Search

Uncertainty regarding the movement and population exchange of Atlantic bluefin tuna (Thunnus thynnus) from the two primary spawning areas (Gulf of Mexico, Mediterranean Sea) is increasingly implicated as a major impediment for the conservation of this species. Here, two mixture methods were applied to natural chemical markers (δ18O and δ13C) in otoliths (ear stones) to comprehensively investigate the nature and degree of transoceanic movement and mixing of eastern and western populations in several areas of the North Atlantic Ocean that potentially represent mixing hotspots. Areas investigated occurred on both sides of the 45°W management boundary as well as waters off the coast of Africa (Morocco, Canary Islands) where both populations are known to occur. Projections of population composition (i.e., natal or nursery origin) from a multinomial logistic regression (MLR) classification method with different probability thresholds were generally in agreement with maximum likelihood estimates from the commonly used mixed-population program HISEA; however, predicted contributions for the less abundant population were occasionally higher for MLR estimates. Both MLR and HISEA clearly showed that mixing of Atlantic bluefin tuna in the Central North Atlantic Ocean was highly variable from year to year with expatriates of eastern or western origin commonly crossing into the other management area. Pronounced transoceanic movement and mixing of western migrants was also present off the coast of Africa, with the occurrence of western migrants in the Canary Islands and Morocco ranging from zero to the majority of the individuals assayed for the years examined. Results indicate highly variable rates of movement and population exchange for Atlantic bluefin tuna, highlighting the need for temporally resolved estimates of natal origin in mixing hotspots to improve population models used to evaluate the status of this threatened species.

Abstract Osteogenesis imperfecta (OI) is characterized by low bone mass and bone fragility. Using data from a large cohort of individuals with OI from the Osteogenesis Imperfecta Foundation's linked clinical research centers, we examined the association between exposure to bisphosphonate (BPN) treatment (past or present) and lumbar spine (LS) areal bone mineral density (aBMD), fractures, scoliosis, and mobility. From 466 individuals, we obtained 1394 participant‐age LS aBMD data points. Though all OI subtypes were examined, primary analyses were restricted to type I OI (OI‐1). Using linear regression, we constructed expected OI‐1 LS aBMD‐for‐age curves from the data from individuals who had never received BPN. LS aBMD in those who had been exposed to BPN was then compared with the computed expected aBMD. BPN exposure in preadolescent years (age 2 years correlated with LS aBMD in preadolescent individuals. BPN exposure also had a significant association with non‐aBMD clinical outcome variables. Logistic regression modeling predicted that with BPN exposure, a 1‐year increase in age would be associated with an 8.2% decrease in fracture probability for preadolescent individuals with OI‐1, compared with no decrease in individuals who had never received any BPN (p

Liver lymphatic vessels support liver function by draining interstitial fluid, cholesterol, fat, and immune cells for surveillance in the liver draining lymph node. Chronic liver disease is associated with increased inflammation and immune cell infiltrate. However, it is currently unknown if or how lymphatic vessels respond to increased inflammation and immune cell infiltrate in the liver during chronic disease. Here we demonstrate that lymphatic vessel abundance increases in patients with chronic liver disease and is associated with areas of fibrosis and immune cell infiltration. Using single-cell mRNA sequencing and multi-spectral immunofluorescence analysis we identified liver lymphatic endothelial cells and found that chronic liver disease results in lymphatic endothelial cells (LECs) that are in active cell cycle with increased expression of CCL21. Additionally, we found that LECs from patients with NASH adopt a transcriptional program associated with increased IL13 signaling. Moreover, we found that oxidized low density lipoprotein, associated with NASH pathogenesis, induced the transcription and protein production of IL13 in LECs both in vitro and in a mouse model. Finally, we show that oxidized low density lipoprotein reduced the transcription of PROX1 and decreased lymphatic stability. Together these data indicate that LECs are active participants in the liver, expanding in an attempt to maintain tissue homeostasis. However, when inflammatory signals, such as oxidized low density lipoprotein are increased, as in NASH, lymphatic function declines and liver homeostasis is impeded.

Most bones in mammals display a limited capacity for natural large-scale repair. The ribs are a notable exception, yet the source of their remarkable regenerative ability remains unknown. Here, we identify a Sox9-expressing periosteal subpopulation that orchestrates large-scale regeneration of murine rib bones. Deletion of the obligate Hedgehog co-receptor, Smoothened, in Sox9-expressing cells prior to injury results in a near-complete loss of callus formation and rib bone regeneration. In contrast to its role in development, Hedgehog signaling is dispensable for the proliferative expansion of callus cells in response to injury. Instead, Sox9-positive lineage cells require Hh signaling to stimulate neighboring cells to differentiate via an unknown signal into a skeletal cell type with dual chondrocyte/osteoblast properties. This type of callus cell may be critical for bridging large bone injuries. Thus despite contributing to only a subset of callus cells, Sox9-positive progenitors play a major role in orchestrating large-scale bone regeneration.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

In the unfolded protein response (UPR), stress in the endoplasmic reticulum (ER) activates a large transcriptional program to increase ER folding capacity. During the budding yeast UPR, Ire1 excises an intron from the HAC1 mRNA and the exon products of cleavage are ligated, and the translated protein induces hundreds of stress-response genes. Using cells with mutations in RNA repair and decay enzymes, we show that phosphorylation of two different HAC1 splicing intermediates is required for their degradation by the 5′→3′ exonuclease Xrn1 to enact opposing effects on the UPR. We also found that ligated but 2′-phosphorylated HAC1 mRNA is cleaved, yielding a decay intermediate with both 5′- and 2′-phosphates at its 5′-end that inhibit 5′→3′ decay and suggesting that Ire1 degrades incompletely processed HAC1. These decay events expand the scope of RNA-based regulation in the budding yeast UPR and have implications for the control of the metazoan UPR.

