Elucidating gene expression programs within a cell-specific manner is a grand challenge for biologists. Harder still is the ability to have kinetic control over such experiments. Metabolic labeling with bioorthogonally-functionalized metabolic intermediates provides a means to profile RNA expression in a cell-specific manner, but there is still a lack of kinetic resolution. Herein we present the synthesis and evaluation of photocaged metabolic uracil intermediates. We compare the photo-decaging properties and demonstrate their utility in metabolic labeling experiments in a cell-specific manner. We anticipate that our approach will have far-reaching impact as it provides control over tagging of nascent RNA.

Despite evidence globally of the heavy HIV burden among sex workers (SWs) as well as other poor health outcomes, including violence, SWs are often excluded from accessing voluntary, confidential and non-coercive health services, including HIV prevention, treatment, care and support. This study therefore assessed the prevalence and association with regular HIV testing among street- and off-street SWs in Vancouver, Canada. Cross-sectional baseline data were used from a longitudinal cohort known as "An Evaluation of Sex Worker's Health Access" (AESHA; January 2010-July 2012). This cohort included youth and adult SWs (aged 14+ years). We used multivariable logistic regression to assess the relationship between explanatory variables and having a recent HIV test (in the last year). Of the 435 seronegative SWs included, 67.1% reported having a recent HIV test. In multivariable logistic regression analysis, having a recent HIV test remained significantly independently associated with elevated odds of inconsistent condom use with clients [adjusted (multivariable) odds ratios, AOR: 2.59, 95% confidence intervals [95% CIs]: 1.17-5.78], injecting drugs (AOR: 2.33, 95% CIs: 1.17-4.18) and contact with a mobile HIV prevention programme (AOR: 1.76, 95% CIs: 1.09-2.84) within the last six months. Reduced odds of having a recent HIV test was also significantly associated with being a migrant/new immigrant to Canada (AOR: 0.33, 95% CIs: 0.19-0.56) and having a language barrier to health care access (AOR: 0.26, 95% CIs: 0.09-0.73). Our results highlight successes of reaching SWs at high risk of HIV through drug and sexual pathways. To maximize the effectiveness of including HIV testing as part of comprehensive HIV prevention and care to SWs, increased mobile outreach and safer-environment interventions that facilitate access to voluntary, confidential and non-coercive HIV testing remain a critical priority, in addition to culturally safe services with language support.

The helical pitch formed by organic molecules, such as the α-helix of proteins, usually requires hydrogen bonding between chiral units and long-range positional order. It was recently found that certain liquid crystal oligomers can have a twist-bend nematic (NTB) phase with nanoscale heliconical structure without hydrogen bonding, molecular chirality or positional order. To understand the nature of this unique structure, here we present hard and resonant tender X-ray scattering studies of two novel sulfur containing dimer materials. We simultaneously measure the temperature dependences of the helical pitch and the correlation length of both the helical and positional order. In addition to an unexpected strong variation of the pitch with the length of the spacer connecting the monomer units, we find that at the transition to the NTB phase the positional correlation length drops. The helical structure was found not only in the NTB phase but observed even in the upper range of a smectic phase that forms just below the NTB state. The coexistence of smectic layering and the heliconical order indicates a layered (SmATB) phase wherein the rigid units of the dimers are tilted with respect to the smectic layer normal in order to accommodate the bent conformation of the dimers and the tilt direction rotates along the heliconical axis.

UNLABELLED: As the closest living relatives of animals, choanoflagellates offer insights into the ancestry of animal cell physiology. Here, we report the isolation and characterization of a colonial choanoflagellate from Mono Lake, California. The choanoflagellate forms large spherical colonies that are an order of magnitude larger than those formed by the closely related choanoflagellate Salpingoeca rosetta. In cultures maintained in the laboratory, the lumen of the spherical colony is filled with a branched network of extracellular matrix and colonized by bacteria, including diverse Gammaproteobacteria and Alphaproteobacteria. We propose to erect Barroeca monosierra gen. nov., sp. nov. Hake, Burkhardt, Richter, and King to accommodate this extremophile choanoflagellate. The physical association between bacteria and B. monosierra in culture presents a new experimental model for investigating interactions among bacteria and eukaryotes. Future work will investigate the nature of these interactions in wild populations and the mechanisms underpinning the colonization of B. monosierra spheres by bacteria. IMPORTANCE: The diversity of organisms that live in the extreme environment of Mono Lake (California, USA) is limited. We sought to investigate whether the closest living relatives of animals, the choanoflagellates, exist in Mono Lake, a hypersaline, alkaline, arsenic-rich environment. We repeatedly isolated members of a new species of choanoflagellate, which we have named Barroeca monosierra. Characterization of B. monosierra revealed that it forms large spherical colonies containing diverse co-isolated bacteria, providing an opportunity to investigate mechanisms underlying physical associations between eukaryotes and bacteria.

