Studying interactions among anthropogenic stressors in freshwater ecosystems: A systematic review of 2396 multiple-stressor experiments.

Understanding the interactions among anthropogenic stressors is critical for effective conservation and management of ecosystems. Freshwater scientists have invested considerable resources in conducting factorial experiments to disentangle stressor interactions by testing their individual and combined effects. However, the diversity of stressors and systems studied has hindered previous syntheses of this body of research.

The combined effects of treated sewage discharge and land use on rivers.

Freshwater ecosystems are increasingly threatened by multiple anthropogenic stressors. Release of treated sewage effluent and pollution from agricultural or urban sources can independently reduce water quality with implications for ecological communities. However, our knowledge of the combined effects of these stressors is limited.

Prediction of Tinnitus Treatment Outcomes Based on EEG Sensors and TFI Score Using Deep Learning.

Tinnitus is a hearing disorder that is characterized by the perception of sounds in the absence of an external source. Currently, there is no pharmaceutical cure for tinnitus, however, multiple therapies and interventions have been developed that improve or control associated distress and anxiety. We propose a new Artificial Intelligence (AI) algorithm as a digital prognostic health system that models electroencephalographic (EEG) data in order to predict patients' responses to tinnitus therapies.

A randomized single-blind controlled trial of a prototype digital polytherapeutic for tinnitus.

Objective: This randomized single-blind controlled trial tested the hypothesis that a prototype digital therapeutic developed to provide goal-based counseling with personalized passive and active game-based sound therapy would provide superior tinnitus outcomes, and similar usability, to a popular passive sound therapy app over a 12 week trial period.

Methods: The digital therapeutic consisted of an app for iPhone or Android smartphone, Bluetooth bone conduction headphones, neck pillow speaker, and a cloud-based clinician dashboard to enable messaging and app personalization. The control app was a popular self-help passive sound therapy app called White Noise Lite (WN).

Activated B Cells and Plasma Cells Are Resistant to Radiation Therapy.

Purpose: B cells play a key role in outcomes of cancer patients and responses to checkpoint blockade immunotherapies. However, the effect of radiation therapy on B cell populations is poorly understood. Here we characterize the effects of radiation on the development, survival, and phenotype of physiological B-cell subsets.

Behavioral Outcomes and Neural Network Modeling of a Novel, Putative, Recategorization Sound Therapy.

The mechanisms underlying sound's effect on tinnitus perception are unclear. Tinnitus activity appears to conflict with perceptual expectations of "real" sound, resulting in it being a salient signal. Attention diverted towards tinnitus during the later stages of object processing potentially disrupts high-order auditory streaming, and its uncertain nature results in negative psychological responses.

Prediction of tinnitus masking benefit within a case series using a spiking neural network model.

Masking has been widely used as a tinnitus therapy, with large individual differences in its effectiveness. The basis of this variation is unknown. We examined individual tinnitus and psychological responses to three masking types, energetic masking (bilateral broadband static or rain noise [BBN]), informational masking (BBN with a notch at tinnitus pitch and 3-dimensional cues) and a masker combining both effects (BBN with spatial cues).

Prediction of Acoustic Residual Inhibition of Tinnitus Using a Brain-Inspired Spiking Neural Network Model.

Auditory Residual Inhibition (ARI) is a temporary suppression of tinnitus that occurs in some people following the presentation of masking sounds. Differences in neural response to ARI stimuli may enable classification of tinnitus and a tailored approach to intervention in the future. In an exploratory study, we investigated the use of a brain-inspired artificial neural network to examine the effects of ARI on electroencephalographic function, as well as the predictive ability of the model.

Distal lung epithelial progenitor cell function declines with age.

Tissue stem cell exhaustion is a key hallmark of aging, and in this study, we characterised its manifestation in the distal lung. We compared the lungs of 3- and 22-month old mice. We examined the gross morphological changes in these lungs, the density and function of epithelial progenitor populations and the epithelial gene expression profile.

On the Timing of Signals in Multisensory Integration and Crossmodal Interactions: a Scoping Review.

A scoping review was undertaken to explore research investigating early interactions and integration of auditory and visual stimuli in the human brain. The focus was on methods used to study low-level multisensory temporal processing using simple stimuli in humans, and how this research has informed our understanding of multisensory perception. The study of multisensory temporal processing probes how the relative timing between signals affects perception.

Diagnostic Accuracy of Serum, Synovial, and Tissue Testing for Chronic Periprosthetic Joint Infection After Hip and Knee Replacements: A Systematic Review.

Background: Chronic periprosthetic joint infection (PJI) is a devastating complication that can occur following total joint replacement. Patients with chronic PJI report a substantially lower quality of life and face a higher risk of short-term mortality. Establishing a diagnosis of chronic PJI is challenging because of conflicting guidelines, numerous tests, and limited evidence.

A review of plasticity induced by auditory and visual tetanic stimulation in humans.

Long-term potentiation is a form of synaptic plasticity thought to play an important role in learning and memory. Recently noninvasive methods have been developed to induce and measure activity similar to long-term potentiation in humans. Sensory tetani (trains of quickly repeating auditory or visual stimuli) alter the electroencephalogram in a manner similar to electrical stimulation that results in long-term potentiation.

Interleukin-33 is activated by allergen- and necrosis-associated proteolytic activities to regulate its alarmin activity during epithelial damage.

Interleukin (IL)-33 is an IL-1 family alarmin released from damaged epithelial and endothelial barriers to elicit immune responses and allergic inflammation via its receptor ST2. Serine proteases released from neutrophils, mast cells and cytotoxic lymphocytes have been proposed to process the N-terminus of IL-33 to enhance its activity. Here we report that processing of full length IL-33 can occur in mice deficient in these immune cell protease activities.

