Interplay of the Indian summer monsoon and intermonsoon precipitation in Sri Lanka due to ITCZ migration during the last 80000 years.

Precipitation variations in the tropical Indian Ocean region result from changes in the Indian Summer Monsoon (ISM), as well as convective and cyclonic rainfall. The relative roles of such forcing can be elucidated by constructing robust paleoclimate records, which help to better predict future variability in precipitation due to rising greenhouse gases. This study was carried out using a suite of paleoclimate proxies on a combination of marine and terrestrial sediment cores from Sri Lanka.

A Novel Load-Sharing System to Simulate the Creep of Strain-Hardening Cementitious Composites (SHCCs) in Practical Situations.

The ductility and exhibition of the multiple, fine, self-controlled cracking of strain-hardening cementitious composites (SHCCs) under tension has made them attractive for enhancing the durability of civil infrastructure. These fine cracks are key to preventing the ingress of water and harmful chemicals into the structure and thereby achieving steel reinforcement. However, several studies have suggested that the short-term fine cracks shown in the laboratory may end up exceeding the acceptable crack widths that are specified in design codes when SHCC members are subjected to sustained constant loads.

Transcranial Doppler ultrasound to evaluate the risk of hyperperfusion after endovascular stroke thrombectomy.

Background And Purpose: Hemorrhagic transformation (HT) has been reported in up to 50% of acute ischemic stroke (AIS) patients with a large vessel occlusion (LVO) treated with endovascular thrombectomy (EVT). HT may be driven by postrecanalization hyperperfusion injury and is independently associated with worse functional outcomes. Strategies to identify patients at risk for HT may assist in developing preventive therapies.

The spatial distribution of GPCR and Gβγ activity across a cell dictates PIP3 dynamics.

Phosphatidylinositol (3,4,5) trisphosphate (PIP3) is a plasma membrane-bound signaling phospholipid involved in many cellular signaling pathways that control crucial cellular processes and behaviors, including cytoskeleton remodeling, metabolism, chemotaxis, and apoptosis. Therefore, defective PIP3 signaling is implicated in various diseases, including cancer, diabetes, obesity, and cardiovascular diseases. Upon activation by G protein-coupled receptors (GPCRs) or receptor tyrosine kinases (RTKs), phosphoinositide-3-kinases (PI3Ks) phosphorylate phosphatidylinositol (4,5) bisphosphate (PIP2), generating PIP3.

The Capability Maturity Model as a Measure of Culture of Care in Laboratory Animal Science.

Culture of care in Laboratory Animal Science (LAS) refers to a commitment toward improving animal welfare, scientific quality, staff wellbeing, and transparency for all stakeholders, ensuring that the animals and personnel involved are treated with compassion and respect. A strong culture of care can be established by the proactive implementation of the Three Rs, sharing best practices, caring for and respecting animals and colleagues, empowering staff, taking responsibility for our actions, and having a caring leadership. Culture of care, when established, should be evaluated continuously, in order to foster its progress and persistence.

Vector of motion measurements in the living cochlea using a 3D OCT vibrometry system.

Optical coherence tomography (OCT) has become an important tool for measuring the vibratory response of the living cochlea. It stands alone in its capacity to measure the intricate motion of the hearing organ through the surrounding otic capsule bone. Nevertheless, as an extension of phase-sensitive OCT, it is only capable of measuring motion along the optical axis.

In vivo functional imaging of the human middle ear with a hand-held optical coherence tomography device.

We describe an optical coherence tomography and vibrometry system designed for portable hand-held usage in the otology clinic on awake patients. The system provides clinically relevant point-of-care morphological imaging with 14-44 µm resolution and functional vibratory measures with sub-nanometer sensitivity. We evaluated various new approaches for extracting functional information including a multi-tone stimulus, a continuous chirp stimulus, and alternating air and bone stimulus.

The Effectiveness of a Pediatric Emergency Medicine Block Education Session for Pediatric Residents.

Background And Objective: There exists no standardized curriculum for pediatric residents to develop procedural skills during residency training. Many pediatric residency programs are transitioning to block education sessions; the effectiveness of this format for delivering pediatric emergency medicine (PEM) procedural curriculum has not been evaluated. The objective is to determine if a PEM block education session improved pediatric residents' knowledge and confidence in 4 domains: laceration repair, splinting of extremities, resuscitation/airway management, and point-of-care ultrasound.

Subtype-dependent regulation of Gβγ signalling.

G protein-coupled receptors (GPCRs) transmit information to the cell interior by transducing external signals to heterotrimeric G protein subunits, Gα and Gβγ subunits, localized on the inner leaflet of the plasma membrane. Though the initial focus was mainly on Gα-mediated events, Gβγ subunits were later identified as major contributors to GPCR-G protein signalling. A broad functional array of Gβγ signalling has recently been attributed to Gβ and Gγ subtype diversity, comprising 5 Gβ and 12 Gγ subtypes, respectively.

Microcystins: Biogenesis, Toxicity, Analysis, and Control.

Microcystins are cyclic peptide toxins formed by cyanobacteria. These toxins are recognized for their association with algal blooms, posing a significant threat to ecosystems and drinking water quality. Due to the growing environmental concerns they raise, a comprehensive review on microcystins' genesis, toxicity, and analytical methods for their quantitative determination is outlined.

Blue light-triggered photochemistry and cytotoxicity of retinal.

The chemical- and photo- toxicity of chromophore retinal on cells have long been debated. Although we recently showed that retinal and blue light exposure interrupt cellular signaling, a comprehensive study examining molecular underpinnings of this perturbation and its consequences to cellular fate is lacking. Here, we report molecular evidence for blue light excited-retinal induced oxidative damage of polyunsaturated lipid anchors in membrane-interacting signaling molecules and DNA damage in cells using live-cell imaging and in vitro experimentation.

A Specialized Pediatric Emergency Medicine Track Decreases Computed Tomography in Head Injured Patients.

Background: There is an increased emphasis on reducing exposure to ionizing radiation in pediatric patients. Guidelines from the Pediatric Emergency Care Applied Research Network help practitioners identify patients at low risk for clinically important traumatic brain injury after head injury.

Objectives: We seek to determine whether the institution of a pediatric track staffed by pediatric emergency medicine physicians (PEMs) within a community emergency department (ED) impacts the overall utilization of head computed tomography (CT) on children younger than 15 years with head injury.

Optical approaches for single-cell and subcellular analysis of GPCR-G protein signaling.

G protein-coupled receptors (GPCRs), G proteins, and their signaling associates are major signal transducers that control the majority of cellular signaling and regulate key biological functions including immune, neurological, cardiovascular, and metabolic processes. These pathways are targeted by over one-third of drugs on the market; however, the current understanding of their function is limited and primarily derived from cell-destructive approaches providing an ensemble of static, multi-cell information about the status and composition of molecules. Spatiotemporal behavior of molecules involved is crucial to understanding in vivo cell behaviors both in health and disease, and the advent of genetically encoded fluorescence proteins and small fluorophore-based biosensors has facilitated the mapping of dynamic signaling in cells with subcellular acuity.

Blue light excited retinal intercepts cellular signaling.

Photoreceptor chromophore, 11-cis retinal (11CR) and the photoproduct, all-trans retinal (ATR), are present in the retina at higher concentrations and interact with the visual cells. Non-visual cells in the body are also exposed to retinal that enters the circulation. Although the cornea and the lens of the eye are transparent to the blue light region where retinal can absorb and undergo excitation, the reported phototoxicity in the eye has been assigned to lipophilic non-degradable materials known as lipofuscins, which also includes retinal condensation products.

G protein γ (Gγ) subtype dependent targeting of GRK2 to M3 receptor by Gβγ.

Interactions of cytosolic G protein coupled receptor kinase 2 (GRK2) with activated G protein coupled receptors (GPCRs) induce receptor phosphorylation and desensitization. GRK2 is recruited to active M3-muscarinic receptors (M3R) with the participation of the receptor, Gαq and Gβγ. Since we have shown that signaling efficacy of Gβγ is governed by its Gγ subtype identity, the present study examined whether recruitment of GRK2 to M3R is also Gγ subtype dependent.

Regulation of G Protein βγ Signaling.

Heterotrimeric guanine nucleotide-binding proteins (G proteins) deliver external signals to the cell interior, upon activation by the external signal stimulated G protein-coupled receptors (GPCRs).While the activated GPCRs control several pathways independently, activated G proteins control the vast majority of cellular and physiological functions, ranging from vision to cardiovascular homeostasis. Activated GPCRs dissociate GαGDPβγ heterotrimer into GαGTP and free Gβγ.

Melanopsin (Opn4) utilizes Gα and Gβγ as major signal transducers.

Melanopsin (Opn4), a ubiquitously expressed photoreceptor in all classes of vertebrates, is crucial for both visual and non-visual signaling. Opn4 supports visual functions of the eye by sensing radiance levels and discriminating contrast and brightness. Non-image-forming functions of Opn4 not only regulate circadian behavior, but also control growth and development processes of the retina.

Pharmacist supply of sildenafil: pharmacists' experiences and perceptions on training and tools for supply.

Background In 2014, New Zealand reclassified sildenafil (for erectile dysfunction) to allow supply by specially trained pharmacists under strict criteria. Objective The study aimed to determine pharmacists' experiences and perspectives on the training for, and supply of sildenafil under this model. Setting New Zealand community pharmacy.

Measurement of GPCR-G protein activity in living cells.

G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors in eukaryotic genomes. They control a variety of cellular and physiological processes such as hormone secretion and heart rate, and therefore are associated with a majority of pathological conditions including cancer and heart diseases. Currently established assays to measure ligand-induced activation of GPCRs and G proteins possess limitations such as being time consuming, indirect, and expensive.

Two independent but synchronized Gβγ subunit-controlled pathways are essential for trailing-edge retraction during macrophage migration.

Chemokine-induced directional cell migration is a universal cellular mechanism and plays crucial roles in numerous biological processes, including embryonic development, immune system function, and tissue remodeling and regeneration. During the migration of a stationary cell, the cell polarizes, forms lamellipodia at the leading edge (LE), and triggers the concurrent retraction of the trailing edge (TE). During cell migration governed by inhibitory G protein (G)-coupled receptors (GPCRs), G protein βγ (Gβγ) subunits control the LE signaling.

Characterization of activated cyclic olefin copolymer: effects of ethylene/norbornene content on the physiochemical properties.

The ethylene/norbornene content within cyclic olefin copolymer (COC) is well known to affect the chemical and physical properties of the copolymer, such as the glass transition temperature (T) and transparency. However, no work has been reported evaluating the effects of the ethylene/norbornene content on the surface properties of COC following UV/O or O plasma activation. Activation with either O plasma or UV/O is often used to assist in thermal assembly of fluidic devices, increasing the wettability of the surfaces, or generating functional scaffolds for the attachment of biological elements.

Reversible G Protein βγ9 Distribution-Based Assay Reveals Molecular Underpinnings in Subcellular, Single-Cell, and Multicellular GPCR and G Protein Activity.

Current assays to measure the activation of G protein coupled receptors (GPCRs) and G proteins are time-consuming, indirect, and expensive. Therefore, an efficient method which directly measures the ability of a ligand to govern GPCR-G protein interactions can help to understand the molecular underpinnings of the associated signaling. A live cell imaging-based approach is presented here to directly measure ligand-induced GPCR and G protein activity in real time.

Os Odontoideum Discovered After Minor Cervical Trauma.

Minor cervical spine injury is a common cause of pediatric emergency department visits. We present a case of a 10-year-old boy with transient paresthesia after minor cervical trauma found to have a rare cervical spine abnormality requiring surgical fusion. We present and discuss the management options for os odontoideum.