Fecal pollution management remains one of the biggest challenges for water quality authorities worldwide. Advanced fecal pollution source identification technologies are now available that can provide quantitative information from many animal groups. As public interest in these methodologies grows, it is vital to use standardized procedures with clearly defined data acceptance metrics and conduct field studies demonstrating the use of these techniques to help resolve real-world water quality challenges. Here we apply recently standardized human-associated qPCR methods with custom data acceptance metrics (HF183/BacR287 and HumM2), along with established procedures for ruminant (Rum2Bac), cattle (CowM2 and CowM3), canine (DG3 and DG37), and avian (GFD) fecal pollution sources to (i) demonstrate the feasibility of implementing standardized qPCR procedures in a large-scale field study, and (ii) characterize trends in fecal pollution sources in the research area. A total of 602 water samples were collected over a one-year period at 29 sites along the Trask, Kilchis, and Tillamook rivers and tributaries in the Tillamook Bay Watershed (OR, USA). Host-associated qPCR results were combined with high-resolution geographic information system (GIS) land use and general indicator bacteria (E. coli) measurements to elucidate water quality fecal pollution trends. Results demonstrate the feasibility of implementing standardized fecal source identification qPCR methods with established data acceptance metrics in a large-scale field study leading to new investigative leads suggesting that elevated E. coli levels may be linked to specific pollution sources and land use activities in the Tillamook Bay Watershed.

Habitat shifts that occur during the life cycles of marine fishes influence population connectivity and structure. A generalized additive modeling approach was used to characterize relationships between environmental variables and the relative abundance of red snapper Lutjanus campechanus over unconsolidated substrate on the continental shelf (300 mm FL). Fisheries independent data (2008-2014) were used to develop separate models for both the eastern and western GoM, and final models were used to predict the relative availability of suitable habitat for each life stage across the two regions. Predictor variables included in final models varied by age class and region, with depth, dissolved oxygen, longitude, and distance to artificial structure common to most models. Depth was among the most influential variables in all models, and preferred depth increased with increasing size/age. Regional differences in fish-habitat relationships were also observed, as relative abundance of larger red snapper over unconsolidated substrates was more closely linked to artificial structure in the eastern GoM. The location of predicted high quality habitat for juvenile red snapper was greatest on the inner Texas shelf and a smaller area east of the Mississippi River Delta, suggesting these two areas may represent important nursery grounds for the respective regions. Clear ontogenetic shifts in the spatial distribution of predicted high quality habitat were evident in both the eastern (expansion from west to east with age) and western (shift from inshore to offshore) GoM. Given the unique population dynamics between the eastern and western GoM, improving our understanding of spatial and temporal variability in habitat quality may be important to maintaining connectivity between juvenile and adult habitats, and may enhance recovery and management of red snapper stocks in the GoM.

Autosomal dominant polycystic kidney disease (ADPKD) is caused mostly by mutations in polycystin-1 or polycystin-2. Fluid flow leads to polycystin-dependent calcium influx and nuclear export of histone deacetylase 5 (HDAC5), which facilitates the maintenance of renal epithelial architecture by de-repression of MEF2C target genes. Here, we screened a small-molecule library to find drugs that promotes nuclear export of HDAC5. We found that dopamine receptor antagonists, domperidone and loxapine succinate, stimulate export of HDAC5, even in Pkd1-/-cells. Domperidone targets Drd3 receptor to modulate the phosphorylation of HDAC5. Domperidone treatment increases HDAC5 phosphorylation likely by reducing protein phosphatase 2A (PP2A) activity, thus shifting the equilibrium towards HDAC5-P and export from the nucleus. Treating Pkd1-/-mice with domperidone showed significantly reduced cystic growth and cell proliferation. Further, treated mice displayed a reduction in glomerular cyst and increased body weight and activity. These results suggest that HDAC5 nucleocytoplasmic shuttling may be modulated to impede disease progression in ADPKD and uncovers an unexpected role for a class of dopamine receptors in renal epithelial morphogenesis.

A number of viruses and bacterial species have been implicated as contributors to atherosclerosis, potentially providing novel pathways for prevention. Epidemiological studies examining the association between Helicobacter pylori and cardiovascular disease have yielded variable results and no studies have been conducted in nonhuman primates. In this investigation, we examined the relationship between H. pylori infection and atherosclerosis development in socially housed, pre- and postmenopausal cynomolgus macaques consuming human-like diets. Ninety-four premenopausal cynomolgus monkeys (Macaca fascicularis) were fed for 36 months an atherogenic diet deriving its protein from either casein lactalbumin(CL) or high isoflavone soy (SOY). Animals were then ovariectomized and fed either the same or the alternate diet for an additional 36 months. Iliac artery biopsies were obtained at the time of ovariectomy and iliac and coronary artery sections were examined at the end of the study. Evidence of H. pylori infection was found in 64% of the monkeys and 46% of animals had live H. pylori within coronary atheromas as determined by mRNA-specific in situ hybridization. There was a significant linear relationship between the densities of gastric and atheroma organisms. Helicobactor pylori infection correlated with increased intimal plaque area and thickness at both the premenopausal and postmenopausal time points and regardless of diet (p< 0.01), although animals consuming the SOY diet throughout had the least amount of atherosclerosis. Additionally, plasma lipid profiles, intimal collagen accumulation, ICAM-1, and plaque macrophage densities were adversely affected by H. pylori infection among animals consuming the CL diet, while the SOY diet had the opposite effect. Plaque measurements were more highly associated with the densities of cagA-positive H. pylori within coronary atheromas than with the densities of gastric organisms, whereas plasma lipid changes were associated with H. pylori infection, but not cagA status. This study provides strong evidence that live H. pylori infects atheromas, exacerbates atherosclerotic plaque development, and alters plasma lipid profiles independently of diet or hormonal status. Finally, socially subordinate animals relative to their dominant counterparts had a greater prevalence of H. pylori, suggesting a stress effect. The results indicate that early H. pylori eradication could prevent or delay development of cardiovascular disease.

In this review, the experimental set-up and functional characteristics of single-wavelength and broad-band femtosecond upconversion spectrophotofluorometers developed in our laboratory are described. We discuss applications of this technique to biophysical problems, such as ultrafast fluorescence quenching and solvation dynamics of tryptophan, peptides, proteins, reduced nicotinamide adenine dinucleotide (NADH), and nucleic acids. In the tryptophan dynamics field, especially for proteins, two types of solvation dynamics on different time scales have been well explored: ~1 ps for bulk water, and tens of picoseconds for “biological water”, a term that combines effects of water and macromolecule dynamics. In addition, some proteins also show quasi-static self-quenching (QSSQ) phenomena. Interestingly, in our more recent work, we also find that similar mixtures of quenching and solvation dynamics occur for the metabolic cofactor NADH. In this review, we add a brief overview of the emerging development of fluorescent RNA aptamers and their potential application to live cell imaging, while noting how ultrafast measurement may speed their optimization.

