Australopithecus afarensis : bipédie stricte ou associée à une composante arboricole ? Critiques et révision du matériel fémoral

Although much research has been carried out on Australopithecus afarensis locomotion, no consensus has yet been reached. Our new critic study on femoral material brings to the fore a strictly bipedal behaviour within this taxon. Our results are based on the pertinence of human anatomical characteristics among A. afarensis and on the absence of characteristics revealing arboreal displacement. These results have emerged from our different observation and interpretation of some preceding authors concerning the anatomy of these fossil hominids. It is important to underline that apomorphic characteristics of this species are difficult to interpret. They must not however be used to support the idea of arboreal displacement simply based on the fact of a no totally human morphe. We believe that present day humans do not necessarily reflect the earliest strict bipedal anatomic model. An the other hand, it appears that the disagreement between the two locomotor hypothesis for A. afarensis that are bipedalism and arboreal displacement, facing the possibility of bipedalism associated with negligible arboreal displacement, results more from an evolutionary fact than from a real scientific conflict.     

·遗传咨询·

1．多囊肾的遗传 问：我有家族多囊肾遗传史,自己双肾有囊肿,现在怀孕29周,胎儿彩超双肾大,有回声,医生判定为多囊肾,我如果不要这胎,再怀孕,有不遗传的可能吗？     

Chronic Atmospheric NO<Stack><Subscript>3</Subscript><Superscript>−</Superscript></Stack> Deposition Does Not Induce NO<Stack><Subscript>3</Subscript><Superscript>−</Superscript></Stack> Use by <Emphasis Type="Italic">Acer saccharum</Emphasis> Marsh.

The ability of an ecosystem to retain anthropogenic nitrogen (N) deposition is dependent upon plant and soil sinks for N, the strengths of which may be altered by chronic atmospheric N deposition. Sugar maple (Acer saccharum Marsh.), the dominant overstory tree in northern hardwood forests of the Lake States region, has a limited capacity to take up and assimilate NO₃⁻. However, it is uncertain whether long-term exposure to NO₃⁻ deposition might induce NO₃⁻ uptake by this ecologically important overstory tree. Here, we investigate whether 10 years of experimental NO₃⁻ deposition (30 kg N ha⁻¹ y⁻¹) could induce NO₃⁻ uptake and assimilation in overstory sugar maple (approximately 90 years old), which would enable this species to function as a direct sink for atmospheric NO₃⁻ deposition. Kinetic parameters for NH₄⁺ and NO₃⁻ uptake in fine roots, as well as leaf and root NO₃⁻ reductase activity, were measured under conditions of ambient and experimental NO₃⁻ deposition in four sugar maple-dominated stands spanning the geographic distribution of northern hardwood forests in the Upper Lake States. Chronic NO₃⁻ deposition did not alter the V _max or K _m for NO₃⁻ and NH₄⁺ uptake nor did it influence NO₃⁻ reductase activity in leaves and fine roots. Moreover, the mean V _max for NH₄⁺ uptake (5.15 μmol ¹⁵N g⁻¹ h⁻¹) was eight times greater than the V _max for NO₃⁻ uptake (0.63 μmol ¹⁵N g⁻¹ h⁻¹), indicating a much greater physiological capacity for NH₄⁺ uptake in this species. Additionally, NO₃⁻ reductase activity was lower than most values for woody plants previously reported in the literature, further indicating a low physiological potential for NO₃⁻ assimilation in sugar maple. Our results demonstrate that chronic NO₃⁻ deposition has not induced the physiological capacity for NO₃⁻ uptake and assimilation by sugar maple, making this dominant species an unlikely direct sink for anthropogenic NO₃⁻ deposition.     

Negative molecular ion of deuterium D<Stack><Subscript>2</Subscript><Superscript>−</Superscript></Stack>

D₂⁻ ions produced in collisions of D⁻ ions with relative energies of 2.5–9.2 eV were detected for the first time. It is shown that the effective cross section for this reaction is no less than 1.5 × 10⁻¹⁴ cm². Along with the theoretically predicted short-lived state of negative molecular deuterium ions, a state existing for more than 1 μs was observed.     

