Reduction of Central-line-Associated Bloodstream Infections in a Tertiary Neonatal Intensive Care Unit through Simulation Education.

Introduction: Critically ill neonates and those with complex medical conditions frequently require the use of central venous lines. Unfortunately, central line-associated bloodstream infections (CLABSIs) result in significant morbidity and mortality, and the cost and increased length of stay burden the healthcare system. Previous studies have demonstrated that standardized care bundles can decrease CLABSI rates, but achieving sustained improvement has proven difficult.

Explainable machine learning improves interpretability in the predictive modeling of biological stream conditions in the Chesapeake Bay Watershed, USA.

Anthropogenic alterations have resulted in widespread degradation of stream conditions. To aid in stream restoration and management, baseline estimates of conditions and improved explanation of factors driving their degradation are needed. We used random forests to model biological conditions using a benthic macroinvertebrate index of biotic integrity for small, non-tidal streams (upstream area ≤200 km) in the Chesapeake Bay watershed (CBW) of the mid-Atlantic coast of North America.

Linking Altered Flow Regimes to Biological Condition: an Example Using Benthic Macroinvertebrates in Small Streams of the Chesapeake Bay Watershed.

Regionally scaled assessments of hydrologic alteration for small streams and its effects on freshwater taxa are often inhibited by a low number of stream gages. To overcome this limitation, we paired modeled estimates of hydrologic alteration to a benthic macroinvertebrate index of biotic integrity data for 4522 stream reaches across the Chesapeake Bay watershed. Using separate random-forest models, we predicted flow status (inflated, diminished, or indeterminant) for 12 published hydrologic metrics (HMs) that characterize the main components of flow regimes.

Using expert knowledge to support Endangered Species Act decision-making for data-deficient species.

Many questions relevant to conservation decision-making are characterized by extreme uncertainty due to lack of empirical data and complexity of the underlying ecologic processes, leading to a rapid increase in the use of structured protocols to elicit expert knowledge. Published ecologic applications often employ a modified Delphi method, where experts provide judgments anonymously and mathematical aggregation techniques are used to combine judgments. The Sheffield elicitation framework (SHELF) differs in its behavioral approach to synthesizing individual judgments into a fully specified probability distribution for an unknown quantity.

Disentangling the potential effects of land-use and climate change on stream conditions.

Land-use and climate change are significantly affecting stream ecosystems, yet understanding of their long-term impacts is hindered by the few studies that have simultaneously investigated their interaction and high variability among future projections. We modeled possible effects of a suite of 2030, 2060, and 2090 land-use and climate scenarios on the condition of 70,772 small streams in the Chesapeake Bay watershed, United States. The Chesapeake Basin-wide Index of Biotic Integrity, a benthic macroinvertebrate multimetric index, was used to represent stream condition.

Brook trout distributional response to unconventional oil and gas development: Landscape context matters.

We conducted a large-scale assessment of unconventional oil and gas (UOG) development effects on brook trout (Salvelinus fontinalis) distribution. We compiled 2231 brook trout collection records from the Upper Susquehanna River Watershed, USA. We used boosted regression tree (BRT) analysis to predict occurrence probability at the 1:24,000 stream-segment scale as a function of natural and anthropogenic landscape and climatic attributes.

A detailed risk assessment of shale gas development on headwater streams in the Pennsylvania portion of the Upper Susquehanna River Basin, U.S.A.

The development of unconventional oil and gas (UOG) involves infrastructure development (well pads, roads and pipelines), well drilling and stimulation (hydraulic fracturing), and production; all of which have the potential to affect stream ecosystems. Here, we developed a fine-scaled (1:24,000) catchment-level disturbance intensity index (DII) that included 17 measures of UOG capturing all steps in the development process (infrastructure, water withdrawals, probabilistic spills) that could affect headwater streams (<200km in upstream catchment) in the Upper Susquehanna River Basin in Pennsylvania, U.S.

Heteroaryldihydropyrimidine (HAP) and Sulfamoylbenzamide (SBA) Inhibit Hepatitis B Virus Replication by Different Molecular Mechanisms.

Heteroaryldihydropyrimidine (HAP) and sulfamoylbenzamide (SBA) are promising non-nucleos(t)ide HBV replication inhibitors. HAPs are known to promote core protein mis-assembly, but the molecular mechanism of abnormal assembly is still elusive. Likewise, the assembly status of core protein induced by SBA remains unknown.

