Androstenedione metabolism in human uterine tissues: Endometrium,myometrium and leiomyoma

Androstenedione was metabolized in vitro by human endometrium, myometrium and leiomyoma, to its 5α-reduced metabolites: 5α-androstan-3,17-dione (5α-androstanedione) and androsterone as well as to testosterone, 17β-hydroxy-5α-androstan-2-one(5α-DHT) and 5α-androstan-3α, 17β-diol (3α-diol). Uterine tissue showed a similar enzymatic profile to the androgen responsive tissues; these data suggest that androgens may have a functional role in the uterine pathophysiology.     

Identification, quantification and fine structural characterization of glycosaminoglycans from uterine leiomyoma and normal myometrium

The type, amount and fine chemical composition of glycosaminoglycans (GAGs) present both in human normal myometrium and uterine leiomyoma have been studied. GAGs were fractionated by ion-exchange chromatography on DEAE-Sephacel, isolated by gel-permeation chromatography on Sepharose CL-6B and characterized using electrophoresis in cellulose acetate membranes, specific enzymic treatments and analysis by high-performance capillary electrophoresis (HPCE). No statistical intrabatch differences in total GAG content in both tissues were identified, whereas significant interbatch differences between normal myometrium and uterine leiomyoma were recorded. Hyaluronan (HA), chondroitin sulphate (CS), dermatan sulphate (DS), heparan sulphate (HS) and keratan sulphate (KS) were identified in both tissues. Statistically significant (P 相似文献   

A comparative analysis of subgroup structure and spatial relationships in captive baboons and squirrel monkeys

Subgroup structure, spacing patterns, and the relationship between spatial and behavioral interations were compared for captive baboons and squirrel monkeys. Analysis of the structure, intensity, and permanence of subgroups revealed that the baboons formed low intensity, overlapping subgroups which were relatively flexible while the squirrel monkeys segregated into permanent, high intensity, mutually exclusive cliques. Clique associations and social proximity relationships were found to be better predictors than dominance rank of the nature and frequency of behavioral interactions in the two colonies.     

X-ray structure determination of human profilin II: A comparative structural analysis of human profilins

Human profilins are multifunctional, single-domain proteins which directly link the actin microfilament system to a variety of signalling pathways via two spatially distinct binding sites. Profilin binds to monomeric actin in a 1:1 complex, catalyzes the exchange of the actin-bound nucleotide and regulates actin filament barbed end assembly. Like SH3 domains, profilin has a surface-exposed aromatic patch which binds to proline-rich peptides. Various multidomain proteins including members of the Ena/VASP and formin families localize profilin:actin complexes through profilin:poly-L-proline interactions to particular cytoskeletal locations (e.g. focal adhesions, cleavage furrows). Humans express a basic (I) and an acidic (II) isoform of profilin which exhibit different affinities for peptides and proteins rich in proline residues. Here, we report the crystallization and X-ray structure determination of human profilin II to 2.2 A. This structure reveals an aromatic extension of the previously defined poly-L-proline binding site for profilin I. In contrast to serine 29 of profilin I, tyrosine 29 in profilin II is capable of forming an additional stacking interaction and a hydrogen bond with poly-L-proline which may account for the increased affinity of the second isoform for proline-rich peptides. Differential isoform specificity for proline-rich proteins may be attributed to the differences in charged and hydrophobic residues in and proximal to the poly-L-proline binding site. The actin-binding face remains nearly identical with the exception of five amino acid differences. These observations are important for the understanding of the functional and structural differences between these two classes of profilin isoforms.     

Differential expression of Akt/protein kinase B, Bcl-2 and Bax proteins in human leiomyoma and myometrium

The expression and activation of serine/threonine protein kinase, Akt, in leiomyoma and in adjacent myometrium of human uteri was studied parallel with the changes of Bcl-2, Bax proteins, estrogen and progesterone receptors during menstrual cycle and early stage of the menopause. Abundant expression of Akt protein was detected in the studied tissues during menstrual cycle, the rate of increase was higher in leiomyoma than in corresponding myometrium. The expression of estrogen receptor alpha, progesterone receptor and of Bcl-2 protein changed parallel with that of Akt protein. The level of phosphorylated Akt (pAkt⁴⁷³) was seen only in leiomyoma samples from the growing period of tumors. At early stage of menopause levels of all studied proteins were lower than that in the menstrual cycle with the exception of Bax protein expression, which was high in leiomyoma. Our data suggest the involvement of phosphatidylinositol 3-kinase/Akt signaling in the pathomechanism of leiomyoma.     

