A Comparative Study of Mercury Bioaccumulation in Bivalve Molluscs from a Shallow Estuarine Embayment.

In estuarine food webs, bivalve molluscs transfer nutrients and pollutants to higher trophic levels. Mercury (Hg) pollution is ubiquitous, but it is especially elevated in estuaries historically impacted by industrial activities, such as those in the U.S. Northeast. Monomethylmercury (MeHg), the organic form of Hg, is highly bioaccumulative and transferable in the food web resulting in the highest concentrations in the largest and oldest marine predators. Patterns of Hg concentrations in marine bivalve molluscs, however, are poorly understood. In this study, inorganic Hg (iHg), MeHg, and the total Hg (THg) in soft tissues of the northern quahogs (Mercenaria mercenaria), eastern oysters (Crassostrea virginica), and ribbed mussels (Geukensia demissa) from eastern Long Island sound, a temperate estuary of the western North Atlantic Ocean was investigated. In all three species, concentrations of THg remained similar between the four sampling months (May, June, July, and September), and were mostly independent of animal size. In quahogs, MeHg and iHg displayed significant (p < 0.05) positive (iHg in May and June) and negative (MeHg in July and September) changes with shell height. Variability in concentrations of THg, MeHg, and iHg, both inter- and intra-specifically was high and greater in quahogs and oysters (THg: 37, 39%, MeHg: 28, 39%, respectively) than in mussels (THg: 13%, MeHg: 20%). The percentage of THg that was MeHg (%MeHg) was also highly variable in the three species (range: 10-80%), highlighting the importance of measuring MeHg and not only THg in molluscs.

The neural and cognitive basis of expository text comprehension.

As science and technology rapidly progress, it becomes increasingly important to understand how individuals comprehend expository technical texts that explain these advances. This study examined differences in individual readers' technical comprehension performance and differences among texts, using functional brain imaging to measure regional brain activity while students read passages on technical topics and then took a comprehension test. Better comprehension of the technical passages was related to higher activation in regions of the left inferior frontal gyrus, left superior parietal lobe, bilateral dorsolateral prefrontal cortex, and bilateral hippocampus. These areas are associated with the construction of a mental model of the passage and with the integration of new and prior knowledge in memory. Poorer comprehension of the passages was related to greater activation of the ventromedial prefrontal cortex and the precuneus, areas involved in autobiographical and episodic memory retrieval. More comprehensible passages elicited more brain activation associated with establishing links among different types of information in the text and activation associated with establishing conceptual coherence within the text representation. These findings converge with previous behavioral research in their implications for teaching technical learners to become better comprehenders and for improving the structure of instructional texts, to facilitate scientific and technological comprehension.

Medical Misadventures as Errors and Mistakes and Motor Vehicular Accidents in the Disproportionate Burden of Childhood Mortality among Blacks/African Americans in the United States: CDC Dataset, 1968-2015.