Flow of Deposited Inorganic N in Two Gleysol-dominated Mountain Catchments Traced with <Superscript>15</Superscript>NO<Subscript>3</Subscript><Superscript>−</Superscript> and <Superscript>15</Superscript>NH<Subscript>4</Subscript><Superscript>+</Superscript>

In two mountain ecosystems at the Alptal research site in central Switzerland, pulses of ¹⁵NO₃ and ¹⁵NH₄ were separately applied to trace deposited inorganic N. One forested and one litter meadow catchment, each approximately 1600 m², were delimited by trenches in the Gleysols. K¹⁵NO₃ was applied weekly or fortnightly over one year with a backpack sprayer, thus labelling the atmospheric nitrate deposition. After the sampling and a one-year break, ¹⁵NH₄Cl was applied as a second one-year pulse, followed by a second sampling campaign. Trees (needles, branches and bole wood), ground vegetation, litter layer and soil (LF, A and B horizon) were sampled at the end of each labelling period. Extractable inorganic N, microbial N, and immobilised soil N were analysed in the LF and A horizons. During the whole labelling period, the runoff water was sampled as well. Most of the added tracer remained in both ecosystems. More NO₃⁻ than NH₄⁺ tracer was retained, especially in the forest. The highest recovery was in the soil, mainly in the organic horizon, and in the ground vegetation, especially in the mosses. Event-based runoff analyses showed an immediate response of ¹⁵NO₃⁻ in runoff, with sharp ¹⁵N peaks corresponding to discharge peaks. NO₃⁻ leaching showed a clear seasonal pattern, being highest in spring during snowmelt. The high capacity of N retention in these ecosystems leads to the assumption that deposited N accumulates in the soil organic matter, causing a progressive decline of its C:N ratio.     

L’art Paléolithique est-il un « art » ?: Réflexions autour d’une question d’actualité

During the last years, an international debate about the concept of “Palaeolithic art” has taken place. On one hand, several specialists have critiqued the use of the concept of “art” in naming the images created by Homo sapiens during the Palaeolithic era. They claim that the use of this term implies the projection of a modern category to a world - that of prehistoric humans - which is completely different from our own. On the other hand, some archaeologists consider that the term “Palaeolithic art” does not imply an anachronistic interpretation of prehistoric representations. In presenting the historical context, which has made such a discussion possible, we consider the causes and effects of this controversy. Firstly, we analyze the traditional interpretation, which considered Palaeolithic images as “works of art”. Secondly, we examine the connections, which can be found between the debate about “Palaeolithic art” and certain polemics, which have arisen from the history of art and anthropological frameworks. Thirdly, we consider the arguments utilized by those who are for and those who are against the term “Palaeolithic art”. Finally, we emphasize the importance of this debate to better understand the categories and the concepts, which determine the scientific practice.     

Determination of the lifetime of D<Stack><Subscript>2</Subscript><Superscript>−</Superscript></Stack> and HD<Superscript>−</Superscript> ions

A method for determining the lifetime of unstable ions is described. The method is based on measuring the decrease in the ion beam current onto a fixed detector with increasing path length of the ion beam from the ion source to the detector. The measurements performed for D^? ₂ and HD^? molecular ions have shown that their lifetimes are 3.5 ± 0.1 and 4.4 ± 0.1 μs, respectively.     

