MR Imaging of Pediatric Neuroblastoma: Is Gadolinium Enhancement Necessary for Evaluation of Image-Defined-Risk Factors?

Background: Pre-treatment stratification and outcomes of neuroblastoma patients often depend on the assessment of image-defined risk factors (IDRFs) on MR Imaging, usually using Gadolinium-contrast materials which are cautioned in pediatrics. We aimed to address whether gadolinium contrast-enhanced sequences are necessary to identify the presence/absence of IDRFs. Methods: Patients with neuroblastoma with MR imaging were retrospectively identified from 2005 to 2021. Ninety confirmed IDRFs were evaluated in 23 patients. Corresponding MR studies were anonymized, randomized, and independently evaluated by 3 fellowship-trained pediatric radiologists. Each radiologist assessed the studies twice. At the first reading, all enhanced sequences were omitted, while in the second reading, the full study with enhanced sequences were included. Consensus reading was obtained among readers. Inter- and intra-rater agreements using Kappa statistics (κ) as well as the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of non-enhanced MR in assessing IDRFs with respect to enhanced MR were calculated. Results: There were substantial (ĸ: 0.64-0.73) intra-reader agreements, and moderate to substantial (ĸ: 0.57-0.62) inter-reader agreements among radiologists in identifying IDRFs using non-enhanced MR. Non-enhanced MR had a sensitivity of 87.8% (95% CI [79-94]), specificity of 93% (89-96), PPV of 82.3 (73-89), NPV of 95.4 (92-98), and accuracy of 91.6 (88-94) in identifying IDRFs. However, 5/23 patients (21.7%) had a change in staging with the inclusion of contrast sequences. Conclusion: Although contrast sequences have a role in IDRF assessment, the majority can be adequately assessed on MR without gadolinium-contrast enhancement. Validation in a larger cohort is an important next step.

Linking Natural Oil Seeps from the Gulf of Mexico to Their Origin by Use of Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.

We report chemical characterization of natural oil seeps from the Gulf of Mexico by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and Gas Chromatography/Atmospheric Pressure Chemical Ionization Mass Spectrometry (GC/APCI-MS), to highlight how FT-ICR MS can also be employed as a means to determine petroleum connectivity, in addition to traditional GC/MS techniques. The source of petroleum is the Green Canyon (GC) 600 lease block in the Gulf of Mexico. Within GC600, two natural oil seepage zones, Mega Plume and Birthday Candles, continuously release hydrocarbons and develop persistent oil slicks at the sea surface above them. We chemically trace the petroleum from the surface oil slicks to the Mega Plume seep itself, and further to a petroleum reservoir 5 km away in lease block GC645 (Holstein Reservoir). We establish the connectivity between oil samples and confirm a common geological origin for the oil slicks, oil seep, and reservoir oil. The ratios of seven common petroleum biomarkers detected by GC/APCI-MS display clear similarity between the GC600 and GC645 samples, as well as a distinct difference from another reservoir oil collected ∼300 km away (Macondo crude oil from MC252 lease block). FT-ICR MS and principal component analysis (PCA) demonstrate further similarities between the GC600 and GC645 samples that distinctly differ from MC252. A common geographical origin is postulated for the GC600/GC645 samples, with petroleum migrating from the GC645 reservoir to the oil seeps found in GC600 and up through the water column to the sea surface as an oil slick.

