872 research outputs found
Differential Interleukin-2 Transcription Kinetics Render Mouse but Not Human T Cells Vulnerable to Splicing Inhibition Early after Activation
T cells are nodal players in the adaptive immune response against pathogens and malignant cells. Alternative splicing plays a crucial role in T cell activation, which is analyzed mainly at later time points upon stimulation. Here we have discovered a 2-h time window early after stimulation where optimal splicing efficiency or, more generally, gene expression efficiency is crucial for successful T cell activation. Reducing the splicing efficiency at 4 to 6âh poststimulation significantly impaired murine T cell activation, which was dependent on the expression dynamics of the Egr1-Nab2-interleukin-2 (IL-2) pathway. This time window overlaps the time of peak IL-2 de novo transcription, which, we suggest, represents a permissive time window in which decreased splicing (or transcription) efficiency reduces mature IL-2 production, thereby hampering murine T cell activation. Notably, the distinct expression kinetics of the Egr1-Nab2-IL-2 pathway between mouse and human render human T cells refractory to this vulnerability. We propose that the rational temporal modulation of splicing or transcription during peak de novo expression of key effectors can be used to fine-tune stimulation-dependent biological outcomes. Our data also show that critical consideration is required when extrapolating mouse data to the human system in basic and translational research
Alternative splicing coupled mRNA decay shapes the temperatureâdependent transcriptome
Mammalian body temperature oscillates with the time of the dayand is altered in diverse pathological conditions. We recently iden-tified a body temperature-sensitive thermometer-like kinase,which alters SR protein phosphorylation and thereby globallycontrols alternative splicing (AS). AS can generate unproductivevariants which are recognized and degraded by diverse mRNAdecay pathwaysâincluding nonsense-mediated decay (NMD). Herewe show extensive coupling of body temperature-controlled AS tomRNA decay, leading to global control of temperature-dependentgene expression (GE). Temperature-controlled, decay-inducingsplicing events are evolutionarily conserved and pervasively foundwithin RNA-binding proteins, including most SR proteins. AS-coupledpoison exon inclusion is essential for rhythmic GE of SR proteins andhas a global role in establishing temperature-dependent rhythmicGE profiles, both in mammals under circadian body temperaturecycles and in plants in response to ambient temperature changes.Together, these data identify body temperature-driven AS-coupledmRNA decay as an evolutionary ancient, core clock-independentmechanism to generate rhythmic GE
A multi-factor trafficking site on the spliceosome remodeling enzyme BRR2 recruits C9ORF78 to regulate alternative splicing
The intrinsically unstructured C9ORF78 protein was detected in spliceosomes but its role in splicing is presently unclear. We find that C9ORF78 tightly interacts with the spliceosome remodeling factor, BRR2, in vitro. Affinity purification/mass spectrometry and RNA UV-crosslinking analyses identify additional C9ORF78 interactors in spliceosomes. Cryogenic electron microscopy structures reveal how C9ORF78 and the spliceosomal B complex protein, FBP21, wrap around the C-terminal helicase cassette of BRR2 in a mutually exclusive manner. Knock-down of C9ORF78 leads to alternative NAGNAG 3â˛-splice site usage and exon skipping, the latter dependent on BRR2. Inspection of spliceosome structures shows that C9ORF78 could contact several detected spliceosome interactors when bound to BRR2, including the suggested 3â˛-splice site regulating helicase, PRPF22. Together, our data establish C9ORF78 as a late-stage splicing regulatory protein that takes advantage of a multi-factor trafficking site on BRR2, providing one explanation for suggested roles of BRR2 during splicing catalysis and alternative splicing
Bandgap Change of Carbon Nanotubes: Effect of Small Tensile and Torsional Strain
We use a simple picture based on the electron approximation to study
the bandgap variation of carbon nanotubes with uniaxial and torsional strain.
