Accurate sample deconvolution of pooled snRNA-seq using sex-dependent gene expression patterns.

Single nucleus RNA sequencing (snRNA-seq) technology offers unprecedented resolution for studying cell type-specific gene expression patterns. However, snRNA-seq poses high costs and technical limitations, often requiring the pooling of independent biological samples and loss of individual sample-level data. Deconvolution of sample identity using inherent features would enable the incorporation of pooled barcoding and sequencing protocols, thereby increasing data throughput and analytical sample size without requiring increases in experimental sample size and sequencing costs.

Treatment Patterns and Clinical Outcomes in Patients With EGFR-Mutated Non-Small-Cell Lung Cancer After Progression on Osimertinib.

Introduction: For patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) who progress on first-line osimertinib, the optimal second-line treatment regimen after progression is not known. We sought to assess practice patterns and evaluate the association between different therapies and survival in patients with EGFR-mutated NSCLC following progression on first-line osimertinib.

Methods: Retrospective cohort study of patients who received first-line treatment with osimertinib using a population-based, multicenter nationwide electronic health record-derived deidentified database.

A human cadaveric model for venous air embolism tool development.

Purpose: A human cadaveric model combining standard lung protective mechanical ventilation and modified cardiac bypass techniques was developed to allow investigation into automated modes of detection of venous air emboli (VAE) prior to in vivo human or animal investigations.

Methods: In this study, in order to create an artificial cardiopulmonary circuit in a cadaver that could mimic VAE physiology, the direction of flow was reversed from conventional cardiac bypass. Saline was circulated in isolation through the heart and lungs as opposed to the peripheral organs by placing the venous cannula into the aorta and the arterial cannula into the inferior vena cava with selective ligation of other vessels.

Amplification and Quantitation of Telomeric Extrachromosomal Circles.

Telomeres are structures that cap the ends of linear chromosomes and play critical roles in maintaining genome integrity and establishing the replicative lifespan of cells. In stem and cancer cells, telomeres are actively elongated by either telomerase or the alternative lengthening of telomeres (ALT) pathway. This pathway is characterized by several hallmark features, including extrachromosomal C-rich circular DNAs that can be probed to assess ALT activity.

Humid tropical vertebrates are at lower risk of extinction and population decline in forests with higher structural integrity.

Reducing deforestation underpins global biodiversity conservation efforts. However, this focus on retaining forest cover overlooks the multitude of anthropogenic pressures that can degrade forest quality and imperil biodiversity. We use remotely sensed indices of tropical rainforest structural condition and associated human pressures to quantify the relative importance of forest cover, structural condition and integrity (the cumulative effect of condition and pressures) on vertebrate species extinction risk and population trends across the global humid tropics.

Morning Exercise Reduces Abdominal Fat and Blood Pressure in Women; Evening Exercise Increases Muscular Performance in Women and Lowers Blood Pressure in Men.

The ideal exercise time of day (ETOD) remains elusive regarding simultaneous effects on health and performance outcomes, especially in women. Given known sex differences in response to exercise training, this study quantified health and performance outcomes in separate cohorts of women and men adhering to different ETOD. Thirty exercise-trained women (BMI = 24 ± 3 kg/m; 42 ± 8 years) and twenty-six men (BMI = 25.

Informing conservation decisions to target private lands of highest ecological value and risk of loss.

Natural habitats on private lands are potentially important components of national biodiversity conservation strategies, yet they are being rapidly lost to development. Conservation easements and other means of protecting these habitats have expanded in use and will be most effective if they target private lands of highest biodiversity value and risk of loss. We developed a Biodiversity Conservation Priority Index (BCPI) based on ecological value and risk of habitat loss for remaining areas of natural vegetation cover (NVC) in the northwestern United States and addressed two questions: (1) Which remaining NVC on private lands is the highest priority for biodiversity conservation based on ecological value and risk of development? And (2) are conservation easements in NVC placed preferentially in locations of high biodiversity conservation priority? Drawing on the concept of ecological integrity, we integrated five metrics of ecological structure, function, and composition to quantify ecological value of NVC.

Telomerase in Cancer: Function, Regulation, and Clinical Translation.

During the process of malignant transformation, cells undergo a series of genetic, epigenetic, and phenotypic alterations, including the acquisition and propagation of genomic aberrations that impart survival and proliferative advantages. These changes are mediated in part by the induction of replicative immortality that is accompanied by active telomere elongation. Indeed, telomeres undergo dynamic changes to their lengths and higher-order structures throughout tumor formation and progression, processes overseen in most cancers by telomerase.

Early Outcomes of Scapholunate Injuries With Concomitant Distal Radius Fractures.

There is limited literature regarding the treatment of concomitant scapholunate ligament (SL) injuries in acute distal radius fractures (DRFs). We hypothesized that surgical treatment of SL injuries in adult patients with DRFs leads to improved functional outcomes. A retrospective review was made of 42 adult patients who underwent surgical treatment of a DRF with a SL injury between 2005 and 2013.

SLX4IP promotes RAP1 SUMOylation by PIAS1 to coordinate telomere maintenance through NF-κB and Notch signaling.

The maintenance of telomere length supports repetitive cell division and therefore plays a central role in cancer development and progression. Telomeres are extended by either the enzyme telomerase or the alternative lengthening of telomeres (ALT) pathway. Here, we found that the telomere-associated protein SLX4IP dictates telomere proteome composition by recruiting and activating the E3 SUMO ligase PIAS1 to the SLX4 complex.