Comparison of the Binding of Reversible Inhibitors to Human Butyrylcholinesterase and Acetylcholinesterase: A Crystallographic, Kinetic and Calorimetric Study.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) hydrolyze the neurotransmitter acetylcholine and, thereby, function as coregulators of cholinergic neurotransmission. Although closely related, these enzymes display very different substrate specificities that only partially overlap. This disparity is largely due to differences in the number of aromatic residues lining the active site gorge, which leads to large differences in the shape of the gorge and potentially to distinct interactions with an individual ligand. Considerable structural information is available for the binding of a wide diversity of ligands to AChE. In contrast, structural data on the binding of reversible ligands to BChE are lacking. In a recent effort, an inhibitor competition approach was used to probe the overlap of ligand binding sites in BChE. Here, we extend this study by solving the crystal structures of human BChE in complex with five reversible ligands, namely, decamethonium, thioflavin T, propidium, huprine, and ethopropazine. We compare these structures to equivalent AChE complexes when available in the protein data bank and supplement this comparison with kinetic data and observations from isothermal titration calorimetry. This new information now allows us to define the binding mode of various ligand families and will be of importance in designing specific reversible ligands of BChE that behave as inhibitors or reactivators.

Practical uses of the BENCHMARK™ BMX®81 in the road less travelled: Guide catheter comparison for radial access in neurovascular intervention.

BACKGROUND: Radial arterial access has gained interest for neurovascular procedures in recent years. Although there are no randomized control trials for neurointervention procedures using radial access, there is growing literature demonstrating its feasibility and favorable outcomes. Equipment technical improvements, like the recently introduced BENCHMARK™ BMX®81 System, have made radial navigation safer, with improved maneuverability and support for a variety of procedures. We present a multicenter case series highlighting our institutional radial access experience comparing the BMX®81 with alternative catheters. METHODS: Multicenter retrospective cohort study of 80 patients who underwent neurovascular procedures through a radial approach. In half of the cases a BENCHMARK™ BMX®81 System was used. The comparison group consisted of the BENCHMARK™071 and 96, Neuron MAX®088 and BALLAST™ systems. Procedures included endovascular thrombectomy, carotid and brachiocephalic artery stenting, middle meningeal artery embolization, flow diverter stenting, vertebral artery sacrifice, aneurysm coiling, and WEB™ device deployment. RESULTS: In our series, the BMX®81 was successful in the navigation of the anatomy to the target location in 95% of cases. No radial access or BMX®81 related complications were identified. There was no significant difference in fluoroscopy time between the BMX81 and the comparison group. Four patients in the comparison group had catheter-related complications due to vasospasm. Eighty-six percent of BMX®81 cases had satisfactory outcomes and no technical difficulties. The remainder presented technical difficulties, but none of these were considered secondary to the puncture site or support structure. CONCLUSIONS: The BENCHMARK™ BMX®81 System is a recently developed guiding catheter which has design and size features supporting radial access for a variety of neurovascular interventions. Early multicenter experience highlights the ease of use and versatility of this new catheter as an alternative to transfemoral access as well as other catheters used for radial access.

Selectivity of phenothiazine cholinesterase inhibitors for neurotransmitter systems.

Synthetic derivatives of phenothiazine have been used for over a century as well-tolerated drugs against a variety of human ailments from psychosis to cancer. This implies a considerable diversity in the mechanisms of action produced by structural changes to the phenothiazine scaffold. For example, chlorpromazine treatment of psychosis is related to its interaction with dopaminergic receptors. On the other hand, antagonistic action of such drugs on cholinergic receptor systems would be counter-productive for treatment of Alzheimer's disease. In a search for phenothiazines that are inhibitors of cholinesterases, especially butyrylcholinesterase, with potential to treat Alzheimer's disease, we wished to ascertain that such molecules could be devoid of neurotransmitter receptor interactions. To that end, a number of our synthetic N-10-carbonyl phenothiazine derivatives, with cholinesterase inhibitory activity, were tested for interaction with a variety of neurotransmitter receptor systems. We demonstrate that phenothiazines can be prepared without significant neurotransmitter receptor interactions while retaining high potency as cholinesterase ligands for treatment of Alzheimer's disease.

Thioesters for the in vitro evaluation of agents to image brain cholinesterases.

