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Teeth are often the first structures that anatomists and paleontologists examine to understand the ecology and morphology of feeding, both because teeth are highly specialized structures that provide precise information, and because they are among the best and most commonly preserved fossils. Unfortunately, many fragmentary fossil and recent specimens lack teeth, and some come from edentulous individuals and taxa, as in mysticete (baleen) whales. In our broad comparative review, we survey non-dental osteological features that, due to size, shape, arrangement, and surface features reflecting muscle attachments, provide useful clues to general or specific aspects of prey capture, intraoral transport, processing, or swallowing. We focus on hyoid, palatal, and pterygoid bones, mandibular symphyses and processes such as the coronoid, and the temporal fossa and zygomatic arch, as well as adjacent cranial bones relating to oral and pharyngeal anatomy. These bones relate to muscles of five general locations especially indicative of feeding: mandibular, hyoid, tongue, pharyngeal, and facial regions. Together these bones and muscles affect feeding and related activities including suckling and breathing. We discuss osteological correlates that provide special relevance to key transitions in cetacean evolutionary history, such as the shift from predominantly terrestrial to aquatic feeding, the shift from typical mammalian mastication to swallowing prey entirely or nearly whole, and the separation of respiratory and digestive passages. We also point to examples of modern specialists in these anatomical optima for different modes of prey capture, intraoral transport, processing, and swallowing. Although we focus on cetaceans, our approach is broadly relevant to all vertebrates, notably other marine tetrapods.

There is evidence that contaminants can transform at the elevated temperatures of thermal remediation; however, the contribution of redox active minerals to transformation has not been investigated. Three redox active minerals (

Groundwater dependency is increasing globally, while millions of potentially contaminated sites are yet to be characterized for contamination levels. In particular, groundwater contamination due to light nonaqueous phase liquids (LNAPLs) continues to be a global challenge. Mathematical approaches (i.e., analytical, semi-analytical, empirical, numerical) are preferred for an initial site assessment to circumvent the high characterization costs and limited site data availability. However, the site-specific nature of contamination restricts the generalization of any single approach. Hence, the requirement is for an easy-to-use computing interface that provides site-specific data management, the selection and use of multiple-model interfaces for computing, and site characterization, with extension for the latest models as they become available. This work provides one such interface called CAST or Contamination Assessment and Site-management Tool. CAST is an open-source browser-based (online/offline) tool that provides an interface for six different analytical models (e.g., BIOSCREEN-AT), a MODFLOW based numerical model, and two empirical models (including a hybrid numerical-analytical model). Additionally, CAST includes interfaces for site data management, their evaluation, and scenario-based modeling. CAST's development is in a modular format, which simplifies the addition of new computing or data interfaces. Furthermore, the entire code-base of CAST is based on open-source (dominantly Python programming) libraries and standards. This further simplifies the modification or extension of this tool. This paper introduces CAST, its different computing, and data management interfaces and provides examples of the tool's functionality primarily for the initial evaluation of contaminated sites.

Purpose A life cycle assessment was performed for the production of a total mixed ration (TMR) fed to finishing feedlot cattle in California, USA. The goal was to determine the climate change impact of the feed supply chain associated with the production of 1 kg finishing TMR (kg CO2e/kg TMR). A secondary goal was to compare the climate change impact of feed versus finished beef (kg CO2e/kg live weight). Methods The TMR was based on feeds commonly fed to finishing cattle in California. The Livestock Environmental Assessment and Performance Partnership (LEAP) guidelines were followed for inventory data collection. System boundaries included the production of crops and feed additives, transportation of TMR components, and compound feed production. Data were sourced from national databases and Ecoinvent™ unit process data. Three scenarios were assessed as a result of allocation at the transportation step: Scenario A (100% empty return load); Scenario B (50% empty return load): and Scenario C (0% empty return load). Energy, mass, and economic allocation, and system expansion of dried distillers grain solubles (DDGS) were assessed for sensitivity analysis. Total feedlot emission data from Stackhouse-Lawson et al. (2012) were used to compare to impacts of TMR production. Results Total emissions were determined to be 0.630 kg CO2e/kg TMR for Scenario A, 0.576 kg CO2e/kg TMR for Scenario B, and 0.521 kg CO2e/kg TMR for Scenario C. Corn production, transportation, and liquid premix production were primary contributors to the life cycle impacts of TMR production. Mass-based allocation of DDGS was found to have the most significant effect on overall impacts of the finishing TMR, with a 42% increase in life cycle emissions compared to other allocation methods. For Scenario A, feed used in Angus feedlot production contributed to 76% of total Angus feedlot emissions. Additionally, feed used in Holstein feedlot production contributed to 58% of total Holstein feedlot emissions. Conclusions and recommendations The present study demonstrates a need to better assess the feed supply chain of feedlot beef production in order to accurately identify areas that have the most significant impacts on overall emissions. This may aid in minimizing impacts associated with feed production and, by extension, beef production. The present study may also serve to inform future decisions for improvements or alterations of the LEAP guidelines.

