Does the Holton–Tan Mechanism Explain How the Quasi-Biennial Oscillation Modulates the Arctic Polar Vortex?

Idealized experiments with the Whole Atmosphere Community Climate Model (WACCM) are used to explore the mechanism(s) whereby the stratospheric quasi-biennial oscillation (QBO) modulates the Northern Hemisphere wintertime stratospheric polar vortex. Overall, the effect of the critical line emphasized in the Holton–Tan mechanism is less important than the effect of the mean meridional circulation associated with QBO winds for the polar response to the QBO. More specifically, the introduction of easterly winds at the equator near 50 hPa 1) causes enhanced synoptic-scale Eliassen–Palm flux (EPF) convergence in the subtropics from 150 to 50 hPa, which leads to the subtropical critical line moving poleward in the lower stratosphere, and 2) creates a barrier to planetary wave propagation from subpolar latitudes to midlatitudes in the middle and upper stratosphere (e.g., less equatorward EPF near 50°N), which leads to enhanced planetary wave convergence in the polar vortex region. These two effects are mechanistically distinct; while the former is related to the subtropical critical line, the latter is due to the mean meridional circulation of the QBO. All of these effects are consistent with linear theory, although the evolution of the entire wind distribution is only quasi-linear because induced zonal wind changes cause the wave driving to shift and thereby positively feed back on the zonal wind changes. Finally, downward propagation of the QBO in the equatorial stratosphere, upper stratospheric equatorial zonal wind, and changes in the tropospheric circulation appear to be less important than lower stratospheric easterlies for the polar stratospheric response. Overall, an easterly QBO wind anomaly in the lower stratosphere leads to a weakened stratospheric polar vortex, in agreement with previous studies, although not because of changes in the subtropical critical line

Engraftment of adult neural progenitor cells transplanted to rat retina injured by transient ischemia

PURPOSE. To optimize delivery parameters for achieving engraftment, migration, and differentiation of adult neural progenitor cells transplanted to the retinas of rats after transient retinal ischemia. METHODS. Retinal ischemia was induced by transiently raising the intraocular pressure. Some animals then received transplantation of green fluorescent protein (GFP)-expressing cells derived from the adult rat hippocampus and were allowed to recover for 6 hours to 9 weeks. Retinal cryosections were prepared for TUNEL analysis to determine the time course of ischemia-induced cell death, and some sections were prepared for immunohistochemistry for retinal neuronal antigens. RESULTS. TUNEL analysis revealed that ischemia-induced cell death peaked at 24 hours. By 96 hours, the inner nuclear (INL) and ganglion cell (GCL) layers were largely obliterated in the central retina, sparing peripheral regions. By 2 weeks after transplantation, numerous GFP-expressing cells had engrafted into the host retina, migrated to the inner retina, and extended processes. At 4 weeks, many GFP-labeled cells were present throughout the INL and displayed horizontal-, bipolar-, and amacrine cell-like morphologies. GFP-expressing cells were also present in the GCL with fibers extending into the nerve fiber layer. At 5 weeks, many GFP-expressing cells were present at the optic nerve head, and some GFP-labeled fibers were present in the optic nerve, occasionally passing through the full extent of the lamina cribrosa. Only rarely were GFPexpressing cells found that coexpressed retinal phenotypic markers at any time point examined. CONCLUSIONS. Adult hippocampus-derived neural progenitor cells transplanted to the subretinal space readily engraft into a host retina that has undergone ischemic injury. Many cells migrate to specific retinal cellular layers and undergo limited morphologic differentiation reminiscent of retinal neurons, including extension of processes into the optic nerve. Concurrent control studies demonstrate that optimal engraftment is achieved by subretinal delivery within a specific temporal window. These results imply that certain inductive cues may be regulated after injury, and they demonstrate the potential for adult neural progenitor cell transplantation for the treatment of retinal neurodegenerative diseases. (Invest Ophthalmol Vis Sci. 2003;44:3194 -3201) DOI:10.1167/iovs.02-0875 N eurodegenerative diseases of the inner retina are major causes of blindness worldwide. These include the glaucomas, which primarily affect retinal ganglion cells, and ischemic retinopathies (including diabetic and hypertensive retinopathies) that affect other populations of inner retinal neurons as well. 1,2 Current therapies for inner retinal degenerations are largely retardant and are not sufficient to restore visual function after severe impairment of inner retinal circuitry. Numerous neuroprotective strategies have been used in an effort to prolong the survival of inner retinal neurons damaged in rodent models of inner retinal degeneration. 3-13 However, many neurodegenerative diseases of the inner retina, such as primary open-angle glaucoma (POAG) are quite protracted, extending over many months to years. Experimental models for these diseases have, by necessity, compressed this time course dramatically. The mechanisms of ganglion cell death (and potential neuroprotection) have been examined extensively in models of optic nerve transection or crush 14 -17 and in models using either acute ischemia followed by reperfusion 18 -20 or chronic elevation of intraocular pressure (IOP). 12,13 These experimental models also often result in degeneration of cells in the inner nuclear layer (INL). However, preservation of these cells and inner retinal circuitry is still problematic. Recent advances in stem cell biology have invigorated the potential for achieving partial restoration of visual function after inner retinal neurodegeneration by augmenting the remaining inner retinal circuitry. It has been demonstrated that neural progenitor cells can be isolated from near the ventricular wall of the adult brain, as well as from the adult hippocampus

