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The role of metals in forming the primary cross-links in slug glue was investigated. Several metal-binding proteins were identified in the defensive glue produced by the slug

Chronic spinal cord injury (SCI) results in an increased predisposition to various metabolic problems that can be exacerbated by consuming a diet rich in calories and saturated fat. In addition, gastrointestinal symptoms have been reported after SCI, including intestinal dysbiosis of the gut microbiome. The effects of both diet and SCI on the gut microbiome of adult male Long Evans rats euthanized 16 wk after injury were investigated. The rats were either thoracic spinal contused or received sham procedures. After 12 wk of either a low-fat or high-fat diet, cecal contents were analyzed, revealing significant microbial changes to every taxonomic level below the kingdom level. Shannon α diversity analyses demonstrated a significant difference in diversity between the groups based on the surgical condition of the rats. SCI produced a unique signature of changes in commensal bacteria that were significantly different than Sham. Specific changes in commensal bacteria as a result of diet manipulation had high fidelity with reports in the literature, such as Clostridia, Thiohalorhabdales, and Pseudomonadales. In addition, novel changes in commensal bacteria were identified that are unique dietary influences on SCI. Linear regression analysis on body fat and lean mass showed that a consequence of chronic SCI produces uncoupled associations between some commensal bacteria and body composition. In conclusion, despite tightly controlling the protein content and varying the carbohydrate and fat contents, Sham and SCI rats respond uniquely to diet. These data provide potential direction for therapeutic modulation of the microbiome to improve health and wellness following SCI.

Purpose: Proliferation of T-follicular helper (TFH) CD4+ T cells is a postulated pathogenic mechanism for T-cell non-Hodgkin lymphomas (T-NHL). The inducible T-cell costimulator (ICOS) is highly expressed by TFH, representing a potential target. MEDI-570 is a monoclonal antibody against ICOS, which eliminates ICOS+ cells in preclinical models. Patients and Methods: We report the safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of MEDI-570 in T-NHL. NCI-9930 is a phase I, first-in-human study of MEDI-570 in relapsed/refractory malignant T-NHL known to express ICOS. MEDI-570 was administered intravenously every 3 weeks for up to 12 cycles. Primary endpoints were safety, dose-limiting toxicities (DLT), and recommended phase II dose (RP2D). Secondary and exploratory endpoints included efficacy parameters and various correlative studies. This study is supported by the National Cancer Institute (NCT02520791). Results: Twenty-three patients were enrolled and received MEDI-570 at five dose levels (0.01–3 mg/kg). Sixteen (70%) had angioimmunoblastic T-cell lymphoma (AITL); median age was 67 years (29–86) and the median prior lines of therapies was 3 (1–16). Most common grade 3 or 4 adverse events were decreased CD4+ T cells (57%), lymphopenia (22%), anemia (13%), and infusion-related reactions (9%). No DLTs were observed. The RP2D was determined at 3 mg/kg. Analysis of T-cell subsets showed reductions in CD4+ICOS+ T cells reflecting its effects on TFH cells. The response rate in AITL was 44%. Conclusions: MEDI-570 was well tolerated and showed promising clinical activity in refractory AITL. MEDI-570 resulted in sustained reduction of ICOS+ T lymphocytes.

Urban forests are recognized worldwide as the most critical component of green infrastructure due to their capacity to provide various environmental goods and services. As cities continue to expand and their environmental problems intensify, there is a growing need for urban forests and green infrastructure to be better incorporated into strategic land-use planning, especially in developing cities. The first step in building an urban forest management plan is to capture characteristics of the urban forest and how these change across the built environment. Here, we used an urban biotope approach to classify urban forest and environmental characteristics in Mexico City. We sampled 500 fixed-area randomly stratified plots across the city to characterize urban forest structural and compositional variables. PCA and the broken-stick method were used to reduce the number of 25 urban forest variables down to five significant principal components that accounted for 78% of the data's cumulative variation. Ward's method helped classify biotopes into a hierarchical system with seven finer-level biotopes defined by urban forest characteristics (Dunn = 0.09, AC = 0.98), nested within two broader-level biotopes defined by forest canopy conditions (Silhouette = 0.59, AC = 0.99). A no-tree canopy biotope was extracted from sampling locations with no trees. The biotopes derived here can fundament biotope mapping, support decision-making in urban forest planning, including the identification of available planting spaces, tree diversity targets, and canopy protection. Our work in Mexico City demonstrates how the biotope approach can be adapted and used to better incorporate urban forests and green infrastructure into future management planning for any city.

