Effectively promoting the stability and quality of ecosystem services involves the successful management of domesticated species and the control of introduced species. In the pollinator literature, ...interest and concern regarding pollinator species and pollinator health dramatically increased in recent years. Concurrently, the use of loaded terms when discussing domesticated and non-native species may have increased. As a result, pollinator ecology has inherited both the confusion associated with invasion biology’s lack of a standardized terminology to describe native, managed, or introduced species as well as loaded terms with very strong positive or negative connotations. The recent explosion of research on native bees and alternative pollinators, coupled with the use of loaded language, has led to a perceived divide between native bee and managed bee researchers. In comparison, the bird literature discusses the study of managed (poultry) and non-managed (all other birds) species without an apparent conflict with regard to the use of terms with strong connotations or sentiment. Here, we analyze word usage when discussing non-managed and managed bee and bird species in 3614 ecological and evolutionary biology papers published between 1990 and 2019. Using time series analyses, we demonstrate how the use of specific descriptor terms (such as wild, introduced, and exotic) changed over time. We then conducted co-citation network analyses to determine whether papers that share references have similar terminology and sentiment. We predicted a negative language bias towards introduced species and positive language bias towards native species. We found an association between the term
invasive
and bumble bees and we observed significant increases in the usage of more ambiguous terms to describe non-managed species, such as
wild
. We detected a negative sentiment associated with the research area of pathogen spillover in bumble bees, which corroborates the subjectivity that language carries. We recommend using terms that acknowledge the role of human activities on pathogen spillover and biological invasions. Avoiding the usage of loaded terms when discussing managed and non-managed species will advance our understanding and promote effective and productive communication across scientists, general public, policy makers and other stake holders in our society.
Pregnancy complications are poorly represented in the archeological record, despite their importance in contemporary and ancient societies. While excavating a Byzantine cemetery in Troy, we ...discovered calcified abscesses among a woman's remains. Scanning electron microscopy of the tissue revealed 'ghost cells', resulting from dystrophic calcification, which preserved ancient maternal, fetal and bacterial DNA of a severe infection, likely chorioamnionitis.
and
dominated the abscesses. Phylogenomic analyses of ancient, historical, and contemporary data showed that
Troy fell within contemporary genetic diversity, whereas
Troy belongs to a lineage that does not appear to be commonly associated with human disease today. We speculate that the ecology of
infection may have differed in the ancient world as a result of close contacts between humans and domesticated animals. These results highlight the complex and dynamic interactions with our microbial milieu that underlie severe maternal infections.
The colonic microenvironment, stemming from microbial, immunologic, stromal, and epithelial factors, serves as an important determinant of the host response to enteric pathogenic colonization. ...Infection with the enteric bacterial pathogen
elicits a strong mucosal Th1-mediated colitis and monocyte-driven inflammation activated via the classical NF-κB pathway. Research has focused on leukocyte-mediated signaling as the main driver for
-induced colitis, however we hypothesize that epithelial cell NF-κB also contributes to the exacerbation of infectious colitis. To test this hypothesis, compartmentalized classical NF-κB defective mice, via the deletion of IKKβ in either intestinal epithelial cells (IKKβ
) or myeloid-derived cells (IKKβ
), and wild type (WT) mice were challenged with
. Both pathogen colonization and colonic histopathology were significantly reduced in IKKβ-deficient mice compared to WT mice. Interestingly, colonic IL-10, RegIIIγ, TNF-α, and iNOS gene expression were increased in IKKβ-deficient mice in the absence of bacterial challenge. This was associated with increased p52, which is involved with activation of NF-κβ through the alternative pathway. IKKβ-deficient mice also had distinct differences in colonic tissue-associated and luminal microbiome that may confer protection against
. Taken together, these data demonstrate that classical NF-κB signaling can lead to enhanced enteric pathogen colonization and resulting colonic histopathology.
Dietary fiber intake leading to short-chain fatty acid (SCFA) production could be a strategy to combat intermittent bouts of inflammation during ulcerative colitis.
Our objective was to evaluate ...dietary potato fiber (PF) in attenuating inflammation using a dextran sodium sulfate (DSS)-induced colitis mouse model. We hypothesized that PF would show anti-inflammatory effects compared with cellulose due in part to SCFA production.