Localization of decorin gene expression in normal human breast tissue and in benign and malignant tumors of the human breast

The small extracellular matrix proteoglycan decorin which possesses a potent antitumor activity has been shown to be present in various amounts in the stroma of several tumors including those of the breast. Regarding decorin in breast malignancies the published data are conflicting, i.e., whether breast cancer cells express it or not. Here, we first compared decorin gene expression levels between healthy human breast tissue and selected types of human breast cancer using GeneSapiens databank. Next, we localized decorin mRNA in tissue specimen of normal human breast, intraductal breast papillomas and various histologic types of human breast cancer using in situ hybridization (ISH) with digoxigenin-labeled RNA probes for decorin. We also examined the effect of decorin transduction on the behavior of cultured human breast cancer MCF7 cells. Analysis of GeneSapiens databank revealed that in various human breast cancers decorin expression is significant. However, ISH results clearly demonstrated that human breast cancer cells independently of the type of the cancer do not express decorin mRNA. This was also true for papilloma-forming cells of the human breast. Indeed, decorin gene expression in healthy human breast tissue as well as in benign and malignant tumors of human breast was shown to take place solely in cells of the original stroma. Decorin transduction using decorin adenoviral vector in decorin-negative MCF7 cells resulted in a significant decrease in the proliferation of these cells and changed cell cohesion. Decorin-transduced MCF7 cells also exhibited increased apoptosis. In conclusion, our study shows that in human breast tissue only cells of the original stroma are capable of decorin gene expression. Our study also shows that transduction of decorin in decorin-negative human breast cancer cells markedly modulates the growth pattern of these cells.     

A comparative collision-based analysis of human gait

This study compares human walking and running, and places them within the context of other mammalian gaits. We use a collision-based approach to analyse the fundamental dynamics of the centre of mass (CoM) according to three angles derived from the instantaneous force and velocity vectors. These dimensionless angles permit comparisons across gait, species and size. The collision angle Φ, which is equivalent to the dimensionless mechanical cost of transport CoT_mech, is found to be three times greater during running than walking of humans. This threefold difference is consistent with previous studies of walking versus trotting of quadrupeds, albeit tends to be greater in the gaits of humans and hopping bipeds than in quadrupeds. Plotting the collision angle Φ together with the angles of the CoM force vector Θ and velocity vector Λ results in the functional grouping of bipedal and quadrupedal gaits according to their CoM dynamics—walking, galloping and ambling are distinguished as separate gaits that employ collision reduction, whereas trotting, running and hopping employ little collision reduction and represent more of a continuum that is influenced by dimensionless speed. Comparable with quadrupedal mammals, collision fraction (the ratio of actual to potential collision) is 0.51 during walking and 0.89 during running, indicating substantial collision reduction during walking, but not running, of humans.     

A comparative analysis of numt evolution in human and chimpanzee

Mitochondrial DNA sequences are frequently transferred into the nuclear genome, giving rise to numts (nuclear DNA sequences of mitochondrial origin). So far, the evolutionary history of numts has largely been studied by using single genomes. Here, we present the first attempt to study numt evolution in a comparative manner by using a pairwise genomic alignment. The total number of numts was estimated to be 452 in human and 469 in chimpanzee. numts that were found in both genomes at identical loci were deemed to be orthologous; 391 numts (>80%) were classified as such. The preponderance of orthologous numts is due to the very short divergence time between the 2 hominoids. The rest of numts were deemed to be nonorthologous. Nonorthologous numts were subdivided into 1) ancestral numts that have lost an ortholog in one species through deletion (12 in human and 11 in chimpanzee), 2) new numts acquired by the insertion of a mitochondrial sequence after the divergence of the 2 species (34 in human and 46 in chimpanzee), and 3) paralogous numts created by the tandem duplication of a preexisting numt (2 in human). This approach also enabled us to reconstruct the numt repertoire in the common ancestor of humans and chimpanzees (409 numts). Our comparative approach is also useful in identifying the exact boundaries of numts.     