Predicting the Occurrence of Cave-Inhabiting Fauna Based on Features of the Earth Surface Environment.

One of the most challenging fauna to study in situ is the obligate cave fauna because of the difficulty of sampling. Cave-limited species display patchy and restricted distributions, but it is often unclear whether the observed distribution is a sampling artifact or a true restriction in range. Further, the drivers of the distribution could be local environmental conditions, such as cave humidity, or they could be associated with surface features that are surrogates for cave conditions.

Cytosolic sulfotransferase 1A1 regulates HIV-1 minus-strand DNA elongation in primary human monocyte-derived macrophages.

Background: The cellular sulfonation pathway modulates key steps of virus replication. This pathway comprises two main families of sulfonate-conjugating enzymes: Golgi sulfotransferases, which sulfonate proteins, glycoproteins, glycolipids and proteoglycans; and cytosolic sulfotransferases (SULTs), which sulfonate various small molecules including hormones, neurotransmitters, and xenobiotics. Sulfonation controls the functions of numerous cellular factors such as those involved in cell-cell interactions, cell signaling, and small molecule detoxification.

Accounting for groundwater in stream fish thermal habitat responses to climate change.

Forecasting climate change effects on aquatic fauna and their habitat requires an understanding of how water temperature responds to changing air temperature (i.e., thermal sensitivity).

BIRC2/cIAP1 Is a Negative Regulator of HIV-1 Transcription and Can Be Targeted by Smac Mimetics to Promote Reversal of Viral Latency.

Combination antiretroviral therapy (ART) is able to suppress HIV-1 replication to undetectable levels. However, the persistence of latent viral reservoirs allows for a rebound of viral load upon cessation of therapy. Thus, therapeutic strategies to eradicate the viral latent reservoir are critically needed.

Senataxin suppresses the antiviral transcriptional response and controls viral biogenesis.

The human helicase senataxin (SETX) has been linked to the neurodegenerative diseases amyotrophic lateral sclerosis (ALS4) and ataxia with oculomotor apraxia (AOA2). Here we identified a role for SETX in controlling the antiviral response. Cells that had undergone depletion of SETX and SETX-deficient cells derived from patients with AOA2 had higher expression of antiviral mediators in response to infection than did wild-type cells.

Using ecological indicators and a decision support system for integrated ecological assessment at two national park units in the mid-Atlantic region, USA.

We implemented an integrated ecological assessment using a GIS-based decision support system model for Upper Delaware Scenic and Recreational River (UPDE) and Delaware Water Gap National Recreation Area (DEWA)-national park units with the mid-Atlantic region of the United States. Our assessment examined a variety of aquatic and terrestrial indicators of ecosystem components that reflect the parks' conservation purpose and reference condition. Our assessment compared these indicators to ecological thresholds to determine the condition of park watersheds.

Sulfonation pathway inhibitors block reactivation of latent HIV-1.

Long-lived pools of latently infected cells are a significant barrier to the development of a cure for HIV-1 infection. A better understanding of the mechanisms of reactivation from latency is needed to facilitate the development of novel therapies that address this problem. Here we show that chemical inhibitors of the sulfonation pathway prevent virus reactivation, both in latently infected J-Lat and U1 cell lines and in a primary human CD4+ T cell model of latency.

CHD1 and CHD2 are positive regulators of HIV-1 gene expression.

Background: Retroviruses encode a very limited number of proteins and therefore must exploit a wide variety of host proteins for completion of their lifecycle.

Methods: We performed an insertional mutagenesis screen to identify novel cellular regulators of retroviral replication.

Results: This approach identified the ATP-dependent chromatin remodeler, chromodomain helicase DNA-binding protein 2 (CHD2), as well as the highly related CHD1 protein, as positive regulators of both MLV and HIV-1 replication in rodent and human cells.

An integrated map of HIV-human protein complexes that facilitate viral infection.

Recent proteomic and genetic studies have aimed to identify a complete network of interactions between HIV and human proteins and genes. This HIV-human interaction network provides invaluable information as to how HIV exploits the host machinery and can be used as a starting point for further functional analyses. We integrated this network with complementary datasets of protein function and interaction to nominate human protein complexes with likely roles in viral infection.

