Grasshopper herbivory immediately affects element cycling but not export rates in an N‐limited grassland system

As a cause of ecosystem disturbances, phytophagous insects are known to directly influence the element and organic matter (OM) cycling in ecosystems by their defoliation and excretion activity. This study focuses on the interplay between short-term, insect herbivory, plant responses to feeding activity, rhizosphere processes, and belowground nutrient availability under nutrient-poor soil conditions. To test the effects of insect herbivory on OM and nutrient cycling in an N-limited pasture system, mesocosm laboratory experiments were conducted using Dactylis glomerata as common grass species and Chorthippus dorsatus, a widespread grasshopper species, to induce strong defoliating herbivory. 13CO2 pulse labeling was used together with labeled 15N feces to trace the fate of C in soil respiration at the beginning of herbivory, and of C and N in above- and belowground plant biomass, grasshopper, feces, bulk soil, soil microbial biomass, throughfall solutions, and soil solutions. Within five days, herbivory caused a reduction in aboveground grass biomass by about 34%. A linear mixed-effects model revealed that herbivory significantly increased total dissolved C and N amounts in throughfall solutions by a factor of 4–10 (P < 0.05) compared with the control. In total, 27.6% of the initially applied feces 15N were translocated from the aboveground to the belowground system. A significant enrichment of 15N in roots led to the assumption that feces-derived 15N was rapidly taken up to compensate for the frass-related foliar N losses in light of N shortage. Soil microorganisms incorporated newly available 13C; however, the total amount of soil microbial biomass remained unaffected, while the exploitative grass species rapidly sequestered resources to facilitate its regrowth after herbivory attack. Heavy herbivory by insects infesting D. glomerata-dominated, N-deficient grasslands remarkably impacted belowground nutrient cycling by an instant amplification of available nutrients, which led to an intensified nutrient competition between plants and soil microorganisms. Consequently, these competitive plant–soil microbe interactions accelerated N cycling and effectively retained herbivory-mediated C and N surplus release resulting in diminished N losses from the system. The study highlighted the overarching role of plant adaptations to in situ soil fertility in short-term ecosystem disturbances

The Boston criteria version 2.0 for cerebral amyloid angiopathy:a multicentre, retrospective, MRI–neuropathology diagnostic accuracy study

BACKGROUND: Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid β in the cerebrovascular wall. The Boston criteria are used worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report an international collaborative study aiming to update and externally validate the Boston diagnostic criteria across the full spectrum of clinical CAA presentations. METHODS: In this multicentre, hospital-based, retrospective, MRI and neuropathology diagnostic accuracy study, we did a retrospective analysis of clinical, radiological, and histopathological data available to sites participating in the International CAA Association to formulate updated Boston criteria and establish their diagnostic accuracy across different populations and clinical presentations. Ten North American and European academic medical centres identified patients aged 50 years and older with potential CAA-related clinical presentations (ie, spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathological assessment for CAA diagnosis. MRI scans were centrally rated at Massachusetts General Hospital (Boston, MA, USA) for haemorrhagic and non-haemorrhagic CAA markers, and brain tissue samples were rated by neuropathologists at the contributing sites. We derived the Boston criteria version 2.0 (v2.0) by selecting MRI features to optimise diagnostic specificity and sensitivity in a prespecified derivation cohort (Boston cases 1994-2012, n=159), then externally validated the criteria in a prespecified temporal validation cohort (Boston cases 2012-18, n=59) and a geographical validation cohort (non-Boston cases 2004-18; n=123), comparing accuracy of the new criteria to the currently used modified Boston criteria with histopathological assessment of CAA as the diagnostic standard. We also assessed performance of the v2.0 criteria in patients across all cohorts who had the diagnostic gold standard of brain autopsy. FINDINGS: The study protocol was finalised on Jan 15, 2017, patient identification was completed on Dec 31, 2018, and imaging analyses were completed on Sept 30, 2019. Of 401 potentially eligible patients presenting to Massachusetts General Hospital, 218 were eligible to be included in the analysis; of 160 patient datasets from other centres, 123 were included. Using the derivation cohort, we derived provisional criteria for probable CAA requiring the presence of at least two strictly lobar haemorrhagic lesions (ie, intracerebral haemorrhages, cerebral microbleeds, or foci of cortical superficial siderosis) or at least one strictly lobar haemorrhagic lesion and at least one white matter characteristic (ie, severe visible perivascular spaces in centrum semiovale or white matter hyperintensities in a multispot pattern). The sensitivity and specificity of these criteria were 74·8% (95% CI 65·4-82·7) and 84·6% (71·9-93·1) in the derivation cohort, 92·5% (79·6-98·4) and 89·5% (66·9-98·7) in the temporal validation cohort, 80·2% (70·8-87·6) and 81·5% (61·9-93·7) in the geographical validation cohort, and 74·5% (65·4-82·4) and 95·0% (83·1-99·4) in all patients who had autopsy as the diagnostic standard. The area under the receiver operating characteristic curve (AUC) was 0·797 (0·732-0·861) in the derivation cohort, 0·910 (0·828-0·992) in the temporal validation cohort, 0·808 (0·724-0·893) in the geographical validation cohort, and 0·848 (0·794-0·901) in patients who had autopsy as the diagnostic standard. The v2.0 Boston criteria for probable CAA had superior accuracy to the current Boston criteria (sensitivity 64·5% [54·9-73·4]; specificity 95·0% [83·1-99·4]; AUC 0·798 [0·741-0854]; p=0·0005 for comparison of AUC) across all individuals who had autopsy as the diagnostic standard. INTERPRETATION: The Boston criteria v2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their specificity in our cohorts of patients aged 50 years and older presenting with spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes. Future studies will be needed to determine generalisability of the v.2.0 criteria across the full range of patients and clinical presentations. FUNDING: US National Institutes of Health (R01 AG26484)