The role of RNA processing and regulation in metastatic dormancy.

Tumor dormancy is a major contributor to the lethality of metastatic disease, especially for cancer patients who develop metastases years-to-decades after initial diagnosis. Indeed, tumor cells can disseminate during early disease stages and persist in new microenvironments at distal sites for months, years, or even decades before initiating metastatic outgrowth. This delay between primary tumor remission and metastatic relapse is known as "dormancy," during which disseminated tumor cells (DTCs) acquire quiescent states in response to intrinsic (i.

Multispectral high resolution sensor fusion for smoothing and gap-filling in the cloud.

Remote sensing optical sensors onboard operational satellites cannot have high spectral, spatial and temporal resolutions simultaneously. In addition, clouds and aerosols can adversely affect the signal contaminating the land surface observations. We present a HIghly Scalable Temporal Adaptive Reflectance Fusion Model (HISTARFM) algorithm to combine multispectral images of different sensors to reduce noise and produce monthly gap free high resolution (30 m) observations over land.

Epigenetic plasticity in metastatic dormancy: mechanisms and therapeutic implications.

The overwhelming majority of cancer-associated morbidity and mortality can be ascribed to metastasis. Metastatic disease frequently presents in a delayed fashion following initial diagnosis and treatment, requiring that disseminated cancer cells (DCCs) spread early in tumor progression and persist in a dormant state at metastatic sites. To accomplish this feat, DCCs exhibit substantial phenotypic plasticity that is mediated by the epigenetic regulation of dormancy programs in response to intrinsic (i.

SLX4IP and telomere dynamics dictate breast cancer metastasis and therapeutic responsiveness.

Metastasis is the leading cause of breast cancer-related death and poses a substantial clinical burden owing to a paucity of targeted treatment options. The clinical manifestations of metastasis occur years-to-decades after initial diagnosis and treatment because disseminated tumor cells readily evade detection and resist therapy, ultimately giving rise to recurrent disease. Using an unbiased genetic screen, we identified SLX4-interacting protein (SLX4IP) as a regulator of metastatic recurrence and established its relationship in governing telomere maintenance mechanisms (TMMs).

Stem cells, immortality, and the evolution of metastatic properties in breast cancer: telomere maintenance mechanisms and metastatic evolution.

Breast cancer is the most significant cause of cancer-related death in women around the world. The vast majority of breast cancer-associated mortality stems from metastasis, which remains an incurable disease state. Metastasis results from evolution of clones that possess the insidious properties required for dissemination and colonization of distant organs.

A non-natural nucleotide uses a specific pocket to selectively inhibit telomerase activity.

Telomerase, a unique reverse transcriptase that specifically extends the ends of linear chromosomes, is up-regulated in the vast majority of cancer cells. Here, we show that an indole nucleotide analog, 5-methylcarboxyl-indolyl-2'-deoxyriboside 5'-triphosphate (5-MeCITP), functions as an inhibitor of telomerase activity. The crystal structure of 5-MeCITP bound to the Tribolium castaneum telomerase reverse transcriptase reveals an atypical interaction, in which the nucleobase is flipped in the active site.

Determination of Fucose Concentration in a Lectin-Based Displacement Microfluidic Assay.

We compare three different methods to quantify the monosaccharide fucose in solutions using the displacement of a large glycoprotein, lactoferrin. Two microfluidic analysis methods, namely fluorescence detection of (labeled) lactoferrin as it is displaced by unlabeled fucose and the displacement of (unlabeled) lactoferrin in SPR, provide fast responses and continuous data during the experiment, theoretically providing significant information regarding the interaction kinetics between the saccharide groups and binding sites. For comparison, we also performed a static displacement ELISA.

Patterns of rangeland productivity and land ownership: Implications for conservation and management.

Rangelands cover 40-50% of the Earth's terrestrial surface. While often characterized by limited, yet variable resource availability, rangelands are vital for humans, providing numerous ecosystem goods and services. In the conterminous United States (CONUS), the dominant component of rangeland conservation is a network of public rangelands, concentrated in the west.

Estimating large carnivore populations at global scale based on spatial predictions of density and distribution - Application to the jaguar (Panthera onca).

Broad scale population estimates of declining species are desired for conservation efforts. However, for many secretive species including large carnivores, such estimates are often difficult. Based on published density estimates obtained through camera trapping, presence/absence data, and globally available predictive variables derived from satellite imagery, we modelled density and occurrence of a large carnivore, the jaguar, across the species' entire range.

Patterning Highly Conducting Conjugated Polymer Electrodes for Soft and Flexible Microelectrochemical Devices.

There is a need for soft actuators in various biomedical applications to manipulate delicate objects such as cells and tissues. Soft actuators are able to adapt to any shape and limit the stress applied to delicate objects. Conjugated polymer (CP) actuators, especially in the so-called trilayer configuration, are interesting candidates for driving such micromanipulators.

Exercise performance and physiological responses: the potential role of redox imbalance.

Increases in oxidative stress or decreases in antioxidant capacity, or redox imbalance, are known to alter physiological function and has been suggested to influence performance. To date, no study has sought to manipulate this balance in the same participants and observe the impact on physiological function and performance. Using a single-blind, placebo-controlled, and counterbalanced design, this study examined the effects of increasing free radicals, via hyperoxic exposure (FO= 1.