4,135 research outputs found
Mechanisms of structure direction in zeolite synthesis
The mechanisms by which the geometries of organic structure-directing agents are translated into the product pore architectures in the synthesis of pure-silica and aluminosilicate zeolites are investigated by numerous spectroscopic techniques and variations in synthesis gel composition. For the tetrapropylammonium- and 1,6-hexanediamine-mediated syntheses of pure-silica ZSM-5 (Si-ZSM-5), 1H-29Si CP MAS NMR is performed between the protons of the organic species and the silicon atoms of the zeolite framework precursors in a deuterated synthesis medium to probe the interactions between the organic and inorganic components. The origin of structural specificity in the synthesis of pure-silica zeolites in the presence of structure-directing agents is attributed to the formation of favorable intermolecular van der Waals interactions within inorganic-organic composite species that form the key components in zeolite self-assembly. Investigation of the 1H-29Si CP MAS NMR profiles of silicate gels containing tetraalkylammonium cations that do not induce the formation of a crystalline zeolite product suggest the significance of hydrophobic hydration of the organic component in the formation of the inorganic-organic composite structures that is essential to the synthesis of pure-silica zeolites. For the syntheses of the hexagonal (EMT) and cubic (FAU) polymorphs of the aluminosilicate zeolite faujasite in the presence of 18-crown-6 and 15-crown-5, respectively, a combination of NMR and vibrational spectroscopic techniques and variations in the synthesis compositions are used to elucidate the structure-directing roles of the crown ethers. Sodium/crown ether complexes facilitate and direct the assembly of sodium-templated extended aluminosilicate structures via ion-dipole interactions to form the EMT and FAU products. Thus, for the synthesis of Si-ZSM-5 and the synthesis of EMT and FAU, two different mechanisms of structure direction and self-assembly via the formation of extended inorganic or inorganic-organic composite species are proposed
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Riparian canopy and channel response to hillslope disturbance in Elk River Basin, southwest Oregon
Elk River is a sixth order stream, draining a 200 square
kilometer basin in the Klainath Mountain province of
southwestern Oregon. Timber harvesting began in the basin
during the 1950's, with peak removal of wood occurring in the
mid to late 1960's. This activity lead to an increase in the
frequency of landsliding and surface erosion. The downstream
effects of this increase in sediment were evaluated by
interpreting aerial photography spanning the period 1956 to
1979. Opening or enlargement of the riparian canopy cover was
used as an indicator of sediment impacts.
Results indicate that in most basins, changes in
downstream channel conditions could not be directly linked to
the increase in sediment delivered from harvested areas.
Opening on higher order channels occurred throughout the study
period, but did not exhibit patterns indicative of a large
pulse of sediment moving through the system. Rather, opening in fourth to fifth order channels was attributed to the
interaction between local sediment sources and channel
morphology, with unconstrained, flat channel segments
exhibiting chronic opening. The distribution of constrained
and unconstrained channel reaches was defined by a Channel
Morphology Index (CMI), which compared relative width and
gradient changes to channel averages.
A 100-year event in 1964 did not produce effects in Elk
River Basin on the same order of magnitude as other basins in
the Pacific Northwest. Downstream effects were important in a
few areas where landslides and high rates of surface erosion
were directly linked to opening and channel widening
downstream. Limited channel response to hillslope. disturbance
in Elk River Basin over the period 1956-79 was attributed to
four factors: lack of debris flows in most areas of the basin,
channels constrained by competent hillslopes and bedrock
limiting the extent of opening, channel conditions inherited
from storms prior to 1956, and essentially pristine conditions
over much of the basin at the time of the 1964 storm.