Cholinesterases are associated with pathology characteristic of conditions such as Alzheimer's disease and are therefore, considered targets for neuroimaging. Ester derivatives of N-methylpiperidinol are promising potential imaging agents; however, methodology is lacking for evaluating these compounds in vitro. Here, we report the synthesis and evaluation of a series of N-methylpiperidinyl thioesters, possessing comparable properties to their corresponding esters, which can be directly evaluated for cholinesterase kinetics and histochemical distribution in human brain tissue. N-methylpiperidinyl esters and thioesters were synthesized and they demonstrated comparable cholinesterase kinetics. Furthermore, thioesters were capable, using histochemical method, to visualize cholinesterase activity in human brain tissue. N-methylpiperidinyl thioesters can be rapidly evaluated for cholinesterase kinetics and visualization of enzyme distribution in brain tissue which may facilitate development of cholinesterase imaging agents for application to conditions such as Alzheimer's disease.

All that glitters: case presentation and review of radial access complications in neurointervention.

Radial artery access has experienced increasing adoption and rapid expansion of indications for neurointerventional procedures. This access is an attractive neurointervention route to be considered, with many advantages over the traditional femoral access in terms of ease of vasculature navigation and decreased risk of complications such as significant bleeding. Although a promising technique for neurointerventional procedures, there are inherent and unique considerations as well as potential complications involved. The following case report highlights some of these vital concepts associated with radial artery access, including appropriate patient selection as well as assessment of arterial size in the context of neurointerventional techniques. Early identification of complications such as arterial injury and compartment syndrome, with an emphasis on appropriate draping and inter-procedure monitoring, is discussed as well as approaches for subsequent management. Finally, the issue of radiation safety in this emerging technique is considered. These concepts are critical for the successful use and the continued growth of radial artery access for neurointervention procedures.

Probing the peripheral site of human butyrylcholinesterase.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) catalyze the hydrolysis of the neurotransmitter acetylcholine and, thereby, function as coregulators of cholinergic neurotransmission. For both enzymes, hydrolysis takes place near the bottom of a 20 Å deep active site gorge. A number of amino acid residues within the gorge have been identified as important in facilitating efficient catalysis and inhibitor binding. Of particular interest is the catalytic triad, consisting of serine, histidine, and glutamate residues, that mediates hydrolysis. Another site influencing the catalytic process is located above the catalytic triad toward the periphery of the active site gorge. This peripheral site (P-site) contains a number of aromatic amino acid residues as well as an aspartate residue that is able to interact with cationic substrates and guide them down the gorge to the catalytic triad. In human AChE, certain aryl residues in the vicinity of the anionic aspartate residue (D74), such as W286, have been implicated in ligand binding and have therefore been considered part of the P-site of the enzyme. The present study was undertaken to explore the P-site of human BuChE and determine whether, like AChE, aromatic side chains near the peripheral aspartate (D70) of this enzyme contribute to ligand binding. Results obtained, utilizing inhibitor competition studies and BuChE mutant species, indicate the participation of aryl residues (F329 and Y332) in the E-helix component of the BuChE active site gorge, along with the anionic aspartate residue (D70), in binding ligands to the P-site of the enzyme.

Chronic oiling in global oceans.

Ocean oil slicks can be attributed to natural seepages or to anthropogenic discharges. To date, the global picture of their distribution and relative natural and anthropogenic contributions remains unclear. Here, by analyzing 563,705 Sentinel-1 images from 2014-2019, we provide the first global map of oil slicks and a detailed inventory of static-and-persistent sources (natural seeps, platforms, and pipelines). About 90% of oil slicks were within 160 kilometers of shorelines, with 21 high-density slick belts coinciding well with shipping routes. Quantified by slick area, the proportion of anthropogenic discharges was an order of magnitude greater than natural seepages (94 versus 6%), in contrast to the previous estimate quantified by volume during 1990-1999 (54 versus 46%). Our findings reveal that the present-day anthropogenic contribution to marine oil pollution may have been substantially underestimated.

Practical use and underlying physics of the BENCHMARK™ BMX™ 96 for large-bore aspiration thrombectomy: Case report of initial institutional experience.

