Antioxidant micropeptins from a Microcoleus autumnalis-dominated benthic cyanobacterial mat from Western Ireland.

Exploring the chemical diversity present in cyanobacterial mats increasingly frequent in fresh and marine waters is imperative for both evaluating risks associated with these diverse biofilms and their potential for biodiscovery. During a project aimed at the study of the (eco)toxicity of benthic cyanobacteria blooming in some lakes of the West of Ireland, three previously undescribed ahp-cyclodepsipeptides micropeptin LOF941 (1), micropeptin LOF925 (2) and micropeptin LOF953 (3) were isolated from the Microcoleus autumnalis-dominated benthic cyanobacterial biofilm collected from the shore of Lough O'Flynn, Co. Roscommon, Ireland. Their structures remain consistent in their amino acid sequence with the presence of an unusual methionine, and differ by their exocyclic side chains. The planar structures of the previously undescribed micropeptins were elucidated by 1D and 2D NMR and HRESIMS analyses, and their 3D configurations assessed by ROESY NMR and Marfey's analyses. The three isolated compounds showed no cytotoxic effects and all three compounds were shown to exhibit antioxidant properties, with 1 showing the highest bioactivity. Additionally, several micropeptin analogues are proposed from the methanolic fraction of the biofilm extract by UHPLC-HRESIMS/MS analysis and molecular networking. Notably, the known cyanotoxins anatoxin-a and dihydroanatoxin-a were annotated in the molecular network therefore raising issues about the toxicity of this cyanobacterial mat.

A previously undescribed scene-selective site is the key to encoding ego-motion in naturalistic environments.

Current models of scene processing in the human brain include three scene-selective areas: the parahippocampal place area (or the temporal place areas), the restrosplenial cortex (or the medial place area), and the transverse occipital sulcus (or the occipital place area). Here, we challenged this model by showing that at least one other scene-selective site can also be detected within the human posterior intraparietal gyrus. Despite the smaller size of this site compared to the other scene-selective areas, the posterior intraparietal gyrus scene-selective (PIGS) site was detected consistently in a large pool of subjects (n = 59; 33 females). The reproducibility of this finding was tested based on multiple criteria, including comparing the results across sessions, utilizing different scanners (3T and 7T) and stimulus sets. Furthermore, we found that this site (but not the other three scene-selective areas) is significantly sensitive to ego-motion in scenes, thus distinguishing the role of PIGS in scene perception relative to other scene-selective areas. These results highlight the importance of including finer scale scene-selective sites in models of scene processing - a crucial step toward a more comprehensive understanding of how scenes are encoded under dynamic conditions.

Using high-resolution functional MRI to differentiate impacts of strabismic and anisometropic amblyopia on evoked ocular dominance activity in humans.

We employed high-resolution functional MRI (fMRI) to distinguish the impacts of anisometropia and strabismus (the two most frequent causes of amblyopia) on the evoked ocular dominance (OD) response. Sixteen amblyopic participants (8 females), comprising 8 individuals with strabismus, 7 with anisometropia, 1 with deprivational amblyopia, along with 8 individuals with normal visual acuity (1 female), participated in this study for whom, we measured the difference between the response to stimulation of the two eyes, across early visual areas (V1-V4). In controls, as expected from the organization of OD columns, the evoked OD response formed a striped pattern that was mostly confined to V1. Compared to controls, the OD response in amblyopic participants formed larger fused patches that extended into downstream visual areas. Moreover, both anisometropic and strabismic participants showed stronger OD responses in V1, as well as in downstream visual areas V2-V4. Although this increase was most pronounced in V1, the correlation between the OD response level and the interocular visual acuity difference (measured behaviorally) was stronger in higher-level visual areas (V2-V4). Beyond these common effects, and despite similar densities of amblyopia between the anisometropic and strabismic participants, we found a greater increase in the size of V1 portion that responded preferentially to fellow eye stimulation in anisometropic compared to strabismic individuals. We also found a greater difference between the amplitudes of the response to binocular stimulation, in those regions that responded preferentially to the fellow vs. amblyopic eye, in anisometropic compared to strabismic subjects. In contrast, strabismic subjects demonstrated increased correlation between the OD responses evoked within V1 superficial and deep cortical depths, whereas anisometropic subjects did not. These results provide some of the first direct functional evidence for distinct impacts of strabismus and anisometropia on the mesoscale functional organization of the human visual system, thus extending what was inferred previously about amblyopia from animal models.

