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Abstract Protein kinases are critical components of a myriad biological processes and strongly associated with various diseases. While kinase research has been a point of focus in biomedical research for several decades, a large portion of the kinome is still considered understudied or “dark,” because prior research is targeted towards a subset of kinases with well-established roles in cellular processes. We present an empirical and in-silico hybrid workflow to extend the functional knowledge of understudied kinases. Utilizing multiplex peptide activity arrays and robust in-silico analyses, we extended the functional knowledge of five dark tyrosine kinases (AATK, EPHA6, INSRR, LTK, TNK1) and explored their roles in schizophrenia, Alzheimer’s dementia (AD), and major depressive disorder (MDD). Using this hybrid approach, we identified 195 novel kinase-substrate interactions with variable degrees of affinity and linked extended functional networks for these kinases to biological processes that are impaired in psychiatric and neurological disorders. Biochemical assays and mass spectrometry were used to confirm a putative substrate of EPHA6, an understudied dark tyrosine kinase. We examined the EPHA6 network and knowledgebase in schizophrenia using reporter peptides identified and validated from the multi-plex array with high affinity for phosphorylation by EPHA6. Identification and confirmation of putative substrates for understudied kinases provides a wealth of actionable information for the development of new drug treatments as well as exploration of the pathophysiology of disease states using signaling network approaches.

Objectives: Deep venous thrombosis (DVT) is a known surgical complication that can lead to pulmonary embolism with subsequent morbidity and mortality. The incidence of DVT following coronary artery bypass grafting is unclear. Prophylaxis regimens vary and some guidelines advocate against use of routine chemoprophylaxis in patients at low-moderate risk for venous thromboembolism. We utilized postoperative lower extremity venous ultrasound to determine the incidence of DVT following coronary artery bypass grafting in patients with low- to moderate-risk of venous thromboembolism receiving aggressive postoperative DVT prophylaxis. Methods: This is a single-center, retrospective study of all patients who underwent coronary artery bypass grafting between April 2022 and January 2023. All patients who completed postoperative venous ultrasound of the bilateral lower extremities were initially included. Patients who underwent concurrent valve or aortic surgery, were at high risk of venous thromboembolism, or were receiving anticoagulation therapy for nonvenous thromboembolism indications were excluded. The primary outcome was in-hospital incidence of DVT. Secondary outcomes were rates of mortality, postoperative bleeding, and thromboembolic events from discharge to 30 days postoperatively and from 30 days to 3 months postoperatively. Results: No DVTs were observed in 211 included patients. In hospital, there were 3 significant bleeding events and 1 stroke. Following discharge there were 3 additional bleeding events, 1 death, 1 transient ischemic attack, and 1 pulmonary embolism. Conclusions: We observed a 0% rate of DVT in low- to moderate-risk patients undergoing isolated coronary artery bypass grafting and receiving a comprehensive DVT prophylaxis regimen. In hospital bleeding and other thromboembolic event rates were 2.84% and 0.47% respectively.

Cyanobacterial Harmful Algal Blooms (CyanoHABs) occur when colonies of photosynthetic bacteria called cyanobacteria grow out of control, usually in warm, nutrient-rich, slow-moving waters. They are becoming increasingly prevalent around the world and release harmful toxins called cyanotoxins into bodies of water, which negatively affect human and ecological health. One such cyanotoxin is microcystin, with microcystin-leucine arginine (MC-LR) being the most widespread. Exposure to MC-LR inhibits serine and threonine protein phosphatase 1 and 2A in humans, causing a myriad of health problems. Fortunately, certain naturally occurring bacteria may be able to degrade MC-LR and reverse its effects. Mice were separated into five experimental groups based on three types of pre-treatments (control drinking water/vehicle, probiotic-supplemented drinking water, and heat-inactivated probiotic-supplemented drinking water) as well as two types of exposures (microcystin-LR and water/vehicle). RNA was extracted from kidneys for sequencing because MC-LR exacerbates kidney disease. Gene expression data were analyzed with 3 Pod Reports, an R package that produces a three-part report consisting of Gene Set Enrichment Analysis (GSEA), EnrichR, and integrative LINCS (iLINCS). MC-LR exposure was associated with upregulated cellular respiration and metabolism pathways and downregulated transcription pathways. Probiotic pre-treatment combined with MC-LR exposure was associated with upregulated lipoprotein particle pathways and downregulated respiration and ribosome pathways. Overall, the probiotic mixture corrected the transcriptional profile resulting from MC-LR exposure. Future high yield pathways that could be targeted for therapeutic benefit include VEGFR inhibitors and increased expression of renal kidney indicator genes such as EGFR.