Estimation of denitrification potential in a karst aquifer using the <Superscript>15</Superscript>N and <Superscript>18</Superscript>O isotopes of NO<Stack><Subscript>3</Subscript><Superscript>−</Superscript></Stack>

A confined aquifer in the Malm Karst of the Franconian Alb, South Germany was investigated in order to understand the role of the vadose zone in denitrifiaction processes. The concentrations of chemical tracers Sr²⁺ and Cl^– and concentrations of stable isotope ¹⁸O were measured in spring water and precipitation during storm events. Based on these measurements a conceptual model for runoff was constructed. The results indicate that pre-event water, already stored in the system at the beginning of the event, flows downslope on vertical and lateral preferential flow paths. Chemical tracers used in a mixing model for hydrograph separation have shown that the pre-event water contribution is up to 30%. Applying this information to a conceptual runoff generation model, the values of ¹⁵N and ¹⁸O in nitrate could be calculated. Field observations showed the occurence of significant microbial denitrification processes above the soil/bedrock interface before nitrate percolates through to the deeper horizon of the vadose zone. The source of nitrate could be determined and denitrification processes were calculated. Assuming that the nitrate reduction follows a Rayleigh process one could approximate a nitrate input concentration of about 170 mg/l and a residual nitrate concentration of only about 15%. The results of the chemical and isotopic tracers postulate fertilizers as nitrate source with some influence of atmospheric nitrate. The combined application of hydrograph separation and determination of isotope values in ¹⁵N and ¹⁸O of nitrate lead to an improved understanding of microbial processes (nitrification, denitrification) in dynamic systems.     

Inhibition of breast and ovarian tumor growth through multiple signaling pathways by using retrovirus-mediated small interfering RNA against Her-2/neu gene expression

The Her-2/neu oncogene is overexpressed in approximately 30% of breast and ovarian cancer cases and often indicates a poor prognosis. Therapeutic agents against Her-2/neu have been intensively sought over the past decade. Here we show that small interfering RNA (siRNA) can silence the expression of Her-2/neu in models of human breast or ovarian cancer through retrovirus-mediated transfer of an siRNA against Her-2/neu. Cells infected with retrovirus expressing anti-Her-2/neu siRNA exhibit slower proliferation, increased apoptosis, increased G0/G1 arrest, and decreased tumor growth. Changes in cell cycle-associated factors included decreased levels of phosphatidylinositol 3-kinase, pAkt, and cyclin D1 and increased levels of p27 and phosphorylated retinoblastoma protein. Knockdown of Her-2/neu expression by siRNA is also associated with increased expression of the anti-angiogenic factor thrombospondin-1 and decreased expression of the pro-angiogenic vascular endothelial growth factor, suggesting that Her-2/neu stimulates tumor growth at least in part by regulating angiogenesis. siRNA-mediated gene silencing of Her-2/neu and increasing the expression of thrombospondin-1 may be a useful therapeutic strategy for Her-2/neu-over-expressing breast or ovarian cancer.     

上皮性卵巢癌中Maspin蛋白与血管内皮生长因子-C的表达及其相关性

目的：探讨上皮性卵巢癌组织中maspin蛋白与血管内皮生长因子-C（VEGF-C）表达的临床意义及其相关性。方法：采用免疫组化技术检测75例上皮性卵巢癌中maspin蛋白与VEGF-C的表达情况,以卵巢良性肿瘤及正常卵巢作为对照。结果：maspin和VEGF-C在上皮性卵巢癌中的阳性表达率分别为61.3%、82.7%,均明显高于卵巢良性肿瘤（13.3%、20%）和正常卵巢组织（0%、0%）,maspin蛋白在上皮性卵巢癌中的表达与FIGO分期高、组织学分级高、腹水形成和淋巴结转移有关;VEGF-C与FIGO分期高、淋巴结转移和腹水形成有关;上皮性卵巢癌中maspin蛋白与VEGF-C的表达成正相关。结论：maspin和VEGF-C在上皮性卵巢癌中表达上调,在卵巢上皮性癌的浸润、转移中起重要作用。     

Phage-Derived Fully Human Monoclonal Antibody Fragments to Human Vascular Endothelial Growth Factor-C Block Its Interaction with VEGF Receptor-2 and 3