Background & Aims: Constipation is a common clinical problem that negatively impacts quality of life and is associated with significant health care costs. Activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is the primary pathway that drives fluid secretion in the intestine, which maintains lubrication of luminal contents. We hypothesized that direct activation of CFTR would cause fluid secretion and reverse the excessive dehydration of stool found in constipation. Methods: A cell-based, high-throughput screen was performed for 120,000 drug-like, synthetic small molecules. Active compounds were characterized for mechanism of action and one lead compound was tested in a loperamide-induced constipation model in mice. Results: Several classes of novel CFTR activators were identified, one of which, the phenylquinoxalinone CFTRact-J027, fully activated CFTR chloride conductance with an half-maximal effective concentration (EC50) of approximately 200 nmol/L, without causing an increase of cytoplasmic cyclic adenosine monophosphate. Orally administered CFTRact-J027 normalized stool output and water content in a loperamide-induced mouse model of constipation with a 50% effective dose of approximately 0.5 mg/kg; CFTRact-J027 was without effect in cystic fibrosis mice lacking functional CFTR. Short-circuit current, fluid secretion, and motility measurements in mouse intestine indicated a prosecretory action of CFTRact-J027 without direct stimulation of intestinal motility. Oral administration of 10 mg/kg CFTRact-J027 showed minimal bioavailability, rapid hepatic metabolism, and blood levels less than 200 nmol/L, and without apparent toxicity after chronic administration. Conclusions: CFTRact-J027 or alternative small-molecule CFTR-targeted activators may be efficacious for the treatment of constipation. Keywords: CFTR, Constipation, High-Throughput Screening, Loperamide

Background: There are many factors that govern growth and resistant of Salmonella typhi. A study had reported that the use of sodium benzoate caused antibiotic resistant. However, no study has directly evaluated the effect of sodium benzoate exposure on S. typhi sensitivity to chloramphenicol. The aim of this study was to evaluate the resistance or sensitivity of S. typhi to chloramphenicol after sodium benzoate exposure. Methods: The study was conducted in seven groups: three treatment groups (sodium benzoate insensitive S. typhi+8 µg/mL, 16 µg/mL, and 32 µg/mL of chloramphenicol), three positive control groups (sodium benzoate sensitive S. typhi+8 µg/mL, 16 µg/mL, and 32 µg/mL of chloramphenicol), and one negative control groups (sodium benzoate sensitive S. typhi+0 µg/mL of chloramphenicol). The effect of sodium benzoate exposure to S. typhi sensitivity to chloramphenicol was measured after 24 hours. Spearman test was used to analyzed this association. Results: In this study, we found that the average S. typhi growth in the treatment groups (A, B, C) was 445 CFU/mL, 385 CFU/mL, and 171 CFU/mL, respectively. While in the positive control group (D, E, F) was not obtained any S. typhi growth. Average S. typhi growth in the negative control group was 430 CFU/mL. Discussion: We found that sodium benzoate exposure inhibited S. typhi growth and affected S. typhi sensitivity to chloramphenicol (p < 0.05). In addition, we found that 32 µg/mL chloramphenicol had the highest mean difference value, so this showed that the dose 32 µg/mL of chloramphenicol had the best effectiveness of various treatment groups (p < 0.05). Conclusions: Sodium benzoate exposure can inhibit S. typhi growth and cause S. typhi resistant to chloramphenicol.

The Trojan Y-Chromosome (TYC) strategy, an autocidal genetic biocontrol method, has been proposed to eliminate invasive alien species. In this work, we develop a Markov jump process model for this strategy, and we verify that there is a positive probability for wild-type females going extinct within a finite time. Moreover, when sex-reversed Trojan females are introduced at a constant population size, we formulate a stochastic differential equation (SDE) model as an approximation to the proposed Markov jump process model. Using the SDE model, we investigate the probability distribution and expectation of the extinction time of wild-type females by solving Kolmogorov equations associated with these statistics. The results indicate how the probability distribution and expectation of the extinction time are shaped by the initial conditions and the model parameters.

Multispectral karyotyping analyzes all chromosomes in a single cell by labeling them with chromosome-specific probes conjugated to unique combinations of fluorophores. Currently available multispectral karyotyping systems require the purchase of specialized equipment and reagents. However, conventional laser scanning confocal microscopes that are capable of separating multiple overlapping emission spectra through spectral imaging and linear unmixing can be utilized for classifying chromosomes painted with multicolor probes. Here, we generated multicolor chromosome paints from single-sorted human and mouse chromosomes and developed the Karyotype Identification via Spectral Separation (KISS) analysis package, a set of freely available open source ImageJ tools for spectral unmixing and karyotyping. Chromosome spreads painted with our multispectral probe sets can be imaged on widely available spectral laser scanning confocal microscopes and analyzed using our ImageJ tools. Together, our probes and software enable academic labs with access to a laser-scanning spectral microscope to perform multicolor karyotyping in a cost-effective manner.

By adopting a 2D time-dependent wave code, we investigate how mode-converted waves at the Ion-Ion Hybrid (IIH) resonance and compressional waves propagate in 2D density structures with a wide range of field-aligned wavenumbers to background magnetic fields. The simulation results show that the mode-converted waves have continuous bands across the field line consistent with previous numerical studies. These waves also have harmonic structures in frequency domain and are localized in the field-aligned heavy ion density well. Our results thus emphasize the importance of a field-aligned heavy ion density structure for ultra-low frequency wave propagation, and suggest that IIH waves can be localized in different locations along the field line.

There is an error in the title [...]

