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Malaria parasite translocon structure and mechanism of effector export.
The putative Plasmodium translocon of exported proteins (PTEX) is essential for transport of malarial effector proteins across a parasite-encasing vacuolar membrane into host erythrocytes, but the mechanism of this process remains unknown. Here we show that PTEX is a bona fide translocon by determining structures of the PTEX core complex at near-atomic resolution using cryo-electron microscopy. We isolated the endogenous PTEX core complex containing EXP2, PTEX150 and HSP101 from Plasmodium falciparum in the 'engaged' and 'resetting' states of endogenous cargo translocation using epitope tags inserted using the CRISPR-Cas9 system. In the structures, EXP2 and PTEX150 interdigitate to form a static, funnel-shaped pseudo-seven-fold-symmetric protein-conducting channel spanning the vacuolar membrane. The spiral-shaped AAA+ HSP101 hexamer is tethered above this funnel, and undergoes pronounced compaction that allows three of six tyrosine-bearing pore loops lining the HSP101 channel to dissociate from the cargo, resetting the translocon for the next threading cycle. Our work reveals the mechanism of P. falciparum effector export, and will inform structure-based design of drugs targeting this unique translocon
Cultural Adaptation of Recipes
Building upon the considerable advances in Large Language Models (LLMs), we
are now equipped to address more sophisticated tasks demanding a nuanced
understanding of cross-cultural contexts. A key example is recipe adaptation,
which goes beyond simple translation to include a grasp of ingredients,
culinary techniques, and dietary preferences specific to a given culture. We
introduce a new task involving the translation and cultural adaptation of
recipes between Chinese and English-speaking cuisines. To support this
investigation, we present CulturalRecipes, a unique dataset comprised of
automatically paired recipes written in Mandarin Chinese and English. This
dataset is further enriched with a human-written and curated test set. In this
intricate task of cross-cultural recipe adaptation, we evaluate the performance
of various methods, including GPT-4 and other LLMs, traditional machine
translation, and information retrieval techniques. Our comprehensive analysis
includes both automatic and human evaluation metrics. While GPT-4 exhibits
impressive abilities in adapting Chinese recipes into English, it still lags
behind human expertise when translating English recipes into Chinese. This
underscores the multifaceted nature of cultural adaptations. We anticipate that
these insights will significantly contribute to future research on
culturally-aware language models and their practical application in culturally
diverse contexts.Comment: Accepted to TAC
Neoplastic cell enrichment of tumor tissues using coring and laser microdissection for proteomic and genomic analyses of pancreatic ductal adenocarcinoma
BACKGROUND: The identification of differentially expressed tumor-associated proteins and genomic alterations driving neoplasia is critical in the development of clinical assays to detect cancers and forms the foundation for understanding cancer biology. One of the challenges in the analysis of pancreatic ductal adenocarcinoma (PDAC) is the low neoplastic cellularity and heterogeneous composition of bulk tumors. To enrich neoplastic cells from bulk tumor tissue, coring, and laser microdissection (LMD) sampling techniques have been employed. In this study, we assessed the protein and KRAS mutation changes associated with samples obtained by these enrichment techniques and evaluated the fraction of neoplastic cells in PDAC for proteomic and genomic analyses.
METHODS: Three fresh frozen PDAC tumors and their tumor-matched normal adjacent tissues (NATs) were obtained from three sampling techniques using bulk, coring, and LMD; and analyzed by TMT-based quantitative proteomics. The protein profiles and characterizations of differentially expressed proteins in three sampling groups were determined. These three PDACs and samples of five additional PDACs obtained by the same three sampling techniques were also subjected to genomic analysis to characterize KRAS mutations.
RESULTS: The neoplastic cellularity of eight PDACs ranged from less than 10% to over 80% based on morphological review. Distinctive proteomic patterns and abundances of certain tumor-associated proteins were revealed when comparing the tumors and NATs by different sampling techniques. Coring and bulk tissues had comparable proteome profiles, while LMD samples had the most distinct proteome composition compared to bulk tissues. Further genomic analysis of bulk, cored, or LMD samples demonstrated that KRAS mutations were significantly enriched in LMD samples while coring was less effective in enriching for KRAS mutations when bulk tissues contained a relatively low neoplastic cellularity.