Endovascular thrombectomy (EVT) is part of first-line intervention for acute ischemic stroke management. Recent technological advances have demonstrated that large-bore catheters are an attractive approach for EVT. A multitude of approaches such as A Direct Aspiration first Pass Technique (ADAPT) or in conjunction with stent retrieval (Solumbra technique) have been developed with increasingly large-bore catheters, demonstrating safety and efficacy. Furthermore, these techniques have demonstrated promise for the intervention of cerebral venous thrombosis as well as posterior circulation ischemic events. Recently, advances in neurointerventional catheters have focused on improved maneuverability to navigate the neurovasculature, as well as larger inner diameters for improved procedural versatility, including aspiration. We describe a case report highlighting our early institutional experience with the recently developed large-bore catheter, the BENCHMARK™ BMX™ 96. The case report entails near complete occlusion of the internal carotid artery from acute thrombus and the utility of the BMX™ 96 catheter for treatment of such extensive clot burden. The applicability of large-bore aspiration catheters, with an emphasis on recent advances, for mechanical thrombectomy in arterial as well as venous systems is discussed. To our knowledge, this is the first reported case of use of the BENCHMARK™ BMX™ 96 access system for EVT in acute ischemic stroke. Such new-generation large-bore catheters are a promising advance in neurointervention, and our early institution experience highlights the ease of use and versatility for neurointerventional procedures such as EVT.

Delayed parent artery occlusions following use of SILK flow diverters for treatment of intracranial aneurysms.

BACKGROUND: The efficacy of SILK flow diverters (SFD) in the management of cerebral aneurysms has been established. However, the risk of complications with parent artery occlusion (PAO) remains to be fully elucidated. The purpose of our study was to analyze intracranial aneurysms treated with SFDs and assess for occurrences and potential risk factors for PAO. MATERIALS AND METHODS: Between September 2010 and September 2017, 34 patients were treated for intracranial aneurysms using SFDs at a Canadian institution. This database was retrospectively analyzed for frequency of PAOs and statistical analysis performed for potential contributing factors. RESULTS: Following treatment with SFDs, average clinical and imaging follow-ups were 31 and 22 months, respectively. PAOs were identified in 21% (7/34) of patients and occurred between 8 days and 1.5 years from intervention but only in 11.8% in those compliant to anti-platelet medications. These were all associated with anterior circulation aneurysms (P=0.131) and had no associated neurological deficits. Of these, 57% (4/7) had a fusiform morphology compared with only 19% (5/27) in non-occluded patients (P=0.039). The presence of clinical symptoms at the time of initial SFD intervention was significantly associated with PAO (P=0.021). CONCLUSION: Delayed PAO is not an uncommon outcome of flow diverter deployment and could be seen up to 1.5 years after treatment with no associated neurological deficits. Anti-platelet non-adherence remains a risk factor for PAO. Fusiform morphology of the aneurysm and symptoms at the time of intervention were associated with subsequent occlusion.

Quantification of Butyrylcholinesterase Activity as a Sensitive and Specific Biomarker of Alzheimer's Disease.

Amyloid-ß (Aß) plaques are a neuropathological hallmark of Alzheimer's disease (AD); however, a significant number of cognitively normal older adults can also have Aß plaques. Thus, distinguishing AD from cognitively normal individuals with Aß plaques (NwAß) based on Aß plaque detection is challenging. It has been observed that butyrylcholinesterase (BChE) accumulates in plaques preferentially in AD. Thus, detecting BChE-associated plaques has the potential as an improved AD biomarker. We present Aß, thioflavin-S, and BChE quantification of 26 postmortem brain tissues; AD (n = 8), NwAß (n = 6), cognitively normal without plaques (n = 8), and other common dementias including corticobasal degeneration, frontotemporal dementia with tau, dementia with Lewy bodies, and vascular dementia. Pathology burden in the orbitofrontal cortex, entorhinal cortex, amygdala, and hippocampal formation was determined and compared. The predictive value of Aß and BChE quantification was determined, via receiver-operating characteristic plots, to evaluate their AD diagnostic performance using sensitivity, specificity, and area under curve (AUC) metrics. In general, Aß and BChE-associated pathology were greater in AD, particularly in the orbitofrontal cortex. In this region, the largest increase (9.3-fold) was in BChE-associated pathology, observed between NwAß and AD, due to the virtual absence of BChE-associated plaques in NwAß brains. Furthermore, BChE did not associate with pathology of the other dementias. In this sample, BChE-associated pathology provided better diagnostic performance (AUC = 1.0, sensitivity/specificity = 100% /100%) when compared to Aß (AUC = 0.98, 100% /85.7%). These findings highlight the predictive value of BChE as a biomarker for AD that could facilitate timely disease diagnosis and management.

