Urokinase-type plasminogen activator and macrophages are required for skeletal muscle hypertrophy in mice

Adult skeletal muscle possesses remarkable potential for growth in response to mechanical loading; however, many of the cellular and molecular mechanisms involved remain undefined. The hypothesis of this study was that the extracellular serine protease, urokinase-type plasminogen activator (uPA), is required for muscle hypertrophy, in part by promoting macrophage accumulation in muscle subjected to increased mechanical loading. Compensatory muscle hypertrophy was induced in mouse plantaris (PLT) muscles by surgical ablation of synergist muscles. Following synergist ablation, PLT muscles in wild-type mice demonstrated edema and infiltration of neutrophils and macrophages but an absence of overt muscle fiber damage. Sham procedures resulted in no edema or accumulation of inflammatory cells. In addition, synergist ablation was associated with a large increase in activity of uPA in the PLT muscle. uPA-null mice demonstrated complete abrogation of compensatory hypertrophy associated with reduced macrophage accumulation, indicating that uPA is required for hypertrophy. Macrophages isolated from wild-type PLT muscle during compensatory hypertrophy expressed uPA and IGF-I, both of which may contribute to hypertrophy. To determine whether macrophages are required for muscle hypertrophy, clodronate liposomes were administered to deplete macrophages in wild-type mice; this resulted in reduced muscle hypertrophy. Decreased macrophage accumulation was associated with reduced cell proliferation but did not alter signaling through the mammalian target of rapamycin pathway. These data indicate that uPA and macrophages are required for muscle hypertrophy following synergist ablation.     

新疆部分地区动物Nipah病毒和Hendra病毒感染的调查

拟建立一步法实时RT-PCR检测Nipah病毒(Nipah virus,NiV)、Hendra病毒(Hendra virus,HeV)的方法,对采集自中国新疆部分地区动物外周血样本进行NiV和HeV检测,以获得我国新疆地区的NiV和HeV的病毒流行病学资料.采用NiV和HeV一步法实时RT-PCR检测方法,对2007年9-12月采集的新疆伊犁河谷地区以及巴音布鲁克草原放养的500匹马、100匹驴和160只犬外周血单个核细胞RNA进行NiV和HeV N基因片段检测.结果:对采集的动物血样本进行NiV和HeV核酸检测,成功进行了一步法实时RT-PCR反应,没有发现阳性样本.初步流行病学研究提示我国新疆部分地区天然牧场放养的动物中可能不存在NiV和HeV感染,该地区出现NiV和HeV爆发的可能性较小.     

Trends in Lung Cancer Incidence Rates,Oklahoma 2005–2010

Purpose

Lung cancer is the second most frequently diagnosed cancer among men and women in the United States. With cigarette smoking causing the majority of cases, patterns in lung cancer are often monitored to understand the impact of anti-tobacco efforts. The purpose of this research was to investigate trends in lung cancer incidence rates for the period 2005–2010 in Oklahoma.

Methods

Data on Oklahoma’s incident cases of lung cancer (2005–2010) were obtained from the Centers for Disease Control and Prevention WONDER system. Annual percent change (APC) was calculated by linear regression to characterize trends in lung cancer incidence rates over time for the overall population, by gender, by age group, and by age group within gender. Rates were considered to increase or decrease if the p-value for trend was <0.05.

Results

From 2005 through 2010, lung cancer incidence rates declined from 81.96 to 68.19 per 100,000 population, with an APC of -3.58% (p-value: 0.0220). When subgroups were examined, declines were observed among all males (APC: -4.25%; p-value: 0.0270), males <65 years (APC: -5.32%; p-value: 0.0008), females <65 years (APC: -4.85%; p-value: 0.0044), and persons aged 55–64 years (APC: -6.38%; p-value: 0.0017).

Conclusions

Declines in lung cancer incidence rates occurred during 2005–2010 among the overall population and within select demographic groups in Oklahoma. Although trends were stable for several demographic groups, rates of lung cancer incidence were lower in 2010 compared to 2005. Continued evidence-based tobacco control efforts are needed to ensure further reductions in lung cancer incidence rates in the state of Oklahoma.     

Terbium binding to axonal membrane vesicles from lobster (Homarus Americanus) peripheral nerve. A probe of calcium binding sites

Tb³⁺, a fluorescent trivalent cation with physicochemical properties similar to Ca²⁺, binds to peripheral nerve membrane vesicles prepared from the walking leg nerve bundle of the lobster (Homarus americanus). Saturable binding is measured for at least two classes of binding site. Bound Tb³⁺ can be displaced by other cations in the order: Ca²⁺ > Mg²⁺ = Zn²⁺ > NH₄⁺. The binding of Tb³⁺ to the lower affinity site (K_D(app) = 6.0 μM) is inhibitable by Na⁺, Mg²⁺ and Ca²⁺, whereas the higher affinity site (K_D(app) = 2.2 μM) is only sensitive to Ca²⁺. Using this spectral probe the role of Ca²⁺ in peripheral nerve membrane function can be investigated.     