The rank-3 antisymmetric tensors which are the magnetic monopoles of SU(N) Yang–Mills gauge theory dynamics, unlike their counterparts in Maxwell’s U(1) electrodynamics, are non-vanishing, and do permit a net flux of Yang–Mills analogs to the magnetic field through closed spatial surfaces. When electric source currents of the same Yang–Mills dynamics are inverted and their fermions inserted into these Yang–Mills monopoles to create a system, this system in its unperturbed state contains exactly three fermions due to the monopole rank-3 and its three additive field strength gradient terms in covariant form. So to ensure that every fermion in this system occupies an exclusive quantum state, the Exclusion Principle is used to place each of the three fermions into the fundamental representation of the simple gauge group with an SU(3) symmetry. After the symmetry of the monopole is broken to make this system indivisible, the gauge bosons inside the monopole become massless, the SU(3) color symmetry of the fermions becomes exact, and a propagator is established for each fermion. The monopoles then have the same antisymmetric color singlet wavefunction as a baryon, and the field quanta of the magnetic fields fluxing through the monopole surface have the same symmetric color singlet wavefunction as a meson. Consequently, we are able to identify these fermions with colored quarks, the gauge bosons with gluons, the magnetic monopoles with baryons, and the fluxing entities with mesons, while establishing that the quarks and gluons remain confined and identifying the symmetry breaking with hadronization. Analytic tools developed along the way are then used to fill the Yang–Mills mass gap.

Backward walking (BW) is being increasingly used in neurologic and orthopedic rehabilitation as well as in sports to promote balance control as it provides a unique challenge to the sensorimotor control system. The identification of initial foot contact (IC) and terminal foot contact (TC) events is crucial for gait analysis. Data of optical motion capture (OMC) kinematics and inertial motion units (IMUs) are commonly used to detect gait events during forward walking (FW). However, the agreement between such methods during BW has not been investigated. In this study, the OMC kinematics and inertial data of 10 healthy young adults were recorded during BW and FW on a treadmill at different speeds. Gait events were measured using both kinematics and inertial data and then evaluated for agreement. Excellent reliability (Interclass Correlation > 0.9) was achieved for the identification of both IC and TC. The absolute differences between methods during BW were 18.5 ± 18.3 and 20.4 ± 15.2 ms for IC and TC, respectively, compared to 9.1 ± 9.6 and 10.0 ± 14.9 for IC and TC, respectively, during FW. The high levels of agreement between methods indicate that both may be used for some applications of BW gait analysis.

Adenovirus (Ad) infections are usually mild and self-limited, with minimal inflammatory responses. During worldwide outbreaks, Ad14p1, an emerging Ad14 variant, has caused severe pulmonary disease, including acute respiratory distress syndrome (ARDS). This increased pathogenicity of Ad14p1 is not completely understood. In initial studies, we observed that infection of Syrian hamsters with Ad14p1 can cause a patchy bronchopneumonia, with an increased intensity of inflammation, compared to wild type Ad14 infection. The current study compared the dynamics of the immunopathogenesis of Ad14 and Ad14p1 infection of hamster lungs through the first two weeks after infection. Little difference was seen in infection-induced inflammation at day 1. Beginning at day 3, Ad14p1-infected hamsters showed marked inflammation that continued through to day 7. The inflammation began to resolve by day 10 but was still detectable at day 14. In contrast, Ad14-infected hamsters showed little inflammation during the 14-day period of observation. Inflammatory cell type analysis revealed that, at day 1, hamsters infected with either virus had predominantly neutrophil infiltration that began to resolve by day 3. However, at day 5, Ad14p1-infected hamsters had a second wave of neutrophil infiltration that was accompanied by edema which persisted to a variable extent through to day 10. These differences were not explained by an increased Ad14p1 replication rate, compared with Ad14 in vitro, but there was prolonged persistence of Ad14p1 in hamster lungs. There were differences in lung tissue cytokine and chemokine responses to Ad14p1 vs. Ad14 infection that might account for the increased leukocyte infiltrates in Ad14p1-infected hamsters. This animal model characterization provides the basis for future translational studies of the viral genetic mechanisms that control the increased immunopathogenesis of the emergent, Ad14p1 strain.

Near-field remote sensing of surface velocity and river discharge (discharge) were measured using coherent, continuous wave Doppler and pulsed radars. Traditional streamgaging requires sensors be deployed in the water column; however, near-field remote sensing has the potential to transform streamgaging operations through non-contact methods in the U.S. Geological Survey (USGS) and other agencies around the world. To differentiate from satellite or high-altitude platforms, near-field remote sensing is conducted from fixed platforms such as bridges and cable stays. Radar gages were collocated with 10 USGS streamgages in river reaches of varying hydrologic and hydraulic characteristics, where basin size ranged from 381 to 66,200 square kilometers. Radar-derived mean-channel (mean) velocity and discharge were computed using the probability concept and were compared to conventional instantaneous measurements and time series. To test the efficacy of near-field methods, radars were deployed for extended periods of time to capture a range of hydraulic conditions and environmental factors. During the operational phase, continuous time series of surface velocity, radar-derived discharge, and stage-discharge were recorded, computed, and transmitted contemporaneously and continuously in real time every 5 to 15 min. Minimum and maximum surface velocities ranged from 0.30 to 3.84 m per second (m/s); minimum and maximum radar-derived discharges ranged from 0.17 to 4890 cubic meters per second (m3/s); and minimum and maximum stage-discharge ranged from 0.12 to 4950 m3/s. Comparisons between radar and stage-discharge time series were evaluated using goodness-of-fit statistics, which provided a measure of the utility of the probability concept to compute discharge from a singular surface velocity and cross-sectional area relative to conventional methods. Mean velocity and discharge data indicate that velocity radars are highly correlated with conventional methods and are a viable near-field remote sensing technology that can be operationalized to deliver real-time surface velocity, mean velocity, and discharge.

We present a study of polycrystalline thin films of the rock salt rare earth nitride GdN grown on amorphous fused silica at ambient temperature with varying N _2 pressure. X-ray diffraction measurements show a strong (111) preferential orientation for all N _2 pressure and the signature of a secondary phase of GdN that develops as the N _2 pressure decreases. The secondary phase is found to have a smaller lattice parameter than the near-stoichiometric GdN. Raman spectroscopy, electrical and magnetic results support the coexistence of such mixed-phase samples with the lattice distortion originating from nitrogen vacancies. Significantly the magnetic data show an increase of the ferromagnetic onset temperature as the secondary phase develops, without affecting the soft ferromagnetic character of GdN.