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Validation of Vitek 2 Nonfermenting Gram-Negative Cards and Vitek 2 Version 4.02 Software for Identification and Antimicrobial Susceptibility Testing of Nonfermenting Gram-Negative Rods from Patients with Cystic Fibrosis▿

Accurate identification and antimicrobial susceptibility testing (AST) of nonfermenters from cystic fibrosis patients are essential for appropriate antimicrobial treatment. This study examined the ability of the newly designed Vitek 2 nonfermenting gram-negative card (NGNC) (new gram-negative identification card; bioMérieux, Marcy-l'Ètoile, France) to identify nonfermenting gram-negative rods from cystic fibrosis patients in comparison to reference methods and the accuracy of the new Vitek 2 version 4.02 software for AST compared to the broth microdilution method. Two hundred twenty-four strains for identification and 138 strains for AST were investigated. The Vitek 2 NGNC identified 211 (94.1%) of the nonfermenters correctly. Among morphologically atypical microorganisms, five strains were misidentified and eight strains were determined with low discrimination, requiring additional tests which raised the correct identification rate to 97.8%. Regarding AST, the overall essential agreement of Vitek 2 was 97.6%, and the overall categorical agreement was 92.9%. Minor errors were found in 5.1% of strains, and major and very major errors were found in 1.6% and 0.3% of strains, respectively. In conclusion, the Vitek NGNC appears to be a reliable method for identification of morphologically typical nonfermenters and is an improvement over the API NE system and the Vitek 2 GNC database version 4.01. However, classification in morphologically atypical nonfermenters must be interpreted with care to avoid misidentification. Moreover, the new Vitek 2 version 4.02 software showed good results for AST and is suitable for routine clinical use. More work is needed for the reliable testing of strains whose MICs are close to the breakpoints

Adult Onset Leukodystrophy with Neuroaxonal Spheroids: Clinical, Neuroimaging and Neuropathologic Observations

Pigmented orthochromatic leukodystrophy (POLD) and Hereditary diffuse leukoencephalopathy with spheroids HDLS are two adult onset leukodystrophies with neuroaxonal spheroids presenting with prominent neurobehavioral, cognitive, and motor symptoms. These are familial or sporadic disorders characterized by cerebral white matter degeneration including myelin and axonal loss, gliosis, macrophages, and axonal spheroids. We report clinical, neuroimaging and pathological correlations of four women ages 34–50 years with adult onset leukodystrophy. Their disease course ranged from 1.5–8 years. Three patients had progressive cognitive and behavioral changes whereas one had acute onset. Neuroimaging revealed white matter abnormalities characterized by symmetric, bilateral, T2 hyperintense and T1 hypointense MRI signal involving frontal lobe white matter in all patients. Extensive laboratory investigations were negative apart from abnormalities in some mitochondrial enzymes and immunologic parameters. Autopsies demonstrated severe leukodystrophy with myelin and axonal loss, axonal spheroids, and macrophages with early and severe frontal white matter involvement. The extent and degree of changes outside the frontal lobe appeared to correlate with disease duration. The prominent neurobehavioral deficits and frontal white matter disease provides clinical-pathologic support for association pathways linking distributed neural circuits subserving cognition. These observations lend further support to the notion that white matter disease alone can account for dementia

Preservation of Neuronal Number Despite Age-Related Cortical Brain Atrophy in Elderly Subjects Without Alzheimer Disease

Cerebral volume loss has long been associated with normal aging but whether this is due to aging itself or to age-related diseases including incipient Alzheimer disease (AD) is uncertain. To understand the changes that occur in the aging brain, we examined the cerebral cortex of 27 normal individuals ranging in age from 56 to 103 years. None fulfilled the criteria for the neuropathological diagnosis of AD or other neurodegenerative disease. Seventeen of the elderly participants had cognitive testing an average of 6.7 months prior to death. We used quantitative approaches to analyze cortical thickness, neuronal number, and density. Frontal and temporal neocortical regions had clear evidence of cortical thinning with age but total neuronal numbers in frontal and temporal neocortical regions remained relatively constant over a 50-year age range. These data suggest that loss of neuronal and dendritic architecture, rather than loss of neurons, underlies neocortical volume loss with increasing age in the absence of AD