Vascular endothelial growth factor C (VEGF-C) is a key mediator of lymphangiogenesis, acting via its receptors VEGF-R2 and VEGF-R3. High expression of VEGF-C in tumors correlates with increased lymphatic vessel density, lymphatic vessel invasion, sentinel lymph node metastasis and poor prognosis. Recently, we found that in a chemically induced skin carcinoma model, increased VEGF-C drainage from the tumor enhanced lymphangiogenesis in the sentinel lymph node and facilitated metastatic spread of cancer cells via the lymphatics. Hence, interference with the VEGF-C/VEGF-R3 axis holds promise to block metastatic spread, as recently shown by use of a neutralizing anti-VEGF-R3 antibody and a soluble VEGF-R3 (VEGF-C/D trap). By antibody phage-display, we have developed a human monoclonal antibody fragment (single-chain Fragment variable, scFv) that binds with high specificity and affinity to the fully processed mature form of human VEGF-C. The scFv binds to an epitope on VEGF-C that is important for receptor binding, since binding of the scFv to VEGF-C dose-dependently inhibits the binding of VEGF-C to VEGF-R2 and VEGF-R3 as shown by BIAcore and ELISA analyses. Interestingly, the variable heavy domain (V_H) of the anti-VEGF-C scFv, which contains a mutation typical for camelid heavy chain-only antibodies, is sufficient for binding VEGF-C. This reduced the size of the potentially VEGF-C-blocking antibody fragment to only 14.6 kDa. Anti-VEGF-C V_H-based immunoproteins hold promise to block the lymphangiogenic activity of VEGF-C, which would present a significant advance in inhibiting lymphatic-based metastatic spread of certain cancer types.     

卵巢上皮肿瘤淋巴转移与血管内皮生长因子C的表达

The aim of the present study was to explore the role of vascular endothelial growth factor-C (VEGF-C) in the process of angiogenesis, lymphangiogenesis and lymphatic metastasis in epithelial ovarian tumors. In situ hybridization and immunohistochemical staining for VEGF-C were performed in 30 epithelial ovarian carcinomas, 9 borderline tumors and 26 benign cystadenomas. Endothelial cells were immunostained with anti-VEGFR-3 pAb and anti-CD31 mAb, and VEGFR-3 positive vessels and microvessel density (MVD) were assessed by image analysis. VEGF-C mRNA and protein expression in ovarian epithelial carcinomas were significantly higher than that in borderline tumors and benign cystadenomas (p < 0.05 or p < 0.01). In ovarian epithelial carcinomas, VEGF-C protein expression, VEGFR-3 positive vessels and MVD were significantly higher in the cases of clinical stage III-IV and with lymphatic metastasis than those of clinical stage I-II and without lymphatic metastasis respectively (p < 0.05 or p < 0.01), VEGFR-3 positive vessels and MVD was significantly higher in the VEGF-C protein positive tumors than negative tumors (p < 0.05), VEGFR-3 positive vessels was significantly correlated with MVD(p < 0.01). These data suggest that VEGF-C might play a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in epithelial ovarian carcinomas, and VEGF-C could be used as a biologic marker of metastasis in ovarian epithelial carcinomas.     

VEGF-C和CCR7的表达与卵巢癌淋巴结转移之间的关系

目的观察血管内皮生长因子(VEGF)-C和趋化因子受体CCR7在卵巢癌组织内的表达情况,分析VEGF-C和CCR7的表达与癌淋巴结转移之间的关系。方法取卵巢癌病例72例,其中,淋巴结转移组46例,无淋巴结转移组26例。应用免疫组化技术观察VEGF-C和CCR7在卵巢癌组织内的表达。结果 VEGF-C和CCR7主要表达于卵巢癌细胞胞浆或/和胞膜内,VEGF-C和CCR7在淋巴结转移组的阳性表达率分别是71.7%和78.2%,在无淋巴结转移组的表达率分别是30.8%和26.9%,二者在淋巴结转移组的表达率均明显高于无淋巴结转移组(P<0.01)。VEGF-C和CCR7蛋白同时阳性表达在淋巴结转移组和非淋巴结转移组中的表达率分别为65.2%和15.4%,VEGF-C和CCR7的表达具有显著的相关性(P<0.01),联合检测VEGF-C和CCR7诊断卵巢癌淋巴结转移具有较高的准确度,ROC曲线下面积达0.791。结论 VEGF-C和CCR7表达在卵巢癌淋巴结转移过程中发挥重要作用,VEGF-C和CCR7在促进卵巢癌淋巴结转移中可能具有一定的协同作用,二者联合检测有助于预示卵巢癌淋巴结转移的判断。     