Butyrylcholinesterase-knockout reduces fibrillar ß-amyloid and conserves 18FDG retention in 5XFAD mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder causing dementia. One hallmark of the AD brain is the deposition of ß-amyloid (Aß) plaques. AD is also a state of cholinergic dysfunction and butyrylcholinesterase (BChE) associates with Aß pathology. A transgenic mouse (5XFAD) is an aggressive amyloidosis model, producing Aß plaques with which BChE also associates. A derived strain (5XFAD/BChE-KO), with the BChE gene knocked out, has significantly lower fibrillar Aß than 5XFAD mice at the same age. Therefore, BChE may have a role in Aß pathogenesis. Furthermore, in AD, diminished glucose metabolism in the brain can be detected in vivo with positron emission tomography (PET) imaging following 2-deoxy-2-(18F)fluoro-D-glucose (18FDG) administration. To determine whether hypometabolism is related to BChE-induced changes in fibrillar Aß burden, whole brain and regional uptake of 18FDG in 5XFAD and 5XFAD/BChE-KO mice was compared to corresponding wild-type (WT5XFAD and WTBChE-KO) strains at 5months. Diminished fibrillar Aß burden was confirmed in 5XFAD/BChE-KO mice relative to 5XFAD. 5XFAD and 5XFAD/BChE-KO mice demonstrated reduction in whole brain 18FDG retention compared to respective wild-types. Regional analysis of relevant AD structures revealed reduction in 18FDG retention in 5XFAD mice in all brain regions analyzed (save cerebellum) compared to WT5XFAD. Alternatively, 5XFAD/BChE-KO mice demonstrated a more selective pattern of reduced retention in the cerebral cortex and thalamus compared to WTBChE-KO, while retention in hippocampal formation, amygdala and basal ganglia remained unchanged. This suggests that in knocking out BChE and reducing fibrillar Aß, a possible protective effect on brain function may be conferred in a number of structures in 5XFAD/BChE-KO mice.

Synthesis and Preliminary Evaluation of Phenyl 4-123I-Iodophenylcarbamate for Visualization of Cholinesterases Associated with Alzheimer Disease Pathology.