PURPOSE: Racial disparities in infant mortality in the United States persist after adjustment for known confounders of race and mortality association, as well as heterogeneity assessment. Epidemiologic and clinical data continue to show the survival disadvantages of Black/AA children: when Black/AAs are compared to whites, they are three times as likely to die from all-cause mortality. The persistent inability to remove the variance in race-mortality association is partly due to unobserved, unmeasured, and residual confounding, as well as implicit biases in public health and clinical medicine in health equity transformation. This current epidemiologic-perspective explanatory model study aimed to examine the possible explanation of racial differences in U.S. infant mortality using medical misadventures as errors and mistakes, and infants' involvement in motor vehicular traffic accidents. MATERIALS AND METHOD: Using CDC WONDER ecologic data from 1968 to 2015, we assessed the infant mortality-rate ratio and percent change associated with medical misadventures as well as motor vehicular accidents or trauma. The rate ratio and percent change were estimated using stratification analysis and trend homogeneity, respectively. RESULTS: There was a Black-white racial difference in medical misadventures during the study period. Relative to the years 1968-1978 (rate ratio [RR], 1.43), there was a steady increase in the mortality-rate ratio in 1979-1998 (52%, RR = 1.52), and mortality was more than two times as likely in 1999-2015 (RR = 2.37). However, with respect to motor vehicular accident/trauma mortality, the mortality ratio, although lower among Blacks in 1968-1978 (RR, 0.92), increased in 1979-1998 by 27% (RR = 1.27) but decreased in 1999-2015 (RR, 1.17), though there was still an excess of 17% mortality among Black/AAs. The percent change for medical misadventures indicated an increasing trend from 9.3% in 1998 to 52% in 2015. However, motor vehicular-related mortality indicated a positive trend in 1998 (38.5%) but a negative trend in 2015 (-8.4%). CONCLUSIONS: There were substantial race differentials or variances in infant mortality associated with medical misadventures compared to traffic accidents, and Black/AA children relative to whites experienced a survival disadvantage. These comparative findings are suggestive of medical misadventures and motor vehicular trauma as potential explanations for some of the persistent Black-white disparities in overall infant mortality in the U.S. From these findings, we recommend a national effort to address these issues, thus narrowing the observed disparities in the U.S. infant mortality burden among Black/AAs.

Properties influencing flux and diatom uptake of mercury and methylmercury from estuarine sediments.

Mercury (Hg) is a conspicuous and persistent global pollutant. Ionic Hg can be methylated into noxious methylmercury (CH3Hg), which biomagnifies in marine tropic webs and poses a health risk to humans and organisms. Sediment Hg methylation rates are variable, and the output flux of created CH3Hg are dependent on sediment characteristics and environmental factors. Thus, uncertainties remain about the formation and flux of CH3Hg from sediment, and how this could contribute to the bioaccumulative burden for coastal organisms in shallow ecosystems. Cores were collected from 3 estuarine locations along the Eastern USA to examine how sediments characteristics influence the introduction of Hg and CH3Hg into the base of the food chain. Stable isotopes of inorganic 200Hg and CH3199Hg were injected into sediments of individual cores, with cultured diatoms constrained to overlying waters. Five different treatments were done on duplicate cores, spiked with: (1) no Hg isotopes (control); (2) inorganic 200Hg; (3) CH3199Hg; (4) both 200Hg and CH3199Hg isotopes, (5) both 200Hg and CH3199Hg into overlying waters (not sediment). Experimental cores were incubated for 3 days under temperature and light controlled conditions. These results demonstrate that upper sediments characteristics lead to high variability in Hg cycling. Notably, sediments which contained abundant and peaty organic material (∼28 %LOI), had the highest pore water DOC (3206 µM) and displayed bands of sulfur reducing bacteria yielded the greatest methylation rate (1.97 % day-1) and subsequent diatom uptake of CH3200Hg (cell quota 0.18 amol/cell) in the overlying water.

Time Thresholds for Using Pressure Reactivity Index in Neuroprognostication for Patients With Severe Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: Severe traumatic brain injury (sTBI) represents a diffuse, heterogeneous disease where therapeutic targets for optimizing clinical outcome remain unclear. Mean pressure reactivity index (PRx) values have demonstrated associations with clinical outcome in sTBI. However, the retrospective derivation of a mean value diminishes its bedside significance. We evaluated PRx temporal profiles for patients with sTBI and identified time thresholds suggesting optimal neuroprognostication. METHODS: Patients with sTBI and continuous bolt intracranial pressure monitoring were identified. Outcomes were dichotomized by disposition status ("good outcome" was denoted by home and acute rehabilitation). PRx values were obtained every minute by taking moving correlation coefficients of intracranial pressures and mean arterial pressures. Average PRx trajectories for good and poor outcome groups were calculated by extending the last daily averaged PRx value to day 18. Each patient also had smoothed PRx trajectories that were used to generate "candidate features." These "candidate features" included daily average PRx's, cumulative first-order changes in PRx and cumulative second-order changes in PRx. Changes in sensitivity over time for predicting poor outcome was then evaluated by generating penalized logistic regression models that were derived from the "candidate features" and maximized specificity. RESULTS: Among 33 patients with sTBI, 18 patients achieved good outcome and 15 patients had poor outcome. Average PRx trajectories for the good and poor outcome groups started on day 6 and consistently diverged at day 9. When targeting a specificity >83.3%, an 85% maximum sensitivity for determining poor outcome was achieved at hospital day 6. Subsequent days of PRx monitoring showed diminishing sensitivities. CONCLUSION: Our findings suggest that in a population of sTBI, PRx sensitivities for predicting poor outcome was maximized at hospital day 6. Additional study is warranted to validate this model in larger populations.