Finally, sequential air photo interpretation proved
useful in deciphering disturbance history and analyzing
processes which create downstream effects
Chromosome painting in the manatee supports Afrotheria and Paenungulata
BACKGROUND: Sirenia (manatees, dugongs and Stellar's sea cow) have no evolutionary relationship with other marine mammals, despite similarities in adaptations and body shape. Recent phylogenomic results place Sirenia in Afrotheria and with elephants and rock hyraxes in Paenungulata. Sirenia and Hyracoidea are the two afrotherian orders as yet unstudied by comparative molecular cytogenetics. Here we report on the chromosome painting of the Florida manatee. RESULTS: The human autosomal and X chromosome paints delimited a total of 44 homologous segments in the manatee genome. The synteny of nine of the 22 human autosomal chromosomes (4, 5, 6, 9, 11, 14, 17, 18 and 20) and the X chromosome were found intact in the manatee. The syntenies of other human chromosomes were disrupted in the manatee genome into two to five segments. The hybridization pattern revealed that 20 (15 unique) associations of human chromosome segments are found in the manatee genome: 1/15, 1/19, 2/3 (twice), 3/7 (twice), 3/13, 3/21, 5/21, 7/16, 8/22, 10/12 (twice), 11/20, 12/22 (three times), 14/15, 16/19 and 18/19. CONCLUSION: There are five derived chromosome traits that strongly link elephants with manatees in Tethytheria and give implicit support to Paenungulata: the associations 2/3, 3/13, 8/22, 18/19 and the loss of the ancestral eutherian 4/8 association. It would be useful to test these conclusions with chromosome painting in hyraxes. The manatee chromosome painting data confirm that the associations 1/19 and 5/21 phylogenetically link afrotherian species and show that Afrotheria is a natural clade. The association 10/12/22 is also ubiquitous in Afrotheria (clade I), present in Laurasiatheria (clade IV), only partially present in Xenarthra (10/12, clade II) and absent in Euarchontoglires (clade III). If Afrotheria is basal to eutherians, this association could be part of the ancestral eutherian karyotype. If afrotherians are not at the root of the eutherian tree, then the 10/12/22 association could be one of a suite of derived associations linking afrotherian taxa
Active drag as a criterion for evidence-based classification in Para swimming
Paralympic classification should provide athletes with an equitable starting point for competition by minimizing the impact their impairment has on the outcome of the event. As swimming is an event conducted in water, the ability to overcome drag (active and passive) is an important performance determinant. It is plausible that the ability to do this is affected by the type and severity of the physical impairment, but the current World Para Swimming classification system does not objectively account for this component. The aim of this study was to quantify active and passive drag in Para swimmers and evaluate the strength of association between these measures and type of physical impairment, swimming performance, and sport class. Methods Seventy-two highly trained Para swimmers from sport classes S1 to S10 and 14 highly trained nondisabled swimmers were towed by a motorized winch while the towing force was recorded. Passive drag was measured with the arms held by the side; active drag was determined during freestyle swimming using an assisted towing method. Results Active and passive drag were higher in Para swimmers with central motor and neuromuscular impairments than for nondisabled swimmers and were associated with severity of swim-specific impairment (sport class) and maximal freestyle performance in these swimmers (r = −0.40 to −0.50, P ≤ 0.02). Para swimmers with anthropometric impairments showed similar active and passive drag to nondisabled swimmers, and between swimmers from different sport classes. Conclusions Para swimmers with central motor and neuromuscular impairments are predisposed to high active drag during freestyle swimming that impacts on their performance. It is recommended that drag measures be considered in revised classification for these swimmers, but not for those with anthropometric impairments
RAD51C deficiency in mice results in early prophase I arrest in males and sister chromatid separation at metaphase II in females