The long-acting lipoglycopeptides (LGPs) dalbavancin and oritavancin are semisynthetic antimicrobials with broad and potent activity against Gram-positive bacterial pathogens. While they are approved by the Food and Drug Administration for acute bacterial skin and soft tissue infections, their pharmacological properties suggest a potential role of these agents for the treatment of deep-seated and severe infections, such as bloodstream and bone and joint infections. The use of these antimicrobials is particularly appealing when prolonged therapy, early discharge, and avoidance of long-term intravascular catheter access are desirable or when multidrug-resistant bacteria are suspected. This review describes the current evidence for the use of oritavancin and dalbavancin in the treatment of invasive infections, as well as the hurdles that are preventing their optimal use. Moreover, this review discusses the current knowledge gaps that need to be filled to understand the potential role of LGPs in highly needed clinical scenarios and the ongoing clinical studies that aim to address these voids in the upcoming years.

Spatial concentration gradients of antibiotics are prevalent in the natural environment. Yet, the microbial response in these heterogeneous systems remains poorly understood. We used a microfluidic reactor to create an artificial microscopic ecosystem that generates diffusive gradients of solutes across interconnected microenvironments. With this reactor, we showed that chemotaxis toward a soluble electron acceptor (nitrate) allowed Shewanella oneidensis MR-1 to inhabit and sustain metabolic activity in highly toxic regions of the antibiotic ciprofloxacin (>80× minimum inhibitory concentration, MIC). Acquired antibiotic resistance was not observed for cells extracted from the reactor, so we explored the role of transient adaptive resistance by probing multidrug resistance (MDR) efflux pumps, ancient elements that are important for bacterial physiology and virulence. Accordingly, we constructed an efflux pump deficient mutant (∆mexF) and used resistance-nodulation-division (RND) efflux pump inhibitors (EPIs). While batch results showed the importance of RND efflux pumps for microbial survival, microfluidic studies indicated that these pumps were not necessary for survival in antibiotic gradients. Our work contributes to an emerging body of knowledge deciphering the effects of antibiotic spatial heterogeneity on microorganisms and highlights differences of microbial response in these systems versus well-mixed batch conditions.

Appeals to human nature are ubiquitous, yet historically many have proven ill-founded. Why? How might frequent errors be remedied towards building a more robust and reliable scientific study of human nature? Our aim is neither to advance specific scientific or philosophical claims about human nature, nor to proscribe or eliminate such claims. Rather, we articulate through examples the types of errors that frequently arise in this field, towards improving the rigor of the scientific and social studies. We seek to analyze such claims rhetorically, cognitively, and epistemically. Namely, how do we think about human nature? Claims about human nature, we show, are susceptible to widely exhibited deficits in cognitive tendencies such as framing, confirmation bias, satisficing, and teleological perspectives, as well as motivated reasoning. Such missteps foster methodological, empirical, and psychological mistakes and biases. Specifically, they promote the naturalizing error, whereby cultural ideology and values are projected onto an apparently objective description of nature. Concrete remedies are offered to aid scientists in conducting and reporting their research goals and findings more responsibly and effectively (relevant also to educators and other communicators who convey these findings publicly). Recommendations include acknowledging that human nature claims are often context-dependent, seeking multiple critical perspectives, and explicitly labeling uncertainties.

Background Increasing multidrug resistance rates in Neisseria gonorrhoeae have raised concerns and an urgent call for new antibiotics for treatment of gonorrhoea. Several decades of subdued drug development in this field and the recent failures of two new antibiotics to show non-inferiority compared with the current first-line antibiotics ceftriaxone plus azithromycin highlight the need for improved preclinical tools to predict clinical outcome of new drugs in the development process. Objectives To summarize current pharmacokinetic/pharmacodynamic (PK/PD) knowledge and dose-finding strategies for antibiotics against gonorrhoea. Sources Literature review of published papers and discussions by global experts at a special workshop on this topic. Content We review current knowledge of gonococcal specific PK/PD principles and provide an update on new in vitro and in vivo models to correlate drug exposure with clinical outcome, and identify challenges and gaps in gonococcal therapeutic research. Implications Identifying the ideal antimicrobial agent and dose for treating uncomplicated urogenital and pharyngeal gonococcal disease requires appropriate validated non-clinical PK/PD models. Recent advances in adapting in vitro and in vivo models for use in gonorrhoea are an important step for enabling the development of new drugs with reduced risk of failure in Phase 3 clinical development and diminish the risk of emergence of resistance.

A parallel-plate thin-layer (PPTL) flow reactor with potential control and custom-made cathode of Pd–In modified activated carbon cloth was developed for electrocatalytic removal of nitrite from wa...