Dissolved organic matter thiol concentrations determine methylmercury bioavailability across the terrestrial-marine aquatic continuum.

The most critical step for methylmercury (MeHg) bioaccumulation in aquatic food webs is phytoplankton uptake of dissolved MeHg. Dissolved organic matter (DOM) has been known to influence MeHg uptake, but the mechanisms have remained unclear. Here we show that the concentration of DOM-associated thiol functional groups (DOM-RSH) varies substantially across contrasting aquatic systems and dictates MeHg speciation and bioavailability to phytoplankton. Across our 20 study sites, DOM-RSH concentrations decrease 40-fold from terrestrial to marine environments whereas dissolved organic carbon (DOC), the typical proxy for MeHg binding sites in DOM, only has a 5-fold decrease. MeHg accumulation into phytoplankton is shown to be directly linked to the concentration of specific MeHg binding sites (DOM-RSH), rather than DOC. Therefore, MeHg bioavailability increases systematically across the terrestrial-marine aquatic continuum as the DOM-RSH concentration decreases. Our results strongly suggest that measuring DOM-RSH concentrations will improve empirical models in phytoplankton uptake studies and will form a refined basis for modeling MeHg incorporation in aquatic food webs under various environmental conditions.

Riverine Discharge Fuels the Production of Methylmercury in a Large Temperate Estuary.

Estuaries are an important food source for the world's growing population, yet human health is at risk from elevated exposure to methylmercury (MeHg) via the consumption of estuarine fish. Moreover, the sources and cycling of MeHg in temperate estuarine ecosystems are poorly understood. Here, we investigated the seasonal and tidal patterns of mercury (Hg) forms in Long Island Sound (LIS), in a location where North Atlantic Ocean waters mix with the Connecticut River. We found that seasonal variations in Hg and MeHg in LIS followed the extent of riverine Hg delivery, while tides further exacerbated the remobilization of earlier deposited riverine Hg. The net production of MeHg near the river plume was significant compared to that in other locations and enhanced during high tide, possibly resulting from the enhanced microbial activity and organic carbon remineralization in the river plume. Statistical models, driven by our novel data, further support the hypothesis that the river-delivered organic matter and inorganic Hg drive net MeHg production in the estuarine water column. Our study sheds light on the significance of water column biogeochemical processes in temperate tidal estuaries in regulating MeHg levels and inspires new questions in our quest to understand MeHg sources and dynamics in coastal oceans.

An examination of the factors influencing the bioaccumulation of methylmercury at the base of the estuarine food web.