Tumor suppressor cylindromatosis (CYLD) controls HIV transcription in an NF-κB-dependent manner.

Unlabelled: Characterizing the cellular factors that play a role in the HIV replication cycle is fundamental to fully understanding mechanisms of viral replication and pathogenesis. Whole-genome small interfering RNA (siRNA) screens have identified positive and negative regulators of HIV replication, providing starting points for investigating new cellular factors. We report here that silencing of the deubiquitinase cylindromatosis protein (CYLD), increases HIV infection by enhancing HIV long terminal repeat (LTR)-driven transcription via the NF-κB pathway.

Discovery of novel inhibitors of HIV-1 reverse transcriptase through virtual screening of experimental and theoretical ensembles.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are potent anti-HIV chemotherapeutics. Although there are FDA-approved NNRTIs, challenges such as the development of resistance have limited their utility. Here, we describe the identification of novel NNRTIs through a combination of computational and experimental approaches.

ZASC1 stimulates HIV-1 transcription elongation by recruiting P-TEFb and TAT to the LTR promoter.

Transcription from the HIV-1 LTR promoter efficiently initiates but rapidly terminates because of a non-processive form of RNA polymerase II. This premature termination is overcome by assembly of an HIV-1 TAT/P-TEFb complex at the transactivation response region (TAR), a structured RNA element encoded by the first 59 nt of HIV-1 mRNA. Here we have identified a conserved DNA-binding element for the cellular transcription factor, ZASC1, in the HIV-1 core promoter immediately upstream of TAR.

Enveloped viruses disable innate immune responses in dendritic cells by direct activation of TAM receptors.

Upon activation by the ligands Gas6 and Protein S, Tyro3/Axl/Mer (TAM) receptor tyrosine kinases promote phagocytic clearance of apoptotic cells and downregulate immune responses initiated by Toll-like receptors and type I interferons (IFNs). Many enveloped viruses display the phospholipid phosphatidylserine on their membranes, through which they bind Gas6 and Protein S and engage TAM receptors. We find that ligand-coated viruses activate TAM receptors on dendritic cells (DCs), dampen type I IFN signaling, and thereby evade host immunity and promote infection.

ZASC1 knockout mice exhibit an early bone marrow-specific defect in murine leukemia virus replication.

Background: ZASC1 is a zinc finger-containing transcription factor that was previously shown to bind to specific DNA binding sites in the Moloney murine leukemia virus (Mo-MuLV) promoter and is required for efficient viral mRNA transcription (J. Virol. 84:7473-7483, 2010).

Identification of a 3-aminoimidazo[1,2-a]pyridine inhibitor of HIV-1 reverse transcriptase.

Background: Despite the effectiveness of highly active antiretroviral therapy (HAART), there remains an urgent need to develop new human immunodeficiency virus type 1 (HIV-1) inhibitors with better pharmacokinetic properties that are well tolerated, and that block common drug resistant virus strains.

Methods: Here we screened an in-house small molecule library for novel inhibitors of HIV-1 replication.

Results: An active compound containing a 3-aminoimidazo[1,2-a]pyridine scaffold was identified and quantitatively characterized as a non-nucleoside reverse transcriptase inhibitor (NNRTI).

Chemical contaminants in water and sediment near fish nesting sites in the Potomac River basin: determining potential exposures to smallmouth bass (Micropterus dolomieu).

The Potomac River basin is an area where a high prevalence of abnormalities such as testicular oocytes (TO), skin lesions, and mortality has been observed in smallmouth bass (SMB, Micropterus dolomieu). Previous research documented a variety of chemicals in regional streams, implicating chemical exposure as one plausible explanation for these biological effects. Six stream sites in the Potomac basin (and one out-of-basin reference site) were sampled to provide an assessment of chemicals in these streams.

Anthrax toxin receptor 2 functions in ECM homeostasis of the murine reproductive tract and promotes MMP activity.

Anthrax Toxin Receptor proteins function as receptors for anthrax toxin, however physiological activity remains unclear. To evaluate the biological role of Antxr2, we generated Antxr2-/- mice. Antxr2-/- mice were viable, however Antxr2 is required for parturition in young females and for preserving fertility in older female mice.