乳腺癌组织中VEGF—C和p38MAPK的表达及与伴淋巴结转移的关系

目的探讨乳腺浸润性导管癌组织中血管内皮生长因子C（VEGF—C）和丝裂原激活蛋白激酶p38（p38MAPK）的表达关系,以及与乳腺浸润性导管癌淋巴结转移等生物学行为的关系。方法采用免疫组织化学sP法检测70例乳腺浸润性导管癌组织及15例癌旁正常组织中VEGF-C和p38MAPK蛋白的表达,并采用Westernblot法检测13例伴有淋巴结转移的乳腺癌及12例无淋巴结转移的乳腺癌的新鲜组织中VEGF—C和p38MAPK蛋白表达。结果VEGF—C和p38MAPK在乳腺浸润性导管癌组织中的表达（阳性率分别为67．0％和61．4％）明显高于癌旁正常组织;VEGF-C和p38MAPK蛋白在伴有淋巴结转移组的乳腺癌组织中的表达均高于无淋巴结转移组（P=0．005,P=0．005）;在乳腺浸润性导管癌组织中VEGF-C和p38MAPK表达存在显著正相关（r=0．383,P=0．001）,并与乳腺浸润性导管癌的TNM分期（P=0．019,P=0．010）有关;VEGF-C和p38MAPK蛋白表达与乳腺浸润性导管癌肿块的大小（P=0．203,P=0．086）和患者的年龄（P=0．0．266,P=0．087）无明显关系。Western blot也证实,VEGF-C和p38MAPK蛋白在有淋巴结转移组中表达高于无淋巴结转移组。结论VEGF-C和p38MAPK的蛋白表达与乳腺浸润性导管癌的淋巴结转移密切相关,其有望成为乳腺癌治疗的新靶点。     

Peritumoral lymphangiogenesis induced by vascular endothelial growth factor C and D promotes lymph node metastasis in breast cancer patients

ABSTRACT: BACKGROUND: Mounting clinical and experimental data suggest that the migration of tumor cells into lymph nodes is greatly facilitated by lymphangiogenesis. Vascular endothelial growth factor (VEGF)-C and D have been identified as lymphangiogenic growth factors and play an important role in tumor lymphangiogenesis. The purpose of this study was to investigate the location of lymphangiogenesis driven by tumor-derived VEGF-C/D in breast cancer, and to determine the role of intratumoral and peritumoral lymphatic vessel density (LVD) in lymphangiogenesis in breast cancer. METHODS: The expression levels of VEGF-C/D were determined by immunohistochemistry, and intratumoral LVD and peritumoral LVD were assessed using immunohistochemistry and the D2-40 antibody in 73 patients with primary breast cancer. The associations of intratumoral LVD and peritumoral LVD with VEGF-C/D expression, clinicopathological features and prognosis were assessed. RESULTS: VEGF-C and D expression were significantly higher in breast cancer than benign disease (P < 0.01). VEGF-C (P < 0.001) and VEGF-D (P = 0.005) expression were significantly associated with peritumoral LVD, but not intratumoral LVD. Intratumoral LVD was associated with tumor size (P = 0.01). Peritumoral LVD was significantly associated with lymph node metastasis (LNM; P = 0.005), lymphatic vessel invasion (LVI; P = 0.017) and late tumor,node,metastasis(TNM) stage (P = 0.011). Moreover, peritumoral LVD was an independent risk factor for axillary lymph node metastasis, overall survival and disease-free survival in multivariate analysis. CONCLUSIONS: This study suggests that tumor-derived VEGF-C/D induce peritumoral lymphangiogenesis, which may be one mechanism that leads to lymphatic invasion and metastatic spread. Peritumoral LVD has potential as an independent prognostic factor in breast cancer patients.     