A previously undescribed scene-selective site is the key to encoding ego-motion in naturalistic environments.

Current models of scene processing in the human brain include three scene-selective areas: the Parahippocampal Place Area (or the temporal place areas; PPA/TPA), the restrosplenial cortex (or the medial place area; RSC/MPA) and the transverse occipital sulcus (or the occipital place area; TOS/OPA). Here, we challenged this model by showing that at least one other scene-selective site can also be detected within the human posterior intraparietal gyrus. Despite the smaller size of this site compared to the other scene-selective areas, the posterior intraparietal gyrus scene-selective (PIGS) site was detected consistently in a large pool of subjects (n=59; 33 females). The reproducibility of this finding was tested based on multiple criteria, including comparing the results across sessions, utilizing different scanners (3T and 7T) and stimulus sets. Furthermore, we found that this site (but not the other three scene-selective areas) is significantly sensitive to ego-motion in scenes, thus distinguishing the role of PIGS in scene perception relative to other scene-selective areas. These results highlight the importance of including finer scale scene-selective sites in models of scene processing - a crucial step toward a more comprehensive understanding of how scenes are encoded under dynamic conditions.

Accumbofrontal tract integrity is related to early life adversity and feedback learning.

Abuse, neglect, exposure to violence, and other forms of early life adversity (ELA) are incredibly common and significantly impact physical and mental development. While important progress has been made in understanding the impacts of ELA on behavior and the brain, the preponderance of past work has primarily centered on threat processing and vigilance while ignoring other potentially critical neurobehavioral processes, such as reward-responsiveness and learning. To advance our understanding of potential mechanisms linking ELA and poor mental health, we center in on structural connectivity of the corticostriatal circuit, specifically accumbofrontal white matter tracts. Here, in a sample of 77 youth (Mean age = 181 months), we leveraged rigorous measures of ELA, strong diffusion neuroimaging methodology, and computational modeling of reward learning. Linking these different forms of data, we hypothesized that higher ELA would be related to lower quantitative anisotropy in accumbofrontal white matter. Furthermore, we predicted that lower accumbofrontal quantitative anisotropy would be related to differences in reward learning. Our primary predictions were confirmed, but similar patterns were not seen in control white matter tracts outside of the corticostriatal circuit. Examined collectively, our work is one of the first projects to connect ELA to neural and behavioral alterations in reward-learning, a critical potential mechanism linking adversity to later developmental challenges. This could potentially provide windows of opportunity to address the effects of ELA through interventions and preventative programming.

A national macroinvertebrate dataset collected for the biomonitoring of Ireland's river network, 2007-2018.

The Environmental Protection Agency (EPA) in Ireland is responsible for the ecological monitoring and assessment of 37 hydrometric areas covering 46 river catchments and over 13,000 km of river channel nationwide. The national river monitoring program commenced in 1971 and has developed further since 2007 into the National Rivers Water Framework Directive (WFD) Monitoring Program following the implementation of the WFD across the European Union. The monitoring program is designed to obtain sufficiently representative information to assess ecological quality for each water body assessed. Consequently, macroinvertebrate data have been collected at over 2,900 river survey stations on a minimum 3-year cycle to fulfil these requirements. While the EPA has collected these data for water quality assessments we recognize that the data have value beyond this one purpose. We provide a summary of how these 10,987 data records, covering the years 2007 to 2018, have been collected and used to deepen understanding of water quality, biodiversity and general ecological health of Ireland's river network.

Amyloid Beta Peptides Block New Synapse Assembly by Nogo Receptor-Mediated Inhibition of T-Type Calcium Channels.