Exceptional Response to Nivolumab and Stereotactic Body Radiation Therapy (SBRT) in Neuroendocrine Cervical Carcinoma with High Tumor Mutational Burden: Management Considerations from the Center For Personalized Cancer Therapy at UC San Diego Moores Cancer Center.

Unlabelled: Neuroendocrine carcinoma of the cervix is an ultra-rare malignancy with a poor prognosis and limited treatment options. Checkpoint blockade immunotherapy has rapidly developed into an emerging standard of care for several common disease types. Interestingly, in preclinical and retrospective clinical data, radiation therapy has been demonstrated to synergize with checkpoint inhibitors.

Diacylglycerol kinase ε deficiency preserves glucose tolerance and modulates lipid metabolism in obese mice.

Diacylglycerol kinases (DGKs) catalyze the phosphorylation and conversion of diacylglycerol (DAG) into phosphatidic acid. DGK isozymes have unique primary structures, expression patterns, subcellular localizations, regulatory mechanisms, and DAG preferences. DGKε has a hydrophobic segment that promotes its attachment to membranes and shows substrate specificity for DAG with an arachidonoyl acyl chain in the sn-2 position of the substrate.

Forced cell cycle exit and modulation of GABAA, CREB, and GSK3β signaling promote functional maturation of induced pluripotent stem cell-derived neurons.

Although numerous protocols have been developed for differentiation of neurons from a variety of pluripotent stem cells, most have concentrated on being able to specify effectively appropriate neuronal subtypes and few have been designed to enhance or accelerate functional maturity. Of those that have, most employ time courses of functional maturation that are rather protracted, and none have fully characterized all aspects of neuronal function, from spontaneous action potential generation through to postsynaptic receptor maturation. Here, we describe a simple protocol that employs the sequential addition of just two supplemented media that have been formulated to separate the two key phases of neural differentiation, the neurogenesis and synaptogenesis, each characterized by different signaling requirements.

Mitochondrial-targeted antioxidant therapy decreases transforming growth factor-β-mediated collagen production in a murine asthma model.

Asthma is a disease of acute and chronic inflammation in which cytokines play a critical role in orchestrating the allergic inflammatory response. IL-13 and transforming growth factor (TGF)-β promote fibrotic airway remodeling, a major contributor to disease severity. Improved understanding is needed, because current therapies are inadequate for suppressing development of airway fibrosis.

CaMKII is essential for the proasthmatic effects of oxidation.

Increased reactive oxygen species (ROS) contribute to asthma, but little is known about the molecular mechanisms connecting increased ROS with characteristic features of asthma. We show that enhanced oxidative activation of the Ca(2+)/calmodulin-dependent protein kinase (ox-CaMKII) in bronchial epithelium positively correlates with asthma severity and that epithelial ox-CaMKII increases in response to inhaled allergens in patients. We used mouse models of allergic airway disease induced by ovalbumin (OVA) or Aspergillus fumigatus (Asp) and found that bronchial epithelial ox-CaMKII was required to increase a ROS- and picrotoxin-sensitive Cl(-) current (ICl) and MUC5AC expression, upstream events in asthma progression.

Lysophosphatidylcholine acyltransferase 3 knockdown-mediated liver lysophosphatidylcholine accumulation promotes very low density lipoprotein production by enhancing microsomal triglyceride transfer protein expression.

After de novo biosynthesis phospholipids undergo extensive remodeling by the Lands' cycle. Enzymes involved in phospholipid biosynthesis have been studied extensively but not those involved in reacylation of lysophosphopholipids. One key enzyme in the Lands' cycle is fatty acyl-CoA:lysophosphatidylcholine acyltransferase (LPCAT), which utilizes lysophosphatidylcholine (LysoPC) and fatty acyl-CoA to produce various phosphatidylcholine (PC) species.

The multifunctional Ca2+/calmodulin-dependent kinase II regulates vascular smooth muscle migration through matrix metalloproteinase 9.

The multifunctional CaMKII has been implicated in vascular smooth muscle cell (VSMC) migration, but little is known regarding its downstream targets that mediate migration. Here, we examined whether CaMKII regulates migration through modulation of matrix metalloproteinase 9 (MMP9). Using CaMKIIδ(-/-) mice as a model system, we evaluated migration and MMP9 regulation in vitro and in vivo.

Sildenafil prevents and reverses transverse-tubule remodeling and Ca(2+) handling dysfunction in right ventricle failure induced by pulmonary artery hypertension.

Right ventricular (RV) failure (RVF) is the main cause of death in patients with pulmonary artery hypertension (PAH). Sildenafil, a phosphodiesterase type 5 inhibitor, was approved recently for treatment of PAH patients. However, the mechanisms underlying RV contractile malfunction and the benefits of sildenafil on RV function are not well understood.

The multifunctional Ca2+/calmodulin-dependent kinase II delta (CaMKIIdelta) controls neointima formation after carotid ligation and vascular smooth muscle cell proliferation through cell cycle regulation by p21.

The multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) promotes vascular smooth muscle (VSMC) proliferation. However, the signaling pathways mediating CAMKII-dependent proliferative effects in vivo are poorly understood. This study tested the hypothesis that CaMKIIδ mediates neointimal proliferation after carotid artery ligation by regulating expression and activity of cell cycle regulators, particularly at the G1/S checkpoint.

AGPAT6 is a novel microsomal glycerol-3-phosphate acyltransferase.

AGPAT6 is a member of the 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) family that appears to be important in triglyceride biosynthesis in several tissues, but the precise biochemical function of the enzyme is unknown. In the current study, we show that AGPAT6 is a microsomal glycerol-3-phosphate acyltransferase (GPAT). Membranes from HEK293 cells overexpressing human AGPAT6 had higher levels of GPAT activity.