Estuarine systems have received ongoing mercury (Hg) inputs from both point sources and regional contamination and have high legacy Hg in sediments. This is an environmental concern given that coastal seafood is an important vector for human exposure to methylmercury (MeHg). The base of the food chain represents the most important trophic steps for MeHg bioaccumulation. The magnitude of the uptake by phytoplankton, and their consumers, is influenced by many factors, in addition to sediment and water MeHg concentrations, that impact MeHg assimilation into phytoplankton and the trophic transfer to higher trophic levels, both benthic and pelagic. For forage fish, such as mummichogs (Fundulus heteroclitus), abiotic and biotic (bioenergetic) factors can influence their MeHg content, and diet is also important as they feed both on benthic and pelagic prey. Given that the importance of sediment MeHg versus pelagic MeHg sources has been debated, we updated a phytoplankton bioaccumulation model, and coupled this with a bioaccumulation model for MeHg concentration in mummichog tissue to examine the controlling factors for sites, from Maine to Maryland, USA, ranging widely in their Hg concentrations and other variables. The study highlighted the importance of DOC in modulating uptake into the pelagic food web, but also demonstrated the importance of diet in controlling mummichog MeHg. Finally, the relative importance of MeHg source - sediment or water column - was correlated with the level of Hg contamination. Sediment-derived MeHg was a more important source for highly Hg contaminated systems. As water column and sediment MeHg are not strongly correlated for the studied ecosystems, their importance as a source of MeHg to mummichogs varies with location. The study highlights the differences across ecosystems in MeHg bioaccumulation pathways, and that uptake into phytoplankton is an important variable controlling forage fish concentration.

Application of Encapsulated and Dry-plated Food Acidulants to Control Salmonella enterica in Raw Meat-based Diets for Dogs.

There is an increasing demand for raw meat-based diets (RMBDs) for dogs, but these foods cannot be heat-pasteurized. Thus, the objective of this study was to evaluate the antimicrobial efficacy of encapsulated and dry-plated glucono delta lactone (GDL), citric acid (CA), and lactic acid (LA) when challenged against Salmonella enterica inoculated in a model raw meat-based diet (RMBDs) for dogs. Nutritionally complete, raw diets were formulated with different levels (1.0, 2.0 and 3.0% (w/w)) of both encapsulated and dry-plated GDL, CA, and LA with both the positive (PC) and the negative controls (NC) without acidulants. The diets were formed into patties of ∼100 g and inoculated with 3-cocktail mixtures of Salmonella enterica serovars, excluding the NC to achieve a final concentration of ∼6.0 Log CFU/patty. Microbial analyses were performed on the inoculated diets and survivors of S. enterica enumerated. Both encapsulated and dry-plated CA and LA had higher log reductions compared to GDL (P < 0.05). However, encapsulated CA and LA at 1.0% (w/w) exhibited higher log reductions (P > 0.05) and preserved product quality compared to the dry-plated acidulants at 1.0%. We concluded that 1.0% (w/w) of encapsulated citric or lactic acids could be successfully applied as an antimicrobial intervention in raw diets for dogs.

Demographic resilience may sustain significant coral populations in a 2°C-warmer world.

Projections of coral reefs under climate change have important policy implications, but most analyses have focused on the intensification of climate-related physical stress rather than explicitly modelling how coral populations respond to stressors. Here, we analyse the future of the Great Barrier Reef (GBR) under multiple, spatially realistic drivers which allows less impacted sites to facilitate recovery. Under a Representative Concentration Pathway (RCP) 2.6 CMIP5 climate ensemble, where warming is capped at ~2°C, GBR mean coral cover declined mid-century but approached present-day levels towards 2100. This is considerably more optimistic than most analyses. However, under RCP4.5, mean coral cover declined by >80% by late-century, and reached near zero under RCP ≥6.0. While these models do not allow for adaptation, they significantly extend past studies by revealing demographic resilience of coral populations to low levels of additional warming, though more pessimistic outcomes might be expected under CMIP6. Substantive coral populations under RCP2.6 would facilitate long-term genetic adaptation, adding value to ambitious greenhouse emissions mitigation.

A synthesis of mercury research in the Southern Hemisphere, part 1: Natural processes.