Rhg1 (Resistance to Heterodera glycines 1) mediates soybean (Glycine max) resistance to soybean cyst nematode (SCN; H. glycines). Rhg1 is a 4-gene, ∼30-kb block that exhibits copy number variation, and the common PI 88788-type rhg1-b haplotype carries 9 to 10 tandem Rhg1 repeats. Glyma.18G022400 (Rhg1-GmAAT), 1 of 3 resistance-conferring genes at the complex Rhg1 locus, encodes the putative amino acid transporter AATRhg1 whose mode of action is largely unknown. We discovered that AATRhg1 protein abundance increases 7- to 15-fold throughout root cells along the migration path of SCN. These root cells develop an increased abundance of vesicles and large vesicle-like bodies (VLB) as well as multivesicular and paramural bodies. AATRhg1 protein is often present in these structures. AATRhg1 abundance remained low in syncytia (plant cells reprogrammed by SCN for feeding), unlike the Rhg1 α-SNAP protein, whose abundance has previously been shown to increase in syncytia. In Nicotiana benthamiana, if soybean AATRhg1 was present, oxidative stress promoted the formation of large VLB, many of which contained AATRhg1. AATRhg1 interacted with the soybean NADPH oxidase GmRBOHG, the ortholog of Arabidopsis thaliana RBOHD previously found to exhibit upregulated expression upon SCN infection. AATRhg1 stimulated reactive oxygen species (ROS) generation when AATRhg1 and GmRBOHG were co-expressed. These findings suggest that AATRhg1 contributes to SCN resistance along the migration path as SCN invades the plant and does so, at least in part, by increasing ROS production. In light of previous findings about α-SNAPRhg1, this study also shows that different Rhg1 resistance proteins function via at least 2 spatially and temporally separate modes of action.

Western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), is a serious pest of corn and is currently managed with corn hybrids that produce insecticidal proteins derived from the bacterium Bacillus thuringiensis (Bt). Bt corn kills rootworm larvae and reduces larval feeding injury to corn roots. The Bt protein Gpp34/Tpp35Ab1, previously named Cry34/35Ab1, has been widely used in transgenic Bt corn for management of western corn rootworm, and field-evolved resistance has been found in some populations. In the United States, the refuge strategy is used to manage Bt resistance, with refuges of non-Bt host plants serving as a source of Bt-susceptible individuals, which in turn reduce the frequency of homozygous resistant individuals within a population. As such, the dominance of resistance strongly influences resistance evolution, with faster evolution of resistance when resistance is not recessive. Additionally, selection for resistance by a Bt crop leads to the accumulation of resistance alleles within refuge populations, thereby reducing the capacity of refuges to delay resistance. However, fitness costs can remove resistance alleles from refuge populations and preserve the dynamic of refuges producing Bt-susceptible genotypes. Bt-susceptible and Gpp34/Tpp35Ab1-resistant western corn rootworm were used to quantify the inheritance and fitness costs of resistance. We found that Gpp34/Tpp35Ab1 resistance was not recessive and had the accompanying fitness costs of slower developmental rate to adulthood and lower egg viability. This research will help improve insect resistance management by providing a better understanding of the risk of western corn rootworm evolving resistance to transgenic corn that produces Gpp34/Tpp35Ab1.

