An unbiased approach elucidates variation in (S)-(+)-linalool, a context-specific mediator of a tri-trophic interaction in wild tobacco

Plant volatile organic compounds (VOCs) mediate many interactions, and the function of common VOCs is especially likely to depend on ecological context. We used a genetic mapping population of wild tobacco, Nicotiana attenuata, originating from a cross of 2 natural accessions from Arizona and Utah, separated by the Grand Canyon, to dissect genetic variation controlling VOCs. Herbivory-induced leaf terpenoid emissions varied substantially, while green leaf volatile emissions were similar. In a field experiment, only emissions of linalool, a common VOC, correlated significantly with predation of the herbivore Manduca sexta by native predators. Using quantitative trait locus mapping and genome mining,we identified an (S)-(+)-linalool synthase (NaLIS). Genome resequencing, gene cloning, and activity assays revealed that the presence/absence of a 766-bp sequence in NaLIS underlies the variation of linalool emissions in 26 natural accessions. We manipulated linalool emissions and composition by ectopically expressing linalool synthases for both enantiomers, (S)-(+)- and (R)-(−)-linalool, reported to oppositely affect M. sexta oviposition, in the Arizona and Utah accessions.We used these lines to test ovipositingmoths in increasingly complex environments. The enantiomers had opposite effects on oviposition preference, but themagnitude of the effect depended strongly both on plant genetic background, and complexity of the bioassay environment. Our study reveals that the emission of linalool, a common VOC, differs by orders-of-magnitude among geographically interspersed conspecific plants due to allelic variation in a linalool synthase, and that the response of a specialist herbivore to linalool depends on enantiomer, plant genotype, and environmental complexity

Lipidomics signature in post-COVID patient sera and its influence on the prolonged inflammatory response

Background: The ongoing issues with post-COVID conditions (PCC), where symptoms persist long after the initial infection, highlight the need for research into blood lipid changes in these patients. While most studies focus on the acute phase of COVID-19, there's a significant lack of information on the lipidomic changes that occur in the later stages of the disease. Addressing this knowledge gap is critical for understanding the long-term effects of COVID-19 and could be key to developing personalized treatments for those suffering from PCC. Methods: We employed untargeted lipidomics to analyze plasma samples from 147 PCC patients, assessing nearly 400 polar lipids. Data mining (DM) and machine learning (ML) tools were utilized to decode the results and ascertain significant lipidomic patterns. Results: The study uncovered substantial changes in various lipid subclasses, presenting a detailed profile of the polar lipid fraction in PCC patients. These alterations correlated with ongoing inflammation and immune response. Notably, there were elevated levels of lysophosphatidylglycerols (LPGs) and phosphatidylethanolamines (PEs), and reduced levels of lysophosphatidylcholines (LPCs), suggesting these as potential lipid biomarkers for PCC. The lipidomic signatures indicated specific anionic lipid changes, implicating antimicrobial peptides (AMPs) in inflammation. Associations between particular medications and symptoms were also suggested. Classification models, such as multinomial regression (MR) and random forest (RF), successfully differentiated between symptomatic and asymptomatic PCC groups using lipidomic profiles. Conclusions: The study's groundbreaking discovery of specific lipidomic disruptions in PCC patients marks a significant stride in the quest to comprehend and combat this condition. The identified lipid biomarkers not only pave the way for novel diagnostic tools but also hold the promise to tailor individualized therapeutic strategies, potentially revolutionizing the clinical approach to managing PCC and improving patient care

The olfactory coreceptor IR8a governs larval feces-mediated competition avoidance in a hawkmoth

Finding a suitable oviposition site is a challenging task for a gravid female moth. At the same time, it is of paramount importance considering the limited capability of most caterpillars to relocate to alternative host plants. The hawkmoth, Manduca sexta, oviposits on solanaceous plants. Larvae hatching on a plant that is already attacked by conspecific caterpillars face food competition. Here, we show that feces from conspecific caterpillars are sufficient to deter a female M. sexta from ovipositing on a plant. Furthermore, we not only identify the responsible compound in the feces but also localize the population of sensory neurons that governs the female’s avoidance. Hence, our work increases the understanding of how animals cope with a competitive environment

A GPU-based Correlator X-engine Implemented on the CHIME Pathfinder

We present the design and implementation of a custom GPU-based compute cluster that provides the correlation X-engine of the CHIME Pathfinder radio telescope. It is among the largest such systems in operation, correlating 32,896 baselines (256 inputs) over 400MHz of radio bandwidth. Making heavy use of consumer-grade parts and a custom software stack, the system was developed at a small fraction of the cost of comparable installations. Unlike existing GPU backends, this system is built around OpenCL kernels running on consumer-level AMD GPUs, taking advantage of low-cost hardware and leveraging packed integer operations to double algorithmic efficiency. The system achieves the required 105TOPS in a 10kW power envelope, making it among the most power-efficient X-engines in use today.Comment: 6 pages, 5 figures. Accepted by IEEE ASAP 201

FGFR1 amplification or overexpression and hormonal resistance in luminal breast cancer: rationale for a triple blockade of ER, CDK4/6, and FGFR1.

