Sensitive LC-MS/MS Method for the Quantification of Macrocyclic Gα Protein Inhibitors in Biological Samples.

The cyclic depsipeptide FR900359 (FR) isolated from the plant and produced by endosymbiotic bacteria acts as a selective Gq protein inhibitor. It is a powerful tool to study G protein-coupled receptor signaling, and has potential as a novel drug for the treatment of pulmonary diseases and cancer. For pharmacokinetic studies, sensitive quantitative measurements of drug levels are required.

The evolution of coexistence from competition in experimental co-cultures of Escherichia coli and Saccharomyces cerevisiae.

Microbial communities are comprised of many species that coexist on small spatial scales. This is difficult to explain because many interspecies interactions are competitive, and ecological theory predicts that one species will drive the extinction of another species that competes for the same resource. Conversely, evolutionary theory proposes that natural selection can lead to coexistence by driving competing species to use non-overlapping resources.

Commercial Serology Assays Predict Neutralization Activity against SARS-CoV-2.

Background: It is unknown whether a positive serology result correlates with protective immunity against SARS-CoV-2. There are also concerns regarding the low positive predictive value of SARS-CoV-2 serology tests, especially when testing populations with low disease prevalence.

Methods: A neutralization assay was validated in a set of PCR-confirmed positive specimens and in a negative cohort.

The Relationship Between Acuity of Organ Failure and Predictive Validity of Sepsis-3 Criteria.

Unlabelled: The Sepsis-3 taskforce defined sepsis as suspicion of infection and an acute rise in the Sequential Organ Failure Assessment score by 2 points over the preinfection baseline. Sepsis-3 studies, though, have not distinguished between acute and chronic organ failure, and may not accurately reflect the epidemiology, natural history, or impact of sepsis. Our objective was to determine the extent to which the predictive validity of Sepsis-3 is attributable to chronic rather than acute organ failure.

Targeted Stimulation of an Orbitofrontal Network Disrupts Decisions Based on Inferred, Not Experienced Outcomes.

When direct experience is unavailable, animals and humans can imagine or infer the future to guide decisions. Behavior based on direct experience versus inference may recruit partially distinct brain circuits. In rodents, the orbitofrontal cortex (OFC) contains neural signatures of inferred outcomes, and OFC is necessary for behavior that requires inference but not for responding driven by direct experience.

Superhydrophobic bowl-like SERS substrates patterned from CMOS sensors for extracellular vesicle characterization.

Using a regular CMOS sensor as a template, we are able to fabricate a simple but highly effective superhydrophobic SERS substrate. Specifically, we decorated the microlens layer of the sensor with 7 μm polystyrene beads to obtain a PDMS patterned replica. The process resulted in a uniform pattern of voids in the PDMS (denoted nanobowls) that are intercalated with a few larger voids (denoted here microbowls).

Cross-reactive serum and memory B cell responses to spike protein in SARS-CoV-2 and endemic coronavirus infection.

Pre-existing immune responses to seasonal endemic coronaviruses could have profound consequences for antibody responses to SARS-CoV-2, either induced in natural infection or through vaccination. Such consequences are well established in the influenza and flavivirus fields. A first step to establish whether pre-existing responses can impact SARS-CoV-2 infection is to understand the nature and extent of cross-reactivity in humans to coronaviruses.

Temporal context guides visual exploration during scene recognition.

Memories for episodes are temporally structured. Cognitive models derived from list-learning experiments attribute this structure to the retrieval of temporal context information that indicates when a memory occurred. These models predict key features of memory recall, such as the strong tendency to retrieve studied items in the order in which they were first encountered.

Population genetic structure of the great star coral, Montastraea cavernosa, across the Cuban archipelago with comparisons between microsatellite and SNP markers.

Coral reef habitats surrounding Cuba include relatively healthy, well-developed shallow and mesophotic (30-150 m) scleractinian communities at the cross-currents of the Tropical Western Atlantic (TWA). However, Cuba's coral communities are not immune to the declines observed throughout the TWA, and there is limited information available regarding genetic connectivity, diversity, and structure among these populations. This represents an immense gap in our understanding of coral ecology and population dynamics at both local and regional scales.

Caco-2 Cell Permeability of Flavonoids and Saponins from : the Immortal Herb.

(the immortal herb) has been an important component of Chinese Traditional Medicine for millennia. Recent clinical studies have revealed that the plant exhibits numerous beneficial biological activities, making it of interest to the pharmaceutical industry. An extract of the herb contains over 200 individual secondary metabolites including flavonol glycosides and dammarane saponins.

Surface-enhanced Raman scattering sensing platform for detecting amyloid-β peptide interaction with an aggregation inhibitor.

Soluble, small amyloid- oligomers () are recognized as significant contributors to the pathology of Alzheimer's disease (AD). Although drugs for treating AD symptoms have been approved, no therapy targeting amyloid- () capable of modifying the course of the disease is available. In an effort to develop a label-free method for screening new anti-AD therapeutic agents, we show the use of a surface-enhanced Raman scattering (SERS) active substrate for detecting the interactions between peptides and spin-labeled fluorine (SLF), a peptide aggregation inhibitor.

Public Health Response to Zika Virus Exposure of Air Force Members Deployed to Caribbean Islands, 2016.