RAD51C is a member of the RecA/RAD51 protein family, which is known to play an important role in DNA repair by homologous recombination. In mice, it is essential for viability. Therefore, we have generated a hypomorphic allele of Rad51c in addition to a null allele. A subset of mice expressing the hypomorphic allele is infertile. This infertility is caused by sexually dimorphic defects in meiotic recombination, revealing its two distinct functions. Spermatocytes undergo a developmental arrest during the early stages of meiotic prophase I, providing evidence for the role of RAD51C in early stages of RAD51-mediated recombination. In contrast, oocytes can progress normally to metaphase I after superovulation but display precocious separation of sister chromatids, aneuploidy, and broken chromosomes at metaphase II. These defects suggest a possible late role of RAD51C in meiotic recombination. Based on the marked reduction in Holliday junction (HJ) resolution activity in Rad51c-null mouse embryonic fibroblasts, we propose that this late function may be associated with HJ resolution
Untangling the controls on bedload transport in a wood‐loaded river with RFID tracers and linear mixed modelling
Bedload transport is a fundamental process by which coarse sediment is transferred through landscapes by river networks and may be well described stochastically by distributions of grain step length and rest time obtained through tracer studies. To date, none of these published tracer studies have specifically investigated the influence of large wood in the river channel on sediment transport dynamics, limiting the applicability of stochastic sediment transport models in these settings. Large wood is a major component of many forested rivers and is increasing due to anthropogenic ‘Natural Flood Management’ (NFM) practices. This study aims to investigate and model the influence of large wood on grain-scale bedload transport. We tagged 957 cobble – pebble sized particles (D50 = 73 mm) and 28 pieces of large wood (> 1 m in length) with RFID tracers in an alpine mountain stream. We monitored the transport distance of tracers annually over three years, building distributions of tracer transport distances with which to compare with published distributions from wood free settings. We also applied linear mixed modelling (LMM), to tease out the influence of wood from other controls on likelihood of entrainment, deposition, and the transport distances of sediments. Tracer sediments accumulated both up and downstream of large wood pieces, with LMM analysis confirming a reduction in the probability of entrainment of tracers closer to wood in all three years. Upon remobilisation, tracers entrained from positions closer to large wood had shorter subsequent transport distances in each year. In 2019, large wood also had a trapping effect, significantly reducing the transport distances of tracer particles entrained from upstream, i.e. forcing premature deposition of tracers. This study demonstrates the role of large wood in influencing bedload transport in alpine stream environments, with implications for both natural and anthropogenic addition of wood debris in fluvial environments
Characterization of BRCA2 R3052Q variant in mice supports its functional impact as a low-risk variant
Pathogenic variants in BRCA2 are known to significantly increase the lifetime risk of developing breast and ovarian cancers. Sequencing-based genetic testing has resulted in the identification of thousands of BRCA2 variants that are considered to be variants of uncertain significance (VUS) because the disease risk associated with them is unknown. One such variant is p.Arg3052Gln, which has conflicting interpretations of pathogenicity in the ClinVar variant database. Arginine at position 3052 in BRCA2 plays an important role in stabilizing its C-terminal DNA binding domain. We have generated a knock-in mouse model expressing this variant to examine its role on growth and survival in vivo. Homozygous as well as hemizygous mutant mice are viable, fertile and exhibit no overt phenotype. While we did not observe any hematopoietic defects in adults, we did observe a marked reduction in the in vitro proliferative ability of fetal liver cells that were also hypersensitive to PARP inhibitor, olaparib. In vitro studies performed on embryonic and adult fibroblasts derived from the mutant mice showed significant reduction in radiation induced RAD51 foci formation as well as increased genomic instability after mitomycin C treatment. We observed mis-localization of a fraction of R3052Q BRCA2 protein to the cytoplasm which may explain the observed in vitro phenotypes. Our findings suggest that BRCA2 R3052Q should be considered as a hypomorphic variant.This research was sponsored by the Intramural Research Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health
Nuclear pore protein NUP210 depletion suppresses metastasis through heterochromatin-mediated disruption of tumor cell mechanical response.
