Bone marrow cells regenerate infarcted myocardium

Myocardial infarction leads to loss of tissue and impairment of cardiac performance. The remaining myocytes are unable to reconstitute the necrotic tissue, and the post-infarcted heart deteriorates with time. Injury to a target organ is sensed by distant stem cells, which migrate to the site of damage and undergo alternate stem cell differentiation; these events promote structural and functional repair. This high degree of stem cell plasticity prompted us to test whether dead myocardium could be restored by transplanting bone marrow cells in infarcted mice. We sorted lineage-negative (Lin-) bone marrow cells from transgenic mice expressing enhanced green fluorescent protein by fluorescence-activated cell sorting on the basis of c-kit expression. Shortly after coronary ligation, Lin- c-kitPOS cells were injected in the contracting wall bordering the infarct. Here we report that newly formed myocardium occupied 68% of the infarcted portion of the ventricle 9 days after transplanting the bone marrow cells. The developing tissue comprised proliferating myocytes and vascular structures. Our studies indicate that locally delivered bone marrow cells can generate de novo myocardium, ameliorating the outcome of coronary artery disease.     

An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus

Hepatitis C virus (HCV) infection is a serious cause of chronic liver disease worldwide with more than 170 million infected individuals at risk of developing significant morbidity and mortality. Current interferon-based therapies are suboptimal especially in patients infected with HCV genotype 1, and they are poorly tolerated, highlighting the unmet medical need for new therapeutics. The HCV-encoded NS3 protease is essential for viral replication and has long been considered an attractive target for therapeutic intervention in HCV-infected patients. Here we identify a class of specific and potent NS3 protease inhibitors and report the evaluation of BILN 2061, a small molecule inhibitor biologically available through oral ingestion and the first of its class in human trials. Administration of BILN 2061 to patients infected with HCV genotype 1 for 2 days resulted in an impressive reduction of HCV RNA plasma levels, and established proof-of-concept in humans for an HCV NS3 protease inhibitor. Our results further illustrate the potential of the viral-enzyme-targeted drug discovery approach for the development of new HCV therapeutics.     

Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis

Familial expansile osteolysis (FEO, MIM 174810) is a rare, autosomal dominant bone disorder characterized by focal areas of increased bone remodelling. The osteolytic lesions, which develop usually in the long bones during early adulthood, show increased osteoblast and osteoclast activity. Our previous linkage studies mapped the gene responsible for FEO to an interval of less than 5 cM between D18S64 and D18S51 on chromosome 18q21.2-21.3 in a large Northern Irish family. The gene encoding receptor activator of nuclear factor-kappa B (RANK; ref. 5), TNFRSF11A, maps to this region. RANK is essential in osteoclast formation. We identified two heterozygous insertion mutations in exon 1 of TNFRSF11A in affected members of four families with FEO or familial Paget disease of bone (PDB). One was a duplication of 18 bases and the other a duplication of 27 bases, both of which affected the signal peptide region of the RANK molecule. Expression of recombinant forms of the mutant RANK proteins revealed perturbations in expression levels and lack of normal cleavage of the signal peptide. Both mutations caused an increase in RANK-mediated nuclear factor-kappaB (NF-kappaB) signalling in vitro, consistent with the presence of an activating mutation.     

Electronic connection to the interior of a mesoporous insulator with nanowires of crystalline RuO2

Highly porous materials such as mesoporous oxides are of technological interest for catalytic, sensing and remediation applications: the mesopores (of size 2-50 nm) permit ingress by molecules and guests that are physically excluded from microporous materials. Connecting the interior of porous materials with a nanoscale or 'molecular' wire would allow the direct electronic control (and monitoring) of chemical reactions and the creation of nanostructures for high-density electronic materials. The challenge is to create an electronic pathway (that is, a wire) within a mesoporous platform without greatly occluding its free volume and reactive surface area. Here we report the synthesis of an electronically conductive mesoporous composite--by the cryogenic decomposition of RuO4--on the nanoscale network of a partially densified silica aerogel. The composite consists of a three-dimensional web of interconnected (approximately 4-nm in diameter) crystallites of RuO2, supported conformally on the nanoscopic silica network. The resulting monolithic (RuO2//SiO2) composite retains the free volume of the aerogel and exhibits pure electronic conductivity. In addition to acting as a wired mesoporous platform, the RuO2-wired silica aerogel behaves as a porous catalytic electrode for the oxidation of chloride to molecular chlorine.     