AMP-deaminase from normal and cirrhotic human liver: A comparative study

AMP-deaminase (EC 3.5.4.6) is an enzyme of nucleotide breakdown involved in regulation of adenine nucleotide pool in mammalian cells. Reaction catalysed by AMP-deaminase constitutes a rate-limiting step in adenine nucleotide catabolism in liver. In this study kinetic and regulatory properties of AMP-deaminase purified from normal and cirrhotic human liver were investigated. In comparison to AMP-deaminase extracted from the normal human liver, AMP-deaminase extracted from the cirrhotic liver was less sensitive towards substrate analogues, and only a very limited response towards pH and adenylate energy charge changes tested for enzyme isolated from this tissue source had been observed. At physiological pH 7.0, in the absence and in the presence of important allosteric effectors (ATP, ADP, GTP and orthophosphate), AMP-deaminases from the two sources studied manifested different regulatory profiles, with half-saturation constant (S0.5) values being distinctly higher for the enzyme extracted from the pathological organ. In contrast to AMP-deaminase isolated from the normal, healthy liver, where presence of relatively large (68 kDa) protein fragment was also detected, only smaller protein fragments were identified, while SDS-PAG electrophoresis of AMP-deaminase isolated from the cirrhotic liver was performed. The obtained results indicate clearly that advanced proteolytic processes occurring in the cirrhotic liver may affect structural integrity of AMP-deaminase studied, making enzyme less active and less sensitive to regulatory action of important allosteric effectors.     

Lipidomic analysis reveals prostanoid profiles in human term pregnant myometrium

Prostanoids modulate the activity of human pregnant myometrium and their functional role can be appreciated through characterisation of prostanoid receptors and tissue concentration of prostanoids. We have applied a lipidomic approach to elucidate the profile of prostanoids in human non-labouring and labouring myometrium. We have identified a total of nineteen prostanoids including prostacyclin, thromboxanes, prostaglandins and dihydro-prostaglandins. Prostacyclin was the predominant prostanoid in both non-labouring and labouring myometria, with PGD₂ and PGF_2α being the second most abundant. Although the total amount of prostanoids was increased in the labouring tissue, PGE₂ and 13,14-dihydro-15-keto-PGE₂ were the only prostanoids to increase significantly at early and late labour (p≤0.001). Our data suggest that PGF_2α plays an important role in parturition, whilst the increase in PGE₂ could occur to facilitate cervical dilation and relaxation of the lower myometrium during labour. Although the elevation in TXA₂ was less marked than expected, in terms of translation to function even a relatively small increase in the level of this potent spasmogen may have significant effects.     

A non-linear analysis for spatial structure in a reaction-diffusion model

A non-linear stability analysis using a multi-scale perturbation procedure is carried out on the practical Thomas reaction-diffusion mechanism which exhibits bifurcation to non-uniform states. The analytical results compare favourably with the numerical solutions. The sequential patterns generated by this model by variations in a parameter related to the reaction-diffusion domain indicate its capacity to represent certain key morphogenetic features required in a recent model by Kauffman for pattern formation in theDrosophila embryo.     

Prevalence and spatial distribution characteristics of human echinococcosis in China