Evidence That the P\u3csub\u3ei\u3c/sub\u3e Release Event Is the Rate-Limiting Step in the Nitrogenase Catalytic Cycle

Nitrogenase reduction of dinitrogen (N2) to ammonia (NH3) involves a sequence of events that occur upon the transient association of the reduced Fe protein containing two ATP molecules with the MoFe protein that includes electron transfer, ATP hydrolysis, Pi release, and dissociation of the oxidized, ADP-containing Fe protein from the reduced MoFe protein. Numerous kinetic studies using the nonphysiological electron donor dithionite have suggested that the rate-limiting step in this reaction cycle is the dissociation of the Fe protein from the MoFe protein. Here, we have established the rate constants for each of the key steps in the catalytic cycle using the physiological reductant flavodoxin protein in its hydroquinone state. The findings indicate that with this reductant, the rate-limiting step in the reaction cycle is not protein–protein dissociation or reduction of the oxidized Fe protein, but rather events associated with the Pi release step. Further, it is demonstrated that (i) Fe protein transfers only one electron to MoFe protein in each Fe protein cycle coupled with hydrolysis of two ATP molecules, (ii) the oxidized Fe protein is not reduced when bound to MoFe protein, and (iii) the Fe protein interacts with flavodoxin using the same binding interface that is used with the MoFe protein. These findings allow a revision of the rate-limiting step in the nitrogenase Fe protein cycle

Basal ganglia morphometry and repetitive behavior in young children with autism spectrum disorder

We investigated repetitive and stereotyped behavior (RSB) and its relationship to morphometric measures of the basal ganglia and thalami in 3-4 year old children with autism spectrum disorder (ASD; n=77) and developmental delay without autism (DD; n=34). Children were assessed through clinical evaluation and parent report using RSB-specific scales extracted from the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview, and the Aberrant Behavior Checklist. A subset of children with ASD (n=45), DD (n=14) and a group of children with typical development (TD; n=25) were also assessed by magnetic resonance imaging (MRI). Children with ASD demonstrated elevated RSB across all measures compared to children with DD. Enlargement of the left and right striatum, more specifically the left and right putamen, and left caudate, was observed in the ASD compared to the TD group. However, nuclei were not significantly enlarged after controlling for cerebral volume. The DD group, in comparison to the ASD group, demonstrated smaller thalami and basal ganglia regions even when scaled for cerebral volume, with the exception of the left striatum, left putamen, and right putamen. Elevated RSB, as measured by the ADOS, was associated with decreased volumes in several brain regions: left thalamus, right globus pallidus, left and right putamen, right striatum and a trend for left globus pallidus and left striatum within the ASD group. These results confirm earlier reports that RSB is common early in the clinical course of ASD and, furthermore, demonstrate that such behaviors may be associated with decreased volumes of the basal ganglia and thalamus

Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis.