On 2022 September 26, the Double Asteroid Redirection Test (DART) mission was the first successful demonstration of a kinetic impactor for planetary defense. The DART mission utilized a novel autonomous data processing pipeline architecture to quickly produce and analyze the quality of raw and calibrated images from the camera mounted on board the spacecraft. Optimization of the data processing pipeline allowed the final 150 images prior to impact to be calibrated and delivered to the Investigation Team and the press within 15 minutes of acquisition. A data quality analysis pipeline allowed for rapid identification of detector misconfigurations, missing data, and other adverse events. DART data products, along with data from LICIACube and data from ground observatories, used common file formats to facilitate the development of analysis and archiving software. This architecture is described for future missions with large volumes of data and an emphasis on quick-turnaround applications such as planetary defense.

The world’s first planetary defense test mission was carried out in late 2022 by NASA’s Double Asteroid Redirection Test (DART) mission. The main DART spacecraft, which was accompanied by the ASI-provided LICIACube cubesat, intentionally impacted Dimorphos, the smaller secondary of the near-Earth object binary system (65803) Didymos, on 2022 September 26. The impact released a large amount of ejecta, which, combined with the spacecraft’s momentum, produced the observed 33 ± 1 minute period change that was subsequently observed from ground-based telescopes. The DART mission, in addition to having successfully changed the orbital period of Dimorphos, also activated the asteroid as a result of the impact but under known conditions, unlike other impacts on asteroids. We have conducted long-term monitoring over 5 months following the impact with the Las Cumbres Observatory Global Telescope (LCOGT) network and Magdalena Ridge Observatory (MRO). This was supplemented by almost 3 months of more sparsely sampled data, primarily from educational users of the LCOGT network during the period from 2022 July 5 to 2022 September 25, prior to the impact date of 2022 September 26. Here we report the observations of the Didymos system and DART impact ejecta with the telescopes of the LCOGT network from T+1.93 days to T+151.3 days after impact, and we study the evolving morphology of the ejecta cloud and evolving tail over the entire length of the data set. In addition, we combined these intensive data sets with the earlier sparse observations over the ∼90 days prior to impact to derive a new disk-integrated phase function model using the H , G _1 , G _2 parameterization.

On 2022 September 26, the Double Asteroid Redirection Test (DART) spacecraft impacted Dimorphos, the satellite of binary near-Earth asteroid (65803) Didymos. This demonstrated the efficacy of a kinetic impactor for planetary defense by changing the orbital period of Dimorphos by 33 minutes. Measuring the period change relied heavily on a coordinated campaign of lightcurve photometry designed to detect mutual events (occultations and eclipses) as a direct probe of the satellite’s orbital period. A total of 28 telescopes contributed 224 individual lightcurves during the impact apparition from 2022 July to 2023 February. We focus here on decomposable lightcurves, i.e., those from which mutual events could be extracted. We describe our process of lightcurve decomposition and use that to release the full data set for future analysis. We leverage these data to place constraints on the postimpact evolution of ejecta. The measured depths of mutual events relative to models showed that the ejecta became optically thin within the first ∼1 day after impact and then faded with a decay time of about 25 days. The bulk magnitude of the system showed that ejecta no longer contributed measurable brightness enhancement after about 20 days postimpact. This bulk photometric behavior was not well represented by an HG photometric model. An HG _1 G _2 model did fit the data well across a wide range of phase angles. Lastly, we note the presence of an ejecta tail through at least 2023 March. Its persistence implied ongoing escape of ejecta from the system many months after DART impact.

Thermoelectric power generation from coal requires large amounts of water, much of which is used for wet flue gas desulfurization (wFGD) systems that minimize sulfur emissions, and consequently, acid rain. The microbial communities in wFGDs and throughout thermoelectric power plants can influence system performance, waste processing, and the long term stewardship of residual wastes. Any microorganisms that survive in wFGD slurries must tolerate high total dissolved solids concentrations (TDS) and temperatures (50–60°C), but the inocula for wFGDs are typically from fresh surface waters (e.g., lakes or rivers) of low TDS and temperatures, and whose activity might be limited under the physicochemically extreme conditions of the wFGD. To determine the extents of microbiological activities in wFGDs, we examined the microbial activities and communities associated with three wFGDs. O2 consumption rates of three wFGD slurries were optimal at 55°C, and living cells could be detected microscopically, indicating that living and active communities of organisms were present in the wFGD and could metabolize at the high temperature of the wFGD. A 16S rRNA gene-based survey revealed that the wFGD-associated microbial communities included taxa attributable to both thermophilic and mesophilic lineages. Metatranscriptomic analysis of one of the wFGDs indicated an abundance of active Burholderiaceae and several Gammaproteobacteria, and production of transcripts associated with carbohydrate metabolism, osmotic stress response, as well as phage, prophages, and transposable elements. These results illustrate that microbial activities can be sustained in physicochemically extreme wFGDs, and these activities may influence the performance and environmental impacts of thermoelectric power plants.