CONCLUSIONS: In addition to bulk tissues, samples from LMD and coring techniques can be used for proteogenomic studies. The greatest enrichment of neoplastic cellularity is obtained with the LMD technique
Photometry of Variable Stars from Dome A, Antarctica
Dome A on the Antarctic plateau is likely one of the best observing sites on
Earth thanks to the excellent atmospheric conditions present at the site during
the long polar winter night. We present high-cadence time-series aperture
photometry of 10,000 stars with i<14.5 mag located in a 23 square-degree region
centered on the south celestial pole. The photometry was obtained with one of
the CSTAR telescopes during 128 days of the 2008 Antarctic winter.
We used this photometric data set to derive site statistics for Dome A and to
search for variable stars. Thanks to the nearly-uninterrupted synoptic
coverage, we find 6 times as many variables as previous surveys with similar
magnitude limits. We detected 157 variable stars, of which 55% are
unclassified, 27% are likely binaries and 17% are likely pulsating stars. The
latter category includes delta Scuti, gamma Doradus and RR Lyrae variables. One
variable may be a transiting exoplanet.Comment: Accepted for publication in the Astronomical Journal. PDF version
with high-resolution figures available at
http://faculty.physics.tamu.edu/lmacri/papers/wang11.pd
MSIsensor-ct: Microsatellite instability detection using cfDNA sequencing data
MOTIVATION: Microsatellite instability (MSI) is a promising biomarker for cancer prognosis and chemosensitivity. Techniques are rapidly evolving for the detection of MSI from tumor-normal paired or tumor-only sequencing data. However, tumor tissues are often insufficient, unavailable, or otherwise difficult to procure. Increasing clinical evidence indicates the enormous potential of plasma circulating cell-free DNA (cfNDA) technology as a noninvasive MSI detection approach.
RESULTS: We developed MSIsensor-ct, a bioinformatics tool based on a machine learning protocol, dedicated to detecting MSI status using cfDNA sequencing data with a potential stable MSIscore threshold of 20%. Evaluation of MSIsensor-ct on independent testing datasets with various levels of circulating tumor DNA (ctDNA) and sequencing depth showed 100% accuracy within the limit of detection (LOD) of 0.05% ctDNA content. MSIsensor-ct requires only BAM files as input, rendering it user-friendly and readily integrated into next generation sequencing (NGS) analysis pipelines.
AVAILABILITY: MSIsensor-ct is freely available at https://github.com/niu-lab/MSIsensor-ct.
SUPPLEMENTARY INFORMATION: Supplementary data are available at Briefings in Bioinformatics online
Gattini 2010: Cutting Edge Science at the Bottom of the World
The high altitude Antarctic sites of Dome A and the South Pole offer intriguing locations for future large scale optical astronomical
Observatories. The Gattini project was created to measure the optical
sky brightness, large area cloud cover and aurora of the winter-time
sky above such high altitude Antarctic sites. The Gattini-DomeA camera
was installed on the PLATO instrument module as part of the Chinese-led
traverse to the highest point on the Antarctic plateau in January 2008.
This single automated wide field camera contains a suite of Bessel
photometric filters (B, V, R) and a long-pass red filter for the
detection and monitoring of OH emission. We have in hand one complete
winter-time dataset (2009) from the camera that was recently returned
in April 2010.
The Gattini-South Pole UV camera is a wide-field optical camera that in
2011 will measure for the first time the UV properties of the
winter-time sky above the South Pole dark sector. This unique dataset
will consist of frequent images taken in both broadband U and B filters
in addition to high resolution (R similar to 5000) long slit
spectroscopy over a narrow bandwidth of the central field. The camera
is a proof of concept for the 2m-class Antarctic Cosmic Web Imager
telescope, a dedicated experiment to directly detect and map the
redshifted lyman alpha fluorescence or Cosmic Web emission we believe
possible due to the unique geographical qualities of the site.
We present the current status of both projects
Proteogenomic characterization of endometrial carcinoma
We undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences of perturbations to the p53 and Wnt/β-catenin pathways, identified a potential role for circRNAs in the epithelial-mesenchymal transition, and provided new information about proteomic markers of clinical and genomic tumor subgroups, including relationships to known druggable pathways. An extensive genome-wide acetylation survey yielded insights into regulatory mechanisms linking Wnt signaling and histone acetylation. We also characterized aspects of the tumor immune landscape, including immunogenic alterations, neoantigens, common cancer/testis antigens, and the immune microenvironment, all of which can inform immunotherapy decisions. Collectively, our multi-omic analyses provide a valuable resource for researchers and clinicians, identify new molecular associations of potential mechanistic significance in the development of endometrial cancers, and suggest novel approaches for identifying potential therapeutic targets
Determination of strain rate dependent through-thickness tensile properties of textile reinforced thermoplastic composites using L-shaped beam specimens
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