Large nucleotide-dependent conformational change in Rab28

AbstractRab GTPases are essential regulators of membrane trafficking. We report crystal structures of Rab28 in the active (GppNHp-bound) and inactive (GDP-3′P-bound) forms at 1.5 and 1.1Å resolution. Rab28 is a distant member of the Rab family. While the overall fold of Rab28 resembles that of other Rab GTPases, it undergoes a larger nucleotide-dependent conformational change than other members of this family. Added flexibility resulting from a double-glycine motif at the beginning of switch 2 might partially account for this observation. The double-glycine motif, which is conserved in the Arf family, only occurs in Rab28 and Rab7B of the Rab family, and may have a profound effect on their catalytic activities

EFFECTS OF LANDING HEIGHT ON LOWER EXTREMITY JOINT BIOMECHANICS DURING UNILATERAL AND BILATERAL LANDINGS

The aim of this study was to examine the lower extremity kinematics and kinetics during landing phase, in response to the effects of landing height during unilateral and bilateral landing. Ten young healthy male subjects (age: 26.1±1.8yr, height: 183.2±4.4cm, weight: 76.1±6.9kg) participated in this study. Each subject performed the unilateral and bilateral landing from a 30cm and 45cm wooden platform. The results showed the peak vertical ground reaction force (PVGRF) was increased during unilateral landing and at greater landing height (

Analysis of volatile compounds from three species of Atractylodes by Gas Chromatography-Mass Spectrometry

A total of 99 different volatile compounds were detected through Gas Chromatography-Mass Spectrometry (GC-MS) from three species of Atractylodes, namely Atractylodes lancea, Atractylodes japonica, and Atractylodes chinensis. Thirteen-volatile flavor compounds i.e., acid, alcohol, aldehyde, alkane, alkene, alkyne, ester, ketone, monoterpene, oxygenated monoterpene, sesquiterpene, oxygenated sesquiterpene, and oxygenated triterpenoid detected from different species of Atractylodes. It was observed that all the species contained 38 common compounds, while A. lancea contained 7 unique compounds, A. japonica has 4 unique compounds, and A. chinensis hold 6 compounds not detected in the other extracts. In addition, essential oils from A. lancea and A. japonica possessed 11 compounds in common, and A. lancea and A. chinensis possessed 19 compounds in common. The remaining 14 compounds were detected only in A. japonica and A. chinensis. The total content of all components in the species was comparable, with 82.528%, 81.766%, and 81.799% of volatile components being detected for A. lancea, A. japonica, and A. chinensis, respectively. Curzerene was found to be the most predominant compound in both A. lancea (14.1%) and A. chinensis (16.7%), while murolan-3,9(11)-diene-10-peroxy was found predominantly in A. japonica (16.8%). The present study suggests that the identified volatile compounds may possess important biological properties, and could be suitable for application in both oriental medicines and the pharmaceutical industry

Avifauna of Bangtaesan Mountain, Gangwon-do, Korea

AbstractAn investigation on avifauna of the Bangtaesan Mountain was carried out from February until November, 2010 and it drew the results as follow. The number of birds observed in the whole Bangtaesan Mountain region was 989 individuals of 51 species (Maximum counts). Considering the results from literature research in addition, at least 90 species 1,000 individuals are thought to live in this region. In result, dominant species proved to be Yellow-throated Bunting (Emberiza elegans), Marsh Tit (Parus palustris), Azure-winged Magpie (Cyanopica cyana), Eastern Crowned Willow Warbler (Phylloscopus coronatus), Varied Tit (Parus varius), and more. Most of birds breeding in the forest of Korea were found to constitute these dominant bird species. Entire species diversity index appeared to be 3.35 relatively a high level; 3.34 in the south slopes while 3.22 in the north slopes showing relatively a high level in the south. Of them, 12 species including Mandarin Duck (Aix galericulata) were the Protected Birds species nominated and protected by the Cultural Heritage Administration or the Ministry of Environment, while 10 and 6 species were the natural monument species and endangered species level, respectively. Should further consistent surveys be carried out, a broader range of species would be found to breed, and therefore the Bangtaesan Mountain region including the area where the protected species are observed is believed to need a conservation and management through protected area designation