Snow influences land–atmosphere interactions in snow-dominated areas, and snow melt contributes to basin streamflows. However, estimating snowpack properties such as the snow depth (SD) and snow water equivalent (SWE) from land surface model simulations remains a challenge. This is, in part, due to uncertainties in the atmospheric forcing variables, which propagate into hydrological model predictions. This study implements the Weather Research and Forecasting (WRF)-Hydro framework with the Noah-Multiparameterization (Noah-MP) land surface model in the NOAA’s National Water Model (NWM) version 2.0 configuration to estimate snow in a single column and subsequently the streamflow across the Aroostook River’s sub-basins in Maine for water years (WY) 2014–2016. This study evaluates how differences between two atmospheric forcing datasets, the North American Land Data Assimilation version 2 (NLDAS-2) and in situ (Station), translate into differences in the simulation of snow. NLDAS-2 was used as the meteorological forcing in the retrospective NWM 2.0 simulations. The results from the single-column study showed that differences in the simulated SWE and SD were linked to differences in the 2 m air temperature (T2m), which influenced the precipitation partitioning of rain and snow, as parameterized in Noah-MP. The negative mean bias of −0.7 K (during the accumulation period) in T2m for NLDAS-2, compared to the Station forcing, was a major factor that contributed to the positive mean bias of +52 mm on average in the peak SWE in the NLDAS-2-forced Noah-MP simulation during the study period. The higher T2m values at the Station led to higher sensible heat fluxes towards the snowpack, which led to a higher amount of net energy at the snow’s surface and melt events during the accumulation season in Station-forced Noah-MP simulations. The results from the retrospective NWM version 2.0′s simulation in the basin showed that the streamflow estimates were closer to the United States Geological Survey gage observations at the two larger sub-basins (NSE = 0.9), which were mostly forested, compared to the two smaller sub-basins (NSE ≥ 0.4), which had more agricultural land-use. This study also showed that the spring snowmelt timing was captured quite well by the timing of the decline in the simulated SWE and SD, providing an early indication of melt in most sub-basins. The simulated fractional snow cover area (fSCA) however provided less information about the changes in snow or onset of snowmelt as it was mostly binary (full snow cover in winter), which differed from the more realistic fSCA values shown by the Moderate Resolution Imaging Spectroradiometer.

Abstract The Agriculture Conservation Planning Framework (ACPF) applies high‐spatial resolution soils and topographic data, now available for many areas of the United States, to precisely locate opportunities for the placement of conservation practices in agricultural watersheds. Application of the ACPF, developed in midwestern landscapes, to watersheds in the eastern United States represents both opportunity and challenge to conservation planning. Based on experience in applying ACPF to eight watersheds in the eastern United States, from Vermont to North Carolina, we assess the toolbox's application in the eastern United States through the lens of strengths, weaknesses, opportunities, and threats (SWOT) analysis framework. We see a great future for the ACPF, but its adoption and utility require interaction with scientists and conservation planners familiar with the region to avoid misapplication and ensure appropriate adaptation and interpretation.

Summary: Salivary proteins are essential for maintaining health in the oral cavity and proximal digestive tract, and they serve as potential diagnostic markers for monitoring human health and disease. However, their precise organ origins remain unclear. Through transcriptomic analysis of major adult and fetal salivary glands and integration with the saliva proteome, the blood plasma proteome, and transcriptomes of 28+ organs, we link human saliva proteins to their source, identify salivary-gland-specific genes, and uncover fetal- and adult-specific gene repertoires. Our results also provide insights into the degree of gene retention during gland maturation and suggest that functional diversity among adult gland types is driven by specific dosage combinations of hundreds of transcriptional regulators rather than by a few gland-specific factors. Finally, we demonstrate the heterogeneity of the human acinar cell lineage. Our results pave the way for future investigations into glandular biology and pathology, as well as saliva’s use as a diagnostic fluid.