PURPOSE Leiomyosarcoma (LMS) harbors frequent mutations in TP53 and RB1 but few actionable genomic alterations. Here, we searched for recurrent actionable genomic alterations in LMS that occur in the absence of common untreatable oncogenic drivers. METHODS Tissues from 276,645 unique advanced cancers, including 2,570 uterine and soft tissue LMS, were sequenced by hybrid-capture–based next-generation DNA and RNA sequencing/comprehensive genomic profiling of up to 406 genes. We characterized clinicopathologic features of relevant patient cases. RESULTS Overall, 77 LMS exhibited homozygous copy loss of CDKN2C at chromosome 1p32.3 (3.0% of LMS). Genomic alterations (GAs) in TP53, RB1, and ATRX were rare compared with the remainder of the LMS cohort (11.7% v 73.4%, 0% v 54.5%, 2.6% v 24.5%, respectively; all P < .0001). CDKN2C-null LMS patient cases were significantly enriched for GAs in CIC (40.3% v 1.4%) at 19q13.2, CDKN2A (46.8% v 7.0%), and RAD51B (16.9% v 1.7%; all P < .0001). Chromosome arm-level aneuploidy analysis of available LMS patient cases (n = 1,284) found that 81% (58 of 72) of CDKN2C-null LMS exhibited 1p/19q-codeletion, a significant enrichment compared with 5.1% in the remainder of the LMS cohort ( P < .0001). In total, 99% of CDKN2C-null LMS were in women; the median age was 61 years at surgery (range, 36-81 years). Fifty-five patient cases were uterine primary, four were nonuterine, and the remaining 18 were of uncertain primary site. Sixty percent of cases showed at least focal epithelioid variant histology. Most patients had advanced-stage disease, with 62% of confirmed uterine primary LMS at International Federation of Gynecology and Obstetrics stage IVB. We further validated our findings in two publicly available datasets: The Cancer Genome Atlas and the Project GENIE initiative. CONCLUSION CDKN2C-null LMS defines a genomically distinct tumor that may have prognostic and/or therapeutic clinical implications, including possible use of specific cyclin-dependent kinase inhibitors.

PURPOSE Vulvar squamous cell carcinoma (vSCC) encompasses two predominant variants: one associated with detectable high-risk strains of human papillomavirus (hrHPV) and a second form often occurring in the context of chronic dermatitis in postmenopausal women. Genomic assessment of a large-scale cohort of patients with aggressive vSCC may identify distinct mutational signatures. MATERIALS AND METHODS Tumor samples from a total of 280 patients with vSCC underwent hybridization capture with analysis of up to 406 cancer-related genes. Human papillomavirus (HPV) sequences were detected by de novo assembly of nonhuman sequencing reads and aligned to the RefSeq database. Immunohistochemistry for programmed death-ligand 1 (PD-L1) was assessed. RESULTS One hundred two of 280 vSCCs (36%) contained hrHPV sequences, predominantly HPV 16 (88%). The HPV-positive (HPV+) group was significantly younger (median age, 59 v 64 years; P = .001). Compared with HPV-negative (HPV–) vSCCs, HPV+ tumors showed more frequent pathogenic alterations in PIK3CA (31% v 16%; P = .004), PTEN (14% v 2%; P < .0001), EP300 (14% v 1%; P < .0001), STK11 (14% v 1%; P < .0001), AR (5% v 0%; P = .006), and FBXW7 (10% v 3%; P = .03). In contrast, HPV– vSCCs showed more alterations in TP53 (83% v 6%; P < .0001), TERTp (71% v 9%; P < .0001), CDKN2A (55% v 2%; P < .0001), CCND1 amplification (22% v 2%; P < .0001), FAT1 (25% v 4%; P < .0001), NOTCH1 (19% v 6%; P = .002), and EGFR amplification (11% v 0%; P < .0001), as well as a higher rate of 9p24.1 ( PDL1/PDL2) amplification (5% v 1%) and PD-L1 immunohistochemistry high-positive tumor staining (33% v 9%; P = .04). CONCLUSION Comprehensive molecular profiles of vSCC vary considerably with hrHPV status and may inform patient selection into clinical trials. Sixty-one percent of HPV+ vSCCs had a pathogenic alteration in the PI3K/mTOR pathway, whereas HPV– vSCCs showed alterations in TP53, TERTp, CDKN2A, CCND1, and EGFR, and biomarkers associated with responsiveness to immunotherapy.

A patient with end-stage renal disease received 2 doses of dalbavancin for methicillin-resistant Staphylococcus aureus (MRSA) arteriovenous fistula infection and presented 5 weeks later with infective endocarditis secondary to vancomycin, daptomycin, and dalbavancin nonsusceptible MRSA. Resistance was associated with walK and scrA mutations, reduced long-chain lipid content, and reduced membrane fluidity.