Introduction: The emergence of Zika virus disease (ZVD) in areas of military operations provided a new opportunity for force health protection. ZVD infection had an estimated 4:1 asymptomatic-to-symptomatic ratio and can cause neurologic sequelae.

Materials And Methods: We provide a brief report of a field investigation utilizing laboratory-based surveillance and survey instruments to characterize ZVD risk among personnel deployed to the Dominican Republic in support of Operation NEW HORIZONS (NH).

B cells expressing authentic naive human VRC01-class BCRs can be recruited to germinal centers and affinity mature in multiple independent mouse models.

Animal models of human antigen-specific B cell receptors (BCRs) generally depend on "inferred germline" sequences, and thus their relationship to authentic naive human B cell BCR sequences and affinities is unclear. Here, BCR sequences from authentic naive human VRC01-class B cells from healthy human donors were selected for the generation of three BCR knockin mice. The BCRs span the physiological range of affinities found in humans, and use three different light chains (VK3-20, VK1-5, and VK1-33) found among subclasses of naive human VRC01-class B cells and HIV broadly neutralizing antibodies (bnAbs).

Evidence for Immediate Enhancement of Hippocampal Memory Encoding by Network-Targeted Theta-Burst Stimulation during Concurrent fMRI.

The hippocampus supports episodic memory via interaction with a distributed brain network. Previous experiments using network-targeted noninvasive brain stimulation have identified episodic memory enhancements and modulation of activity within the hippocampal network. However, mechanistic insights were limited because these effects were measured long after stimulation and therefore could have reflected various neuroplastic aftereffects with extended time courses.

Cerebellar Theta and Beta Noninvasive Stimulation Rhythms Differentially Influence Episodic Memory versus Semantic Prediction.

The human cerebellum is thought to interact with distributed brain networks to support cognitive abilities such as episodic memory and semantic prediction. Hippocampal and fronto-temporo-parietal networks that respectively support episodic memory versus semantic prediction have been associated with distinct endogenous oscillatory activity frequency bands: theta (∼3-8 Hz) versus beta (∼13-30 Hz) respectively. We sought to test whether it is possible to toggle cerebellar participation in episodic memory versus semantic prediction by noninvasively stimulating with theta versus beta rhythmic transcranial magnetic stimulation.

Musculoskeletal Injuries and Automation in Aerial Port Operations.

: Aerial ports are being modernized with automated technologies, but the impact on musculoskeletal injury (MSKI) is unknown.: In this retrospective cohort study of U.S.

On the shape-dependent propulsion of nano- and microparticles by traveling ultrasound waves.

We address the propulsion mechanism of ultrasound-propelled nano- and microparticles that are exposed to a traveling ultrasound wave. Based on direct computational fluid dynamics simulations, we study the effect of two important aspects of the particle shape on the propulsion: rounded pointed and filled hollow shapes. We also study the flow field generated around such particles.

Secondary renal neoplasia following chemotherapy or radiation in pediatric patients.

Renal neoplasia occurring as a second malignancy following childhood cancer has been most closely associated with neuroblastoma and Wilms tumor. While some cases have been associated with a genetic predisposition, nearly all are thought to result from "late effects" of therapy-related toxicity that involves chemotherapy or radiation. It is unclear if these tumors are enriched for specific molecular or morphologic characteristics.

Reinforcing Telehealth Competence Through Nurse Practitioner Student Clinical Experiences.

Background: Telehealth is becoming increasingly integral in providing improved access to care, especially for patients who reside in frontier and rural areas. Nurse practitioner (NP) faculty are charged with preparing NP students through curriculum and clinical experiences that align with the health care environment and the health care access needs of the populations they serve.

Method: To meet this need, NP faculty at a land-grant university located in a frontier and rural midwestern state reinforced NP student telehealth curriculum and competency through application in a clinical environment.

Discovery and mechanistic characterization of a structurally-unique membrane active peptide.

Membrane active peptides (MAPs) have gained wide interest due to their far reaching applications in drug discovery and drug delivery. The search for new MAPs, however, has been largely skewed with bias selecting for physicochemical parameters believed to be important for membrane activity, such as alpha helicity, cationicity and hydrophobicity. Here we carry out a search-and-find strategy to screen a 100,000-membered one-bead-one-compound (OBOC) combinatorial peptide library for lead compounds, agnostic of those physicochemical constraints.

Sexual risk behaviors and influencing factors among Muslim adolescents on southern border of Thailand.

Objectives: To describe individual, interpersonal, and environmental factors and sexual risk behaviors among Thai Muslim adolescents.

Methods: We recruited adolescents from four schools and one vocational college on the Southern border of Thailand during October 2018 to January 2019. We used password-protected online questionnaires for each respondent to protect their privacy.

HIV envelope trimer-elicited autologous neutralizing antibodies bind a region overlapping the N332 glycan supersite.

To date, immunization studies of rabbits with the BG505 SOSIP.664 HIV envelope glycoprotein trimers have revealed the 241/289 glycan hole as the dominant neutralizing antibody epitope. Here, we isolated monoclonal antibodies from a rabbit that did not exhibit glycan hole-dependent autologous serum neutralization.

Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model.

Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled a cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-recovered participants, developed neutralization assays to investigate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen more than 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein.