Age-Related Attenuation of Dominant Hand Superiority

The decline of motor performance of the human hand-arm system with age is well-documented. While dominant hand performance is superior to that of the non-dominant hand in young individuals, little is known of possible age-related changes in hand dominance. We investigated age-related alterations of hand dominance in 20 to 90 year old subjects. All subjects were unambiguously right-handed according to the Edinburgh Handedness Inventory. In Experiment 1, motor performance for aiming, postural tremor, precision of arm-hand movement, speed of arm-hand movement, and wrist-finger speed tasks were tested. In Experiment 2, accelerometer-sensors were used to obtain objective records of hand use in everyday activities

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Expression of cytokine and chemokine mRNA and secretion of tumor necrosis factor-α by gallbladder epithelial cells: Response to bacterial lipopolysaccharides

BACKGROUND: In addition to immune cells, many other cell types are known to produce cytokines. Cultured normal mouse gallbladder epithelial cells, used as a model system for gallbladder epithelium, were examined for their ability to express the mRNA of various cytokines and chemokines in response to bacterial lipopolysaccharide. The synthesis and secretion of the tumor necrosis factor-α (TNF-α) protein by these cells was also measured. RESULTS: Untreated mouse gallbladder cells expressed mRNA for TNF-α, RANTES, and macrophage inflammatory protein-2 (MIP-2). Upon treatment with lipopolysaccharide, these cells now produced mRNA for Interleukin-1β (IL-1β), IL-6, monocyte chemoattractant protein-1 (MCP-1), and showed increased expression of TNF-α and MIP-2 mRNA. Untreated mouse gallbladder cells did not synthesize TNF-α protein; however, they did synthesize and secrete TNF-α upon treatment with lipopolysaccharide. METHODS: Cells were treated with lipopolysaccharides from 3 strains of bacteria. Qualitative and semi-quantitative RT-PCR, using cytokine or chemokine-specific primers, was used to measure mRNA levels of TNFα, IL-1β, IL-6, IL-10, KC, RANTES, MCP-1, and MIP-2. TNF-α protein was measured by immunoassays. CONCLUSION: This research demonstrates that gallbladder epithelial cells in response to lipopolysaccharide exposure can alter their cytokine and chemokine RNA expression pattern and can synthesize and secrete TNFα protein. This suggests a mechanism whereby gallbladder epithelial cells in vivo may mediate gallbladder secretory function, inflammation and diseases in an autocrine/paracrine fashion by producing and secreting cytokines and/or chemokines during sepsis

High Extracellular Ca2+ Stimulates Ca2+-Activated Cl− Currents in Frog Parathyroid Cells through the Mediation of Arachidonic Acid Cascade

Elevation of extracellular Ca2+ concentration induces intracellular Ca2+ signaling in parathyroid cells. The response is due to stimulation of the phospholipase C/Ca2+ pathways, but the direct mechanism responsible for the rise of intracellular Ca2+ concentration has remained elusive. Here, we describe the electrophysiological property associated with intracellular Ca2+ signaling in frog parathyroid cells and show that Ca2+-activated Cl− channels are activated by intracellular Ca2+ increase through an inositol 1,4,5-trisphophate (IP3)-independent pathway. High extracellular Ca2+ induced an outwardly-rectifying conductance in a dose-dependent manner (EC50∼6 mM). The conductance was composed of an instantaneous time-independent component and a slowly activating time-dependent component and displayed a deactivating inward tail current. Extracellular Ca2+-induced and Ca2+ dialysis-induced currents reversed at the equilibrium potential of Cl− and were inhibited by niflumic acid (a specific blocker of Ca2+-activated Cl− channel). Gramicidin-perforated whole-cell recording displayed the shift of the reversal potential in extracellular Ca2+-induced current, suggesting the change of intracellular Cl− concentration in a few minutes. Extracellular Ca2+-induced currents displayed a moderate dependency on guanosine triphosphate (GTP). All blockers for phospholipase C, diacylglycerol (DAG) lipase, monoacylglycerol (MAG) lipase and lipoxygenase inhibited extracellular Ca2+-induced current. IP3 dialysis failed to induce conductance increase, but 2-arachidonoylglycerol (2-AG), arachidonic acid and 12S-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HPETE) dialysis increased the conductance identical to extracellular Ca2+-induced conductance. These results indicate that high extracellular Ca2+ raises intracellular Ca2+ concentration through the DAG lipase/lipoxygenase pathway, resulting in the activation of Cl− conductance

Advances in Extracellular Matrix-Associated Diagnostics and Therapeutics

\ua9 2025 by the authors.The extracellular matrix (ECM) is the common denominator of more than 50 chronic diseases. Some of these chronic pathologies lead to enhanced tissue formation and deposition, whereas others are associated with increased tissue degradation, and some exhibit a combination of both, leading to severe tissue alterations. To develop effective therapies for diseases affecting the lung, liver, kidney, skin, intestine, musculoskeletal system, heart, and solid tumors, we need to modulate the ECM’s composition to restore its organization and function. Across diverse organ diseases, there are common denominators and distinguishing factors in this fibroinflammatory axis, which may be used to foster new insights into drug development across disease indications. The 2nd Extracellular Matrix Pharmacology Congress took place in Copenhagen, Denmark, from 17 to 19 June 2024 and was hosted by the International Society of Extracellular Matrix Pharmacology. The event was attended by 450 participants from 35 countries, among whom were prominent scientists who brought together state-of-the-art research on organ diseases and asked important questions to facilitate drug development. We highlight key aspects of the ECM in the liver, kidney, skin, intestine, musculoskeletal system, lungs, and solid tumors to advance our understanding of the ECM and its central targets in drug development. We also highlight key advances in the tools and technology that enable this drug development, thereby supporting the ECM