Damage to an ectodermal-mesodermal interface like that in the equine hoof and human finger nail bed can permanently alter tissue structure and associated function. The purpose of this study was to establish and validate in vitro culture of primary progenitor cell isolates from the ectodermal-mesodermal tissue junction in equine hooves, the stratum internum, with and without chronic inflammation known to contribute to lifelong tissue defects. The following were evaluated in hoof stratum internum cell isolates up to 5 cell passages (P): expansion capacity by cell doublings and doubling time; plasticity with multi-lineage differentiation and colony-forming unit (CFU) frequency percentage; immunophenotype with immunocytochemistry and flow cytometry; gene expression with RT-PCR; and ultrastructure with transmission electron microscopy. The presence of keratin (K)14, 15 and K19 as well as cluster of differentiation (CD)44 and CD29 was determined in situ with immunohistochemistry. To confirm in vivo extracellular matrix (ECM) formation, cell-scaffold (polyethylene glycol/poly-L-lactic acid and tricalcium phosphate/hydroxyapatite) constructs were evaluated with scanning electron microscopy 9 weeks after implantation in athymic mice. Cultured cells had characteristic progenitor cell morphology, expansion, CFU frequency percentage and adipocytic, osteoblastic, and neurocytic differentiation capacity. CD44, CD29, K14, K15 and K19 proteins were present in native hoof stratum internum. Cultured cells also expressed K15, K19 and desmogleins 1 and 3. Gene expression of CD105, CD44, K14, K15, sex determining region Y-box 2 (SOX2) and octamer-binding transcription factor 4 (OCT4) was confirmed in vitro. Cultured cells had large, eccentric nuclei, elongated mitochondria, and intracellular vacuoles. Scaffold implants with cells contained fibrous ECM 9 weeks after implantation compared to little or none on acellular scaffolds. In vitro expansion and plasticity and in vivo ECM deposition of heterogeneous, immature cell isolates from the ectodermal-mesodermal tissue interface of normal and chronically inflamed hooves are typical of primary cell isolates from other adult tissues, and they appear to have both mesodermal and ectodermal qualities in vitro. These results establish a unique cell culture model to target preventative and restorative therapies for ectodermal-mesodermal tissue junctions.

Environmental change is thought to have driven the recent emergence of Lyme disease in Europe. Using a decade of human disease incidence data across a large area in Norway, Mysterud et al.show that incidence correlates with deer population, but that deer population plays a limited role in recent disease emergence.

Patients with liver disease and portal hypertension who have had surgical formation of an abdominal stoma are at risk of developing peristomal varices. These varices have a predilection for bleeding. Ideally, portal decompression via TIPS procedure is performed, with or without direct embolization of the bleeding varix. When TIPS is not an appropriate option due to significant liver disease and hepatic encephalopathy there are other approaches to treat peristomal variceal hemorrhage. We report the embolization of such a varix via direct percutaneous puncture under ultrasound guidance when portal decompression was not an appropriate option.

Budding yeast centromeres are sequence-defined point centromeres and are, unlike in many other organisms, not embedded in heterochromatin. Here we show that Fun30, a poorly understood SWI/SNF-like chromatin remodeling factor conserved in humans, promotes point centromere function through the formation of correct chromatin architecture at centromeres. Our determination of the genome-wide binding and nucleosome positioning properties of Fun30 shows that this enzyme is consistently enriched over centromeres and that a majority of CENs show Fun30-dependent changes in flanking nucleosome position and/or CEN core micrococcal nuclease accessibility. Fun30 deletion leads to defects in histone variant Htz1 occupancy genome-wide, including at and around most centromeres. FUN30 genetically interacts with CSE4, coding for the centromere-specific variant of histone H3, and counteracts the detrimental effect of transcription through centromeres on chromosome segregation and suppresses transcriptional noise over centromere CEN3. Previous work has shown a requirement for fission yeast and mammalian homologs of Fun30 in heterochromatin assembly. As centromeres in budding yeast are not embedded in heterochromatin, our findings indicate a direct role of Fun30 in centromere chromatin by promoting correct chromatin architecture.

Thermal infrared sensing from space is a well-developed field, but mixed pixels pose a problem for many applications. We present a field study in Dana Meadows, Yosemite National Park, California to scale from point (~2-m resolution) to aerial (~5-m resolution gridded, 1 km × 6 km extent) to satellite (MODIS, ~1000-m resolution, global extent) observations. We demonstrate how multiple thermal bands on MODIS can be used to separate snow and forest temperatures and determine the fractional snow-covered area (fSCA) over a 3 km × 3 km array of 9 MODIS grid cells. During the day, visible, near-infrared, and shortwave-infrared bands provide a first guess of fSCA and help to constrain the solution. This technique, which has estimated errors

The article is a book review of "Blood and Lightning: On Becoming a Tattooer" by Dustin Kiskaddon. The book explores the world of tattooing as a form of embodied labor and examines the craft of tattooing through a sociological lens. The author, who became a tattooist himself, provides a unique perspective on the subject and discusses key events in the contemporary tattoo industry, such as the impact of the Black Lives Matter movement and the #MeToo reckoning. The book also delves into the racial dynamics within tattoo culture and the challenges faced by tattooers. Overall, "Blood and Lightning" offers an in-depth and immersive study of the sociology of tattooing and the sociology of work. [Extracted from the article]