertal child cannot be older than 51ka or younger than 41ka. The lowermost layer 4 is shown to be older than 43ka by the principle of superposition and ESR dating in the immediately overlying layer 5. This study shows that the MTA type B had been manufactured by Neandertals before the arrival of anatomically modern humans in the local region. Additionally, by providing a firm chronological framework for the specific morphometric the features of Pech-de-l'Azé I Neandertal child, this study is a new step toward the understanding of temporal and spatial changes in the ontogenesis of Neandertals in south-western Europe during oxygen isotope stages 5-3. 相似文献
7.
The ramus of Neandertal mandibles is said to show a suite of uniquely Neandertal character states that demonstrate the independent course of Neandertal evolution. This is the latest of numerous attempts to define cranial and mandibular autapomorphies for Neandertals. We examine variation in the four presumably autapomorphic ramal features and show they are neither monomorhic within Neandertals (to the contrary Neandertals are at least as variable as other human samples) nor unique to Neandertals, since they regularly appear in populations predating and postdating them. Neandertals differ from other human populations, both contemporary and recent, but the question of whether this fact reflects a divergent evolutionary trajectory must be addressed by the pattern of differences. In this case, as in the other attempts to establish Neandertal autapomorphies, rather than showing restricted variation and increased specialization, the Neandertal sample shows that the range of human variation in the recent past encompasses, and in some cases exceeds, human variation today, even in the very features claimed to be autapomorphic. 相似文献
8.
N. H. Thuy L. A. Tien P. N. Tuyet D. T. T. Huong N. V. Cong M. Bayley T. Wang S. Lefevre 《Journal of fish biology》2010,76(4):1025-1031
Oxygen uptake () and critical oxygen tension (Pcrit) were measured in resting perch Perca fluviatilis that were either fasting or digesting. Digestion caused to double (from 61 to 117 mg O2 kg?1h?1) and was associated with a rise in Pcrit (from 3·4 to 4·9 kPa), showing that the animal's digestive state must be considered when assessing the effect of hypoxia in natural conditions, and when defining optimal oxygen conditions in aquaculture. 相似文献
9.
M R Zingeser 《American journal of physical anthropology》1969,31(2):205-213
The form of the unworn male Cercopithecoid maxillary canine tooth (C') is effectively adapted for stabbing and slashing. Its essential features are maintained by wear against the mandibular canine (C1) and first premolar (P3) teeth. The cusp tip of C1 is sharpened by reciprocal wear against C'. The distribution of apposing wear facets indicates that functional attrition results from honing activity largely distinct from mastication. Functional attrition also occurs in reduced form in females and is produced within the masticatory excursive range. The significance of the “sectorial” form of P3 is analyzed. Its elongated mesiobuccal surface serves the dual purpose of honing the distal cutting edge of C' and functioning as a cutting block against which vegetation is stabilized and shredded by the cervical third of the distal cutting edge of C'. Behavioral aspects of honing are correlated with field observations linking tooth grinding with aggression, tension release, and communication. Parallel human behavior is cited and the suggestion is made that human tooth grinding with its highly charged emotional overtones is largely relict behavior that once had high survival value in a canine tooth honing context. 相似文献
10.
Mahiuddin Ahmed Ming Cheng Qi Zhao Yehuda Goldgur Sarah M. Cheal Hong-Fen Guo Steven M. Larson Nai-Kong V. Cheung 《The Journal of biological chemistry》2015,290(50):30018-30029
B7-H3 (CD276) is both an inhibitory ligand for natural killer cells and T cells and a tumor antigen that is widely expressed among human solid tumors. Anti-B7-H3 mouse monoclonal antibody 8H9 has been successfully used for radioimmunotherapy for patients with B7-H3(+) tumors. We present the humanization, affinity maturation, and epitope mapping of 8H9 based on structure determination, modeling, and yeast display methods. The crystal structure of ch8H9 Fab fragment was solved to 2.5-Å resolution and used as a template for humanization. By displaying the humanized 8H9 single chain Fv (scFv) on the surface of yeast, the affinity was matured by sequential random mutagenesis and fluorescence-activated cell sorting. Six mutations (three in the complementarity-determining region and three in the framework regions) were identified and incorporated into an affinity-matured humanized 8H9 construct (hu8H9-6m) and an affinity-matured chimeric 8H9 construct (ch8H9-6m). The hu8H9-6m scFv had a 160-fold improvement in affinity (0.9 nm
KD) compared with parental hu8H9 scFv (144 nm
KD). The IgG formats of ch8H9-6m and hu8H9-6m (nanomolar to subnanomolar KD) had 2–9-fold enhancements in affinity compared with their parental forms, potent in vitro antibody-dependent cell-mediated cytotoxicity (0.1–0.3 μg/ml EC50), and high tumor uptake in mouse xenografts. Based on in silico docking studies and experimental validation, the molecular epitope of 8H9 was determined to be dependent on the FG loop of B7-H3, a region critical to its function in immunologic blockade and unique among anti-B7-H3 antibodies published to date. 相似文献
11.