The Early Discovery of SN 2017ahn: Signatures of Persistent Interaction in a Fast-declining Type II Supernova

We present high-cadence, comprehensive data on the nearby (D 33 Mpc) Type II supernova (SN II) 2017ahn, discovered within about one day of the explosion, from the very early phases after explosion to the nebular phase. The observables of SN 2017ahn show a significant evolution over the 470 days of our follow-up campaign, first showing prominent, narrow Balmer lines and other high-ionization features purely in emission (i.e., flash spectroscopy features), which progressively fade and lead to a spectroscopic evolution similar to that of more canonical SNe II. Over the same period, the decline of the light curves in all bands is fast, resembling the photometric evolution of linearly declining H-rich core-collapse SNe. The modeling of the light curves and early flash spectra suggests that a complex circumstellar medium surrounds the progenitor star at the time of explosion, with a first dense shell produced during the very late stages of its evolution that is swept up by the rapidly expanding ejecta within the first similar to 6 days of the SN evolution, while signatures of interaction are observed also at later phases. Hydrodynamical models support the scenario in which linearly declining SNe II are predicted to arise from massive yellow super- or hypergiants depleted of most of their hydrogen layers

Assessing ecological resilience to human induced environmental change in shallow lakes

Sudden unpredictable changes in ecosystems are an increasing source of concern because of their inherent unpredictability and the difficulties involved in restoration. Our understanding of the changes that occur across different trophic levels and the form of this change is lacking. This is especially true of large shallow lakes, where characteristics such as fetch and depth are close to theoretical boundary values for hysteretic behaviour. The development of reliable indicators capable of predicting these changes has been the focus of much research in recent years. The success of these early warning indicators (EWIs) has so far been mixed. There remain many unknowns about how they perform under a wide variety of conditions and parameters. Future climate change is predicted to have a wide range of impacts through the interaction of combined pressures, making the understanding of EWIs and the in-lake processes that occur during regime shifts imperative. Loch Leven, Scotland, UK, is a large shallow lake with a history of eutrophication, research and management and as such is an ideal study site to better understand resilience and regime shifts under a range of interacting stressors. The objectives of this research are to: (1) analyse long term data to identify the occurrence of common tipping points within the chemical (water column nutrient concentrations) and biological (macrophytes, phytoplankton, zooplankton) components of the loch, then test these tipping points using five statistical early warning indicators (EWIs) across multiple rolling window sizes; and (2) quantify the changes in lake ecology using a before/after analysis and testing for non-linearity, combined with modelling using the aquatic ecosystem process model PCLake to determine the level of resilience following a regime shift during recovery from eutrophication; (3) using PCLake, examine the sensitivity of Loch Leven to regime shifts in the face of predicted environmental change (e.g. climate change, nutrient pollution). Statistical analysis identified tipping points across all trophic levels included, from physical and chemical variables through to apex predators. The success of EWIs in predicting the tipping points was highly dependent on the number of EWIs used, with window size having a smaller impact. The 45% window size had the highest overall accuracy across all EWIs but only detected 16.5% more tipping points than the window size with the lowest overall accuracy. Differences between individual EWI performance and usage of them as a group was substantial with a 29.7% increase between the two. In both individual and group use of EWIs, false positives (early warning without a tipping point) were more common than true positives (tipping point preceded by EWI), creating significant doubts about their reliability as management tools. Significant change was seen across multiple variables and trophic levels in the before/after analysis following sudden recovery from eutrophication, with most variables also showing evidence of non-linear change. Modelling of responses to nutrient loading for chlorophyll, zooplankton and macrophytes, under states from before and after the shift, indicate hysteresis and thus the presence of feedback mechanisms. The modelling of responses to nutrient loading and predicted climate change in temperature and precipitation demonstrated that increases in temperature and decreases in summer precipitation individually had large impacts on chlorophyll and zooplankton at medium to high phosphorus (P) loads. However, modelling of the combined effects of these changes resulted in the highest lake chlorophyll concentrations of all tested scenarios. At low P loads higher temperatures and increased winter precipitation had the greatest impact on system resilience with a lower Critical Nutrient Load (CNL). The difference between chlorophyll and zooplankton as opposed to macrophytes was in the presence of a lower CNL for the increased winter precipitation-only scenarios which was not seen in the macrophytes. This highlights the potential role of high winter inputs potentially loaded with particulate matter in reducing resilience at lower P loads. This research has highlighted the vulnerability and low resilience of Loch Leven to environmental change. The presence of multiple tipping points and high levels of EWI activity show a high level of flexibility in the system. Coupled with the occurrence of widespread trophic change during a sudden recovery and a small level of hysteresis and high levels of sensitivity to climate change, the low levels of resilience become clear. The impact of lake-specific characteristics such as moderate depth, large fetch and a heterogeneous bed morphology is particularly evident in the limitations on macrophyte cover and the reliance on zooplankton to determine the hysteresis offset (amount of phosphorus (P) loading between the two CNL). The presence of these characteristics can be used to identify other lakes vulnerable to change. Improving the predictive capabilities of resilience indicators such as EWIs, and better understanding of the ecological changes that occur during non-linear change in response to recovery and climate change, can help target relevant ecosystem components for preventative management. These actions may become necessary under even the most conservative estimates of environmental change