Periostin directly and indirectly promotes tumor lymphangiogenesis of head and neck cancer

Background

Metastasis to regional lymph nodes via lymphatic vessels plays a key role in cancer progression. Tumor lymphangiogenesis is known to promote lymphatic metastasis, and vascular endothelial growth factor C (VEGF-C) is a critical activator of tumor lymphangiogenesis during the process of metastasis. We previously identified periostin as an invasion- and angiogenesis-promoting factor in head and neck squamous cell carcinoma (HNSCC). In this study, we discovered a novel role for periostin in tumor lymphangiogenesis.

Methods and Findings

Periostin overexpression upregulated VEGF-C mRNA expression in HNSCC cells. By using conditioned media from periostin-overexpressing HNSCC cells, we examined tube formation of lymphatic endothelial cells. Conditioned media from periostin-overexpressing cells promoted tube formation. To know the correlation between periostin and VEGF-C, we compared Periostin expression with VEGF-C expression in 54 HNSCC cases by immunohistochemistry. Periostin expression was correlated well with VEGF-C expression in HNSCC cases. Moreover, correlation between periostin and VEGF-C secretion was observed in serum from HNSCC patients. Interestingly, periostin itself promoted tube formation of lymphatic endothelial cells independently of VEGF-C. Periostin-promoted lymphangiogenesis was mediated by Src and Akt activity. Indeed possible correlation between periostin and lymphatic status in periostin-overexpressing xenograft tumors and HNSCC cases was observed.

Conclusions

Our findings suggest that periostin itself as well as periostin-induced upregulation of VEGF-C may promote lymphangiogenesis. We suggest that periostin may be a marker for prediction of malignant behaviors in HNSCC and a potential target for future therapeutic intervention to obstruct tumoral lymphatic invasion and lymphangiogenesis in HNSCC patients.     

Lysophosphatidic Acid Enhances Vascular Endothelial Growth Factor-C Expression in Human Prostate Cancer PC-3 Cells

Clinical evidence suggests that lymphangiogenesis and lymphatic metastasis are important processes during the progression of prostate cancer. Vascular endothelial growth factor (VEGF)-C was shown to be a key regulator in these processes. Our previous studies demonstrated that lysophosphatidic acid (LPA), a low-molecular-weight lipid growth factor, enhances VEGF-C expression in human endothelial cells. We previously demonstrated that the LPA receptor plays an important role in lymphatic development in zebrafish embryos. However, the effects of LPA on VEGF-C expression in prostate cancer are not known. Herein, we demonstrate that LPA up-regulated VEGF-C expression in three different human prostate cancer cell lines. In PC-3 human prostate cancer cells, the enhancing effects of LPA were mediated through both LPA1 and LPA3. In addition, reactive oxygen species (ROS) production and lens epithelium-derived growth factor (LEDGF) expression were involved in LPA(1/3)-dependent VEGF-C expression. Furthermore, autotaxin (ATX), an enzyme responsible for LPA synthesis, also participates in regulating VEGF-C expression. By interrupting LPA(1/3) of PC-3, conditioned medium (CM) -induced human umbilical vein endothelial cell (HUVEC) lymphatic markers expression was also blocked. In summary, we found that LPA enhances VEGF-C expression through activating LPA(1/3)-, ROS-, and LEDGF-dependent pathways. These novel findings could potentially shed light on developing new strategies for preventing lymphatic metastasis of prostate cancer.