Recent studies demonstrate a short 3-6-month atmospheric lifetime for mercury (Hg). This implies Hg emissions are predominantly deposited within the same hemisphere in which they are emitted, thus placing increasing importance on considering Hg sources, sinks and impacts from a hemispheric perspective. In the absence of comprehensive Hg data from the Southern Hemisphere (SH), estimates and inventories for the SH have been drawn from data collected in the NH, with the assumption that the NH data are broadly applicable. In this paper, we centre the uniqueness of the SH in the context of natural biogeochemical Hg cycling, with focus on the midlatitudes and tropics. Due to its uniqueness, Antarctica warrants an exclusive review of its contribution to the biogeochemical cycling of Hg and is therefore excluded from this review. We identify and describe five key natural differences between the hemispheres that affect the biogeochemical cycling of Hg: biome heterogeneity, vegetation type, ocean area, methylation hotspot zones and occurence of volcanic activities. We review the current state of knowledge of SH Hg cycling within the context of each difference, as well as the key gaps that impede our understanding of natural Hg cycling in the SH. The differences demonstrate the limitations in using NH data to infer Hg processes and emissions in the SH.

Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways.

Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma. SIGNIFICANCE: Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA. See related commentary by Shain, p. 1294. This article is highlighted in the In This Issue feature, p. 1275.

A synthesis of mercury research in the Southern Hemisphere, part 2: Anthropogenic perturbations.

Environmental mercury (Hg) contamination is a global concern requiring action at national scales. Scientific understanding and regulatory policies are underpinned by global extrapolation of Northern Hemisphere Hg data, despite historical, political, and socioeconomic differences between the hemispheres that impact Hg sources and sinks. In this paper, we explore the primary anthropogenic perturbations to Hg emission and mobilization processes that differ between hemispheres and synthesize current understanding of the implications for Hg cycling. In the Southern Hemisphere (SH), lower historical production of Hg and other metals implies lower present-day legacy emissions, but the extent of the difference remains uncertain. More use of fire and higher deforestation rates drive re-mobilization of terrestrial Hg, while also removing vegetation that would otherwise provide a sink for atmospheric Hg. Prevalent Hg use in artisanal and small-scale gold mining is a dominant source of Hg inputs to the environment in tropical regions. Meanwhile, coal-fired power stations continue to be a significant Hg emission source and industrial production of non-ferrous metals is a large and growing contributor. Major uncertainties remain, hindering scientific understanding and effective policy formulation, and we argue for an urgent need to prioritize research activities in under-sampled regions of the SH.

Setting sustainable limits on anchoring to improve the resilience of coral reefs.

Boat anchoring is common at coral reefs that have high economic or social value, but anchoring has received relatively little attention in reef resilience studies. We developed an individual-based model of coral populations and simulated the effects of anchor damage over time. The model allowed us to estimate the carrying capacity of anchoring for four different coral assemblages and different starting levels of coral cover. The carrying capacity of small to medium-sized recreational vessels across these four assemblages was between 0 and 3.1 anchor strikes ha-1 day-1. In a case study of two Great Barrier Reef archipelagos, we modelled the benefits of anchoring mitigation under bleaching regimes expected for four climate scenarios. The partial mitigation of even a very mild anchoring incidence (1.17 strikes ha-1 day-1) resulted in median coral gains of 2.6-7.7 % absolute cover under RCP2.6, though benefits varied temporally and depended on the Atmosphere-Ocean General Circulation Model used.

Ulnohumeral joint static cartilage compression is affected by radial head implant size.