Restudy of Campyloprion annectans Eastman, 1902 from North America demonstrated that neither specimen included is diagnostic at the species level; thus, the species name is a nomen dubium. Since this species was designated as the type species of the genus, this requires suppression of the generic name also. Another species earlier assigned to Campyloprion, Campyloprion ivanovi Karpinsky, 1924 is used as a type for a newly established genus Karpinskiprion Lebedev et Itano gen. nov. The composition of the family Helicoprionidae Karpinsky, 1911 is reviewed, and a new family Helicampodontidae Itano et Lebedev fam. nov. is erected. A new specimen of Karpinskiprion ivanovi (Karpinsky, 1924) recently discovered in the Volgograd Region of Russia is the most complete Karpinskiprion specimen ever found. It unambiguously demonstrates the coiled nature of these tooth whorls and presents information on their developmental stages. During organogeny, cutting blades of the crown became reshaped, and basal spurs progressively elongated, forming a grater. Whorl growth occurred by addition of new crowns to the earlier mineralised base followed by later spur growth. In contrast to consistently uniform cutting blades, spurs are often malformed and bear traces of growth interruption. Both sides of the outer coil of the tooth whorl bear lifetime wear facets. The youngest (lingual) crowns are as yet unaffected by wear. The best-preserved facets show parallel radially directed scratch marks. The upper jaw dentition of Karpinskiprion is unknown, but we suggest that the faceted areas resulted from interaction with the antagonistic dental structures here. Three possible hypotheses for this interaction are suggested: (a) two opposing whorls acted as scissor blades, moving alternately from one side to another; (b) the lower tooth whorl fitted between paired parasymphyseal tooth whorls of the opposing jaw; or (c) the lower tooth whorl fitted into a dental pavement in the upper jaw.

Fisheries managers are in need of quantitative tools to inform decisions regarding selection of robust management practices, prioritising research gaps and stocks to focus on, particularly where there are limited resources or data. To support these decisions, the use of Management Strategy Evaluation (MSE), that is, closed loop simulation-testing of management procedures, is widely regarded as best practice. However, applying MSE is time- and computationally intensive, and requires highly skilled expertise and processes for stakeholder input and peer review. For data- and capacity-limited fisheries, MSE may be particularly challenging to implement. Yet, these are the contexts where it is most critical to test assumptions, evaluate the implications of all sources of uncertainty and identify the most informative data sources. To facilitate wider use of MSE, the Method Evaluation and Risk Assessment (MERA) framework was developed as an accessible online interface, with quick processing time, focused on generic data-limited management procedures, but allowing progression to tailored and more data-rich methods. The framework links a quantitative questionnaire and data input standard to a flexible operating model with optional customisation via command line access to the back-end open-source R libraries. Here, we illustrate a case study application of MERA for the bocinegro (Pagrus pagrus, Sparidae) fishery in the Gulf of Cadiz, where in conjunction with fishery stakeholders, a custom management procedure was developed and tested and key research gaps and data collection priorities were identified. We discuss implications for wider use of MSE in various contexts, including eco-certification and fishery improvement projects., MERA was initially commissioned by the Marine Stewardship Council, and benefits from the ongoing support of the David & Lucile Packard Foundation, the Marine Stewardship Council, the Natural Resources Defense Council, the Walton Family Foundation and the United Nations Food and Agricultural Organization.

Giant cell arteritis (GCA) is a large vessel vasculitis whereby up to half of all patients show ocular involvement, highlighting the importance of treating GCA before it leads to irreversible blindness. Most of the research published for GCA and associated adverse ocular events are based on majority Caucasian populations establishing the current belief that Hispanics have a much lower incident of GCA. We sought to investigate the incidence of GCA in Hispanics and characterize associated ocular events, stroke rates, and comorbid diseases. We conducted a retrospective cohort study of GCA-coded medical records in self-identified Hispanics assessed at the University Medical Center Hospital in El Paso, Texas. From 2000 to 2019, there were 68 new cases of GCA in the Hispanics which represents an average incidence of 0.062% with a 95% confidence interval of [0.05, 0.09] of Hispanics over the age of 50 admitted to University Medical Center hospital. Of the subjects diagnosed with GCA, the majority had ocular involvement such as blurry vision (47.06%), ocular pain (26.47%), and blindness (14.71%). We did not observe a history of stroke had a statistically significant difference associated with GCA with ophthalmic disease compared to GCA without ophthalmic disease. Polymyalgia rheumatica (PMR) was identified in only 2.94% of the Hispanic subjects with GCA. Major conclusions in our study advocate Hispanics with GCA are prevalent and unique in its associations with other comorbid diseases. Unlike non-Hispanic White populations, Hispanic subjects with GCA do not show an association with PMR nor an increased association with stroke.