Epidermal Growth Factor Receptor Mutation and Pathologic-Radiologic Correlation Between Multiple Lung Nodules with Ground-Glass Opacity Differentiates Multicentric Origin from Intrapulmonary Spread

IntroductionNo standard guidelines detailing recommendations for the selection and treatment for multiple lung nodules with ground-glass opacity (GGO) have been established. For treatment decision, we analyzed epidermal growth factor receptor (EGFR)/K-ras somatic aberrations and pathologic-radiologic correlation in multiple lung nodules presented as GGO to differentiate multifocal lesions from intrapulmonary spread.MethodsTwenty-four patients with multiple lung nodules presented as GGO were identified to investigate somatic mutations of EGFR (exon 18–21) and K-ras (codons 2, 13, and 61). This series included 18 atypical adenomatous hyperplasias (AAH), 15 bronchioloalveolar carcinomas (BAC), and 23 adenocarcinomas (ADC) obtained from 24 patients.ResultsHigh frequency of discordant EGFR mutations (17 of 24, 70.8%) could discriminate tumor clonality (18 of 24, 75%) of multiple lung neoplastic nodules presented as GGO. EGFR mutations were common in AAH (38.9%), BAC (46.7%), and ADC (39.1%). In case 4, AAH and BAC had different mutational changes, and in case 10, the BAC lesion contains EGFR mutation that is not in the invasive ADC. In case 17, the BAC had more mutational changes than the carcinoma. The pure GGO appearance in the radiologic examination corresponded preinvasive pathologic change.ConclusionsThis study showed that synchronous BAC and/or ADC can have different EGFR or K-ras mutational profiles suggesting these lesions arise as independent events rather than intrapulmonary spread or systemic metastasis. This has significant implication in staging and treatment. These findings might be a clue to establish guidelines of the multiple neoplastic lung nodules with GGO

High adaptability of the omega loop underlies the substrate-spectrum-extension evolution of a class A β-lactamase, PenL

The omega loop in β-lactamases plays a pivotal role in substrate recognition and catalysis, and some mutations in this loop affect the adaptability of the enzymes to new antibiotics. Various mutations, including substitutions, deletions, and intragenic duplications resulting in tandem repeats (TRs), have been associated with β-lactamase substrate spectrum extension. TRs are unique among the mutations as they cause severe structural perturbations in the enzymes. We explored the process by which TRs are accommodated in order to test the adaptability of the omega loop. Structures of the mutant enzymes showed that the extra amino acid residues in the omega loop were freed outward from the enzyme, thereby maintaining the overall enzyme integrity. This structural adjustment was accompanied by disruptions of the internal α-helix and hydrogen bonds that originally maintained the conformation of the omega loop and the active site. Consequently, the mutant enzymes had a relaxed binding cavity, allowing for access of new substrates, which regrouped upon substrate binding in an induced-fit manner for subsequent hydrolytic reactions. Together, the data demonstrate that the design of the binding cavity, including the omega loop with its enormous adaptive capacity, is the foundation of the continuous evolution of β-lactamases against new drugs

Effects of Huang Bai (Phellodendri Cortex) and Three Other Herbs on GnRH and GH Levels in GT1–7 and GH3 Cells