INTRODUCTION: Radiocapitellar joint arthroplasty is a commonly performed procedure, which often leads to early failure or instability. Few studies assess the effect of radiocapitellar joint arthroplasty on the ulnohumeral joint. We hypothesized that static forces of contact (compressing cartilage, or cartilage relaxation contact force) would reveal the effect of varying radial head implant size and elbow position on the ulnohumeral joint. METHODS: A minimally-invasive method of measuring cartilage relaxation contact force was utilized in 10 fresh-frozen human cadaveric specimens that did not require significant dissection or intraarticular sensor placement. Specimens were rigidly fixed in various positions of elbow flexion and forearm pronosupination with increasing radial head implant lengths. Uniaxial distracting forces were applied and displacement was repeatedly measured with resultant best-fit polynomial curves to determine inflections corresponding to the force required to overcome static cartilage relaxation as in previous work. FINDINGS: Baseline mean (intra-cadaver) cartilage relaxation contact force was 11.8 N (standard error of the mean = 0.3) at 90° of elbow flexion and neutral rotation. There was little variation within specimens (Intraclass correlation coefficient > 0.94). Cartilage relaxation contact force increased at the ulnohumeral joint with radial head implant overstuffing (> 4 mm, P < 0.05) and elbow flexion (120°, P < 0.001). Pronosupination altered cartilage relaxation contact force in an implant-length independent manner (P < 0.05). INTERPRETATION: Radiocapitellar joint arthroplasty implant length and elbow joint position independently contribute to increased cartilage relaxation contact force at the ulnohumeral joint. This further supports attempts at anatomic reconstruction of the radiocapitellar joint to prevent pathologic ulnohumeral joint loading.

Evaluation of a new emergency department avoidance model of care, the Cancer Urgent Assessment Clinic, in response to the COVID-19 pandemic.

Introduction: The Cancer Urgent Assessment Clinic (CUAC) was an emergency department (ED) avoidance/unscheduled model of care implemented in response to the COVID-19 pandemic. The aim was to reduce the risk of COVID-19 exposure and infection by providing an alternative to ED for cancer patients while undergoing anticancer treatments. Methods: The clinic incorporated a telephone triage process and face-to-face appointments 8am to 8pm, 7 days per week. CUAC operated between 23 March '20 and 31 July '20, led by a nurse practitioner candidate, oncology registrars, cancer nurse specialists, and overseen by oncology consultants. Evaluation followed a mixed-methods approach through (1) analysis of CUAC patient data, (2) comparison of ED cancer patient presentation data from a previous period (23 March 2019-31 July 2019), and (3) a patient survey. Results: In total, 400 patients were telephone triaged via CUAC, with 166 recorded as having avoided ED. There was a reduction in the number of cancer patient admissions to the ED short stay unit during the clinic period compared with the same time-period in 2019: 130 vs. 234, associated with 615 fewer hours. Patient satisfaction was positive particularly regarding ease of access, time to treatment, confidence in assessment and treatment of cancer-related concerns, and likelihood of presenting to hospital when unwell during the pandemic. Discussion: While initially being implemented to reduce the risk of COVID-19 exposure, this evaluation demonstrated the CUAC model was an efficient and potentially cost-saving model of care for the management of cancer patients with mild to moderate severity of disease and treatment-related concerns.

Description of a Dimethylmercury Automatic Analyzer for the High-Resolution Measurement of Dissolved Gaseous Mercury Species in Surface Ocean Waters.

Our understanding of the significance of dimethylmercury (DMHg) to the mercury (Hg) global ocean biogeochemical cycle is unclear because of the lack of detailed DMHg measurements in the water column. To our knowledge, 30 years of published studies have generated no more than 200 DMHg data points in the ocean surface waters and marine boundary layer (MBL). To improve the precision and reduce the uncertainty in determining DMHg in surface seawater, we developed a simple and robust DMHg automatic analyzer (DAA). This DAA system couples the main sampling and analytic steps, including a continuous flow chamber, with dual Carbotrap preconcentration, a gas chromatographic column, a cold vapor atomic fluorescence spectrometry, and a data logger for signal integration. We compared the operation, performance, and reproducibility between our DAA and the traditional manual analytic method. Its advantages include the ease of operation, the high time resolution and precision (30 min sampling and <5% relative variation), and long-term stability (2 weeks). The DAA can determine DMHg in both the MBL and surface seawater. The estimated detection limits for DMHg with the DAA in the atmosphere and in surface seawater are 10 pg/m3 and 0.2 fM, respectively. The successful DAA field measurement in coastal waters indicates that it can help detect the low DMHg concentration in surface seawater, and the time series DMHg data helped our understanding of the DMHg behavior (sources and sinks) and its flux into the MBL. The comparison of DMHg concentration in various oceans also suggests that the coastal region had the lowest averaged DMHg, up to an order of magnitude lower than other ecosystems.

