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 6 h 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

Long slit spectroscopy of NH2 in comets Halley, Wilson, and Nishikawa-Takamizawa-Tago

Long-slit spectra of comets Halley, Wilson and Nishikawa-Takamizawa-Tago were obtained with the 3.9 meter Anglo-Australian Telescope. Spectra of comets Halley and Wilson were obtained with the IPCS at a spectral resolution of 0.5 A and a spatial resolution of 10(exp 3) km. Spectra of comets Wilson and Nishikawa-Takamizawa-Tago were obtained with a CCD at a spectral resolution of 1.5 A and a spatial resolution of approximately 3 x 10(exp 3) km. Surface brightness profiles for NH2 were extracted from the long-slit spectra of each comet. The observed surface brightness profiles extend along the slit to approximately 6 x 10(exp 4) km from the nucleus in both sunward and tailward directions. By comparing surface distribution calculated from an appropriate coma model with observed surface brightness distributions, the photodissociation timescale of the parent molecule of NH2 can be inferred. The observed NH2 surface brightness profiles in all three comets compares well with a surface brightness profile calculated using the vectorial model, an NH3 photodissociation timescale of 7 x 10(exp 3) seconds, and an NH2 photodissociation timescale of 34,000 seconds

Response to Open Peer Commentaries on "Diagnosis By Television Documentary: Professional Responsibilities in Informal Encounters".

In presenting the situation of a health professional witnessing an instance of misdiagnosis and mistreatment in a television documentary, we hoped to stimulate discussion of the professional responsibilities of health workers in informal encounters in a rapidly changing environment comprising print, television, and more recently social media platforms. The commentaries on our article do not disappoint in this respect, providing insightful and sometimes challenging reactions to the position we outlined in response to our original case. In our reply here, we choose to focus on two themes running through all of the commentaries: (1) the distinction between axiological and deontic perspectives invoked by Salloch, and the open-endedness of the former that we see as crucial in addressing the constantly changing media landscape through which health workers may confront medical need; and (2) the role of institutional, structural, and social factors in constraining or enabling virtuous professional practice—suggesting perhaps a further need for health workers to take action directly against structural injustices that prevent them from fulfilling their professional responsibilities

Developmental stage-specific regulation of the circadian Clock by Temperature in Zebrafish

The circadian clock enables animals to adapt their physiology and behaviour in anticipation of the day-night cycle. Light and temperature represent two key environmental timing cues (zeitgebers) able to reset this mechanism and so maintain its synchronization with the environmental cycle. One key challenge is to unravel how the regulation of the clock by zeitgebers matures during early development. The zebrafish is an ideal model for studying circadian clock ontogeny since the process of development occurs ex utero in an optically transparent chorion and many tools are available for genetic analysis. However, the role played by temperature in regulating the clock during zebrafish development is poorly understood. Here, we have established a clock-regulated luciferase reporter transgenic zebrafish line (Tg (−3.1) per1b::luc) to study the effects of temperature on clock entrainment. We reveal that under complete darkness, from an early developmental stage onwards (48 to 72 hpf), exposure to temperature cycles is a prerequisite for the establishment of self-sustaining rhythms of zfper1b, zfaanat2, and zfirbp expression and also for circadian cell cycle rhythms. Furthermore, we show that following the 5–9 somite stage, the expression of zfper1b is regulated by acute temperature shifts

Jewish Dimensions in Modern Visual Culture: Antisemitism, Assimilation, Affirmation

Gavriel Rosenfeld is a contributing author, “Postwar Jewish Architecture and the Memory of the Holocaust”, pp.285-302. Book description: A fascinating look at key aspects of visual culture in modern Jewish history In modern western history, the cultural and social developments of modernism have long been associated with Jews. Usually this has been a negative association: the perceived breakdown of traditional norms was blamed on Jewish influence in politics, society, and the arts. Throughout Europe, Jews were viewed as carriers of industrialized and cosmopolitan developments that threatened to undermine a cherished way of life. This anthology speaks to this issue through the lens of modernist visual production including paintings, posters, sculpture, and architecture. Essays by scholars from the U.S. and Israel confront the contradictory impulses that modernism’s interaction with Jewish culture provoked. Discussing how religion, class, race, and political alignments were used to provide attacks on modern art, the scholars also comment on visual responses to anti-semitism and the mainstream success of artists in the U.S. and Israel since World War II.https://digitalcommons.fairfield.edu/history-books/1013/thumbnail.jp

Alternative splicing coupled mRNA decay shapes the temperature‐dependent 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 pathways—including 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

Bandgap Change of Carbon Nanotubes: Effect of Small Tensile and Torsional Strain

We use a simple picture based on the $\pi$ 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 $(n-m) \bmod 3$ 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 $\pi$ orbital results are valid.Comment: Revised. Method explained in detai

Magnetic Boron Nitride Nanoribbons with Tunable Electronic Properties

We present theoretical evidence, based on total-energy first-principles calculations, of the existence of spin-polarized states well localized at and extended along the edges of bare zigzag boron nitride nanoribbons. Our calculations predict that all the magnetic configurations studied in this work are thermally accessible at room temperature and present an energy gap. In particular, we show that the high spin state, with a magnetic moment of 1 $\mu_B$ at each edge atom, presents a rich spectrum of electronic behaviors as it can be controlled by applying an external electric field in order to obtain metallic $\leftrightarrow$ semiconducting $\leftrightarrow$ half-metallic transitions.Comment: 12 pages, 5 figures, 2 table

"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 $\pi$-$\pi$ 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"