We find (i) that the magnitude of slope of bandgap versus strain has an almost
universal behaviour that depends on the chiral angle, (ii) that the sign of
slope depends on the value of and (iii) a novel change in sign
of the slope of bandgap versus uniaxial strain arising from a change in the
value of the quantum number corresponding to the minimum bandgap. Four orbital
calculations are also presented to show that the orbital results are
valid.Comment: Revised. Method explained in detai
Increased versatility despite reduced molecular complexity evolution, structure and function of metazoan splicing factor PRPF39
In the yeast U1 snRNP the Prp39/Prp42 heterodimer is essential for early steps of spliceosome assembly. In metazoans no Prp42 ortholog exists, raising the question how the heterodimer is functionally substituted. Here we present the crystal structure of murine PRPF39, which forms a homodimer. Structure-guided point mutations disrupt dimer formation and inhibit splicing, manifesting the homodimer as functional unit. PRPF39 expression is controlled by NMD-inducing alternative splicing in mice and human, suggesting a role in adapting splicing efficiency to cell type specific requirements. A phylogenetic analysis reveals coevolution of shortened U1 snRNA and the absence of Prp42, which correlates with overall splicing complexity in different fungi. While current models correlate the diversity of spliceosomal proteins with splicing complexity, our study highlights a contrary case. We find that organisms with higher splicing complexity have substituted the Prp39/Prp42 heterodimer with a PRPF39 homodimer
Screening of suitable cationic dopants for solar absorber material CZTS/Se: A first principles study
The earth abundant and non-toxic solar absorber material kesterite Cu2ZnSn(S/Se)(4) has been studied to achieve high power conversion efficiency beyond various limitations, such as secondary phases, antisite defects, band gap adjustment and microstructure. To alleviate these hurdles, we employed screening based approach to find suitable cationic dopant that can promote the current density and the theoretical maximum upper limit of the energy conversion efficiency (P(%)) of CZTS/Se solar devices. For this task, the hybrid functional (Heyd, Scuseria and Ernzerhof, HSE06) were used to study the electronic and optical properties of cation (Al, Sb, Ga, Ba) doped CZTS/Se. Our in-depth investigation reveals that the Sb atom is suitable dopant of CZTS/CZTSe and also it has comparable bulk modulus as of pure material. The optical absorption coefficient of Sb doped CZTS/Se is considerably larger than the pure materials because of easy formation of visible range exciton due to the presence of defect state below the Fermi level, which leads to an increase in the current density and P(%). Our results demonstrate that the lower formation energy, preferable energy gap and excellent optical absorption of the Sb doped CZTS/Se make it potential component for relatively high efficient solar cells
"Narrow" Graphene Nanoribbons Made Easier by Partial Hydrogenation
It is a challenge to synthesize graphene nanoribbons (GNRs) with narrow
widths and smooth edges in large scale. Our first principles study on the
hydrogenation of GNRs shows that the hydrogenation starts from the edges of
GNRs and proceeds gradually toward the middle of the GNRs so as to maximize the
number of carbon-carbon - bonds. Furthermore, the partially
hydrogenated wide GNRs have similar electronic and magnetic properties as those
of narrow GNRs. Therefore, it is not necessary to directly produce narrow GNRs
for realistic applications because partial hydrogenation could make wide GNRs
"narrower"
Electronic Properties of Vinylene-Linked Heterocyclic Conducting Polymers: Predictive Design and Rational Guidance from DFT Calculations
The band structure and electronic properties in a series of vinylene-linked
heterocyclic conducting polymers are investigated using density functional
theory (DFT). In order to accurately calculate electronic band gaps, we utilize
hybrid functionals with fully periodic boundary conditions to understand the
effect of chemical functionalization on the electronic structure of these
materials. The use of predictive first-principles calculations coupled with
simple chemical arguments highlights the critical role that aromaticity plays
in obtaining a low band gap polymer. Contrary to some approaches which
erroneously attempt to lower the band gap by increasing the aromaticity of the
polymer backbone, we show that being aromatic (or quinoidal) in itself does not
insure a low band gap. Rather, an iterative approach which destabilizes the
ground state of the parent polymer towards the aromatic \leftrightarrow
quinoidal level-crossing on the potential energy surface is a more effective
way of lowering the band gap in these conjugated systems. Our results highlight
the use of predictive calculations guided by rational chemical intuition for
designing low band gap polymers in photovoltaic materials.Comment: Accepted by the Journal of Physical Chemistry
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Precision farming and archaeology
With a significant growth in the agricultural technology industry a vast amount of agricultural data is now being collected on farms throughout the world. Farmers aim to utilise these technologies to regularly record and manage the variation of crops and soils within their fields, to reduce inputs, increase yields and enhance environmental sustainability. In this paper we aim to highlight the variety of different data types and methodological processes involved in modern precision farming and explore how potentially interconnected these systems are with the archaeological communit
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