IκB激酶家族新成员:IKKε

IΚB激酶家族(IΚB kinases,IKKs)是NF-ΚB信号途径最为重要的成员之一,已发现其在先天性免疫以及炎症反应的调节中发挥关键作用.除IKKα/β/γ之外,作为IKKs的最新成员,IKKε不仅具有与IKKα/β/γ类似的作用,而且最近的研究数据证实IKKε还能通过凋亡蛋白抑制物(inhibitor of apoptosis proteins,IAPs)调节caspases的活性,参加caspases的凋亡和非凋亡依赖性信号途径.     

单纯性肥胖者和糖尿病患者血清胰多肽水平观察

本文用自制胰多肽(PP)放射免疫分析试剂盒,观察了24例单纯性肥胖者和34例糖尿病患者空腹和餐后PP的分泌水平,结果与18例正常人比较,发现肥胖者PP、胰岛素、C肽和血糖均呈高分泌现象;糖尿病病人PP水平也增高,但C肽和胰岛素则降低。     

Iron colloids dominate sedimentary supply to the ocean interior

Dissolution of marine sediment is a key source of dissolved iron (Fe) that regulates the ocean carbon cycle. Currently, our prevailing understanding, encapsulated in ocean models, focuses on low-oxygen reductive supply mechanisms and neglects the emerging evidence from iron isotopes in seawater and sediment porewaters for additional nonreductive dissolution processes. Here, we combine measurements of Fe colloids and dissolved δ⁵⁶Fe in shallow porewaters spanning the full depth of the South Atlantic Ocean to demonstrate that it is lithogenic colloid production that fuels sedimentary iron supply away from low-oxygen systems. Iron colloids are ubiquitous in these oxic ocean sediment porewaters and account for the lithogenic isotope signature of dissolved Fe (δ⁵⁶Fe = +0.07 ± 0.07‰) within and between ocean basins. Isotope model experiments demonstrate that only lithogenic weathering in both oxic and nitrogenous zones, rather than precipitation or ligand complexation of reduced Fe species, can account for the production of these porewater Fe colloids. The broader covariance between colloidal Fe and organic carbon (OC) abundance suggests that sorption of OC may control the nanoscale stability of Fe minerals by inhibiting the loss of Fe(oxyhydr)oxides to more crystalline minerals in the sediment. Oxic ocean sediments can therefore generate a large exchangeable reservoir of organo-mineral Fe colloids at the sediment water interface (a “rusty source”) that dominates the benthic supply of dissolved Fe to the ocean interior, alongside reductive supply pathways from shallower continental margins.

