Grazing and Virus-Induced Mortality of Microbial Populations Before and During the Onset of Annual Hypoxia in Lake Erie

Lake Erie is the most productive of the North American Great Lakes and experiences annual periods of hypolimnetic hypoxia with unknown consequences for the microbial food web. We established the abundances and mortality rates of microbes in Lake Erie during thermal stratification and determined how they varied with changes in bottom-water dissolved oxygen concentrations. The microbial plankton community (heterotrophic bacteria, Cyanobacteria, eukaryotic phytoplankton, nanozooplankton, microzooplankton) was quantified in surface and bottom waters along with measurements of herbivory and bacterivory rates on eukaryotic and prokaryotic picoplankton and rates of viral lysis of bacteria. High rates of grazing mortality of prokaryotic picoplankton (1.4 +/- 0.6 d(-1)) and eukaryotic algae (0.66 +/- 0.27 d(-1)) and significant correlations between microzooplankton abundances and all picoplankton populations quantified demonstrated the strong impacts of grazing on Lake Erie picoplanktonic communities. Microbial herbivory accounted for half of total phytoplankton mortality per day. Bacterivory and viral lysis turned over 85% of the heterotrophic bacterial community each day. During the onset of hypolimnetic hypoxia, abundances of ciliates and rotifers decreased significantly and herbivory was undetectable. Concurrently, bacterivory persisted at rates equal to those found in shallower oxygenated waters, and abundances of heterotrophic nanoflagellates did not change significantly. These results suggest that, during hypoxia events in Lake Erie, herbivory by microzooplankton is disrupted, but bacterivory by heterotrophic nanoflagellates persists. Finally, rates of viral lysis of heterotrophic bacteria were higher in the hypolimnion than in surface waters, suggesting that increased viral lysis may enhance regeneration of organic matter in bottom waters during hypoxic events

Multidrug resistant Kluyvera ascorbata septicemia in an adult patient: a case report

<p>Abstract</p> <p>Introduction</p> <p><it>Kluyvera ascorbata </it>has become increasingly significant due to its potential to cause a wide range of infections, as well as its ability to transfer gene encoding for CTX-M- type extended spectrum B-lactamases (ESBLs) to other Enterobacteriaceae.</p> <p>Case presentation</p> <p>We report the case of a 64-year-old African-American male diagnosed with severe sepsis due to a multidrug resistant <it>Kluyvera ascorbata</it>, which was isolated from his blood. He was treated with meropenem and had a favorable outcome.</p> <p>Conclusion</p> <p>To the best of our knowledge, this is the first case report of a multidrug resistant <it>Kluyvera ascorbata </it>isolated from the blood in an adult patient with sepsis.</p

The Student Movement Volume 105 Issue 7: Please Pass the Plexiglass: Friends Unite for Shielded Bite

NEWS Receiving the COVID-19 Vaccine, Interviewed by TJ Hunter Andrews University Choral Performs “Celebrating the Light” Concert, Jenae Rogers AUSA Hosts Sabbath Experience at PMC, Caralynn Chan Dr. Kizzmekia Shanta Corbett Gives Lecture on the Safety and Effectiveness of COVID-19 mRNA Vaccines, Terika Williams Loving in the Grey: This Semester’s First In-Person Chapel, Kristin Ferrer PULSE Holilday Recap, Gloria Oh New Year’s Aspirations, Wambui Karanja The Wellness Column: No Longer Sitting Ducks, Jessica Rim Winter Break Endeavors, by HeeYun Oh HUMANS AU Christmas Album Interview, Interview by Abigail Lee My Experience in COVID Isolation, Interview by Terika Williams Spring Semester 2021 Club Events, Interview by Celeste Richardson ARTS & ENTERTAINMENT Creative Spotlight: Brent LaPorre, Interviewed by Megan Napod Current February Favorites, Megan Napod Long Live the King, Joshua Deonarine IDEAS Insurrection, Impeachment, and Inauguration: Three Wednesdays in January, Solana Campbell What We Learned from 2020 and Are Keeping in 2021, Sion Kimhttps://digitalcommons.andrews.edu/sm-105/1000/thumbnail.jp

Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer

An autochthonous model of pancreatic ductal adenocarcinoma (PDA) permitted the analysis of why immunotherapy is ineffective in this human disease. Despite finding that PDA-bearing mice had cancer cell-specific CD8+ T cells, the mice, like human patients with PDA, did not respond to two immunological checkpoint antagonists that promote the function of T cells: anti-cytotoxic T-lymphocyte-associated protein 4 (α-CTLA-4) and α-programmed cell death 1 ligand 1 (α-PD-L1). Immune control of PDA growth was achieved, however, by depleting carcinoma-associated fibroblasts (CAFs) that express fibroblast activation protein (FAP). The depletion of the FAP+ stromal cell also uncovered the antitumor effects of α-CTLA-4 and α-PD-L1, indicating that its immune suppressive activity accounts for the failure of these T-cell checkpoint antagonists. Three findings suggested that chemokine (C-X-C motif) ligand 12 (CXCL12) explained the overriding immunosuppression by the FAP+ cell: T cells were absent from regions of the tumor containing cancer cells, cancer cells were coated with the chemokine, CXCL12, and the FAP+ CAF was the principal source of CXCL12 in the tumor. Administering AMD3100, a CXCL12 receptor chemokine (C-X-C motif) receptor 4 inhibitor, induced rapid T-cell accumulation among cancer cells and acted synergistically with α-PD-L1 to greatly diminish cancer cells, which were identified by their loss of heterozygosity of Trp53 gene. The residual tumor was composed only of premalignant epithelial cells and in flammatory cells. Thus, a single protein, CXCL12, from a single stromal cell type, the FAP+ CAF, may direct tumor immune evasion in a model of human PDA

Computed tomographic pulmonary angiography and pulmonary embolism: predictive value of a d-dimer assay

<p>Abstract</p> <p>Background</p> <p>Computed tomographic pulmonary angiography (CTPA) is increasingly being used as first investigation for suspected pulmonary embolism (PE). The investigation has high predictive value, but is resource and time intensive and exposes patients to considerable radiation. Our aim was to assess the potential value of a negative d-dimer assay to exclude pulmonary emboli and reduce the number of performed CTPAs.</p> <p>Methods</p> <p>All CTPAs performed in a Scottish secondary care hospital for a fourteen month period were retrospectively reviewed. Collected data included the presence or absence of PE, d-dimer results and patient demographics. PE positive CTPAs were reviewed by a specialist panel.</p> <p>Results</p> <p>Pulmonary embolisms were reported for 66/405 (16.3%) CTPAs and d-dimer tests were performed for 216 (53%). 186/216 (86%) patients had a positive and 30 (14%) a negative d-dimer result. The panel agreed 5/66 (7.6%) false positive examinations. The d-dimer assay's negative predictive value was 93.3% (95% CI = 76.5%-98.8%) based on the original number of positive CTPAs and 100% (95% CI = 85.9%-100%) based on expert review. Significant non-PE intrapulmonary pathology was reported for 312/405 (77.0) CTPAs, including 13 new diagnoses of carcinoma.</p> <p>Conclusions</p> <p>We found that a low d-dimer score excluded all pulmonary embolisms, after a further specialist panel review identified initial false positive reports. However, current evidence-based guidelines still recommend that clinicians combine a d-dimer result with a validated clinical risk score when selecting suitable patients for CTPA. This may result in better use of limited resources, prevent patients being exposed to unnecessary irradiation and prevent potential complications as a result of iodinated contrast.</p

FPC conditioning cart at BNL

The 703 MHz superconducting gun for the BNL Energy Recovery Linac (ERL) prototype has two fundamental power couplers (FPCs), and each of them will deliver up to 500 kW of CW RF power. In order to prepare the couplers for high power RF service and process multipacting, the FPCs should be conditioned prior to installation into the gun cryomodule. A conditioning cart based test stand, which includes a vacuum pumping system, controllable bake-out system, diagnostics, interlocks and data log system has been designed, constructed and commissioned by collaboration of BNL and AES. This paper presents FPC conditioning cart systems and the conditioning process

Characterization of the Proteostasis Roles of Glycerol Accumulation, Protein Degradation and Protein Synthesis during Osmotic Stress in C. elegans