BackgroundEchinococcosis is a zoonotic parasitic disease caused by larval stages of cestodes belonging to the genus Echinococcus. The infection affects people’s health and safety as well as agropastoral sector. In China, human echinococcosis is a major public health burden, especially in western China. Echinococcosis affects people health as well as agricultural and pastoral economy. Therefore, it is important to understand the prevalence status and spatial distribution of human echinococcosis in order to advance our knowledge of basic information for prevention and control measures reinforcement.MethodsReport data on echinococcosis were collected in 370 counties in China in 2018 and were used to assess prevalence and spatial distribution. SPSS 21.0 was used to obtain the prevalence rate for CE and AE. For statistical analyses and mapping, all data were processed using SPSS 21.0 and ArcGIS 10.4, respectively. Chi-square test and Exact probability method were used to assess spatial autocorrelation and spatial clustering.ResultsA total of 47,278 cases of echinococcosis were recorded in 2018 in 370 endemic counties in China. The prevalence rate of human echinococcosis was 10.57 per 10,000. Analysis of the disease prevalence showed obvious spatial positive autocorrelation in globle spatial autocorrelation with two aggregation modes in local spatial autocorrelation, namely high-high and low-high aggregation areas. The high-high gathering areas were mainly concentrated in northern Tibet, western Qinghai, and Ganzi in the Tibetan Autonomous Region and in Sichuan. The low-high clusters were concentrated in Gamba, Kangma and Yadong counties of Tibet. In addition, spatial scanning analysis revealed two spatial clusters. One type of spatial clusters included 71 counties in Tibet Autonomous Region, 22 counties in Qinghai, 11 counties in Sichuan, three counties in Xinjiang Uygur Autonomous Region, two counties in Yunnan, and one county in Gansu. In the second category, six types of spatial clusters were observed in the counties of Xinjiang Uygur Autonomous Region, and the Qinghai, Gansu, and Sichuan Provinces.ConclusionThis study showed a serious prevalence of human echinococcosis with obvious spatial aggregation of the disease prevalence in China. The Qinghai-Tibet Plateau is the "hot spot" area of human echinococcosis in China. Findings from this study indicate that there is an urgent need of joint strategies to strengthen efforts for the prevention and control of echinococcosis in China, especially in the Qinghai-Tibet Plateau.     

北京地区黄檗种群数量结构及空间分布特征

黄檗(Phellodendron amurense)为我国二级国家重点保护野生植物,在北京地区黄檗多散生于阔叶林中,数量稀少,为了解北京地区黄檗种群的年龄结构和空间分布特征,促进种群扩繁,在北京百花山、松山和雾灵山自然保护区共设置了12个20 m×20 m的样地,从种群的径级结构、静态生命表、空间分布格局等3个方面分析了黄檗种群的数量特征与空间分布格局。结果表明:1)黄檗幼龄期个体数较多,中龄期个体数相对稳定,老龄期个体数量稀少,倒"J"的径级结构表明黄檗种群总体属于增长型种群;但局部小种群的径级结构组成比例差异很大。2)在整个黄檗种群的静态生命表中有3个死亡率高峰,第一个是从幼树阶段至小树阶段,第二个是从小树阶段至大树阶段,第二阶段死亡率最高,第三个是大树阶段的末期;3)黄檗空间分布格局总体为集群分布,在不同发育阶段的分布格局受其生物学、生态学特性以及种群发展过程中种内、种间关系的影响呈现出不同的分布格局。因此,调整局部种群的径级结构,采取促进黄檗小树集群分布的措施是促进其种群扩大的重要环节。     

A new eigenfunction spatial analysis describing population genetic structure

Several methods of spatial analyses have been proposed to infer the relative importance of evolutionary processes on genetic population structure. Here we show how a new eigenfunction spatial analysis can be used to model spatial patterns in genetic data. Considering a sample of n local populations, the method starts by modeling the response variable (allele frequencies or phenotypic variation) against the eigenvectors sequentially extracted from a geographic distance matrix (n × n). The relationship between the coefficient of determination (R ²) of the models and the cumulative eigenvalues, which we named the spatial signal-representation (SSR) curve, can be more efficient than Moran’s I correlograms in describing different patterns. The SSR curve was also applied to simulated data (under distinct scenarios of population differentiation) and to analyze spatial patterns in alleles from microsatellite data for 25 local populations of Dipteryx alata, a tree species endemic to the Brazilian Cerrado. The SSR curves are consistent with previous phylogeographical patterns of the species, revealing combined effects of isolation-by-distance and range expansion. Our analyses demonstrate that the SSR curve is a useful exploratory tool for describing spatial patterns of genetic variability and for selecting spatial eigenvectors for models aiming to explain spatial responses to environmental variables and landscape features.     

Copper distribution in the normal human brain

Copper concentration was determined in samples from 38 areas of 7 normal human brains. The grey matter contained higher concentrations of copper than the white matter. Identical areas of the grey and white matter of the cerebral cortex showed significant differences between individuals. In the caudate nucleus the highest concentrations of copper were found in the tail followed by the body and the head, respectively. A negative linear regression between age and brain copper levels was demonstrated.