Sediments undergo early diagenetic transformations that are understood to provide an important source of dissolved iron (dFe) to the ocean that is used to fuel primary production and secondary food webs, fix nitrogen, and support the air–sea transfer of carbon dioxide (1, 2). Nevertheless, fundamental questions remain concerning the magnitude of dFe released from ocean sediments and the mechanisms through which this supply may be moderated. Such uncertainty is most acute in oxic and deep-water regions, which bear the fewest observations, but represent the largest area of the ocean sediment–water interface (3). Here, comparatively small sedimentary releases of dFe have the cumulative potential to enhance the dFe inventory of the deep ocean and—in so far as it connects with surface water—relieve iron deficiency for phytoplankton. Porewaters in these deep-water regions maintain a persistently oxic and/or nitrogenous state adjacent to bottom waters that is largely unexamined for its role in the marine iron cycle. These gaps in knowledge hinder our ability to make more accurate simulations of the carbon cycle in ocean biogeochemical models (4).Two principle processes are thought to be driving Fe dissolution from sediments that underpin the magnitude and variability of dFe inputs to the ocean. The first is a reductive-dissolution (RD) process, which demonstrably occurs during early diagenetic oxidation of organic carbon (OC) and produces high abundances of reduced, soluble, and isotopically light Fe in ferruginous porewaters, generally beneath the Fe-oxidizing fronts of nitrous oxides and oxygen (5–7). The second is a nonreductive-dissolution (NRD) process to account for the comparatively unfractionated or heavy isotope compositions of dFe attributed to sedimentary inputs in some oxygenated regions of the open ocean (8) and in the oxic zones of marine sediment porewaters (9), but the mechanisms governing so-called NRD in oxic sediments are unclear.RD of Fe is coupled to OC oxidation and is widely observed in shallow porewater in sediments with high-oxygen consumption rates, under productive shelf seas, near zones of upwelling, and overlain by oxygen-depleted seawater (10). Low seawater oxygen content serves to enhance the efflux of reduced and soluble Fe (sFe, filtered <0.02 µm) from ferruginous porewaters and enables sFe(II) to propagate further in the water column (11–14). Subsequently, without sufficient chelation by organic ligands sFe(II) will be lost to oxidative precipitation (7, 15, 16), scavenging (12), and sedimentation in deeper water (16, 17). Sedimentary RD provides a key component of the ocean’s dFe inventory that is most pronounced in the upper ocean (1, 10, 11, 13). It is also the only mechanism by which most ocean biogeochemical models simulate the sedimentary release of dFe (4), since model parameterizations rely on empirical relationships between dFe fluxes, OC oxidation rates, bottom water oxygen contents, and/or water depth (1, 11, 18, 19).NRD is a term previously used to describe a sedimentary source of isotopically heavy dFe to the water column (8) and has since been used to describe the presence of lithogenic isotope compositions observed in oxidizing zones from some deep ocean sediment porewaters (9). Similar observations have become commonplace in the ocean interior (20–23), such that nonreductive sedimentary processes appear to be important for the ocean’s dFe inventory. However, the detection of lithogenic dFe isotope signatures in porewaters (6, 9), within western North Atlantic benthic nepheloid layers, and in the water column far from sediment sources have been difficult to explain (24). The role played by this additional source of dFe is not yet included in global ocean models.Based on the very low solubility of silicate minerals and Fe(III) oxides in circumneutral pH and oxygenated seawater, NRD ought to be incapable of sustaining a benthic flux of dFe to the ocean without significant chelation by organic ligands (25). Because of a strong isotope fractionation effect, however, ligand complexation of Fe would produce a much heavier Fe isotope signal in the ocean (26), which is at odds with the isotopic evidence for NRD (20–23). To reconcile these differences between NRD theories and dFe isotope observations, we need to consider any physicochemical partitioning within the dFe pool. The abundance and isotope composition of dFe (<0.2 µm) may reflect variable contributions of mineral or organo-mineral Fe colloids (cFe, 0.02 to 0.2 µm) in addition to any ligand-bound Fe and sFe(II/III) species (<0.02 µm) in the ocean (23, 27). Such components of the dFe pool are often unaccounted for and have been neglected in previous studies reporting the occurrence of sedimentary NRD in the water column. However, sizable concentrations of cFe (10¹ µmoles ⋅ L⁻¹) have been observed in oxic-nitrogenous porewaters from deep ocean turbidites of the Southern Ocean, where dFe isotope compositions also matched the solid phase inputs from ocean island basalt. Whether these colloids were formed in situ through organic complexation and/or as secondary minerals from either reductive or nonreductive processes was unresolved. A comparison to fresh tephra layers in the Caribbean Sea showed that ocean island basalt weathering and production of nanoscale ferrihydrite or Fe-bearing smectite clays were thermodynamically plausible explanations for cFe in the Southern Ocean porewaters (28). Recently, Klar et al. (7) looked for Fe colloids in porewaters from a shallow shelf sediment, but found few if any, and that the porewaters were dominated by light dFe isotope signatures and sFe(II) attributable to RD by bacteria. Previous studies have not resolved where or why cFe occurs in sediment porewaters of the continental shelf–slope–basin transition or the extent to which they may influence the inventory and isotope composition of dFe input to the ocean (20, 22). These lessons need to be learned by examining the soluble and colloidal partitioning of dFe in porewaters and comparing them to dFe isotope signatures from a wider range of sedimentary carbon and oxygen regimes in the ocean environment.Without appropriate simulation of this dFe source, ocean biogeochemical models will fail to represent spatial patterns in dFe flux from the seafloor, the response of these fluxes to changing ocean environments, and their consequences for ocean biogeochemistry. Confounding this issue is the omitted role of advective transport mechanisms, internal waves, and benthic boundary layers that will facilitate exchanges between oxic sediments and the ocean interior (3, 29, 30). To make progress on this important issue, we require new understanding on the mechanisms by which Fe dissolves and is supplied to the ocean by oxic sediments.Herein, we present findings from surface sediment cores from sites that span the depth and breadth of the Southwest Atlantic Ocean. The UK-led GEOTRACES expedition, GA10W, recovered porewaters in 2011 from the Uruguayan continental shelf and slope, Argentine abyssal floor, and Mid-Atlantic Ridge (SI Appendix, Table S1). We report porewater dFe isotope compositions and further evidence of the physicochemical partitioning of dFe between soluble and colloidal size fractions (where cFe = dFe−sFe) at selected locations and depths where porewater inventories of Fe were sufficient to permit these determinations. We apply principles of isotope fractionation and mass balance across the dissolved and soluble size classes to test hypothetical controls on the dFe pool in these porewaters. Our study reveals that oxidizing zones of marine sediments are important regions of nonreductive cFe production derived from lithogenic material, which ultimately determine the dFe inventory and isotope composition supplied to the deep ocean.     