Objectives Tedizolid is an oxazolidinone antimicrobial with activity against Gram-positive bacteria, including MRSA. Tedizolid resistance is uncommon and tedizolid’s capacity to select for cross-resistance to other antimicrobials is incompletely understood. The objective of this study was to further explore the phenotypic and genetic basis of tedizolid resistance in MRSA. Methods We selected for tedizolid resistance in an MRSA laboratory strain, N315, by serial passage until an isolate with an MIC ≥1 log2 dilution above the breakpoint for resistance (≥2 mg/L) was recovered. This isolate was subjected to WGS and susceptibility to a panel of related and unrelated antimicrobials was tested in order to determine cross-resistance. Homology modelling was performed to evaluate the potential impact of the mutation on target protein function. Results After 10 days of serial passage we recovered a phenotypically stable mutant with a tedizolid MIC of 4 mg/L. WGS revealed only one single nucleotide variant (A1345G) in rpoB, corresponding to amino acid substitution D449N. MICs of linezolid, chloramphenicol, retapamulin and quinupristin/dalfopristin increased by ≥2 log2 dilutions, suggesting the emergence of the so-called ‘PhLOPSa’ resistance phenotype. Susceptibility to other drugs, including rifampicin, was largely unchanged. Homology models revealed that the mutated residue of RNA polymerase would be unlikely to directly affect oxazolidinone action. Conclusions To the best of our knowledge, this is the first time that an rpoB mutation has been implicated in resistance to PhLOPSa antimicrobials. The mechanism of resistance remains unclear, but is likely indirect, involving σ-factor binding or other alterations in transcriptional regulation.

Nitrate (NO3–) has impacted more groundwater supplies than any other pollutant in the world. It is currently removed at water treatment plants by ion exchange, which is effective but comes at a ste...

History is littered with scientifically ill-founded claims about human nature. They frequently appear in normative contexts, projecting ideology or values onto nature (what we call the naturalizing error). In considering a remedy, we adopt a naturalized epistemology approach to how we think about human nature. The “nature” in “human nature” fosters unproductive essentialist thinking, epitomized in the adage “a tiger cannot change its stripes.” Universalist, fixist, and teleological perspectives each erode epistemic reasoning and blur the distinction between normative and descriptive justification. We articulate strategies to guide more responsible claims about human nature in science and science communication.

Nitrite (NO2–) is the primary reduction product of nitrate (NO3–), which is the most predominant contaminant in global freshwater. Both species present major environmental challenges; NO2– is also ...

Nitrite (NO2–) is an abundant contaminant in nature that threatens human health. A catalytic process that converts NO2– to less harmful products has been proven to be an effective strategy for NO2–...

Extant cetaceans (whales, dolphins, and porpoises) and their extinct ancestors offer some of the strongest and best-known examples of macroevolutionary transition as well as microevolutionary adaptation. Unlike most reviews of cetacean evolution, which are intended to chronicle the timeline of cetacean ancestry, document the current knowledge of cetacean adaptations, or simply validate the brute fact of evolution, this review is instead intended to demonstrate how cetaceans fittingly illustrate hundreds of specific, detailed terms and concepts within evolutionary biology and evolutionary ecology. This review, arrayed in alphabetical glossary format, is not meant to offer an exhaustive listing of case studies or scholarly sources, but aims to show the breadth and depth of cetacean research studies supporting and investigating numerous evolutionary themes.

Baleen, a unique oral α-keratin, has flat cortical layers enclosing hollow horn tubules. Baleen grows continuously to replace erosive loss from feeding-related wear. This is essential for maintaining efficient filtration over a whale’s long life history. Baleen fragments are seen in stomach contents and feces. We focused on fin (Balaenoptera physalus) and bowhead whales (Balaena mysticetus), but examined eleven mysticete species. Histological features including variably sized tubules plus differential growth along plate axes (growing faster along the medial fringed edge) and between plates of a rack (central plates growing faster than others) relate to baleen strength and flexibility. Sheet-like cortical layers provide strength and probably hinder erosive shedding, whereas medullary (tubular/intertubular) keratin provides flexibility and likely promotes shedding. To calculate amounts of grown/lost baleen, we considered both erosive wear and basal growth, recognizing that each plate represents several years of growth. We estimate average annual loss of 70–100,000 cm2 (20–40,000 cm3) of baleen in balaenids and 25–50,000 cm2 (7–14,000 cm3) in balaenopterids. Baleen growth rates depend on age, size, and other life history parameters; the most reliable calculations come from morphometric data with plate dimensions measured along full racks. We argue that baleen turnover has been under-rated and baleen growth rates underestimated in the published literature. Baleen turnover maintains filter integrity/porosity, while gut passage possibly clears gastrointestinal tracts of endoparasites. Large volumes of shed keratin hold potential ecological consequences by providing food for microbial decomposers and detritivores throughout ocean ecosystems, especially in polar regions where most mysticete feeding occurs.

Adsorption of surfactants in shales is not well studied. The goal of this work is to quantify and understand surfactant adsorption in several shale samples. Shale samples were obtained from several...