Compelling evidence links amyloid beta (Aß) peptide accumulation in the brains of Alzheimer's disease (AD) patients with the emergence of learning and memory deficits, yet a clear understanding of the events that drive this synaptic pathology are lacking. We present evidence that neurons exposed to Aß are unable to form new synapses, resulting in learning deficits in vivo. We demonstrate the Nogo receptor family (NgR1-3) acts as Aß receptors mediating an inhibition of synapse assembly, plasticity, and learning. Live imaging studies reveal Aß activates NgRs on the dendritic shaft of neurons, triggering an inhibition of calcium signaling. We define T-type calcium channels as a target of Aß-NgR signaling, mediating Aß's inhibitory effects on calcium, synapse assembly, plasticity, and learning. These studies highlight deficits in new synapse assembly as a potential initiator of cognitive pathology in AD, and pinpoint calcium dysregulation mediated by NgRs and T-type channels as key components. VIDEO ABSTRACT.

Genome Sequences of Gordonia terrae Phages Benczkowski14 and Katyusha.

Bacteriophages Katyusha and Benczkowski14 are newly isolated phages that infect Gordonia terrae 3612. Both have siphoviral morphologies with isometric heads and long tails (500 nm). The genomes are 75,380 bp long and closely related, and the tape measure genes (9 kbp) are among the largest to be identified.

Assessing patient awareness of proper hand hygiene.

BACKGROUND: The authors hypothesized that patients may not understand the forms of effective hand hygiene employed in the hospital environment. LITERATURE REVIEW: Multiple studies demonstrate the importance of hand hygiene in reducing healthcare-associated infections (HAIs). Extensive research about how to improve compliance has been conducted. METHODOLOGY: Patients' perceptions of proper hand hygiene were evaluated when caregivers used soap and water, waterless hand cleaner, or a combination of these. RESULTS: No significant differences were observed, but many patients reported they did not notice whether their providers cleaned their hands. DISCUSSION: Educating patients and their caregivers about the protection afforded by proper, consistent hand hygiene practices is important. IMPLICATIONS FOR NURSING PRACTICE: Engaging patients to monitor healthcare workers may increase compliance, reduce the spread of infection, and lead to better overall patient outcomes. IMPLICATIONS FOR RESEARCH: This study revealed a need to investigate the effects of patient education on patient perceptions of hand hygiene. CONCLUSION: Results of this study appear to indicate a need to focus on patient education and the differences between soap and water versus alcohol-based hand sanitizers as part of proper hand hygiene. Researchers could be asking: "Why have patients not been engaged as members of the healthcare team who have the most to lose?"

Three nursing interventions' impact on HCAHPS scores.

Staff on a 28-bed surgical unit in a suburban 461-bed medical center implemented 3 interventions to improve patient satisfaction. This quality improvement study investigated the effects of nurse manager rounding, postdischarge phone follow-up, and improved discharge teaching skills on patients' ratings of their care. HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) survey scores demonstrated a steady upward trend over 18 months following implementation of the changes.

Receptor activator of NF-kappa B ligand inhibition suppresses bone resorption and hypercalcemia but does not affect host immune responses to influenza infection.

Receptor activator of NF-kappaB (RANK) and its ligand (RANKL) are essential for osteoclast formation, function, and survival. Osteoprotegerin (OPG) inhibits RANK signaling by sequestering RANKL. This study evaluated the antiosteoclast and immunoregulatory effects of mouse rRANK-Fc, which, similar to OPG, can bind RANKL. The effect of RANKL inhibition by RANK-Fc on osteoclast function was determined by inhibition of vitamin D(3) (1,25(OH)(2)D(3))-induced hypercalcemia. Mice were injected with a single dose of 0, 10, 100, 500, or 1000 microg of RANK-Fc; 100 microg of OPG-Fc; or 5 microg of zoledronate 2 h before 1,25(OH)(2)D(3) challenge on day 0, and sacrificed on days 1, 2, 4, 6, 8, 12, 16, and 20. RANK-Fc doses of 100 or 500 microg were tested in a mouse respiratory influenza virus host-resistance model. A single dose of RANK-Fc > or =100 microg suppressed elevation of serum calcium levels and suppressed the bone turnover marker serum pyridinoline at day 4 and later time points, similar to those observed with OPG-Fc and zoledronate (p < or = 0.01 vs controls). By day 6, both immature and mature osteoclasts were depleted by high doses of RANK-Fc (500 and 1000 microg) or 100 microg of OPG-Fc. RANK-Fc doses of 100 or 500 microg had no detectable effect on immune responses to influenza infection, as measured by activation of cytotoxic T cell activity, influenza-specific IgG response, and virus clearance. RANK-Fc inhibition of RANKL has antiosteoclast activity at doses that have no detectable immunoregulatory activity, suggesting that RANKL inhibitors be further studied for their potential to treat excess bone loss.