Male C57Bl/6J mice were fed diets containing either 8% cellulose or 14.5% PF for a 22-d feeding study. Starting on study day 14, mice were provided either distilled water (control) or 2% (wt:vol) DSS in drinking water for 5 d (cellulose+control, n = 17; PF+control, n = 16; cellulose+DSS, n = 17; and PF+DSS, n = 16). Body weights and food and water intakes were collected daily from day 14 through day 22. Distal colon tissue was analyzed for histologic outcomes and changes in gene expression, and cecal contents were analyzed for SCFA concentrations. Data were analyzed by ANOVA, with repeated measures applied where necessary.
At day 5 post-DSS induction, cellulose+DSS mice exhibited a 2% reduction (P < 0.05) in body weight compared with PF+DSS and PF+ and cellulose+control mice. PF+DSS mice had greater (P < 0.05) cecal butyrate concentrations 24.5 μmol/g dry matter (DM) than did cellulose+DSS mice (4.93 μmol/g DM). Mice fed PF+DSS had lower (P < 0.05) infiltration of leukocytes in the distal colon than did mice fed cellulose+DSS (mean histology scores of 1.22 and 2.30, respectively). Furthermore, mice fed cellulose+DSS exhibited 1.42, 11.5, 8.48, and 35.5 times greater (P < 0.05) colon mRNA expression of tumor necrosis factor α (Tnfa) and interleukin (Il) 1b, Il6, and Il17a, respectively, and 7.10 times greater (P < 0.05) expression of C-X-C motif ligand 1 (Cxc1) compared with mice fed PF+DSS.
These results suggest that PF fed to mice before and during DSS colitis attenuates inflammation, potentially through SCFA production; however, future studies are needed to understand the role of dietary fiber intake and immune activation.
A novel magnetostatic responsive structure (MRS) that does not require a direct connection to biasing circuitry for microwave applications is presented. This allows the placement of the MRSs in ...locations that may not be accessible with traditional printed traces. The MRS measures 3.0 mm × 3.0 mm × 0.508 mm in the x-, y-, and z-directions, respectively, with a 0.9 mm diameter cylindrical cavity. The axis of this cavity is along the z-axis and is partially filled with microparticles (diameter ~10-40 μm) composed of a magnetite core with a silver coating. A copper foil is placed on the top and bottom to enclose the particles in the cavity. When a static magnetic field is introduced, the magnetic particles stack and align in columns in the direction of the field lines, connecting the foil layers. Conversely, when the magnetic field is removed, the columns collapse and disconnect the layers. A microstrip transmission line is used to extract the equivalent circuit of the MRS, and compare to full-wave simulations and measurements for both states. Agreement was shown up to 3.0 GHz. Finally, the MRS was embedded into a host material to explore the bandwidth, signal integrity, benefits of remote biasing, and the field-strength/scalability relationship.
KRAS
, the most common oncogenic KRAS mutation, is a promising target for the treatment of solid tumors. However, when compared to KRAS
, selective inhibition of KRAS
presents a significant challenge ...due to the requirement of inhibitors to bind KRAS
with high enough affinity to obviate the need for covalent interactions with the mutant KRAS protein. Here, we report the discovery and characterization of the first noncovalent, potent, and selective KRAS
inhibitor, MRTX1133, which was discovered through an extensive structure-based activity improvement and shown to be efficacious in a KRAS
mutant xenograft mouse tumor model.
Understanding space-charge-limited current density (SCLCD) is fundamentally and practically important for characterizing many high-power and high-current vacuum devices. Despite this, no analytic ...equations for SCLCD with nonzero monoenergetic initial velocity have been derived for nonplanar diodes from first principles. Obtaining analytic equations for SCLCD for nonplanar geometries is often complicated by the nonlinearity of the problem and over constrained boundary conditions. In this Letter, we use the canonical coordinates obtained by identifying Lie-point symmetries to linearize the governing differential equations to derive SCLCD for any orthogonal diode. Using this method, we derive exact analytic equations for SCLCD with a monoenergetic injection velocity for one-dimensional cylindrical, spherical, tip-to-tip (t-t), and tip-to-plate (t-p) diodes. We specifically demonstrate that the correction factor from zero initial velocity to monoenergetic emission depends only on the initial kinetic and electric potential energies and not on the diode geometry and that SCLCD is universal when plotted as a function of the canonical gap size. We also show that SCLCD for a t-p diode is a factor of four larger than a t-t diode independent of injection velocity. The results reduce to previously derived results for zero initial velocity using variational calculus and conformal mapping.
We conducted a 2-part study to evaluate the incorporation of veliparib, a PARP inhibitor, into chemoradiotherapy (CRT) for stage III non–small-cell lung cancer.