Background Glycopeptides (GPs), lipopeptides (LPs) and lipoglycopeptides (LGPs) are related antimicrobials important for the management of invasive MRSA infections. Cross-resistance among these antibiotics in MRSA is well documented, as is the observation that susceptibility of MRSA to β-lactams increases as susceptibility to GPs and LPs decreases (i.e. the seesaw effect). Efforts to understand the relationship between GP/LP/LGP cross-resistance and the seesaw effect have focused on the PBPs, but the role of lipid metabolism has not been investigated. Objectives Since the cell membrane is structurally and metabolically integrated with the cell wall and anchors associated proteins, including PBPs, we examined the relationship between membrane lipid composition and the phenomena of cross-resistance among GPs/LPs/LGPs and the β-lactam seesaw effect. Methods We selected for daptomycin, vancomycin and dalbavancin resistance using the USA300 strain JE2 and evaluated the resulting mutants by WGS, MS-based lipidomics and antimicrobial susceptibility testing to assess the relationship between membrane composition, cross-resistance, and the seesaw effect. Results We observed cross-resistance to GPs/LPs/LGPs among the selected strains and the seesaw effect against various β-lactams, depending on the PBP targets of the particular β-lactam. We found that modification of membrane composition occurs not only in daptomycin-selected strains, but also vancomycin- and dalbavancin-selected strains. Significantly, we observed that the abundance of most phosphatidylglycerols positively correlates with MICs of GPs/LPs/LGPs and negatively correlates with the MICs of β-lactams. Conclusions These studies demonstrate a major association between membrane remodelling, cross-resistance and the seesaw effect.

We report a series of acidified brine flow-through experiments designed to quantify the coupled alteration of geochemical, structural and fluid transport properties of a Mt. Simon sandstone core recovered at a depth of 2110.5 m as part of the Illinois Basin Decatur Project (IBDP). Flow-through experiments were completed at representative in-situ conditions to isolate the stages of initial CO2 injection: first, a single-phase (CO2–saturated brine, Stage 1) followed by a second multi-phase (CO2–saturated brine and supercritical CO2, Stage 2) experiment. During both stages, effluent major and trace cation concentrations were tracked through time. Two imaging methods were employed to analyze the structural alterations of the rock core induced by the percolation of CO2-saturated brine and supercritical CO2: (1) scanning electron microscopy-petrography before Stage 1 and after Stage 2 and (2) computed tomography (CT) scans before and after Stage 2. The time series of Stage 1 effluent solutes were used to constrain a reactive transport simulation of the system. Modeling results suggest the evolution of the solute composition is a result of coupled dissolution of K-feldspar, calcite, illite and pyrite, and precipitation of montmorillonite, mesolite, alunite, diaspore, goethite and muscovite. The model predicted a net opening of pore space and associated increased permeability at the inlet. However, across the whole core, an overall decrease in permeability of approximately 23% ± 0.01 after Stage 1 was determined experimentally. CT analysis confirmed a corresponding decrease in porosity. A comparable permeability decrease was directly measured during Stage 2, concurrent with a decrease in the volume of macro-pores based on multiple CT-resolution methods. In total, this coupled approach demonstrates that geochemical alterations exert a first order control on the evolution of fluid transport properties through time at the earliest stages of in-situ CO2 injection and suggest that chemical dynamics ultimately influence both the magnitude and timing of alterations to the physical integrity of Mt. Simon reservoir over these timescales.

Mandibular mobility accompanying gape change in Northern and Antarctic minke whales was investigated by manipulating jaws of carcasses, recording jaw movements via digital instruments (inclinometers, accelerometers, and goniometers), and examining osteological and soft tissue movements via computed tomography (CT)-scans. We investigated longitudinal (α) rotation of the mandible and mediolateral displacement at the symphysis (Ω1 ) and temporomandibular joint (Ω2 ) as the mouth opened (Δ). Results indicated three phases of jaw opening. In the first phase, as gape increased from zero to 8°, there was slight (

