Farm Production Analysis Training for Small Farmers

A partnership between Penn State Cooperative Extension and the Farm Service Agency has developed a successful production training program for more than 367 farmers. Farmers received training in producing planning and budgets, partial budgeting, and livestock and agronomic basics. Significant gains in knowledge occurred in multi-year planning, enterprise budgeting, and use of the Penn State Agronomy Guide. Designing workshop material for low-producing farmers proved difficult because most participants, while finding the topics helpful, also found the material too advanced. Future focus will encourage greater involvement with private-sector institutions and coordination between production and management Extension specialists

Provenance and Paleogeography of the 25-17 Ma Rainbow Gardens Formation: Evidence for Tectonic Activity at Ca. 19 Ma and Internal Drainage rather than Throughgoing Paleorivers on the Southwestern Colorado Plateau

The paleogeographic evolution of the Lake Mead region of southern Nevada and northwest Arizona is crucial to understanding the geologic history of the U.S. Southwest, including the evolution of the Colorado Plateau and formation of the Grand Canyon. The ca. 25–17 Ma Rainbow Gardens Formation in the Lake Mead region, the informally named, roughly coeval Jean Conglomerate, and the ca. 24–19 Ma Buck and Doe Conglomerate southeast of Lake Mead hold the only stratigraphic evidence for the Cenozoic pre-extensional geology and paleogeography of this area. Building on prior work, we present new sedimentologic and stratigraphic data, including sandstone provenance and detrital zircon data, to create a more detailed paleogeographic picture of the Lake Mead, Grand Wash Trough, and Hualapai Plateau region from 25 to 18 Ma. These data confirm that sediment was sourced primarily from Paleozoic strata exposed in surrounding Sevier and Laramide uplifts and active volcanic fields to the north. In addition, a distinctive signal of coarse sediment derived from Proterozoic crystalline basement first appeared in the southwestern corner of the basin ca. 25 Ma at the beginning of Rainbow Gardens Formation deposition and then prograded north and east ca. 19 Ma across the southern half of the basin. Regional thermochronologic data suggest that Cretaceous deposits likely blanketed the Lake Mead region by the end of Sevier thrusting. Post-Laramide northward cliff retreat off the Kingman/Mogollon uplifts left a stepped erosion surface with progressively younger strata preserved northward, on which Rainbow Gardens Formation strata were deposited. Deposition of the Rainbow Gardens Formation in general and the 19 Ma progradational pulse in particular may reflect tectonic uplift events just prior to onset of rapid extension at 17 Ma, as supported by both thermochronology and sedimentary data. Data presented here negate the California and Arizona River hypotheses for an “old” Grand Canyon and also negate models wherein the Rainbow Gardens Formation was the depocenter for a 25–18 Ma Little Colorado paleoriver flowing west through East Kaibab paleocanyons. Instead, provenance and paleocurrent data suggest local to regional sources for deposition of the Rainbow Gardens Formation atop a stripped low-relief western Colorado Plateau surface and preclude any significant input from a regional throughgoing paleoriver entering the basin from the east or northeast

Recombinant Listeria promotes tumor rejection by CD8+ T cell-dependent remodeling of the tumor microenvironment.

Agents that remodel the tumor microenvironment (TME), prime functional tumor-specific T cells, and block inhibitory signaling pathways are essential components of effective immunotherapy. We are evaluating live-attenuated, double-deleted Listeria monocytogenes expressing tumor antigens (LADD-Ag) in the clinic. Here we show in numerous mouse models that while treatment with nonrecombinant LADD induced some changes in the TME, no antitumor efficacy was observed, even when combined with immune checkpoint blockade. In contrast, LADD-Ag promoted tumor rejection by priming tumor-specific KLRG1+PD1loCD62L- CD8+ T cells. These IFNγ-producing effector CD8+ T cells infiltrated the tumor and converted the tumor from an immunosuppressive to an inflamed microenvironment that was characterized by a decrease in regulatory T cells (Treg) levels, a proinflammatory cytokine milieu, and the shift of M2 macrophages to an inducible nitric oxide synthase (iNOS)+CD206- M1 phenotype. Remarkably, these LADD-Ag-induced tumor-specific T cells persisted for more than 2 months after primary tumor challenge and rapidly controlled secondary tumor challenge. Our results indicate that the striking antitumor efficacy observed in mice with LADD-based immunotherapy stems from TME remodeling which is a direct consequence of eliciting potent, systemic tumor-specific CD8+ T cells

A Potent and Effective Suicidal Listeria Vaccine Platform.