The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis

Data access for the 1,000 Plants (1KP) project

© 2014 Matasci et al.; licensee BioMed Central Ltd. The 1,000 plants (1KP) project is an international multi-disciplinary consortium that has generated transcriptome data from over 1,000 plant species, with exemplars for all of the major lineages across the Viridiplantae (green plants) clade. Here, we describe how to access the data used in a phylogenomics analysis of the first 85 species, and how to visualize our gene and species trees. Users can develop computational pipelines to analyse these data, in conjunction with data of their own that they can upload. Computationally estimated protein-protein interactions and biochemical pathways can be visualized at another site. Finally, we comment on our future plans and how they fit within this scalable system for the dissemination, visualization, and analysis of large multi-species data sets

Interactions among mitochondrial proteins altered in glioblastoma

Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral to mitochondrial function. Alterations in proteins in mitochondrial enriched fractions from patients with GBM were defined with label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated proteins were identified in mitochondrial enriched fractions and 117 of these mitochondrial proteins were markedly (fold-change ≥2) and significantly altered in GBM (p ≤ 0.05). Proteins associated with oxidative damage (including catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were increased in GBM. Protein–protein interaction analysis highlighted a reduction in multiple proteins coupled to energy metabolism (in particular respiratory chain proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis in GBM with electron microscopy showed a notably higher prevalence of mitochondria with cristolysis in GBM. This study highlights the complex mitochondrial proteomic adjustments which occur in GBM pathophysiology

Phylotranscriptomic analysis of the origin and early diversification of land plants

Reconstructing the origin and evolution of land plants and their algal relatives is a fundamental problem in plant phylogenetics, and is essential for understanding how critical adaptations arose, including the embryo, vascular tissue, seeds, and flowers. Despite advances inmolecular systematics, some hypotheses of relationships remain weakly resolved. Inferring deep phylogenies with bouts of rapid diversification can be problematic; however, genome-scale data should significantly increase the number of informative characters for analyses. Recent phylogenomic reconstructions focused on the major divergences of plants have resulted in promising but inconsistent results. One limitation is sparse taxon sampling, likely resulting from the difficulty and cost of data generation. To address this limitation, transcriptome data for 92 streptophyte taxa were generated and analyzed along with 11 published plant genome sequences. Phylogenetic reconstructions were conducted using up to 852 nuclear genes and 1,701,170 aligned sites. Sixty-nine analyses were performed to test the robustness of phylogenetic inferences to permutations of the datamatrix or to phylogeneticmethod, including supermatrix, supertree, and coalescent-based approaches, maximumlikelihood and Bayesian methods, partitioned and unpartitioned analyses, and amino acid versus DNA alignments. Among other results, we find robust support for a sister-group relationship between land plants and one group of streptophyte green algae, the Zygnematophyceae. Strong and robust support for a clade comprising liverworts and mosses is inconsistent with a widely accepted view of early land plant evolution, and suggests that phylogenetic hypotheses used to understand the evolution of fundamental plant traits should be reevaluated

Q2Q^2 Dependence of Quadrupole Strength in the γ∗p→Δ+(1232)→pπ0\gamma^*p\to\Delta^+(1232)\to p \pi^0 Transition

Models of baryon structure predict a small quadrupole deformation of the nucleon due to residual tensor forces between quarks or distortions from the pion cloud. Sensitivity to quark versus pion degrees of freedom occurs through the $Q^2$ dependence of the magnetic ($M_{1+}$), electric ($E_{1+}$), and scalar ($S_{1+}$) multipoles in the $\gamma^* p \to \Delta^+ \to p \pi^0$ transition. We report new experimental values for the ratios $E_{1+}/M_{1+}$ and $S_{1+}/M_{1+}$ over the range $Q^2$= 0.4-1.8 GeV$^2$, extracted from precision $p(e,e 'p)\pi^{\circ}$ data using a truncated multipole expansion. Results are best described by recent unitary models in which the pion cloud plays a dominant role.Comment: 5 pages, 5 figures, 1 table. To be published in Phys. Rev. Lett. (References, figures and table updated, minor changes.