The human microbiome plays an important role in our health and identifying factors associated with microbiome composition provides insights into inherent disease mechanisms. By amplifying and sequencing the marker genes in high-throughput sequencing, with highly similar sequences binned together, we obtain operational taxonomic units (OTUs) profiles for each subject. Due to the high-dimensionality and nonnormality features of the OTUs, the measure of diversity is introduced as a summarization at the microbial community level, including the distance-based beta-diversity between individuals. Analyses of such between-subject attributes are not amenable to the predominant within-subject-based statistical paradigm, such as t-tests and linear regression. In this paper, we propose a new approach to model beta-diversity as a response within a regression setting by utilizing the functional response models (FRMs), a class of semiparametric models for between- as well as within-subject attributes. The new approach not only addresses limitations of current methods for beta-diversity with cross-sectional data, but also provides a premise for extending the approach to longitudinal and other clustered data in the future. The proposed approach is illustrated with both real and simulated data.

We report a measurement of the E-mode polarization power spectrum of the cosmic microwave background (CMB) using 150 GHz data taken from 2014 July to 2016 December with the POLARBEAR experiment. We reach an effective polarization map noise level of 32 mK-arcmin across an observation area of 670 square degrees. We measure the EE power spectrum over the angular multipole range 500 ≤ ℓ < 3000, tracing the third to seventh acoustic peaks with high sensitivity. The statistical uncertainty on E-mode bandpowers is ∼2.3 μK2 at ℓ ∼ 1000, with a systematic uncertainty of 0.5 mK2. The data are consistent with the standard ΛCDM cosmological model with a probability-to-exceed of 0.38. We combine recent CMB E-mode measurements and make inferences about cosmological parameters in ΛCDM as well as in extensions to ΛCDM. Adding the ground-based CMB polarization measurements to the Planck data set reduces the uncertainty on the Hubble constant by a factor of 1.2 to H0 = 67.20 ±0.57 km s- Mpc- 1 1. When allowing the number of relativistic species (Neff ) to vary, we find Neff = 2.94 ±0.16, which is in good agreement with the standard value of 3.046. Instead allowing the primordial helium abundance (YHe) to vary, the data favor YHe = 0.248 ±0.012. This is very close to the expectation of 0.2467 from big bang nucleosynthesis. When varying both YHe and Neff , we find Neff = 2.70 ±0.26 and YHe = 0.262 ±0.015.

The polarization of the atmosphere has been a long-standing concern for ground-based experiments targeting cosmic microwave background (CMB) polarization. Ice crystals in upper tropospheric clouds scatter thermal radiation from the ground and produce a horizontally polarized signal. We report a detailed analysis of the cloud signal using a ground-based CMB experiment, Polarbear, located at the Atacama desert in Chile and observing at 150 GHz. We observe horizontally polarized temporal increases of low-frequency fluctuations ("polarized bursts," hereafter) of ≲0.1 K when clouds appear in a webcam monitoring the telescope and the sky. The hypothesis of no correlation between polarized bursts and clouds is rejected with >24σ statistical significance using three years of data. We consider many other possibilities including instrumental and environmental effects, and find no reasons other than clouds that can explain the data better. We also discuss the impact of the cloud polarization on future ground-based CMB polarization experiments.

Long non-coding RNAs (lncRNAs) have a critical role in cancer initiation and progression, and thus may mediate oncogenic or tumor suppressing effects, as well as be a new class of cancer therapeutic targets. We performed high-throughput sequencing of RNA (RNA-seq) to investigate the expression level of lncRNAs and protein-coding genes in 30 esophageal samples, comprised of 15 esophageal squamous cell carcinoma (ESCC) samples and their 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE, to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. A number of known onco-lncRNA and many putative novel ones were effectively identified by URW-LPE. Importantly, we identified lncRNA625 as a novel regulator of ESCC cell proliferation, invasion and migration. ESCC patients with high lncRNA625 expression had significantly shorter survival time than those with low expression. LncRNA625 also showed specific prognostic value for patients with metastatic ESCC. Finally, we identified E1A-binding protein p300 (EP300) as a downstream executor of lncRNA625-induced transcriptional responses. These findings establish a catalog of novel cancer-associated functional lncRNAs, which will promote our understanding of lncRNA-mediated regulation in this malignancy.