Exposure of C. elegans to hypertonic stress-induced water loss causes rapid and widespread cellular protein damage. Survival in hypertonic environments depends critically on the ability of worm cells to detect and degrade misfolded and aggregated proteins. Acclimation of C. elegans to mild hypertonic stress suppresses protein damage and increases survival under more extreme hypertonic conditions. Suppression of protein damage in acclimated worms could be due to 1) accumulation of the chemical chaperone glycerol, 2) upregulation of protein degradation activity, and/or 3) increases in molecular chaperoning capacity of the cell. Glycerol and other chemical chaperones are widely thought to protect proteins from hypertonicity-induced damage. However, protein damage is unaffected by gene mutations that inhibit glycerol accumulation or that cause dramatic constitutive elevation of glycerol levels. Pharmacological or RNAi inhibition of proteasome and lyosome function and measurements of cellular protein degradation activity demonstrated that upregulation of protein degradation mechanisms plays no role in acclimation. Thus, changes in molecular chaperone capacity must be responsible for suppressing protein damage in acclimated worms. Transcriptional changes in chaperone expression have not been detected in C. elegans exposed to hypertonic stress. However, acclimation to mild hypertonicity inhibits protein synthesis 50–70%, which is expected to increase chaperone availability for coping with damage to existing proteins. Consistent with this idea, we found that RNAi silencing of essential translational components or acute exposure to cycloheximide results in a 50–80% suppression of hypertonicity-induced aggregation of polyglutamine-YFP (Q35::YFP). Dietary changes that increase protein production also increase Q35::YFP aggregation 70–180%. Our results demonstrate directly for the first time that inhibition of protein translation protects extant proteins from damage brought about by an environmental stressor, demonstrate important differences in aging- versus stress-induced protein damage, and challenge the widely held view that chemical chaperones are accumulated during hypertonic stress to protect protein structure/function

Potency analysis of cellular therapies: the emerging role of molecular assays

Potency testing is an important part of the evaluation of cellular therapy products. Potency assays are quantitative measures of a product-specific biological activity that is linked to a relevant biological property and, ideally, a product's in vivo mechanism of action. Both in vivo and in vitro assays can be used for potency testing. Since there is often a limited period of time between the completion of production and the release from the laboratory for administration to the patient, in vitro assays such are flow cytometry, ELISA, and cytotoxicity are typically used. Better potency assays are needed to assess the complex and multiple functions of cellular therapy products, some of which are not well understood. Gene expression profiling using microarray technology has been widely and effectively used to assess changes of cells in response to stimuli and to classify cancers. Preliminary studies have shown that the expression of noncoding microRNA which play an important role in cellular development, differentiation, metabolism and signal transduction can distinguish different types of stem cells and leukocytes. Both gene and microRNA expression profiling have the potential to be important tools for testing the potency of cellular therapies. Potency testing, the complexities associated with potency testing of cellular therapies, and the potential role of gene and microRNA expression microarrays in potency testing of cellular therapies is discussed

Realization and Properties of Biochemical-Computing Biocatalytic XOR Gate Based on Enzyme Inhibition by a Substrate

We consider a realization of the XOR logic gate in a process biocatalyzed by an enzyme (here horseradish peroxidase: HRP), the function of which can be inhibited by a substrate (hydrogen peroxide for HRP), when the latter is inputted at large enough concentrations. A model is developed for describing such systems in an approach suitable for evaluation of the analog noise amplification properties of the gate. The obtained data are fitted for gate quality evaluation within the developed model, and we discuss aspects of devising XOR gates for functioning in "biocomputing" systems utilizing biomolecules for information processing

A systematic approach to biomarker discovery; Preamble to "the iSBTc-FDA taskforce on immunotherapy biomarkers"

The International Society for the Biological Therapy of Cancer (iSBTc) has initiated in collaboration with the United States Food and Drug Administration (FDA) a programmatic look at innovative avenues for the identification of relevant parameters to assist clinical and basic scientists who study the natural course of host/tumor interactions or their response to immune manipulation. The task force has two primary goals: 1) identify best practices of standardized and validated immune monitoring procedures and assays to promote inter-trial comparisons and 2) develop strategies for the identification of novel biomarkers that may enhance our understating of principles governing human cancer immune biology and, consequently, implement their clinical application. Two working groups were created that will report the developed best practices at an NCI/FDA/iSBTc sponsored workshop tied to the annual meeting of the iSBTc to be held in Washington DC in the Fall of 2009. This foreword provides an overview of the task force and invites feedback from readers that might be incorporated in the discussions and in the final document