Climate change could have dire effects on hydropower systems, especially in southwest China, where hydropower dominates the regional power system. This study examines two large cascade hydropower systems in Yunnan province in southwest China for 10 climate change projections made with 5 global climate models (GCMs) and 2 representative concentration pathways (RCPs) under Coupled Model Intercomparison Project Phase 5 (CMIP5). First, a back propagation neural network rain-runoff model is built for each hydropower station to estimate inflows with climate change. Then, a progressive optimality algorithm maximizes hydropower generation for each projection. The results show generation increasing in each GCM projection, but increasing more in GCMs under scenario RCP8.5. However, yearly generation fluctuates more: generation decreases dramatically with potential for electricity shortages in dry years and more electricity as well as spill during wet years. Average annual spill, average annual inflow and average storage have similar trends. The analysis indicates that a planned large dam on the upper Jinsha River would increase seasonal regulation ability, increase hydropower generation, and decrease spill. Increased turbine capacity increases generation slightly and decreases spill for the Lancang River. Results from this study demonstrate effects of climate change on hydropower systems and identify which watersheds might be more vulnerable, along with some actions that could help adapt to climate change.

A pilot study was conducted to explore student preferences, performance, and perceptions of experiential learning assessment following experiential learning instruction. A learning experience, using semi-directed instruction and experiential learning methods, was given to 13 student volunteers who were then assessed using a case study, presentation, journal, and essay, representing both group and individual assessment. Student performance in terms of their understanding and their engagement was compared to student perceptions and preferences. Student performance indicated that although the journal (individual assessment) appeared to be the best venue for students to express their understanding, they were the least engaged in it. The case study and the presentation (group assessments) were most preferred overall and students also perceived these to be the best forms of assessment in a number of aspects (helpful, beneficial, engaging, challenging, etc.). It is possible that the collaborative nature of the group assessments matched the teaching style suggesting that the mode of assessment should follow a similar format to the learning experience in courses that use experiential learning methods. The essay, as a traditional form of assessment, was valued for its structure, possibly reflecting student familiarity with that type of assessment, but less so overall because it was also an individual exercise. Each assessment method used in the pilot demonstrated value, albeit in different forms and this finding speaks to assessing both authentically and using a mixture of methods.

Homeostasis at mucosal surfaces requires cross-talk between the environment and barrier epithelial cells. Disruption of barrier function typifies mucosal disease. Here we elucidate a bifunctional role in coordinating this cross-talk for the inflammatory bowel disease risk-gene INAVA. Both activities require INAVA’s DUF3338 domain (renamed CUPID). CUPID stably binds the cytohesin ARF-GEF ARNO to effect lateral membrane F-actin assembly underlying cell-cell junctions and barrier function. Unexpectedly, when bound to CUPID, ARNO affects F-actin dynamics in the absence of its canonical activity as a guanine nucleotide-exchange factor. Upon exposure to IL-1β, INAVA relocates to form cytosolic puncta, where CUPID amplifies TRAF6-dependent polyubiquitination and inflammatory signaling. In this case, ARNO binding to CUPID negatively-regulates polyubiquitination and the inflammatory response. INAVA and ARNO act similarly in primary human macrophages responding to IL-1β and to NOD2 agonists. Thus, INAVA-CUPID exhibits dual functions, coordinated directly by ARNO, that bridge epithelial barrier function with extracellular signals and inflammation.

Abstract The mangrove–seagrass–patch reef (MSP) ecosystem serves as the principal back‐reef nursery for many reef fishes in the Caribbean, but the functional roles of habitats that form this seascape remain unclear. We assessed ecosystem and trophic connectivity of two common reef fishes (schoolmaster, Lutjanus apodus; white grunt, Haemulon plumierii) and one predator (great barracuda, Sphyraena barracuda) in a Caribbean MSP ecosystem using acoustic telemetry and natural dietary tracers. Triangulated positions from an acoustic positioning system indicated that L. apodus and H. plumierii relied on multiple habitats within this MSP ecosystem, occupying areas with more cover (lower risk) during the day and areas with less cover (higher risk) at night. During the day, both species exhibited limited movement away from structured habitats (e.g., mangroves, patch reef) and avoided the primary activity space of S. barracuda in the central channel over sand bottom or seagrass. At night, L. apodus moved into the channel and adjacent seagrass beds on the margin of this high‐risk area when S. barracuda occurrence was reduced, suggesting that this species adjusts its foraging activities to minimize encounter rates with predators. Haemulon plumierii also displayed distinct day–night shifts with directed movements at twilight across higher risk habitat to nighttime locations in seagrass. Conspicuous changes in the rate of movement were also detected at different times of the day, and observed mismatches between movement rates of S. barracuda and our two potential prey species appeared to be a behavioral response to reduce their vulnerability. Dietary tracer analysis supported the premise that observed shifts to nocturnal habitats were associated with foraging, with significant contributions of organic matter derived from nighttime locations. Findings from this study clearly demonstrate that the configuration of habitats and spatiotemporal variability in predation risk are key determinants of movement and foraging activities for these species, indicating that an improved understanding of seascape connectivity is critical to the management of reef‐dependent species.

Facebook, the online social network, has more than 2 billion global users. Because those users do not pay for the service, its benefits are hard to measure. We report the results of a series of three non-hypothetical auction experiments where winners are paid to deactivate their Facebook accounts for up to one year. Though the populations sampled and the auction design differ across the experiments, we consistently find the average Facebook user would require more than $1000 to deactivate their account for one year. While the measurable impact Facebook and other free online services have on the economy may be small, our results show that the benefits these services provide for their users are large.