Determining calcium concentration in heterogeneous model systems using multiple indicators.

Intracellular free calcium concentrations ([Ca2+]i) are assessed by measuring indicator fluorescence in entire cells or subcellular regions using fluorescence microscopy. [Ca2+]i is calculated using equations which link fluorescence intensities (or intensity ratios) to calcium concentrations [G. Grynkiewicz, M. Poenie, R.Y. Tsien, A new generation of Ca2+ indicators with greatly improved fluorescence properties, J. Biol. Chem. 260 (1985) 3440-3450]. However, if calcium ions are heterogeneously distributed within a region of interest, then the observed average fluorescence intensity may not reflect average [Ca2+]i. We assessed potential calcium determination errors in mathematical and experimental models consisting of 'low' and 'high' calcium compartments, using indicators with different affinity for calcium. [Ca2+] calculated using average fluorescence intensity was lower than the actual mean concentrations. Low affinity indicators reported higher (more accurate) values than their high affinity counterparts. To estimate compartment dimensions and respective [Ca2+], we extended the standard approach by using different indicator responses to the same [Ca2+]. While two indicators were sufficient to provide a partial characterization of two-compartment model systems, the use of three or more indicators offered full description of the model provided compartmental [Ca2+] were within the indicator sensitivity ranges. These results show that uneven calcium distribution causes underestimation of actual [Ca2+], and offers novel approaches to estimating calcium heterogeneity.

Cooling produces minimal neuropathology in neocortex and hippocampus.

Cooling is a potential treatment for several neurological diseases. We have examined rodent and cat neocortex, cooled to 5 and 3 degrees C, respectively, to identify a lower limit for safely cooling brain. Rat neocortex, intermittently cooled with a thermoelectric device for 2 h, showed no signs of neuronal injury after cresyl violet or TUNEL staining. Neurons were also preserved in cat cortex cooled for up to 2 h daily for 10 months. Cooled rat and cat cortex showed glial proliferation, but this was also observed in sham-operated rat cortex. When hippocampal slices from mice expressing the Green Fluorescent Protein (GFP) in neurons were cooled to 5 degrees C, but not higher temperatures, we saw reversible dendritic beading and spine loss after 15-30 min. While there may be biochemical and functional alterations in brain cooled as low as 5 degrees C, the neuropathological consequences of brain cooling appear to be insignificant.

Cooling blocks rat hippocampal neurotransmission by a presynaptic mechanism: observations using 2-photon microscopy.

Over the past decade there has been great interest in the therapeutic potential of brain cooling for epilepsy, stroke, asphyxia and other neurological diseases. However, there is still no consensus regarding the neurophysiological effect(s) of brain cooling. We employed standard physiological techniques and 2-photon microscopy to directly examine the effect of temperature on evoked neurotransmitter release in rat hippocampal slices. We observed a monotonic decline in extracellular synaptic potentials and their initial slope over the temperature range 33-20 degrees C, when the slices were cooled to a new set point in less than 5 s. Imaging the fluorescent synaptic marker FM1-43 with 2-photon microscopy showed that the same cooling protocol dramatically reduced transmitter release between 33 and 20 degrees C. Cooling also reduced the terminal FM1-43 destaining that was induced by direct depolarization with elevated K+, indicating that axonal conduction block cannot account for our observations. The temperature dependence of FM1-43 destaining correlated well with the effect of temperature on field potential slope, compatible with a presynaptic explanation for our electrophysiological observations. Optical measurement of FM1-43 dissociation from cell membranes was not affected by temperature, and rapid cooling of slices loaded with FM1-43 did not increase their fluorescence. Our experiments provide visible evidence that a major neurophysiological effect of cooling in the mammalian brain is a reduction in the efficacy of neurotransmitter release. This presynaptic effect may account for some of the therapeutic benefits of cooling in epilepsy and possibly stroke.