Ubc9 is required for damage-tolerance and damage-induced interchromosomal homologous recombination in S. cerevisiae

Ubc9 is an enzyme involved in the conjugation of small ubiquitin related modifier (SUMO) to target proteins. A Saccharomyces cerevisiae ubc9 temperature sensitive (ts) mutant showed higher sensitivity to various DNA damaging agents such as methylmethanesulfonate (MMS) and UV at a semi-permissive temperature than wild-type cells. The sensitivity of ubc9ts cells was not suppressed by the introduction of a mutated UBC9 gene, UBC9-C93S, whose product is unable to covalently bind to SUMO and consequently fails to conjugate SUMO to target proteins. Diploid ubc9ts cells were more sensitive to various DNA damaging agents than haploid ubc9ts cells suggesting the involvement of homologous recombination in the sensitivity of ubc9ts cells. The frequency of interchromosomal recombination between heteroalleles, his1-1/his1-7 loci, in wild-type cells was remarkably increased upon exposure to MMS or UV. Although the frequency of spontaneous interchromosomal recombination between the heteroalleles in ubc9ts cells was almost the same as that of wild-type cells, no induction of interchromosomal recombination was observed in ubc9ts cells upon exposure to MMS or UV.     

The Exogenous Application of Brassinosteroids to Zea mays (L.) Stressed by Long-Term Chilling Does Not Affect the Activities of Photosystem 1 or 2

The effect of various concentrations of exogenously applied 24-epibrassinolide (E) and 2α,3α,17β-trihydroxy-5α-androstan-6-one (A) on the activities of Photosystem 1 and the Hill reaction, the contents of photosynthetic pigments, and the growth of plants was examined in young maize (Zea mays L.) plants subjected to long-term chilling stress or grown in normal-temperature conditions. Neither the activity of Photosystem 1 nor the Hill reaction activity of plants was in any way affected by the treatment with brassinosteroids (BRs), which suggests that the photosynthetic complexes of thylakoid membranes are not the primary site of the influence of BRs on photosynthesis. An extremely low (10⁻¹⁴ M) concentration of A applied to the nonstressed plants significantly increased the length of their 4th to the 7th leaves and their height, as well as the contents of chlorophylls a and b and total carotenoids. However, under chilling conditions, this positive effect was significant for the chlorophyll content only and higher concentrations of BRs (10⁻¹², 10⁻¹⁰, 10⁻⁸ M) usually had no effect at all.     

Human mesenchymal stem cells express neuronal markers after osteogenic and adipogenic differentiation

Mesenchymal stem cells (MSCs) are multipotent cells that are able to differentiate into mesodermal lineages (osteogenic, adipogenic, chondrogenic), but also towards non-mesodermal derivatives (e.g. neural cells). Recent in vitro studies revealed that, in the absence of any kind of differentiation stimuli, undifferentiated MSCs express neural differentiation markers, but the literature data do not all concur. Considering their promising therapeutic potential for neurodegenerative diseases, it is very important to expand our knowledge about this particular biological property of MSCs. In this study, we confirmed the spontaneous expression of neural markers (neuronal, glial and progenitor markers) by undifferentiated human MSCs (hMSCs) and in particular, we demonstrated that the neuronal markers βIII-tubulin and NeuN are expressed by a very high percentage of hMSCs, regardless of the number of culture passages and the culture conditions. Moreover, the neuronal markers βIII-tubulin and NeuN are still expressed by hMSCs after in vitro osteogenic and adipogenic differentiation. On the other hand, chondrogenically differentiated hMSCs are negative for these markers. Our findings suggest that the expression of neuronal markers could be common to a wide range of cellular types and not exclusive for neuronal lineages. Therefore, the expression of neuronal markers alone is not sufficient to demonstrate the differentiation of MSCs towards the neuronal phenotype. Functional properties analysis is also required.     

Empirical tests of the role of disruptive coloration in reducing detectability

Disruptive patterning is a potentially universal camouflage technique that is thought to enhance concealment by rendering the detection of body shapes more difficult. In a recent series of field experiments, artificial moths with markings that extended to the edges of their 'wings' survived at higher rates than moths with the same edge patterns inwardly displaced. While this result seemingly indicates a benefit to obscuring edges, it is possible that the higher density markings of the inwardly displaced patterns concomitantly reduced their extent of background matching. Likewise, it has been suggested that the mealworm baits placed on the artificial moths could have created differential contrasts with different moth patterns. To address these concerns, we conducted controlled trials in which human subjects searched for computer-generated moth images presented against images of oak trees. Moths with edge-extended disruptive markings survived at higher rates, and took longer to find, than all other moth types, whether presented sequentially or simultaneously. However, moths with no edge markings and reduced interior pattern density survived better than their high-density counterparts, indicating that background matching may have played a so-far unrecognized role in the earlier experiments. Our disruptively patterned non-background-matching moths also had the lowest overall survivorship, indicating that disruptive coloration alone may not provide significant protection from predators. Collectively, our results provide independent support for the survival value of disruptive markings and demonstrate that there are common features in human and avian perception of camouflage.     

The plug domain of the SecY protein stabilizes the closed state of the translocation channel and maintains a membrane seal

Proteins are translocated across membranes through a channel that is formed by the prokaryotic SecY or eukaryotic Sec61 complex. The crystal structure of the SecY channel from M. jannaschii revealed a plug domain that appears to seal the channel in its closed state. However, the role of the plug remains unclear, particularly because plug deletion mutants in S. cerevisiae are functional. Here, we demonstrate that plug deletion mutants in E. coli SecY are also functional and even efficiently translocate proteins with defective or missing signal sequences. The crystal structures of equivalent plug deletions in SecY of M. jannaschii show that, although the overall structures are maintained, new plugs are formed. These lack many interactions that normally stabilize the closed channel, explaining why the channels can open for proteins with signal-sequence mutations. Our data show that the plug domain is required to maintain a closed state of the channel and suggest a mechanism for channel gating.