Coordination of branch orientation and photosynthetic physiology in the Joshua tree ( Yucca brevifolia )

Despite the profusion of light in deserts, morphological adaptations to increase light interception are common among desert plants. We studied branch orientation and related physiological parameters in the Mojave Desert Joshua tree, Yucca brevifolia (Agavaceae). Azimuth and inclination were measured on all leaf rosettes of 44 Y. brevifolia trees. Interception of solar radiation was modeled for leaves in hypothetical rosettes facing due south and due north in December, March, and June. Carbon isotope discrimination, nitrogen content, and conductance of water vapor were measured in leaves from north- and south-facing rosettes. Rosette azimuths were nonrandom; rosettes predominantly faced southeast. North-facing rosettes were more steeply inclined than those facing south. The preponderance of south-facing rosettes reduces self-shading and increases interception of solar radiation during the winter-spring growth period. Stomatal conductance was higher for leaves in south-facing than in north-facing rosettes. Nevertheless, discrimination against 13 C was less in leaves of south-facing rosettes, indicating that average intercellular CO 2 concentration was also lower. South-facing whorls had higher leaf nitrogen content. Greater allocation of nitrogen to leaves in south-facing whorls probably results in those leaves having a greater photosynthetic capacity than their north-facing counterparts. Orientation of rosettes to increase interception of sunlight during the period most favorable for photosynthesis, coupled with allocation of nutrients to maintain a higher photosynthetic capacity in those rosettes, should significantly increase whole-plan carbon gain in Y. brevifolia .     

Differential responses to nitrogen form and concentration for Oryzopsis hymenoides and Elymus lanceolatus

In a greenhouse experiment, effects of nitrogen form and concentration on productivity and dry matter allocation differed between two species native to semiarid ecosystems of the Great Basin. Aboveground production of green surface area and of dry matter were consistently enhanced by increased nitrogen for the rhizomatous grass Elymus lanceolatus , but not for the bunchgrass Oryzopsis hymenoides . These differences were likely due to inherently low growth rates of O. hymenoides . Aboveground dry matter allocation also differed between the two species. O. hymenoides had more leaves per tiller with increased nitrogen, whereas leaf size but not number increased for E. lanceolatus . Furthermore, increases in tiller density with increased nitrogen for E. lanceolatus were almost three times greater than those for O. hymenoides . E. lanceolatus , but not O. hymenoides , was sensitive to the form of nitrogen supplied to the plants. When NH 4 -N was the only form of nitrogen supplied, high concentrations of NH 4 -N inhibited aboveground production of E. lanceolatus .     

一种新型高效生物可降解ε-多聚赖氨酸修饰阳离子聚合物抗菌剂的合成与性能（英文）

目前临床上使用的大多数抗生素杀菌或抑菌的主要机制为:选择性的作用于细菌细胞核酸和蛋白合成系统的特定环节,妨碍细菌生命活动,导致细菌死亡.然而,细菌形态结构完整性仍然保持,导致细菌产生耐药性.最近研究发现大肠杆菌和金黄色葡萄球菌感染是一些慢性疾病发生的重要因素.纳米颗粒能够选择性的作用于微生物表面,破坏细菌结构完整性,抑制细菌耐药性的产生.本文设计并合成一种生物相容性好且生物可降解ε-多聚赖氨酸修饰阳离子聚合物(EPL-PCL).该多聚物能够自主装形成单分散的纳米颗粒,且对大肠杆菌、金黄色葡萄球菌和枯草芽孢杆菌具有广谱的抗菌活性.相比于ε-多聚赖氨酸,EPL-PCL纳米颗粒具有更强的抗菌活性.进一步研究发现,EPL-PCL纳米颗粒抗菌作用的主要机制为:(1)带正电的EPL-PCL纳米颗粒与带负电的细菌表面相互作用并穿透细胞壁和细胞膜,破坏细菌表面完整性,抑制细菌耐药性的生成;(2)EPL-PCL纳米颗粒暴露显著提高细菌内ROS水平;(3)ROS水平升高显著的破坏细菌细胞代谢,例如提高碱性磷酸酶活性破坏细菌磷的稳态平衡.因此,本文合成的可降解ε-多聚赖氨酸修饰阳离子纳米聚合物可以作为一种有效且广谱的抗菌剂,特别是用于病原菌感染的疾病.     

The anatomy and taxonomy of Vanclevea (Asteraceae)

Wood, leaf, and floral anatomy of Vanclevea stylosa is compared with that of several possibly related species in the genera Acamptopappus, Eastwoodia, Grindelia, Haplopappus, and Petradoria. Although V. stylosa was originally described as a Grindelia, it is clearly distinct from that genus. Of the taxa studied, it is most closely allied to Haplopappus salincinus and H. scopulorum. The taxonomy, morphology, and distribution of the monotypic Vanclevea are detailed, and known exsiccatae are listed.     

Depletion of soil moisture by two cold-desert bunchgrasses and effects on photoshythetic performance

This study compared the abilities of two cool-season bunchgrasses to extract moisture from a drying soil and compared photosynthetic and stomatal responses of the two species as soil moisture supplies were depleted. When grown in 49-L pots in a greenhouse, Leymus cinereus extracted more water from the soil and maintained higher gas exchange rates to lower absolute amounts of soil water than did Agropyron desertorum . The soil water content at the lower limit of extraction was 10.3% for L. cinereus and 13.3% for A. desertorum . When soil moisture was expressed as extractable soil water, there was little difference between the species in pattern of water use. Both species maintained high stomatal conductances (g w ) and photosynthetic rates (A) until extractable soil moisture was reduced to about 15%. For field-grown plants under severe water stress, A was higher in L. cinereus than in A. desertorum at comparable leaf water potentials. The relationship between A and g w was similar for the two species; higher A in L. cinereus was a consequence of higher g w . Thus, higher A in L. cinereus is achieved through some sacrifice of water-use efficiency.