Inactivating mutations in tumor suppressor genes TP53 and RB1 are considered central drivers in leiomyosarcomas (LMSs). In high-risk human papillomavirus (HPV)-related tumors, a similar functional outcome is achieved through oncoproteins E6 and E7, which inactivate the p53 and RB1 proteins, respectively. Here, we hypothesized that HPV infection could provide an alternative mechanism for tumorigenesis in a subset of TP53/RB1-wildtype LMS. We evaluated tumor samples from 2585 consecutive unique patients carrying a diagnosis of gynecologic or soft tissue LMS. Tumor DNA and available RNA were analyzed by hybrid-capture-based next-generation sequencing/comprehensive genomic profiling of 406 genes and transcripts (FoundationOneHeme). Of the initial 2585 cases, we excluded 16 based on the presence of molecular alterations that are considered defining for sarcomas other than LMS. In the remaining 2569 cases, we searched for LMS that were TP53/RB1-wildtype (n=486 of 2569; 18.9%). We also searched LMS tumors for HPV sequences that we then classified into genotypes by de novo assembly of nonhuman sequencing reads followed by alignment to the RefSeq database. Among TP53/RB1-wildtype LMS, we identified 18 unique cases harboring HPV sequences. Surprisingly, most (n=11) were HPV51-positive, and these 11 represented all HPV51-positive tumors in our entire LMS database (n=11 of 2569; 0.4%). The absence of genomic alterations in TP53 or RB1 in HPV51-positive LMS represented a marked difference from HPV51-negative LMS (n=2558; 0% vs. 72% [P0.00001], 0% vs. 53% [P=0.0002]). In addition, compared with HPV51-negative LMS, HPV51-positive LMS were significantly enriched for genomic alterations in ATRX (55% vs. 24%, P=0.027) and TSC1 (18% vs. 0.6%, P=0.0047). All HPV51-positive LMS were in women; median age was 54 years at surgery (range: 23 to 74 y). All known primary sites were from the gynecologic tract or adjacent anogenital area, including 5 cases of vaginal primary site. Histology was heterogeneous, with evaluable cases showing predominant epithelioid (n=5) and spindle (n=5) morphology. In situ hybridization confirmed the presence of high-risk HPV E6/E7 mRNA in tumor cells in three of three evaluable cases harboring HPV51 genomic sequences. Overall, in our pan-LMS analysis, HPV reads were identified in a subset of TP53/RB1-wildtype LMS. For all HPV51-associated LMS, the striking absence of any detectable TP53 or RB1 mutations and predilection for the female lower reproductive tract supports our hypothesis that high-risk HPV can be an alternative tumorigenic mechanism in this distinct class of LMS.

The development of technologies that promote environmental stewardship while maintaining or improving the efficiency of food animal production is essential to the sustainability of producing a food supply to meet the demands of a growing population. As such, Elanco (Greenfield, IN) pursued an environmental indication for a selective β-modulator (lubabegron; LUB). LUB was recently approved by the United States Food and Drug Administration (FDA) to be fed to feedlot cattle during the last 14 to 91 d of the feeding period for reductions in gas emissions/kg of unshrunk final BW and HCW. A 4 × 2 factorial arrangement of treatments was used with the factors of dose (0.0, 1.38, 5.5, or 22.0 mg·kg−1 DM basis) and sex (steers or heifers). Three 91-d cycles were conducted (112 cattle/cycle) with each dose × sex combination being represented by a single cattle pen enclosure (CPE; 14 cattle/CPE) resulting in a total of 168 steers and 168 heifers (n = 6 replicates/dose). There were no interactions observed between dose and sex for any variable measured in the study (P ≥ 0.063). Five gases were evaluated for all pens based on CPE concentrations relative to ambient air: NH3, CH4, N2O, H2S, and CO2. Cumulative NH3 gas emissions were reduced by feeding cattle 5.5 and 22.0 mg·kg−1 LUB (P ≤ 0.023) and tended (P = 0.076) to be lower for the cattle fed 1.38 mg·kg−1 LUB compared with the negative controls (CON). The cumulative NH3 gas emission reductions of 960 to 1032 g, coupled with HCW increases (P ≤ 0.019) of 15 to 16 kg for all LUB doses vs. CON, led to reductions in NH3 gas emissions/kg HCW for all three LUB treatments (P ≤ 0.004). Similar to HCW, reductions in NH3 gas emissions/kg of unshrunk final BW were observed for all LUB doses (P ≤ 0.009) and were attributable to both decreases in NH3 gas emissions and numerical increases in BW. Dose had no effect on cumulative emissions or emissions standardized by BW or HCW for the other four gases (P ≥ 0.268). LUB is a novel tool to reduce emissions of NH3 gas per kilogram of unshrunk live BW and hot carcass weight.

Visual predators rely on fast-acting optokinetic responses to track and capture agile prey. Most toothed whales, however, rely on echolocation for hunting and have converged on biosonar clicking rates reaching 500/s during prey pursuits. If echoes are processed on a click-by-click basis, as assumed, neural responses 100× faster than those in vision are required to keep pace with this information flow. Using high-resolution biologging of wild predator-prey interactions, we show that toothed whales adjust clicking rates to track prey movement within 50–200 ms of prey escape responses. Hypothesising that these stereotyped biosonar adjustments are elicited by sudden prey accelerations, we measured echo-kinetic responses from trained harbour porpoises to a moving target and found similar latencies. High biosonar sampling rates are, therefore, not supported by extreme speeds of neural processing and muscular responses. Instead, the neurokinetic response times in echolocation are similar to those of tracking responses in vision, suggesting a common neural underpinning., eLife digest In the animal world, split-second decisions determine whether a predator eats, or its prey survives. There is a strong evolutionary advantage to fast reacting brains and bodies. For example, the eye muscles of hunting cheetahs must lock on to a gazelle and keep track of it, no matter how quickly or unpredictably it moves. In fact, in monkeys and primates, these muscles can react to sudden movements in as little as 50 milliseconds – faster than the blink of an eye. But what about animals that do not rely on vision to hunt? To find food at night or in the deep ocean, whales and porpoises make short ultrasonic sounds, or ‘clicks’, and then listen for returning echoes. As they close in on a prey, they need to click faster to get quicker updates on its location. What is unclear is how fast they react to the echoes. Just before a kill, a harbour porpoise can click over 500 times a second: if they wait for the echo from one click before making the next one, they would need responses 100 times faster than human eyes. Exploring this topic is difficult, as it requires tracking predator and prey at the same time. Vance et al. took up the challenge by building sound and movement recorders that attach to whales with suction cups. These were used on two different hunters: deep-diving beaked whales and shallow-hunting harbour porpoises. Both species adapted their click rate depending on how far they were from their prey, but their response times were similar to visual responses in monkeys and humans. This means that whales and porpoises do not act on each echo before clicking again: instead, they respond to groups of tens of clicks at a time. This suggests that their brains may be wired in much the same way as the ones of visual animals. In the ocean, increased human activity creates a dangerous noise pollution that disrupts the delicate hunting mechanism of whales and porpoises. Better understanding how these animals find their food may therefore help conservation efforts.