The feeding ecology of two reef fishes associated with artificial reefs in the northwest Gulf of Mexico (GoM) was examined using gut contents and natural stable isotopes. Reefs were divided into three regions (east, central, west) across an east to west gradient of increasing reef complexity and salinity. Gray triggerfish (Balistes capriscus) primarily consumed reef-associated prey (xanthid crabs, bivalves, barnacles) and pelagic gastropods, while red snapper (Lutjanus campechanus) diets were mainly comprised of non-reef prey (stomatopods, fishes, portunid crabs). Natural stable isotopes of carbon (δ13C), nitrogen (δ15N), and sulfur (δ34S) were measured in consumer muscle tissue as well as potential primary producers. Gray triggerfish occupied a lower trophic position than red snapper, with lower δ13C and δ15N values across all size classes and regions, and generally higher δ34S values. Red snapper had a smaller range of stable isotope values and corrected standard ellipse areas across all size classes and regions, indicating a smaller isotopic niche. Contribution estimates of particulate organic matter (26 to 54%) and benthic microalgae (BMA, 47 to 74%) for both species were similar, with BMA contributions greater across all three size classes (juveniles, sub-adults, adults) of red snapper and all but the juvenile size class for gray triggerfish. Species gut contents and stable isotopes differed by region, with fishes consuming more crabs in the east region and more gastropods in the central and west regions. δ13C and δ15N values generally decreased from east to west, while δ34S increased across this gradient. Results highlight species-specific feeding differences associated with artificial reefs, where gray triggerfish may be more dependent on the reef structure for foraging opportunities. In addition, results offer further information on the integral role of BMA in primary production at nearshore artificial reefs.

Resistance training may differentially affect morphological adaptations along the length of uni-articular and bi-articular muscles. The purpose of this study was to compare changes in muscle morphology along the length of the rectus femoris (RF) and vastus lateralis (VL) in response to resistance training. Following a 2-wk preparatory phase, 15 resistance-trained men (24.0 ± 3.0 y, 90.0 ± 13.8 kg, 174.9 ± 20.7 cm) completed pre-training (PRE) assessments of muscle thickness (MT), pennation angle (PA), cross-sectional area (CSA), and echo-intensity in the RF and VL at 30, 50, and 70% of each muscle's length; fascicle length (FL) was estimated from respective measurements of MT and PA within each muscle and region. Participants then began a high intensity, low volume (4 x 3-5 repetitions, 3min rest) lower-body resistance training program, and repeated all PRE-assessments after 8 weeks (2 d ∙ wk-1) of training (POST). Although three-way (muscle [RF, VL] x region [30, 50, 70%] x time [PRE, POST]) repeated measures analysis of variance did not reveal significant interactions for any assessment of morphology, significant simple (muscle x time) effects were observed for CSA (p = 0.002) and FL (p = 0.016). Specifically, average CSA changes favored the VL (2.96 ± 0.69 cm2, p < 0.001) over the RF (0.59 ± 0.20 cm2, p = 0.011), while significant decreases in average FL were noted for the RF (-1.03 ± 0.30 cm, p = 0.004) but not the VL (-0.05 ± 0.36 cm, p = 0.901). No other significant differences were observed. The findings of this study demonstrate the occurrence of non-homogenous adaptations in RF and VL muscle size and architecture following 8 weeks of high-intensity resistance training in resistance-trained men. However, training does not appear to influence region-specific adaptations in either muscle.

The Tasmanian tiger or thylacine (Thylacinus cynocephalus) was an iconic Australian marsupial predator that was hunted to extinction in the early 1900s. Despite sharing striking similarities with canids, they failed to evolve many of the specialized anatomical features that characterize carnivorous placental mammals. These evolutionary limitations are thought to arise from functional constraints associated with the marsupial mode of reproduction, in which otherwise highly altricial young use their well-developed forelimbs to climb to the pouch and mouth to suckle. Here we present the first three-dimensional digital developmental series of the thylacine throughout its pouch life using X-ray computed tomography on all known ethanol-preserved specimens. Based on detailed skeletal measurements, we refine the species growth curve to improve age estimates for the individuals. Comparison of allometric growth trends in the appendicular skeleton (fore- and hindlimbs) with that of other placental and marsupial mammals revealed that despite their unique adult morphologies, thylacines retained a generalized early marsupial ontogeny. Our approach also revealed mislabelled specimens that possessed large epipubic bones (vestigial in thylacine) and differing vertebral numbers. All of our generated CT models are publicly available, preserving their developmental morphology and providing a novel digital resource for future studies of this unique marsupial.

This research project examined the impact on student engagement of a makerspace approach in an all-First Nations high school. First Nations learners have many factors limiting their success in the K-12 system such as lack of connection to the curriculum, limited cultural relevance of course content, and poor attendance. A common concern for those working with First Nations students is how to deliver a learning experience that is engaging and assists students in earning enough credits to graduate. In this case study, a makerspace approach to learning was used to engage and support learners. A makerspace is a learning context where participants are supported and encouraged to design and create as part of required learning, to meet curricular objectives, or to creatively explore their own ideas. The program at the focus of this research introduced students to 3D computer design technology and (computer numerical control) CNC wood milling technology to make electric guitars. This project used a case study design to determine ways to improve the school experience of First Nations students through unique course design. The findings show that the experience for students was positive, engagement increased, and attendance showed improvement. Ce projet de recherche s’est penché sur l’incidence d’une approche « Makerspace » (laboratoire ouvert) sur l’engagement des élèves dans une école secondaire fréquentée uniquement par des membres des Premières Nations. Plusieurs facteurs limitent la réussite des apprenants des Premières Nations dans le système scolaire de la maternelle à la 12e année, comme un manque de connexion au programme, la pertinence limitée du contenu des cours et un haut taux d’absentéisme. Les personnes qui travaillent auprès des élèves issus des Premières Nations ont comme préoccupation commune l’offre d’une expérience d’apprentissage qui engage les élèves et les aide à obtenir suffisamment de crédits pour obtenir leur diplôme. Dans cette étude de cas, une approche de laboratoire ouvert a été utilisée pour faire participer les apprenants et les appuyer. Un laboratoire ouvert est un contexte d’apprentissage dans lequel les participants sont soutenus et encouragés à concevoir et à créer, que ce soit en vue de l’apprentissage requis, pour atteindre des objectifs du programme ou pour explorer avec créativité leurs propres idées. Le programme au cœur de cette étude a fait connaître aux élèves la technologie informatique de conception en 3D et la technologie de fraisage du bois par CNC (commande numérique par ordinateur) pour fabriquer des guitares électriques. Ce projet a utilisé une conception d’étude de cas afin de déterminer des façons d’améliorer l’expérience scolaire des élèves des Premières Nations par l’entremise d’une conception de cours unique. Les conclusions démontrent que l’expérience a été positive pour les élèves, que leur engagement a augmenté et que leur taux de présence s’est amélioré.