34例弥漫性肺疾病肺活检组织结构观察

３４例肺弥漫性疾病患者作肺活检组织的光镜和电镜检查。２例作局限性开胸肺活检，３２例经纤维支气管镜（纤支镜）检的肺活检，经肺活检组织病理学检查结合临床综合分析诊断为特发性肺间质纤维化１９例（５６％），肺泡蛋白沉积症３例（９％），肺结节病３例（９％），特发性含铁血黄素沉积症１例（３％），肺霉菌病２例（６％），肺结核２例（６％），肺泡细胞癌１例（３％），胶原性疾病致肺纤维化３例（９％）。肺活检组织的光镜和电镜观察对弥漫性肺疾病的诊断具有重要意义。     

Clinical analysis of 130 patients with fever of unknown origin

Hospital records of 130 patients with fever of unknown origin (FUO) from 1985 to 1989 were studied. Etiologic diagnoses were made in 117 (90%) patients, 60 (46.1%) patients had infections, 22 (16.9%) neoplasms, 19 (14.6%) connective tissue diseases, and 16(12.3%) various diseases grouped under "miscellaneous", 10% of the FUO cases remained undiagnosed and the death rate was 13.8%. This clinical analysis showed that infection was the most frequent cause of FUO in this series.     

糖尿病患者红细胞膜磷脂成分的改变

应用高效液相色谱法分析７２例ＮＩＤＤＭ患者红细胞膜磷脂成分。结果显示，ＮＩＤＤＭ患者红细胞膜磷脂酰乙醇胺、磷脂酰肌醇、磷脂酰丝氨酸、磷脂酰胆碱、神经鞘磷脂均显著降低，而溶血磷脂酰胆碱显著增高，并且红细胞膜磷脂成分的改变与空腹血糖、糖化血红蛋白、血脂及过氧化脂质有关。提示糖尿病代谢紊乱与脂质过氧化可能是导致红细胞膜磷脂成分改变的重要因素。     

Cytokine production by primary bone marrow megakaryocytes

Primary human bone marrow megakaryocytes were studied for their ability to express and release cytokines potentially relevant to their proliferation and/or differentiation. The purity of the bone marrow megakaryocytes was assessed by morphologic and immunocytochemical criteria. Unstimulated marrow megakaryocytes constitutively expressed genes for interleukin-1 beta (IL-1 beta), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha), by the polymerase chain reaction (PCR) and Northern blot analysis. At the protein level, megakaryocytes secreted significant amounts of IL-1 beta (53.6 +/- 3.6 pg/mL), IL-6 (57.6 +/- 15.6 pg/mL), and GM-CSF (24 +/- 4 pg/mL) but not TNF-alpha. Exposure of human marrow megakaryocytes to IL-1 beta increased the levels of IL-6 (87.3 +/- 2.3 pg/mL) detected in the culture supernatants. Transforming growth factor- beta was also able to stimulate IL-6, IL-1 beta, and GM-CSF secretion, but was less potent than stimulation with phorbol-12-myristate-13- acetate (PMA). The secreted cytokines acted additively to maintain and increase the number of colony-forming unit-megakaryocytes colonies (approximately 35%). These studies demonstrate the production of multiple cytokines by isolated human bone marrow megakaryocytes constitutively or stimulated in vitro. The capacity of human megakaryocytes to synthesize several cytokines known to modulate hematopoietic cells supports the concept that there may be an autocrine mechanism operative in the regulation of megakaryocytopoiesis.     

