The RNA polymerase II C-terminal domain-interacting domain of yeast Nrd1 contributes to the choice of termination pathway and couples to RNA processing by the nuclear exosome

The RNA polymerase II (RNApII) C-terminal domain (CTD)- interacting domain (CID) proteins are involved in two distinct RNApII termination pathways and recognize different phosphorylated forms of CTD. To investigate the role of differential CTD-CID interactions in the choice of termination pathway, we altered the CTD-binding specificity of Nrd1 by domain swapping. Nrd1 with the CID from Rtt103 (Nrd1(CIDRtt103)) causes read-through transcription at many genes, but can also trigger termination where multiple Nrd1/Nab3-binding sites and the Ser(P)-2 CTD co-exist. Therefore, CTD-CID interactions target specific termination complexes to help choose an RNApII termination pathway. Interactions of Nrd1 with bothCTDand nascent transcripts contribute to efficient termination by the Nrd1 complex. Surprisingly, replacing the Nrd1 CID with that from Rtt103 reduces binding to Rrp6/Trf4, and RNA transcripts terminated by Nrd1(CIDRtt103) are predominantly processed by core exosome. Thus, the Nrd1 CID couples Ser(P)-5 CTD not only to termination, but also to RNA processing by the nuclear exosome

Methods for reduced cost and lower sample prep volumes for genetic analysis applications

As the cost of NGS has decreased, the library preparation cost has become a larger portion of the total expenditure. This is especially true for high-throughput applications, such as single-cell analysis. Therefore, there is a need to develop methods that can not only study the transcriptomes of single cells, but can also feasibly analyze large numbers of single cells. Miniaturizing the sample preparation volume provides the opportunity for significant cost savings. Using TTP Labtech’s mosquito liquid handlers, reagent and sample quantities can be scaled down to picogram values

An unusual anatomical variant of the left phrenic nerve encircling the transverse cervical artery

During educational dissection of cadavers, we encountered anatomical variability of the left phrenic nerve. In this cadaver, nerve fibers from C3 and C4 descended and crossed behind the transverse cervical artery (TCA), a branch of the thyrocervical trunk, at the level of the anterior scalene muscle. On the other hand, nerve fibers from C5 descended obliquely above the TCA and then joined the fibers from C3-4 on the medial side of the anterior scalene muscle to form the phrenic nerve. To our knowledge, the encircling of the TCA by the left phrenic nerve in the neck has not yet been reported and may pose as a potential risk for nerve compression during movement of the neck. We discuss several types of anatomical variants of the phrenic nerve and the associated risk during thorax and neck dissection procedures

Atomistic origins of high-performance in hybrid halide perovskite solar cells

The performance of organometallic perovskite solar cells has rapidly surpassed that of both conventional dye-sensitised and organic photovoltaics. High power conversion efficiency can be realised in both mesoporous and thin-film device architectures. We address the origin of this success in the context of the materials chemistry and physics of the bulk perovskite as described by electronic structure calculations. In addition to the basic optoelectronic properties essential for an efficient photovoltaic device (spectrally suitable band gap, high optical absorption, low carrier effective masses), the materials are structurally and compositionally flexible. As we show, hybrid perovskites exhibit spontaneous electric polarisation; we also suggest ways in which this can be tuned through judicious choice of the organic cation. The presence of ferroelectric domains will result in internal junctions that may aid separation of photoexcited electron and hole pairs, and reduction of recombination through segregation of charge carriers. The combination of high dielectric constant and low effective mass promotes both Wannier-Mott exciton separation and effective ionisation of donor and acceptor defects. The photoferroic effect could be exploited in nanostructured films to generate a higher open circuit voltage and may contribute to the current-voltage hysteresis observed in perovskite solar cells.Comment: 6 pages, 5 figure

Effects of purinergic stimulation on ciliary beat frequency and chloride secretion in sinusitis

OBJECTIVES: We aimed to identify the functional abnormality of sinusitis-affected mucosa by observing the responsiveness of the mucosa to purinergic stimulation after the onset of sinusitis and during the recovery period. We also aimed to identify possible beneficial effects of purinergic agonists on sinusitis. METHODS: A rabbit sinusitis model was developed by blocking maxillary ostia. Sinus mucosae were harvested immediately and 1 and 4 weeks after reopening the ostia. We measured chloride secretion and ciliary beat frequencies responding to purinergic stimulation. RESULTS: The increases of ciliary beat frequency by adenosine triphosphate (100 micromol/L) were 3.2%+/-8.5%, 7.9%+/-2.3%, and 12.2%+/-1.9% immediately after establishment of sinusitis and 1 week and 4 weeks after reopening of ostia, respectively. Chloride secretion stimulated by adenosine triphosphate also showed gradual increase during the recovery period. Grossly, the mucosae appeared to have normalized in 80% (4 of 5) after 4 weeks; however, functional and microscopic improvements were still incomplete. CONCLUSIONS: Mucosal functions, assessed by increase of ciliary activity and ion secretion by purinergic stimulation, and microscopic findings showed gradual but incomplete recovery after 4 weeks of recovery, in contrast to the gross normalization. Purinergic agonists may have beneficial effects on sinusitis by stimulating decreased ciliary motility and chloride secretion in sinusitis

Acoustical characterisation of carbon nanotube-loaded polydimethylsiloxane used for optical ultrasound generation