ObjectivesSevere infections contribute to morbidity and mortality in antineutrophil cytoplasm antibody-associated vasculitis (AAV). This study aimed to identify risk factors associated with severe infections in participants of the Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial.MethodsData on 197 patients recruited into the RAVE trial were analysed. Participants received either rituximab (RTX) or cyclophosphamide (CYC), followed by azathioprine (AZA). Clinical and laboratory data of patients with and without severe infections (≥grade 3, according to the Common Terminology Criteria for Adverse Events version 3.0) were compared. Risk factors for severe infections were investigated using Cox-regression models.ResultsEighteen of 22 (82%) severe infections occurred within 6 months after trial entry, most commonly respiratory tract infections (15/22, 68%). At baseline, lower absolute numbers of CD19+ cells were observed in patients with severe infections either receiving RTX or CYC/AZA at baseline, while CD5+B and CD3+T cells did not differ between groups. In Cox-regression analysis, higher baseline serum immunoglobulin M levels were associated with the risk of severe infections, whereby a higher baseline total CD19+B cell number and prophylaxis againstPneumocystis jiroveciiwith trimethoprim-sulfamethoxazole (TMP/SMX) with decreased risk of severe infections. Use of TMP/SMX was associated with lower risk of severe infections in both groups, receiving either RTX or CYC/AZA.ConclusionsThe use of low-dose TMP/SMX is associated with reduced risk of severe infections in patients with AAV treated with either RTX or CYC/AZA. Reduced B cell subpopulations at start of treatment might be a useful correlate of reduced immunocompetence.

To address the longstanding issue of provenance interpretation of non-unique detrital zircon age populations, we integrated zircon U-Pb, rare earth element (REE), and εHf(t) data from upper Paleozoic strata in the northern Central Colorado Trough and Cambrian intrusions with petrography, paleocurrent data, and structural and stratigraphic observations. This data set indicates that Cambrian sediment was shed by multiple local sources instead of distant sources hundreds of kilometers away, and it reveals a detailed history of tectonic drainage reorganization in the northern Central Colorado Trough during Ancestral Rocky Mountain deformation. During the Early–Middle Pennsylvanian, Cambrian detrital zircons were a minor constituent of northern Central Colorado Trough sediment. However, during the Late Pennsylvanian–early Permian, westward advancement of the adjacent Apishapa Uplift deformation front precipitated drainage reorganization, which resulted in an episode of dominant Cambrian detrital zircon sourcing. Paleocurrent and petrographic data indicate that the source of Cambrian detritus was shed by an igneous rock body that was ≤15 km northeast of the depocenter, which has since been eroded away or mantled by Tertiary volcanic rocks. The addition of zircon petrochronology to the data set applied here was critical in confirming this hidden source of detritus and elucidating the compositional characteristics of that igneous rock. Zircon εHf(t) provided a regional provenance indicator of a western Laurentian affinity, and REE composition aided in discriminating possible local sources of Cambrian zircon. Furthermore, this work serves as a case study of a dominant Cambrian detrital zircon signature sourced from outside of the wellknown Amarillo-Wichita Uplift, and it has implications for the interpretation of such detrital spectra in the context of a direct-from-basement source or the recycling of Cambrian zircon-dominated rocks. In summary, we demonstrate the utility of this multi-provenance proxy approach in interpreting a complex structural history of a dynamic hinterland and concomitant drainage reorganization through an in-depth investigation into the basin record.