Semi-skeletonized internal mammary artery grafts and sternal wound complications

This study aimed to evaluate the risk factors for sternal wound complications in patients undergoing myocardial revascularization using bilateral semi-skeletonized internal mammary arteries. Prospectively collected data on 751 patients undergoing coronary artery surgery from September 1994 to August 2002 were analyzed. The mean age of the patients was 56 years, 633 (84%) were male, 44 (6%) were over 66 years of age, and 170 (23%) were diabetic. Forty-four (5.9%) patients developed sternal wound complications. Among these cases, sternal infection occurred in 22 (2.9%) patients, of which 15 (2.0%) had sternal infection with mediastinitis and 7 (0.9%) had sternal infection alone. Independent risk factors for any sternal wound complications were peripheral vascular disease, diet-controlled diabetes, and delayed sternal closure. The risk factors for sternal infection were diabetes, postoperative pulmonary complications, and postoperative stroke. The perioperative mortality rate was 1.5% (11 patients), including 2 patients who had sternal wound complications. The use of bilateral semi-skeletonized internal mammary artery conduits carries a comparable sternal wound complication rate as conduits harvested by other techniques.     

重症急性呼吸综合征患者血浆细胞因子水平的动态改变

目的　探讨重症急性呼吸综合征 (SARS)患者肺部严重炎症反应的发生机制。方法　选择 2 4例本院确诊的SARS患者 ,于发病第 1、第 2、第 3～ 4周及康复出院后 1个月 (发病 8～ 9周 )收集抗凝静脉血 ,以定量ELISA法检测其血浆白细胞介素 (IL) 1β、IL 2、IL 4、IL 8、IL 10、IL 12 p70、干扰素γ(IFNγ)及肿瘤坏死因子α(TNFα)水平在病程中的改变。并选择 12例正常人作为对照。结果　数据以中位数 (四分位数间距 )表示 ,与正常对照组 [IL 8:6 2 8ng/L( 3 4 3ng/L) ;TNFα :3 77ng/L( 3 4 0ng/L) ]相比 ,所有SARS病人在发病第 1周血浆IL 8浓度明显升高 [31 2 3ng/L( 78 5 1ng/L) ],P <0 0 1,75 % ( 18/2 4 )的病人在发病 3～ 4周达到最高峰 14 9 6 5ng/L( 2 4 5 97ng/L) ,P <0 0 1,至出院后 1个月 (发病 8～ 9周 )平均血浆IL 8浓度降至 8 2 3ng/L( 8 0 7ng/L)。血浆TNFα浓度也有异常升高 ,在发病第 2周为 2 3 12ng/L( 2 6 7 33ng/L) ,P <0 0 1,发病 3～ 4周达到高峰136 35ng/L( 4 76 83ng/L) ,P <0 0 5 ,出院后 1个月下降至 94 88ng/L( 2 77 18ng/L) ,仍高于正常水平 (P <0 0 1)。其他 6种细胞因子与对照组比较 ,差异无显著性。结论　SARS病人体内发生着复杂的细胞因子网络性连锁反应 ,由此产     

Expression of the mouse cerberus-related gene, Cerr1, suggests a role in anterior neural induction and somitogenesis

The Xenopus cerberus gene encodes a secreted factor that is expressed in the anterior endomesoderm of gastrula stage embryos and can induce the formation of ectopic heads when its mRNA is injected into Xenopus embryos [Bouwmeester, T., Kim, S., Lu, B. & De Robertis, E. M. (1996) Nature (London) 382, 595–601]. Here we describe the existence of a cerberus-related gene, Cerr1, in the mouse. Cerr1 encodes a putative secreted protein that is 48% identical to cerberus over a 110-amino acid region. Analysis of a mouse interspecific backcross panel demonstrated that Cerr1 mapped to the central portion of mouse chromosome 4. In early gastrula stage mouse embryos, Cerr1 is expressed in the anterior visceral endoderm and in the anterior definitive endoderm. In somite stage embryos, Cerr1 expression is restricted to the most recently formed somites and in the anterior presomitic mesoderm. Germ layer explant recombination assays demonstrated that Cerr1-expressing somitic-presomitic mesoderm, but not older Cerr1-nonexpressing somitic mesoderm, was able to mimic the anterior neuralizing ability of anterior mesendoderm and maintain Otx2 expression in competent ectoderm. In most Lim1−/− headless embryos, Cerr1 expression in the anterior endoderm was weak or absent. These results suggest that Cerr1 may play a role in anterior neural induction and somite formation during mouse development.