BACKGROUND: FGFR1 amplification, but not overexpression, has been related to adverse prognosis in hormone-positive breast cancer (HRPBC). Whether FGFR1 overexpression and amplification are correlated, what is their distribution among luminal A or B HRPBC, and if there is a potential different prognostic role for amplification and overexpression are currently unknown features. The role of FGFR1 inhibitors in HRPBC is also unclear. METHODS: FGFR1 amplification (FISH) and overexpression (RNAscope) were investigated in a N = 251 HRPBC patients cohort and the METABRIC cohort; effects on survival and FISH-RNAscope concordance were determined. We generated hormonal deprivation resistant (LTED-R) and FGFR1-overexpressing cell line variants of the ER+ MCF7 and T47-D and the ER+, FGFR1-amplified HCC1428 cell lines. The role of ER, CDK4/6, and/or FGFR1 blockade alone or in combinations in Rb phosphorylation, cell cycle, and survival were studied. RESULTS: FGFR1 overexpression and amplification was non-concordant in > 20% of the patients, but both were associated to a similar relapse risk (~ 2.5-fold; P < 0.05). FGFR1 amplification or overexpression occurred regardless of the luminal subtype, but the incidence was higher in luminal B (16.3%) than A (6.6%) tumors; P < 0.05. The Kappa index for overexpression and amplification was 0.69 (P < 0.001). Twenty-four per cent of the patients showed either amplification and/or overexpression of FGFR1, what was associated to a hazard ratio for relapse of 2.6 (95% CI 1.44-4.62, P < 0.001). In vitro, hormonal deprivation led to FGFR1 overexpression. Primary FGFR1 amplification, engineered mRNA overexpression, or LTED-R-acquired FGFR1 overexpression led to resistance against hormonotherapy alone or in combination with the CDK4/6 inhibitor palbociclib. Blocking FGFR1 with the kinase-inhibitor rogaratinib led to suppression of Rb phosphorylation, abrogation of the cell cycle, and resistance-reversion in all FGFR1 models. CONCLUSIONS: FGFR1 amplification and overexpression are associated to similar adverse prognosis in hormone-positive breast cancer. Capturing all the patients with adverse prognosis-linked FGFR1 aberrations requires assessing both features. Hormonal deprivation leads to FGFR1 overexpression, and FGFR1 overexpression and/or amplification are associated with resistance to hormonal monotherapy or in combination with palbociclib. Both resistances are reverted with triple ER, CDK4/6, and FGFR1 blockade

Calibrating CHIME, A New Radio Interferometer to Probe Dark Energy

The Canadian Hydrogen Intensity Mapping Experiment (CHIME) is a transit interferometer currently being built at the Dominion Radio Astrophysical Observatory (DRAO) in Penticton, BC, Canada. We will use CHIME to map neutral hydrogen in the frequency range 400 -- 800\,MHz over half of the sky, producing a measurement of baryon acoustic oscillations (BAO) at redshifts between 0.8 -- 2.5 to probe dark energy. We have deployed a pathfinder version of CHIME that will yield constraints on the BAO power spectrum and provide a test-bed for our calibration scheme. I will discuss the CHIME calibration requirements and describe instrumentation we are developing to meet these requirements

Canadian Hydrogen Intensity Mapping Experiment (CHIME) Pathfinder

A pathfinder version of CHIME (the Canadian Hydrogen Intensity Mapping Experiment) is currently being commissioned at the Dominion Radio Astrophysical Observatory (DRAO) in Penticton, BC. The instrument is a hybrid cylindrical interferometer designed to measure the large scale neutral hydrogen power spectrum across the redshift range 0.8 to 2.5. The power spectrum will be used to measure the baryon acoustic oscillation (BAO) scale across this poorly probed redshift range where dark energy becomes a significant contributor to the evolution of the Universe. The instrument revives the cylinder design in radio astronomy with a wide field survey as a primary goal. Modern low-noise amplifiers and digital processing remove the necessity for the analog beamforming that characterized previous designs. The Pathfinder consists of two cylinders 37\,m long by 20\,m wide oriented north-south for a total collecting area of 1,500 square meters. The cylinders are stationary with no moving parts, and form a transit instrument with an instantaneous field of view of $\sim$100\,degrees by 1-2\,degrees. Each CHIME Pathfinder cylinder has a feedline with 64 dual polarization feeds placed every $\sim$30\,cm which Nyquist sample the north-south sky over much of the frequency band. The signals from each dual-polarization feed are independently amplified, filtered to 400-800\,MHz, and directly sampled at 800\,MSps using 8 bits. The correlator is an FX design, where the Fourier transform channelization is performed in FPGAs, which are interfaced to a set of GPUs that compute the correlation matrix. The CHIME Pathfinder is a 1/10th scale prototype version of CHIME and is designed to detect the BAO feature and constrain the distance-redshift relation.Comment: 20 pages, 12 figures. submitted to Proc. SPIE, Astronomical Telescopes + Instrumentation (2014