UNLABELLED: Acetylcholinesterase and butyrylcholinesterase accumulate with brain ß-amyloid (Aß) plaques in Alzheimer disease (AD). The overall activity of acetylcholinesterase is found to decline in AD, whereas butyrylcholinesterase has been found to either increase or remain the same. Although some cognitively normal older adults also have Aß plaques within the brain, cholinesterase-associated plaques are generally less abundant in such individuals. Thus, brain imaging of cholinesterase activity associated with Aß plaques has the potential to distinguish AD from cognitively normal older adults, with or without Aß accumulation, during life. Current Aß imaging agents are not able to provide this distinction. To address this unmet need, synthesis and evaluation of a cholinesterase-binding ligand, phenyl 4-(123)I-iodophenylcarbamate ((123)I-PIP), is described. METHODS: Phenyl 4-iodophenylcarbamate was synthesized and evaluated for binding potency toward acetylcholinesterase and butyrylcholinesterase using enzyme kinetic analysis. This compound was subsequently rapidly radiolabeled with (123)I and purified by high-performance liquid chromatography. Autoradiographic analyses were performed with (123)I-PIP using postmortem orbitofrontal cortex from cognitively normal and AD human brains. Comparisons were made with an Aß imaging agent, 2-(4'-dimethylaminophenyl)-6-(123)I-iodo-imidazo[1,2-a]pyridine ((123)I-IMPY), in adjacent brain sections. Tissues were also stained for Aß and cholinesterase activity to visualize Aß plaque load for comparison with radioligand uptake. RESULTS: Synthesized and purified PIP exhibited binding to cholinesterases. (123)I was successfully incorporated into this ligand. (123)I-PIP autoradiography with human tissue revealed accumulation of radioactivity only in AD brain tissues in which Aß plaques had cholinesterase activity. (123)I-IMPY accumulated in brain tissues with Aß plaques from both AD and cognitively normal individuals. CONCLUSION: Radiolabeled ligands specific for cholinesterases have potential for use in neuroimaging AD plaques during life. The compound herein described, (123)I-PIP, can detect cholinesterases associated with Aß plaques and can distinguish AD brain tissues from those of cognitively normal older adults with Aß plaques. Imaging cholinesterase activity associated with Aß plaques in the living brain may contribute to the definitive diagnosis of AD during life.

Cholinesterase inhibition in Alzheimer's disease: is specificity the answer?

Cholinesterase inhibitors are the standard of care for Alzheimer's disease (AD). Acetylcholinesterase (AChE) catalyzes the hydrolysis of the cholinergic neurotransmitter acetylcholine. However, the related enzyme butyrylcholinesterase (BuChE) also breaks down acetylcholine and is likewise targeted by the same clinical cholinesterase inhibitors. The lack of clinical efficacy for the highly specific and potent AChE inhibitor, (-) huperzine A, is intriguing, given the known cholinergic deficit in AD. Based on the proven efficacy of inhibitors affecting both cholinesterases and the apparent failure of specific AChE inhibition, focused BuChE inhibition seems important for more effective treatment of AD. Therefore, BuChE-selective inhibitors provide promise for improved benefit.

Cysteine thioesters as myelin proteolipid protein analogues to examine the role of butyrylcholinesterase in myelin decompaction.

Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disorder involving demyelination, axonal transection, and neuronal loss in the brain. Recent studies have indicated that active MS lesions express elevated levels of butyrylcholinesterase (BuChE). BuChE can hydrolyze a wide variety of esters, including fatty acid esters of protein. Proteolipid protein (PLP), an important transmembrane protein component of myelin, has six cysteine residues acylated, via thioester linkages, with fatty acids, usually palmitic, that contribute to the stability of myelin. Experimental chemical deacylation of PLP has been shown to lead to decompaction of myelin. Because of elevated levels of BuChE in active MS lesions and its propensity to catalyze the hydrolysis of acylated protein, we hypothesized that this enzyme may contribute to deacylation of PLP in MS, leading to decompaction of myelin and contributing to demyelination. To test this hypothesis, a series of increasing chain length (C2-C16) acyl thioester derivatives of N-acetyl-l-cysteine methyl ester were synthesized and examined for hydrolysis by human cholinesterases. All N-acetyl-l-cysteine fatty acyl thioester derivatives were hydrolyzed by BuChE but not by the related enzyme acetylcholinesterase. In addition, it was observed that the affinity of BuChE for the compound increased the longer the fatty acid chain, with the highest affinity for cysteine bound to palmitic acid. This suggests that the elevated levels of BuChE observed in active MS lesions could be related to the decompaction of myelin characteristic of the disorder.

Synthesis and preliminary evaluation of piperidinyl and pyrrolidinyl iodobenzoates as imaging agents for butyrylcholinesterase.