Cefiderocol is a siderophore cephalosporin active against MDR Gram-negatives includingWe selected cefiderocol resistance in three clinical strains ofEach parent strain was initially susceptible to cefiderocol (MICs of 0.03125, 0.03125 and 0.125 mg/L), and one initially tested susceptible to ceftazidime/avibactam (MIC 4 mg/L). We recovered evolved isolates achieving cefiderocol resistance at MICs of 8-32 mg/L from each parental strain. Some cefiderocol resistant isolates reverted following one to four drug-free passages. Ceftazidime/avibactam MICs of passaged isolates repeatedly increased to ≥256 mg/L, and while other MICs were largely unchanged, trimethoprim/sulfamethoxazole MICs declined 4-fold in two strains. WGS revealed one evolved isolate carrying six coding mutations, while four were isogenic mutants of

Surfactants are common additives to hydraulic fracturing and enhanced oil recovery (EOR) fluids, and are under consideration for amendment to supercritical carbon dioxide for geological carbon sequestration (GCS). The effect of a common anionic surfactant, internal olefin sulfonate (IOS), on mineral dissolution from shale into brine was evaluated. When added to brine at concentrations exceeding the critical micelle concentration (94 mg/L), IOS inhibited carbonate mineral dissolution in an Eagle Ford shale, as well as dissolution of optical quality calcite (the dominant carbonate in the shale). Laser profilometry images provide spatial resolution across > 3 orders of magnitude, and indicate that IOS addition to brine both enhances the formation of new etch pits in calcite, and impedes their further growth. Time-of-flight secondary ion mass spectrometry surface profiles show for the first time that IOS preferentially adsorbs at calcite pit edges versus flat calcite surfaces (i.e., terraces). Surface pressure calculations, sulfur K-edge near edge X-ray absorption fine structure (NEXAFS) spectroscopy results, and density functional theory (DFT) calculations support this observation; the DFT results indicate that the sulfonate head group of the IOS molecule binds strongly to the calcite step site as compared to the terrace site. The S K-edge NEXAFS results indicate that IOS adsorbed more to etched calcite surfaces compared to smooth calcite surfaces. Overall, the results indicate that weak adsorption on flat calcite surfaces (i.e., terraces) disrupts water structure and enhances mass transfer of dissolution, while strong adsorption on calcite pit edges displaces adsorbed water and inhibits further etch pit growth. This work provides the first direct evidence of preferential adsorption of IOS to etched calcite surfaces and links it to macroscopic dissolution kinetics. This work has implications for surfactant-containing fluids used in hydraulic fracturing, EOR and potentially GCS for subsurface injection into carbonate rich reservoirs.

Background The assessment of stability recovery performance following perturbations contributes to the determination of fall resisting skills. This study investigated the association between stability recovery performances in two perturbation tasks (lean-and-release versus tripping). Methods Healthy adults (12 young: 24 ± 3 years; 21 middle-aged: 53 ± 5 years; 11 old: 72 ± 5 years) were suddenly released from a forward-inclined position attempting to recover stability with a single step. In a second task, all participants experienced a mechanically induced trip during treadmill walking. To assess dynamic stability performance, the antero-posterior margin of stability (MoS), the base of support (BoS), and the rate of increase in BoS were determined at each foot touchdown (TD) for both tasks. Results Only weak to moderate correlations in dynamic stability performance parameters were found between the two tasks (0.568 > r > 0.305, 0.001 p p = 0.003; g = 1.151), lower BoS at TD (p = 0.019; g = 0.888) and lower rate of increase in BoS until TD (p = 0.002; g = 1.212) after release. Despite these profound subgroup differences in the lean-and-release task, no differences between multiple- and single-steppers were observed in the stability recovery performance during tripping. Conclusion The results provide evidence that the ability to effectively control dynamic stability following a sudden balance disturbance in adults across a wide age range is limited in its generalisation for different perturbation tasks.