Live-attenuated Listeria monocytogenes has shown encouraging potential as an immunotherapy platform in preclinical and clinical settings. However, additional safety measures will enable application across malignant and infectious diseases. Here, we describe a new vaccine platform, termed Lm-RIID (L. monocytogenes recombinase-induced intracellular death), that induces the deletion of genes required for bacterial viability yet maintains potent T cell responses to encoded antigens. Lm-RIID grows normally in broth but commits suicide inside host cells by inducing Cre recombinase and deleting essential genes flanked by loxP sites, resulting in a self-limiting infection even in immunocompromised mice. Lm-RIID vaccination of mice induces potent CD8+ T cells and protects against virulent challenges, similar to live L. monocytogenes vaccines. When combined with α-PD-1, Lm-RIID is as effective as live-attenuated L. monocytogenes in a therapeutic tumor model. This impressive efficacy, together with the increased clearance rate, makes Lm-RIID ideal for prophylactic immunization against diseases that require T cells for protection

ACCOMMODATING MIXED-SEVERITY FIRE TO RESTORE AND MAINTAIN ECOSYSTEM INTEGRITY WITH A FOCUS ON THE SIERRA NEVADA OF CALIFORNIA, USA

Existing fire policy encourages the maintenance of ecosystem integrity in fire management, yet this is difficult to implement on lands managed for competing economic, human safety, and air quality concerns. We discuss a fire management approach in the mid-elevations of the Sierra Nevada, California, USA, that may exemplify similar challenges in other fire-adapted regions of the western USA. We also discuss how managing for pyrodiversity through mixed-severity fires can promote ecosystem integrity in Sierran mixed conifer and ponderosa pine (Pinus ponderosa Laws) forests. To illustrate, we show how coarse-filter (landscape-level) and complementary fine-filter (species-level) approaches can enhance forest management and conservation biology objectives as related to wildfire management. At the coarse-filter level, pyrodiverse mixed-severity fires provide landscape heterogeneity. Species and ecosystem characteristics associated with pyrodiversity can be maintained or enhanced by accommodating moderately severe fires, which hasten restoration by recreating a complex vegetation mosaic otherwise at risk from suppression. At the fine-filter level, managers can select focal species and species of conservation concern based on the degree to which those species depend on fire and accommodate their specific conservation needs. The black-backed woodpecker (Picoides arcticus [Swainson, 1832]) is an ideal focal species for monitoring the ecological integrity of forests restored through mixed-severity fire, and the California spotted owl (Strix occidentalis occidentalis [Xantus de Vesey, 1860]) is a species of conservation concern that uses post-fire habitat mosaics and is particularly vulnerable to logging. We suggest a comprehensive approach that integrates wildland fire for ecosystem integrity and species viability with strategic deployment of fire suppression and ecologically based restoration of pyrodiverse landscapes. Our approach would accomplish fire management goals while simultaneously maintaining biodiversity

A Case of Successful Treatment of Recurrent Urinary Tract infection By Extended-Spectrum Β-Lactamase Producing

Recurrent urinary tract infections (UTIs) are a challenging clinical entity that can be frustrating for patient and physician alike. Repeated rounds of antibiotics can select for multidrug-resistant organisms, further complicating care. We describe the successful use of fecal microbiota transplantation (FMT) for the treatment of recurrent extended-spectrum β-lactamase (ESBL)-producin

A–C Estrogens as Potent and Selective Estrogen Receptor-Beta Agonists (SERBAs) to Enhance Memory Consolidation under Low-Estrogen Conditions

Estrogen receptor-beta (ERβ) is a drug target for memory consolidation in postmenopausal women. Herein is reported a series of potent and selective ERβ agonists (SERBAs) with in vivo efficacy that are A–C estrogens, lacking the B and D estrogen rings. The most potent and selective A–C estrogen is selective for activating ER relative to seven other nuclear hormone receptors, with a surprising 750-fold selectivity for the β over α isoform and with EC50s of 20–30 nM in cell-based and direct binding assays. Comparison of potency in different assays suggests that the ER isoform selectivity is related to the compound’s ability to drive the productive conformational change needed to activate transcription. The compound also shows in vivo efficacy after microinfusion into the dorsal hippocampus and after intraperitoneal injection (0.5 mg/kg) or oral gavage (0.5 mg/kg). This simple yet novel A–C estrogen is selective, brain penetrant, and facilitates memory consolidation