Kynurenine 3-Monooxygenase Interacts with Huntingtin at the Outer Mitochondrial Membrane.

The flavoprotein kynurenine 3-monooxygenase (KMO) is localised to the outer mitochondrial membrane and catalyses the synthesis of 3-hydroxykynurenine from L-kynurenine, a key step in the kynurenine pathway (KP) of tryptophan degradation. Perturbation of KP metabolism due to inflammation has long been associated with the pathogenesis of several neurodegenerative disorders, including Huntington's disease (HD)-which is caused by the expansion of a polyglutamine stretch in the huntingtin (HTT) protein. While HTT is primarily localised to the cytoplasm, it also associates with mitochondria, where it may physically interact with KMO. In order to test this hypothesis, we employed bimolecular fluorescence complementation (BiFC) and found that KMO physically interacts with soluble HTT exon 1 protein fragment in living cells. Notably, expansion of the disease-causing polyglutamine tract in HTT leads to the formation of proteinaceous intracellular inclusions that disrupt this interaction with KMO, markedly decreasing BiFC efficiency. Using confocal microscopy and ultrastructural analysis, we determined KMO and HTT localisation within the cell and found that the KMO-HTT interaction is localized to the outer mitochondrial membrane. These data suggest that KMO may interact with a pool of HTT at the mitochondrial membrane, highlighting a possible physiological role for mitochondrial HTT. The KMO-HTT interaction is abrogated upon polyglutamine expansion, which may indicate a heretofore unrecognized relevance in the pathogenesis of this disorder.

The kinetic energy of PAH dication and trication dissociation determined by recoil-frame covariance map imaging.

We investigated the dissociation of dications and trications of three polycyclic aromatic hydrocarbons (PAHs), fluorene, phenanthrene, and pyrene. PAHs are a family of molecules ubiquitous in space and involved in much of the chemistry of the interstellar medium. In our experiments, ions are formed by interaction with 30.3 nm extreme ultraviolet (XUV) photons, and their velocity map images are recorded using a PImMS2 multi-mass imaging sensor. Application of recoil-frame covariance analysis allows the total kinetic energy release (TKER) associated with multiple fragmentation channels to be determined to high precision, ranging 1.94-2.60 eV and 2.95-5.29 eV for the dications and trications, respectively. Experimental measurements are supported by Born-Oppenheimer molecular dynamics (BOMD) simulations.

Composition of trace residues from the contents of 11th-12th century sphero-conical vessels from Jerusalem.

The residues from the internal surface of four archaeological ceramic sherds, excavated from the Armenian Gardens, Jerusalem were analysed to characterise the contents of the original vessel. The sherds derive from four small, thick-walled, sphero-conical vessels recovered from a destruction layer, dating between the 11th and 12th century, Jerusalem. The residue has been analysed using light microscopy, biochemical characterisation, gas chromatography mass spectroscopy, inductively coupled plasma atomic emission spectroscopy and cold vapour atomic fluorescence spectrometry. This analysis established the presence of various compounds including fatty acids and notable levels of mercury, sulphur, aluminium, potassium, magnesium, nitrates and phosphorous. The contents and probable functions of the four vessels were characterised from the residues on these sherds as different from each other, reflecting their different decoration, manufacture and ceramic typologies. One of these vessels contains residue that indicate the vessel held oils. The residue of the second vessel is consistent with either scented materials or medicinal contents, while a third probably contained medicinal material. The unique fourth sherd is from a stoneware sphero-conical vessel with very thick walls, no decoration and the residue supports the possibility it was used for the storage of chemicals or may have held the chemical ingredients for an explosive device, consistent with a medieval grenade. This residue analysis of Mamluk sphero-conical vessels provides insight into luxury items, medicines, technology and trade in medieval Jerusalem.