G. Villa 《Human Evolution》1996,11(1):85-96
A recent paper concerning characteristic groove-shaped wear in interproximal attritional facets of Neandertal posterior teeth
correlated groove formation with deep enamel structural traits (Villa & Giacobini, 1995). Further studies were carried out
on modern human teeth in order to evaluate a possible correlation between deep enamel structure and some crown complex morphological
features.
Seventy-five isolated molars from medieval and recent ossuaries as well as five molars recently extracted for therapeutic
purpose were examined using scanning electron and optic microscope ground sections of interproximal enamel. The results showed
possible correlations between deep enamel structural characteristics (i.e., Hunter-Schreger band verticalization) and some
crown complex traits (i.e., occlusal groove pattern, mesial and distalfovea, mesial and distal accessory tubercules, interproximal marginal ridges).
Observations reported in this study showed a significantly higher frequency of Hunter-Schreger band verticalization in lower
molars with an occlusal complex pattern (i.e. primitive fissure pattern “Y” or “+”). This observation suggests a positive
correlation among crown complex traits (which occur frequently in Neandertal teeth) with deep enamel structural characteristics.
In addition, analysis of teeth grouped according to individual showed crown morphological traits and deep enamel structural
characteristics corresponding to the same individual. This observation supports a genetic basis in occlusal shape and microstructural
dental traits. 相似文献
12.
On the basis of eight independent quantitative trait loci (QTL) studies of ethanol (alcohol) preference drinking in mice,
a meta-analysis was carried out to examine the replicability of QTLs across studies and to enhance the power of QTL detection
and parameter estimation. To avoid genetic heterogeneity, we analyzed only studies of mapping populations derived from the
C57BL/6 (B6) and DBA/2 (D2) inbred progenitor strains. Because these studies were carried out in five different laboratories,
there were substantial differences in testing procedure, data analysis, and especially in the choice of mapping population
(BXD recombinant inbred strains, F2, backcross, selected lines, or congenic strains). Despite this, we found several QTLs that were sufficiently robust as to
appear consistently across studies given the strengths and weaknesses of the mapping populations employed. These were on Chromosomes
(Chrs) 2 (proximal to mid), 3 (mid to distal), 4 (distal), and 9 (proximal to mid). The P value for each of these QTLs, combined across all applicable studies, ranged from 10−7 to 10−15, with the additive effect of each QTL accounting for 3–5% of the trait variance extrapolated to an F2 population. Two other QTLs on Chrs 1 (distal) and 11 (mid) were less consistent, but still reached overall significance (P < .0001).
Received: 18 April 2001 / Accepted: 25 July 2001 相似文献
13.
The preparation and X-ray structure of [Ag(9-EtGH-N7)2]NO3·H2O(9-EtGH=neutral 9-ethylguanine) is reported. The compound crystallizes in the triclinic system, space group P
with a=7.063(6), b=7.153(3), c=11.306(10) Å, α=83.36(6), β=76.66(7), γ=81.44(6)°. The cation is centrosymmetric with Ag(I) coordinated via two N7 positions and Ag---N7 bond lengths of 2.11(1) Å. Applying 109Ag NMR spectroscopy, complex formation constants for both the 1:1 complex (log β1=0.6) and the title compound (log β2=1.6) in Me2SO have been determined. 相似文献
14.
Middle Paleolithic human remains from the Gruta da Oliveira (Torres Novas), Portugal 总被引:1,自引:0,他引:1
Ongoing excavations in the Middle Paleolithic levels at the Gruta da Oliveira, Portugal have yielded four fragmentary human remains, a manual phalanx and an ulna from levels 9 and 10, and a humerus and a tibia from levels 18 and 19. The first two remains date to approximately 39 ka 14C BP ( approximately 43.5 ka cal BP), whereas the latter two derive from earlier in oxygen isotope stage 3. The preserved portions of the phalanx, humerus, and tibia align them morphologically with the Neandertals. In addition, the Oliveira 4 tibial diaphysis shows evidence of carnivore (probably canid) gnawing. 相似文献
15.