An optical ultrasound generator was used to perform broadband (2-35 MHz) acoustical characterisation measurements of a nanocomposite comprising carbon nanotubes (CNT) and polydimethylsiloxane (PDMS), a composite that is commonly used as optical ultrasound generator. Samples consisting of either pure PDMS or CNT-loaded PDMS were characterised to determine the influence of CNTs on the speed of sound and power-law acoustic attenuation parameters. A small weight fraction (<; 1.8%) of added CNTs was found to yield a prominent increase in the exponent of the power law, resulting in a significant increase in acoustic attenuation at higher frequencies. The speed of sound was found to be nearly identical, however. These results could prove useful in the numerical modelling and design of future optical ultrasound sources based on CNT-loaded PDMS

Prevalence of Depression among Households in Three Capital Cities of Pakistan: Need to Revise the Mental Health Policy

BACKGROUND: Pakistan, among the other developing countries, has a higher prevalence rate of depression because of the current social adversities. There is, thus, a great need for systematic studies on prevalence of depression. The current study aims at exploring the prevalence of depression among households in three capital cities of Pakistan. METHODOLOGY AND PRINCIPAL FINDINGS: A sample of N = 820 was randomly selected, and a cross sectional telephone-based study was conducted for a duration of six months. It was found that there was a regional variation in prevalence rates for depression among the three cities. Lahore had the highest number of depressives (53.4%), as compared to Quetta (43.9%) and Karachi (35.7%). Middle age, female gender and secondary school level of education were significantly associated with depression among the study group. CONCLUSIONS/SIGNIFICANCE: The different rates of prevalence among the three cities could be attributed to local cultural influence, geographical locations and social adversities. There is a need for revision of existing health policy by the government

Regulation of the let-7a-3 Promoter by NF-κB

Changes in microRNA expression have been linked to a wide array of pathological states. However, little is known about the regulation of microRNA expression. The let-7 microRNA is a tumor suppressor that inhibits cellular proliferation and promotes differentiation, and is frequently lost in tumors. We investigated the transcriptional regulation of two let-7 family members, let-7a-3 and let-7b, which form a microRNA cluster and are located 864 bp apart on chromosome 22q13.31. Previous reports present conflicting data on the role of the NF-κB transcription factor in regulating let-7. We cloned three fragments upstream of the let-7a-3/let-7b miRNA genomic region into a plasmid containing a luciferase reporter gene. Ectopic expression of subunits of NF-κB (p50 or p65/RelA) significantly increased luciferase activity in HeLa, 293, 293T and 3T3 cells, indicating that the let-7a-3/let-7b promoter is highly responsive to NF-κB. Mutation of a putative NF-κB binding site at bp −833 reduced basal promoter activity and decreased promoter activity in the presence of p50 or p65 overexpression. Mutation of a second putative binding site, at bp −947 also decreased promoter activity basally and in response to p65 induction, indicating that both sites contribute to NF-κB responsiveness. While the levels of the endogenous primary let-7a and let-7b transcript were induced in response to NF-κB overexpression in 293T cells, the levels of fully processed, mature let-7a and let-7b miRNAs did not increase. Instead, levels of Lin-28B, a protein that blocks let-7 maturation, were induced by NF-κB. Increased Lin-28B levels could contribute to the lack of an increase in mature let-7a and let-7b. Our results suggest that the final biological outcome of NF-κB activation on let-7 expression may vary depending upon the cellular context. We discuss our results in the context of NF-κB activity in repressing self-renewal and promoting differentiation

Broken mirror symmetry in excitonic response of reconstructed domains in twisted MoSe2_2/MoSe2_2 bilayers

Structural engineering of van der Waals heterostructures via stacking and twisting has recently been used to create moir\'e superlattices, enabling the realization of new optical and electronic properties in solid-state systems. In particular, moir\'e lattices in twisted bilayers of transition metal dichalcogenides (TMDs) have been shown to lead to exciton trapping, host Mott insulating and superconducting states, and act as unique Hubbard systems whose correlated electronic states can be detected and manipulated optically. Structurally, these twisted heterostructures also feature atomic reconstruction and domain formation. Unfortunately, due to the nanoscale sizes (~10 nm) of typical moir\'e domains, the effects of atomic reconstruction on the electronic and excitonic properties of these heterostructures could not be investigated systematically and have often been ignored. Here, we use near-0$^o$ twist angle MoSe$_2$/MoSe$_2$ bilayers with large rhombohedral AB/BA domains to directly probe excitonic properties of individual domains with far-field optics. We show that this system features broken mirror/inversion symmetry, with the AB and BA domains supporting interlayer excitons with out-of-plane (z) electric dipole moments in opposite directions. The dipole orientation of ground-state $\Gamma$-K interlayer excitons (X$_{I,1}$) can be flipped with electric fields, while higher-energy K-K interlayer excitons (X$_{I,2}$) undergo field-asymmetric hybridization with intralayer K-K excitons (X$_0$). Our study reveals the profound impacts of crystal symmetry on TMD excitons and points to new avenues for realizing topologically nontrivial systems, exotic metasurfaces, collective excitonic phases, and quantum emitter arrays via domain-pattern engineering.Comment: 29 pages, 4 figures in main text, 6 figures in supplementary informatio