Mechanical signals from the extracellular microenvironment have been implicated in tumor and metastatic progression. Here, we identify nucleoporin NUP210 as a metastasis susceptibility gene for human estrogen receptor positive (ER+) breast cancer and a cellular mechanosensor. Nup210 depletion suppresses lung metastasis in mouse models of breast cancer. Mechanistically, NUP210 interacts with LINC complex protein SUN2 which connects the nucleus to the cytoskeleton. In addition, the NUP210/SUN2 complex interacts with chromatin via the short isoform of BRD4 and histone H3.1/H3.2 at the nuclear periphery. In Nup210 knockout cells, mechanosensitive genes accumulate H3K27me3 heterochromatin modification, mediated by the polycomb repressive complex 2 and differentially reposition within the nucleus. Transcriptional repression in Nup210 knockout cells results in defective mechanotransduction and focal adhesion necessary for their metastatic capacity. Our study provides an important role of nuclear pore protein in cellular mechanosensation and metastasis
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Mesothelioma patient derived tumor xenografts with defined BAP1 mutations that mimic the molecular characteristics of human malignant mesothelioma
Background: The development and evaluation of new therapeutic approaches for malignant mesothelioma has been sparse due, in part, to lack of suitable tumor models. Methods: We established primary mesothelioma cultures from pleural and ascitic fluids of five patients with advanced mesothelioma. Electron microscopy and immunohistochemistry (IHC) confirmed their mesothelial origin. Patient derived xenografts were generated by injecting the cells in nude or SCID mice, and malignant potential of the cells was analyzed by soft agar colony assay. Molecular profiles of the primary patient tumors, early passage cell cultures, and patient derived xenografts were assessed using mutational analysis, fluorescence in situ hybridization (FISH) analysis and IHC. Results: Primary cultures from all five tumors exhibited morphologic and IHC features consistent to those of mesothelioma cells. Mutations of BAP1 and CDKN2A were each detected in four tumors. BAP1 mutation was associated with the lack of expression of BAP1 protein. Three cell cultures, all of which were derived from BAP1 mutant primary tumors, exhibited anchorage independent growth and also formed tumors in mice, suggesting that BAP1 loss may enhance tumor growth in vivo. Both early passage cell cultures and mouse xenograft tumors harbored BAP1 mutations and CDKN2A deletions identical to those found in the corresponding primary patient tumors. Conclusions: The mesothelioma patient derived tumor xenografts with mutational alterations that mimic those observed in patient tumors which we established can be used for preclinical development of novel drug regimens and for studying the functional aspects of BAP1 biology in mesothelioma. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1362-2) contains supplementary material, which is available to authorized users
EML4-ALK induces cellular senescence in mortal normal human cells and promotes anchorage-independent growth in hTERT-transduced normal human cells
Background: Chromosomal inversions involving anaplastic lymphoma kinase (ALK) and echinoderm microtubule associated protein like 4 (EML4) generate a fusion protein EML4-ALK in non-small cell lung cancer (NSCLC). The understanding of EML4-ALK function can be improved by a functional study using normal human cells.
Methods: Here we for the first time conduct such study to examine the effects of EML4-ALK on cell proliferation, cellular senescence, DNA damage, gene expression profiles and transformed phenotypes.
Results: The lentiviral expression of EML4-ALK in mortal, normal human fibroblasts caused, through its constitutive ALK kinase activity, an early induction of cellular senescence with accumulated DNA damage, upregulation of p16INK4A and p21WAF1, and senescence-associated β-galactosidase (SA-β-gal) activity. In contrast, when EML4-ALK was expressed in normal human fibroblasts transduced with telomerase reverse transcriptase (hTERT), which is activated in the vast majority of NSCLC, the cells showed accelerated proliferation and acquired anchorage-independent growth ability in soft-agar medium, without accumulated DNA damage, chromosome aberration, nor p53 mutation. EML4-ALK induced the phosphorylation of STAT3 in both mortal and hTERT-transduced cells, but RNA sequencing analysis suggested that the different signaling pathways contributed to the different phenotypic outcomes in these cells. While EML4-ALK also induced anchorage-independent growth in hTERT-immortalized human bronchial epithelial cells in vitro, the expression of EML4-ALK alone did not cause detectable in vivo tumorigenicity in immunodeficient mice.
Conclusions: Our data indicate that the expression of hTERT is critical for EML4-ALK to manifest its in vitro transforming activity in human cells. This study provides the isogenic pairs of human cells with and without EML4-ALK expression
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