Distinct isoforms of the PI3K catalytic subunit have specialized functions in the brain, but their role in cognition is unknown. Here, we show that the catalytic subunit p110β plays an important role in prefrontal cortex (PFC)-dependent cognitive defects in mouse models of Fragile X syndrome (FXS), an inherited intellectual disability. FXS is caused by loss of function of the fragile X mental retardation protein (FMRP), which binds and translationally represses mRNAs. PFC-selective knockdown of p110β, an FMRP target that is translationally upregulated in FXS, reverses deficits in higher cognition in Fmr1 knockout mice. Genetic full-body reduction of p110β in Fmr1 knockout mice normalizes excessive PI3K activity, restores stimulus-induced protein synthesis, and corrects increased dendritic spine density and behavior. Notably, adult-onset PFC-selective Fmr1 knockdown mice show impaired cognition, which is rescued by simultaneous p110β knockdown. Our results suggest that FMRP-mediated control of p110β is crucial for neuronal protein synthesis and cognition.

The PI3K enhancer PIKE links PI3K catalytic subunits to group 1 metabotropic glutamate receptors (mGlu1/5) and activates PI3K signaling. The roles of PIKE in synaptic plasticity and the etiology of mental disorders are unknown. Here, we show that increased PIKE expression is a key mediator of impaired mGlu1/5-dependent neuronal plasticity in mouse and fly models of the inherited intellectual disability fragile X syndrome (FXS). Normalizing elevated PIKE protein levels in FXS mice reversed deficits in molecular and cellular plasticity and improved behavior. Notably, PIKE reduction rescued PI3K-dependent and -independent neuronal defects in FXS. We further show that PI3K signaling is increased in a fly model of FXS and that genetic reduction of the Drosophila ortholog of PIKE, CenG1A rescued excessive PI3K signaling, mushroom body defects, and impaired short-term memory in these flies. Our results demonstrate a crucial role of increased PIKE expression in exaggerated mGlu1/5 signaling causing neuronal defects in FXS.

The rare-earth nitrides appear as attractive alternatives to dilute ferromagnetic semiconductors for spintronics device applications. Most of them combine the properties of the ferromagnet and the semiconductor, an exceedingly rare combination. In this work we have grown n-type polycrystalline semiconducting GdN layers between pre-deposited contacts made of Cr/Au and Cr/Ag. The resistivity of the GdN layers ranges from 4.4×10-4 Ωcm to 3.1×10-2 Ωcm depending on the nitrogen pressure during the growth. The electrical properties of metal/n-type GdN/metal planar junctions are investigated as a function of the temperature. The current voltage characteristics of the junctions were linear for temperatures ranging from 300 K down to 5 K, suggesting an ohmic contact between the Au or Ag metal and the n-type GdN layer.

Dysregulation of protein synthesis is one of the key mechanisms underlying autism spectrum disorder (ASD). However, the role of a major pathway controlling protein synthesis, the integrated stress response (ISR), in ASD remains poorly understood. Here, we demonstrate that the main arm of the ISR, eIF2α phosphorylation (p-eIF2α), is suppressed in excitatory, but not inhibitory, neurons in a mouse model of fragile X syndrome (FXS; Fmr1-/y). We further show that the decrease in p-eIF2α is mediated via activation of mTORC1. Genetic reduction of p-eIF2α only in excitatory neurons is sufficient to increase general protein synthesis and cause autism-like behavior. In Fmr1-/y mice, restoration of p-eIF2α solely in excitatory neurons reverses elevated protein synthesis and rescues autism-related phenotypes. Thus, we reveal a previously unknown causal relationship between excitatory neuron-specific translational control via the ISR pathway, general protein synthesis, and core phenotypes reminiscent of autism in a mouse model of FXS.

Experience and activity refine cortical circuits through synapse elimination, but little is known about the activity patterns and downstream molecular mechanisms that mediate this process. We used optogenetics to drive individual mouse CA1 hippocampal neurons to fire in theta frequency bursts to understand how cell autonomous, postsynaptic activity leads to synapse elimination. Brief (1 hr) periods of postsynaptic bursting selectively depressed AMPA receptor (R) synaptic transmission, or silenced excitatory synapses, whereas more prolonged (24 hr) firing depressed both AMPAR and NMDAR EPSCs and eliminated spines, indicative of a synapse elimination. Both synapse silencing and elimination required de novo transcription, but only silencing required the activity-dependent transcription factors MEF2A/D. Burst firing induced MEF2A/D-dependent induction of the target gene Arc which contributed to synapse silencing and elimination. This work reveals new and distinct forms of activity and transcription-dependent synapse depression and suggests that these processes can occur independently.

https://doi.org/10.15447/sfews.2017v15iss2art3Uncertainties in understanding ecosystems increase the risk that management will fail to achieve desired results. Adaptive management is a structured, iterative application of science-based knowledge to reduce uncertainties and build flexibility into decision-making. However, adaptive management is more easily planned than implemented, and it is only beginning to be applied in the California’s Sacramento–San Joaquin Delta. We draw from two assessments of adaptive management in the Delta and examples of its use elsewhere to suggest how the process can be facilitated. Although a highly structured adaptive-management process may not always be needed, several elements are essential. Adaptive management should begin by clearly identifying the problem, goals, and objectives; recognizing uncertainties; identifying decision points and alternative approaches; recognizing when adjustments are needed and having the flexibility to make them; and considering societal and political constraints. Model complexity should be matched to that of the system and management needs; experiments can help unravel causal relationships. Monitoring, analyses, and syntheses require comprehensive data-management systems. More frequent and organized communications among scientists, managers, stakeholders, and decision-makers are necessary. We propose the establishment of an “Adaptive Management Team” to coordinate efforts across the management spectrum of the Delta and to provide guidance and link individual projects to shared approaches and experiences. Reliable long-term support will be needed to assess results of management actions, adjust approaches where improvement is likely, and strive toward the legislated goals of enhancing the Delta ecosystem while also providing reliable water supplies to much of California, and doing both these things in a manner that protects values of the Delta as a place where people live and work.