Alpha-bag cell peptide [α-BCP (Ala-Pro-Arg-Leu-Arg-Phe-Tyr-Ser-Leu)] is a neurotransmitter that mediates bag cell-induced inhibition of left-upper-quadrant (LUQ) neurons L2, L3, L4, and L6 in the abdominal ganglion of Aplysia. Our recent biochemical studies have shown that α-BCP[1–9] is cleaved into α-BCP[1–2], [3–9], [1–5], [6–9], and [7–9] by a combination of three distinct peptidase activities located within the extracellular spaces of the CNS: A diaminopeptidase-IV (DAP-IV)-like enzyme cleaves α-BCP[1–9] at the 2–3 peptide bond; a neutral metalloendopeptidase (NEP)-like enzyme cleaves either α-BCP[1–9] or α-BCP[3–9] at the 5–6 bond; an aminopeptidase M-II (APM-II)-like enzyme cleaves α-BCP[6–9] at the 6–7 bond, but cleaves neither α-BCP[1–9], nor the other ganglionic peptidase products. To further understand the manner in which α-BCP is inactivated after release, that is loses its electro-physiological activity, we studied its structure-activity relationship by recording intracellularly from LUQ neurons in isolated abdominal ganglia that were arterially perfused with peptides dissolved in artificial sea water. The effects of α-BCP[1–9] and 15 of its fragments ([1–8], [1–7], [1–6], [1–5], [2–9], [3–9], [3–8], [6–9], [7–9], [8–9], [6–7], [6–8], [1–2], Phe, Tyr) indicated that the sequence Phe6-Tyr7 was both necessary and sufficient to produce LUQ inhibitory activity. The combined results of our electrophysiological and biochemical studies strongly suggest that α-BCP[1–9] is inactivated by the serial actions of the NEP-like and APM-II-like peptidases; that is, the NEP-like enzyme yields an electro-physiologically active product, α-BCP[6–9], that is cleaved by the APM-II-like enzyme to yield inactive α-BCP[7–9]. Furthermore, because α-BCP[6–9] is more active than α-BCP[1–9], cleavage by the NEP-like enzyme potentiates α-BCP's activity. © 1992 John Wiley & Sons, Inc. 相似文献
16.
Kyohei Itsuki Yuko Imai Hideharu Hase Yasushi Okamura Ryuji Inoue Masayuki X. Mori 《The Journal of general physiology》2014,143(2):183-201
Transient receptor potential classical (or canonical) (TRPC)3, TRPC6, and TRPC7
are a subfamily of TRPC channels activated by diacylglycerol (DAG) produced
through the hydrolysis of phosphatidylinositol 4,5-bisphosphate
(PI(4,5)P2) by phospholipase C (PLC). PI(4,5)P2
depletion by a heterologously expressed phosphatase inhibits TRPC3, TRPC6, and
TRPC7 activity independently of DAG; however, the physiological role of
PI(4,5)P2 reduction on channel activity remains unclear. We used
Förster resonance energy transfer (FRET) to measure PI(4,5)P2
or DAG dynamics concurrently with TRPC6 or TRPC7 currents after agonist
stimulation of receptors that couple to Gq and thereby activate PLC.
Measurements made at different levels of receptor activation revealed a
correlation between the kinetics of PI(4,5)P2 reduction and those of
receptor-operated TRPC6 and TRPC7 current activation and inactivation. In
contrast, DAG production correlated with channel activation but not
inactivation; moreover, the time course of channel inactivation was unchanged in
protein kinase C–insensitive mutants. These results suggest that
inactivation of receptor-operated TRPC currents is primarily mediated by the
dissociation of PI(4,5)P2. We determined the functional dissociation
constant of PI(4,5)P2 to TRPC channels using FRET of the PLCδ
Pleckstrin homology domain (PHd), which binds PI(4,5)P2, and used
this constant to fit our experimental data to a model in which channel gating is
controlled by PI(4,5)P2 and DAG. This model predicted similar FRET
dynamics of the PHd to measured FRET in either human embryonic kidney cells or
smooth muscle cells, whereas a model lacking PI(4,5)P2 regulation
failed to reproduce the experimental data, confirming the inhibitory role of
PI(4,5)P2 depletion on TRPC currents. Our model also explains
various PLC-dependent characteristics of channel activity, including limitation
of maximum open probability, shortening of the peak time, and the bell-shaped
response of total current. In conclusion, our studies demonstrate a fundamental
role for PI(4,5)P2 in regulating TRPC6 and TRPC7 activity triggered
by PLC-coupled receptor stimulation. 相似文献
17.