PURPOSE: The purpose of this study is to synthesize and evaluate specific agents for molecular imaging of butyrylcholinesterase (BuChE), known to be associated with neuritic plaques and neurofibrillary tangles in Alzheimer's disease (AD). In this study, these agents were tested in a normal rat model. The distribution of radiolabel was compared with known BuChE histochemical distribution in the rat brain. PROCEDURES: Iodobenzoate esters were synthesized and tested, through spectrophotometric analysis, as specific substrates for BuChE. These compounds were converted to the corresponding (123)I esters from tributyltin intermediates and purified for studies in the rat model. Whole body dynamic scintigraphic images were obtained for biodistribution studies. Autoradiograms of brain sections were obtained and compared to histochemical distribution of the enzyme in this model system. RESULTS: The three iodobenzoate esters studied were specific substrates for BuChE. Whole body biodistribution studies with (123)I-labeled compounds showed rapid disappearance from the body while radioactivity was retained in the head region. Brain section autoradiography of animals injected with these labeled compounds indicated that most areas known to contain BuChE corresponded to areas of radioactivity accumulation. CONCLUSION: BuChE-specific radiolabeled iodobenzoates enter the brain and, in general, label areas known to exhibit BuChE activity in histochemical studies. Such molecules may represent a new direction for the development of agents for the molecular imaging of BuChE in the living brain, especially in regions where BuChE-containing neuropathological structures appear in AD.

Comment on "A persistent oxygen anomaly reveals the fate of spilled methane in the deep Gulf of Mexico".

Kessler et al. (Reports, 21 January 2011, p. 312) reported that methane released from the 2010 Deepwater Horizon blowout, approximately 40% of the total hydrocarbon discharge, was consumed quantitatively by methanotrophic bacteria in Gulf of Mexico deep waters over a 4-month period. We find the evidence explicitly linking observed oxygen anomalies to methane consumption ambiguous and extension of these observations to hydrate-derived methane climate forcing premature.

Butyrylcholinesterase activity in multiple sclerosis neuropathology.

Butyrylcholinesterase (BuChE) is an enzyme capable of hydrolysing a wide variety of esters including acetylcholine, a molecule involved in neurotransmission and modulation of immune cell activity. In the brain, BuChE is expressed in white matter and certain populations of neurons and glia. Multiple sclerosis (MS) is an autoimmune disease affecting white matter characterized by neuroinflammation and neurodegeneration in the central nervous system. Here we demonstrate alterations in BuChE activity in MS white matter lesions, including diminished enzyme activity associated with myelin and an increased activity in cells with microglial morphology. Increased BuChE activity within MS lesions could contribute to the pro-inflammatory immune responses through hydrolysis of acetylcholine and to demyelination through hydrolytic deacylation of myelin proteins such as proteolipid protein. This suggests that BuChE could be a potential target for novel disease-modifying strategies for MS.

Global patterns and predictions of seafloor biomass using random forests.

A comprehensive seafloor biomass and abundance database has been constructed from 24 oceanographic institutions worldwide within the Census of Marine Life (CoML) field projects. The machine-learning algorithm, Random Forests, was employed to model and predict seafloor standing stocks from surface primary production, water-column integrated and export particulate organic matter (POM), seafloor relief, and bottom water properties. The predictive models explain 63% to 88% of stock variance among the major size groups. Individual and composite maps of predicted global seafloor biomass and abundance are generated for bacteria, meiofauna, macrofauna, and megafauna (invertebrates and fishes). Patterns of benthic standing stocks were positive functions of surface primary production and delivery of the particulate organic carbon (POC) flux to the seafloor. At a regional scale, the census maps illustrate that integrated biomass is highest at the poles, on continental margins associated with coastal upwelling and with broad zones associated with equatorial divergence. Lowest values are consistently encountered on the central abyssal plains of major ocean basins The shift of biomass dominance groups with depth is shown to be affected by the decrease in average body size rather than abundance, presumably due to decrease in quantity and quality of food supply. This biomass census and associated maps are vital components of mechanistic deep-sea food web models and global carbon cycling, and as such provide fundamental information that can be incorporated into evidence-based management.