New tools for reproducible exploratory data analysis of large datasets are important to address the rising size and complexity of genomic data. We developed the valr R package to enable flexible and efficient genomic interval analysis. valr leverages new tools available in the ”tidyverse”, including dplyr. Benchmarks of valr show it performs similar to BEDtools and can be used for interactive analyses and incorporated into existing analysis pipelines.

Position statement The International Society of Sports Nutrition (ISSN) provides an objective and critical review related to the intake of protein for healthy, exercising individuals. Based on the current available literature, the position of the Society is as follows:An acute exercise stimulus, particularly resistance exercise, and protein ingestion both stimulate muscle protein synthesis (MPS) and are synergistic when protein consumption occurs before or after resistance exercise. For building muscle mass and for maintaining muscle mass through a positive muscle protein balance, an overall daily protein intake in the range of 1.4–2.0 g protein/kg body weight/day (g/kg/d) is sufficient for most exercising individuals, a value that falls in line within the Acceptable Macronutrient Distribution Range published by the Institute of Medicine for protein. There is novel evidence that suggests higher protein intakes (>3.0 g/kg/d) may have positive effects on body composition in resistance-trained individuals (i.e., promote loss of fat mass). Recommendations regarding the optimal protein intake per serving for athletes to maximize MPS are mixed and are dependent upon age and recent resistance exercise stimuli. General recommendations are 0.25 g of a high-quality protein per kg of body weight, or an absolute dose of 20–40 g. Acute protein doses should strive to contain 700–3000 mg of leucine and/or a higher relative leucine content, in addition to a balanced array of the essential amino acids (EAAs). These protein doses should ideally be evenly distributed, every 3–4 h, across the day. The optimal time period during which to ingest protein is likely a matter of individual tolerance, since benefits are derived from pre- or post-workout ingestion; however, the anabolic effect of exercise is long-lasting (at least 24 h), but likely diminishes with increasing time post-exercise. While it is possible for physically active individuals to obtain their daily protein requirements through the consumption of whole foods, supplementation is a practical way of ensuring intake of adequate protein quality and quantity, while minimizing caloric intake, particularly for athletes who typically complete high volumes of training. Rapidly digested proteins that contain high proportions of essential amino acids (EAAs) and adequate leucine, are most effective in stimulating MPS. Different types and quality of protein can affect amino acid bioavailability following protein supplementation. Athletes should consider focusing on whole food sources of protein that contain all of the EAAs (i.e., it is the EAAs that are required to stimulate MPS). Endurance athletes should focus on achieving adequate carbohydrate intake to promote optimal performance; the addition of protein may help to offset muscle damage and promote recovery. Pre-sleep casein protein intake (30–40 g) provides increases in overnight MPS and metabolic rate without influencing lipolysis.

Intramyocellular triacylglycerol (IMTG) is utilized as metabolic fuel during exercise and is linked to insulin resistance, but the long-term effect of weight loss strategies on IMTG among participants with abdominal fat, remain unclear.In an 18-month trial, sedentary participants with abdominal fat/dyslipidemia were randomized to either a low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC) diet (including 28g·day-1 of walnuts). After 6-months, the participants were re-randomized to moderate intense physical activity (PA+) or non-physical activity (PA-). Magnetic resonance imaging (MRI) was used to quantify changes of IMTG, abdominal sub-depots, hepatic and intermuscular fats.Across the 277 participants [86% men, age = 48 years, body-mass-index (BMI) = 31kg/m2, visceral fat = 33%] 86% completed the 18-m trial. At baseline, women had higher IMTG than men (3.4% vs. 2.3%, p

Winter air pollution in Ulaanbaatar, Mongolia is among the worst in the world. The health impacts of policy decisions affecting air pollution exposures in Ulaanbaatar were modeled and evaluated under business as usual and two more-strict alternative emissions pathways through 2024. Previous studies have relied on either outdoor or indoor concentrations to assesses the health risks of air pollution, but the burden is really a function of total exposure. This study combined projections of indoor and outdoor concentrations of PM2.5 with population time-activity estimates to develop trajectories of total age-specific PM2.5 exposure for the Ulaanbaatar population. Indoor PM2.5 contributions from secondhand tobacco smoke (SHS) were estimated in order to fill out total exposures, and changes in population and background disease were modeled. The health impacts were derived using integrated exposure-response curves from the Global Burden of Disease Study.Annual average population-weighted PM2.5 exposures at baseline (2014) were estimated at 59 μg/m3. These were dominated by exposures occurring indoors, influenced considerably by infiltrated outdoor pollution. Under current control policies, exposures increased slightly to 60 μg/m3 by 2024; under moderate emissions reductions and under a switch to clean technologies, exposures were reduced from baseline levels by 45% and 80%, respectively. The moderate improvement pathway decreased per capita annual disability-adjusted life year (DALY) and death burdens by approximately 40%. A switch to clean fuels decreased per capita annual DALY and death burdens by about 85% by 2024 with the relative SHS contribution increasing substantially.This study demonstrates a way to combine estimated changes in total exposure, background disease and population levels, and exposure-response functions to project the health impacts of alternative policy pathways. The resulting burden analysis highlights the need for aggressive action, including the elimination of residential coal burning and the reduction of current smoking rates.

Experience refines synaptic connectivity through neural activity-dependent regulation of transcription factors. Although activity-dependent regulation of transcription factors has been well described, it is unknown whether synaptic activity and local, dendritic regulation of the induced transcripts are necessary for mammalian synaptic plasticity in response to transcription factor activation. Neuronal depolarization activates the myocyte enhancer factor 2 (MEF2) family of transcription factors that suppresses excitatory synapse number. We report that activation of metabotropic glutamate receptor 5 (mGluR5) on the dendrites, but not cell soma, of hippocampal CA1 neurons is required for MEF2-induced functional and structural synapse elimination. We present evidence that mGluR5 is necessary for synapse elimination to stimulate dendritic translation of the MEF2 target gene Arc/Arg3.1. Activity-regulated cytoskeletal-associated protein (Arc) is required for MEF2-induced synapse elimination, where it plays an acute, cell-autonomous, and postsynaptic role. This work reveals a role for dendritic activity in local translation of specific transcripts in synapse refinement.