The present study was to evaluate the effects of Huang Bai, Zhi Mu, Mai Ya, and Xia Ku Cao on hormone using the GT1–7 and GH3 cells. The GT1–7 and GH3 cell lines were incubated with DW; DMSO; and 30, 100, or 300 μg/mL of one of the four extract solutions in serum-free media for 24 hours. The MTT assay was performed to determine the cytotoxicity of the four herbs. The GT1–7 and GH3 cells were incubated in DW, estradiol (GT1–7 only), or noncytotoxic herb solutions in serum-free medium for 24 hours. A quantitative RT-PCR and western blot were performed to measure the GnRH expression in GT1–7 cells and GH expression in GH3 cells. Huang Bai, Zhi Mu, Xia Ku Cao, and Mai Ya inhibited the GnRH mRNA expression in GT1–7 cells, whereas Huang Bai enhanced GH mRNA expression in GH3 cells. Additionally, Xia Ku Cao inhibited GnRH protein expression in GT1–7 cells and Huang Bai promoted GH protein expression in GH3 cells. The findings suggest that Huang Bai can delay puberty by inhibiting GnRH synthesis in the hypothalamus while also accelerating growth by promoting GH synthesis and secretion in the pituitary

Lenalidomide and Programmed Death-1 Blockade Synergistically Enhances the Effects of Dendritic Cell Vaccination in a Model of Murine Myeloma

The therapeutic efficacy of dendritic cell (DC)-based immunotherapy may be potentiated in combination with other anticancer therapies that enhance DC function by modulating immune responses and the tumor microenvironment. In this study, we investigated the efficacy of DC vaccination in combination with lenalidomide and programmed death (PD)-1 blockade in a model of murine myeloma. MOPC-315 cell lines were injected subcutaneously to establish myeloma-bearing mice and the following five test groups were established: PBS control, DCs, DCs + lenalidomide, DCs + PD-1 blockade, and DCs + lenalidomide + PD-1 blockade. The combination of DCs plus lenalidomide and PD-1 blockade more potently inhibited tumor growth compared to the other groups. This effect was associated with a reduction in immune suppressor cells (such as myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells) and an increase in immune effector cells [such as CD4+ and CD8+ T cells, natural killer (NK) cells, and M1 macrophages] in the spleen. Functional activities of cytotoxic T lymphocytes and NK cells were also enhanced by the triple combination. Levels of immunosuppressive cytokines, such as TGF-β and IL-10, were significantly reduced in the tumor microenvironment. These findings suggest that the combination of DCs plus lenalidomide and PD-1 blockade synergistically establishes a robust anti-myeloma immunity through a two-way mechanism, which inhibits immunosuppressive cells while activating effector cells with superior polarization of the Th1/Th2 balance in favor of the tumor immune response. This result should provide an experimental ground for incorporating check point inhibitors to existing immunotherapeutic modalities against multiple myeloma

Epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangements in lung cancer with nodular ground-glass opacity

Vår uppsats handlar om formativ bedömning och vad det innebär att arbeta så i undervisningen. Vi tolkar att rådande läroplaner beskriver ett uppdrag som ligger i linje med ett formativt arbetssätt. Syftet var att ta reda på om lärare i samhällskunskap som arbetar på gymnasiet arbetar formativt och hur de gör det. Ett annat vanligt namn för formativ bedömning är bedömning för lärande (BFL). Genom kvalitativa intervjuer har vi frågat gymnasielärare i samhällskunskap hur de arbetar med bedömning, om de arbetar formativt och om det finns någon samsyn på deras respektive gymnasieskolor kring bedömning. Vi ville också veta vad formativt arbete innebär. Bedömning för lärande fokuserar på lärandet och hur eleven kan utvecklas och nå framgång i lärandet. Genom att konkretisera mål, syfte och kunskapskvaliteter så att eleven förstår dessa kan eleven få syn på sitt eget lärande. När eleven ges makt över sitt eget lärande leder det till ökad motivation. I formativ bedömning arbetar läraren bland annat med feedback och kamrat- och självvärdering. Vårt resultat visar att lärarna vi intervjuat i stor utsträckning arbetar summativt med formativa inslag i varierande grad, förutom en av lärarna som arbetar på en gymnasieskola i Borås som arbetar enligt bedömning för lärande. Studien visar att det råder brist på samsyn kring bedömning på gymnasie-skolorna, förutom på skolan i Borås där det finns tid avsatt för möten och samtal kring formativ bedömning. Litteraturen visar på de positiva effekterna av bedömning för lärande vilket också styrks av intervjun med läraren i Borås