A series of 1, 3-dialkylxanthines was examined as antagonists of adenosine-induced accumulation of cyclic AMP in guinea pig cerebral cortical slices and as inhibitors of brain phosphodiesterases. The order of potency as adenosine-antagonists was: 8-phenyltheophylline (IC50 6 μM) > 1, 3-dibutylxanthine (IC50 30 μM), 1, 3-dipropylxanthine > theophylline (IC50 60 μM), 3-isobutyl-1-methylxanthine (IBMX), 1, 3, 7-triethylxanthine > 7-benzyl IBMX (IC50 100 μM), 8-methyl IBMX > 7-benzyl-8-bromo IBMX, 9-methyl IBMX, 8-bromo IBMX, 1-isoamyl-3-isobutylxanthine. The order of potency as inhibitors of brain calcium-dependent phosphodiesterase was: 7-benzyl IBMX (IC50 1.5 μM), 7-benzyl-8-bromo IBMX > 8-methyl IBMX (IC50 4.5 μM) > IBMX (IC50 7.5 μM), 8-bromo IBMX > 9-methyl IBMX (IC50 40 μM), 1, 3, 7-triethylxanthine > 1, 3-dibutylxanthine (IC50 100 μM), 1-isoamyl-3-isobutylxanthine > theophylline. 8-Phenyltheophylline and 1, 3-dibutylxanthine represented potent adenosine-antagonists with relatively low activity as phosphodiesterase inhibitors whereas 7-benzyl IBMX and 7-benzyl-8-bromo-IBMX were potent inhibitors of the calcium-dependent phosphodiesterase with relatively low activity as adenosine-antagonists. None of the compounds were potent inhibitors of the brain calcium-independent phosphodiesterase, although 1-isoamyl-3-isobutylxanthine might prove useful as an inhibitor of this enzyme because of its very low activity as an adenosine-antagonist. 相似文献
18.
Omer Gokcumen Qihui Zhu Lubbertus C. F. Mulder Rebecca C. Iskow Christian Austermann Christopher D. Scharer Towfique Raj Jeremy M. Boss Shamil Sunyaev Alkes Price Barbara Stranger Viviana Simon Charles Lee 《PLoS genetics》2013,9(4)
Ancient population structure shaping contemporary genetic variation has been recently appreciated and has important implications regarding our understanding of the structure of modern human genomes. We identified a ∼36-kb DNA segment in the human genome that displays an ancient substructure. The variation at this locus exists primarily as two highly divergent haplogroups. One of these haplogroups (the NE1 haplogroup) aligns with the Neandertal haplotype and contains a 4.6-kb deletion polymorphism in perfect linkage disequilibrium with 12 single nucleotide polymorphisms (SNPs) across diverse populations. The other haplogroup, which does not contain the 4.6-kb deletion, aligns with the chimpanzee haplotype and is likely ancestral. Africans have higher overall pairwise differences with the Neandertal haplotype than Eurasians do for this NE1 locus (p<10−15). Moreover, the nucleotide diversity at this locus is higher in Eurasians than in Africans. These results mimic signatures of recent Neandertal admixture contributing to this locus. However, an in-depth assessment of the variation in this region across multiple populations reveals that African NE1 haplotypes, albeit rare, harbor more sequence variation than NE1 haplotypes found in Europeans, indicating an ancient African origin of this haplogroup and refuting recent Neandertal admixture. Population genetic analyses of the SNPs within each of these haplogroups, along with genome-wide comparisons revealed significant FST (p = 0.00003) and positive Tajima''s D (p = 0.00285) statistics, pointing to non-neutral evolution of this locus. The NE1 locus harbors no protein-coding genes, but contains transcribed sequences as well as sequences with putative regulatory function based on bioinformatic predictions and in vitro experiments. We postulate that the variation observed at this locus predates Human–Neandertal divergence and is evolving under balancing selection, especially among European populations. 相似文献
19.
TRPC3/C6/C7 channels, a subgroup of classical/canonical TRP channels, are activated by diacylglycerol produced via activation of phospholipase C (PLC)-coupled receptors. Recognition of the physiological importance of these channels has been steadily growing, but the mechanism by which they are regulated remains largely unknown. We recently used a membrane-resident danio rerio voltage-sensing phosphatase (DrVSP) to study TRPC3/C6/C7 regulation and found that the channel activity was controlled by PtdIns(4,5)P2-DAG signaling in a self-limiting manner (Imai Y et al., the Journal of Physiology, 2012). In this addendum, we present the advantages of using DrVSP as a molecular tool to study PtdIns(4,5)P2 regulation. DrVSP should be readily applicable for studying phosphoinositide metabolism-linked channel regulation as well as lipid dynamics. Furthermore, in comparison to other modes of self-limiting ion channel regulation, the regulation of TRPC3/C6/C7 channels seems highly susceptible to activation signal strength, which could potentially affect both open duration and the time to peak activation and inactivation. Dysfunction of such self-limiting regulation may contribute to the pathology of the cardiovascular system, gastrointestinal tract and brain, as these channels are broadly distributed and affected by numerous neurohormonal agonists. 相似文献
20.