It has been suggested that daptomycin can be inactivated by lipids released by Staphylococcus aureus and that this effect is antagonized by phenol soluble modulins (PSMs), which bind to the shed lipids. PSM production is regulated by the Agr system, and others have shown that loss of the Agr function enhances S. aureus survival in the presence of daptomycin. Here we assessed the impact of Agr function on daptomycin activity and lipid metabolism under various conditions. Daptomycin activity was evaluated against three sets of isogenic strain series with wild-type or dysfunctional Agr using static daptomycin time-kills over 24 h and against one strain pair using in vitro pharmacokinetic/pharmacodynamic (PK/PD) models simulating clinical daptomycin exposure for 48 h. We performed comprehensive lipidomics on bacterial membranes and the spent media to correlate lipid shedding with survival. In static time-kill experiments, two agr-deficient strains (SH1000- and USA300 LAC ΔagrA) showed improved survival for 8 h compared with their corresponding wild-type strains as seen in previous studies, but this difference did not persist for 24 h. However, four other agr-deficient strains (SH1001 and JE2 agr KOs) did not demonstrate improved survival compared to isogenic wild-type strains at any time in the time-kills. Lipidomics analysis of SH1000, SH1001, and SH1000- strains showed daptomycin exposure increased lipid shedding compared to growth controls in all strains with phosphatidylglycerols (PGs), lysylPGs and cardiolipins predominating. In the cell pellets, PGs and lysylPGs decreased but cardiolipins were unchanged with daptomycin exposure. The shed lipid profiles in SH1001 and SH1000- were similar, suggesting that the inability to resist daptomycin by SH1001 was not because of differences in lipid shedding. In the PK/PD model, the agr mutant SH1000- strain did not show improved survival relative to SH1000 either. In conclusion, inactivation of daptomycin by shed lipids may be dependent on genetic background, the specific agr mutations, or the techniques used to generate these KOs rather than the overall function of the Agr system, and its contribution to daptomycin tolerance seems to be varied, transient, and growth-condition dependent.

With a growing global population and increased environmental concerns around animal agriculture, it is essential to humanely maximize animal performance and reduce environmental emissions. This study aims to determine the efficacy of feeding ractopamine hydrochloride (RAC), an orally active, β 1-adrenergic agonist (β1AA), to feedlot steers in the last 42 d of finishing to reduce ammonia (NH3) emissions and improve animal performance. A randomized complete block design was used to allocate 112 Angus and crossbred Angus steers (initial body weight [BW] = 566.0 ± 10.4 kg) to 8 cattle pen enclosures. Pens (n = 4 per treatment, 14 steers per pen, and 56 steers per treatment) were randomly assigned to one of two treatments: 1) CON; finishing ration containing no RAC, 2) RAC; finishing ration containing 27.3 g/907 kg dry matter (DM) basis RAC. Steers were weighed on day −1 and 0 before treatment and day 14, 28, and 42 during treatment. Treatment rations were mixed and delivered daily by masked personnel. Measured emissions included NH3, nitrous oxide (N2O), methane (CH4), hydrogen sulfide (H2S), and carbon dioxide (CO2). The primary response variables assessed were emissions standardized by live weight (LW) and hot carcass weight (HCW). Steers were harvested on day 43 and carcass data were collected on day 43 and 44. Steers fed RAC reduced NH3 emissions by 17.21% from day 0 to 28 (P = 0.032) and tended to reduce NH3 from day 0 to 42 by 11.07% (P = 0.070) vs. CON. When standardized for LW, NH3 was reduced by 23.88% from day 0 to 14 (P = 0.018), 17.80% from day 0 to 28 (P = 0.006), and 12.50% for day 0 to 42 (P = 0.027) in steers fed RAC vs. CON. Steers fed RAC had 14.05% (P = 0.013) lower cumulative NH3 emissions when standardized by HCW vs. CON. Feeding RAC to Steers reduced H2S by 29.49% from day 0 to 14 (P = 0.009) and tended to reduce H2S over day 0 to 28 by 11.14% (P = 0.086) vs. CON. When H2S emissions were standardized for LW, RAC fed steers had a 28.81% reduction from day 0 to 14 (P = 0.008) vs. CON. From day 0 to 42 the RAC fed steers tended to have a 0.24 kg/d greater average daily gain (ADG) (P = 0.066) and tended to eat 4.27% less (P = 0.069) on a DM basis vs. CON. The RAC fed steers had a 19.95% greater gain to feed ratio (G:F) compared to CON (P = 0.012). Steers fed RAC had an average of 12.52 kg greater HCW (P = 0.006) and an increase of 1.93 percentage units in dressing percent (DP) (P = 0.004) vs. CON. Ractopamine is an effective medicated feed additive for reducing NH3 and improving end product performance through HCW yields.