In the phase I part, patients were ...treated successively at 3 dose levels of veliparib (40, 80, and 120 mg) twice daily during CRT. In the phase II part, patients were randomized to receive veliparib or placebo during thoracic radiotherapy with concurrent weekly carboplatin and paclitaxel, followed by 2 cycles of consolidation carboplatin and paclitaxel with veliparib or placebo. The study was prematurely discontinued owing to the emergence of adjuvant immunotherapy as standard of care.
Of 21 patients enrolled in phase I, 2 patients developed dose-limiting toxicities (DLTs): 1 grade 3 esophagitis with dysphagia (at 40 mg) and 1 grade 3 esophagitis with dehydration (at 80 mg). No DLTs were seen at veliparib dose of 120 mg twice daily, which was selected for the phase II part that enrolled 31 eligible patients. Progression-free survival (PFS) was not different between the 2 arms (P = .20). For the veliparib and placebo arms, response rates were 56% and 69%, PFS at 1 year 47% and 46%, and overall survival at 1 year 89% and 54%, respectively.
Veliparib with CRT was feasible and well tolerated. Efficacy could not accurately be determined because of early study closure. Nonetheless, there is enthusiasm for the evaluation of PARP inhibitors in lung cancer as predictive biomarkers are being developed and combinations with immunotherapy are attractive.
We evaluated the incorporation of veliparib, a PARP inhibitor, into chemoradiotherapy with carboplatin and paclitaxel for stage III non–small-cell lung cancer. In the phase I part that enrolled 21 patients we selected veliparib dose of 120 mg twice daily as the recommended phase II dose. The phase II part enrolled 31 eligible patients. Progression-free survival was not different between the 2 arms (P = .20). Veliparib with chemoradiotherapy was feasible and well tolerated. Efficacy could not be accurately determined because of early study closure.
We have previously shown that 6weeks of a diet containing epigallocatechin gallate (EGCG) and beta-alanine (B-ALA) was not effective in improving either cognitive or muscle function in aged (18month) ...mice (Gibbons et al. Behav Brain Res 2014). However, diet reduced oxidative stress in the brain, and previous studies using longer-term interventions have documented beneficial effects in cognitive, but not muscle, function. Therefore, we investigated the effect of 6months of feeding on measures of cognitive and muscle function in mice. Mice (12months, N=15/group) were fed AIN-93M containing 0.15% EGCG and 0.34% B-ALA or standard AIN-93M for 6months, then underwent a battery of tests for cognitive and muscle function at 18months. Interestingly, a higher percentage of mice receiving EGCG and B-ALA (E+B, 80%) survived to study end compared to control (Ctrl, 40%) mice (p=0.02). E+B did not affect arm preference in the Y-maze test (p=0.74, novel arm) and did not alter performance in an active avoidance test (p=0.16, avoidances per 50 trials). E+B increased rotarod performance (p=0.03), did not affect grip strength (p=0.91), and decreased time to exhaustion in a treadmill fatigue test (p=0.02) compared to Ctrl. In conclusion, E+B reduced mortality, had no effect on cognitive function and variable effects on muscle function.
•Long-term feeding with EGCG and beta-alanine in mice delayed mortality•EGCG and beta-alanine feeding did not alter cognition•EGCG and beta-alanine had variable effects on muscle function, increasing rotarod performance but decreasing treadmill time to exhaustion
Ancient human remains of paleopathological interest typically contain highly degraded DNA in which pathogenic taxa are often minority components, making sequence-based metagenomic characterization ...costly. Microarrays may hold a potential solution to these challenges, offering a rapid, affordable, and highly informative snapshot of microbial diversity in complex samples without the lengthy analysis and/or high cost associated with high-throughput sequencing. Their versatility is well established for modern clinical specimens, but they have yet to be applied to ancient remains. Here we report bacterial profiles of archaeological and historical human remains using the Lawrence Livermore Microbial Detection Array (LLMDA). The array successfully identified previously-verified bacterial human pathogens, including Vibrio cholerae (cholera) in a 19th century intestinal specimen and Yersinia pestis ("Black Death" plague) in a medieval tooth, which represented only minute fractions (0.03% and 0.08% alignable high-throughput shotgun sequencing reads) of their respective DNA content. This demonstrates that the LLMDA can identify primary and/or co-infecting bacterial pathogens in ancient samples, thereby serving as a rapid and inexpensive paleopathological screening tool to study health across both space and time.
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