Lumbar Intradural Neurenteric Cyst: A Rare Pathology in an Unusual Location.

A previously healthy 48-year-old female presented to the emergency department with a 2-week history of low back pain, progressive lower extremities weakness, and right leg numbness. There were no bowel or bladder dysfunction symptoms. Spine magnetic resonance imaging (MRI) showed an intradural cystic lesion dorsal to the spinal cord at the level of L1 measuring 1.6 × 2.1 × 4.1 cm, which was T1 hypointense and T2 hyperintense, with a small soft tissue component and no gadolinium enhancement (Figure 1). A small lipomatous component was also noted. There were no associated vertebral anomalies. The patient underwent a T12-L2 laminectomy and cyst resection, which was subtotal due to the cyst adherence to the conus medullaris. Histopathology showed characteristic features of a neurenteric cyst, with respiratory-type epithelium in the cyst wall (Figure 2). Eight months later, follow-up MRI showed no evidence of recurrence. The patient reported improved sensation in the lower extremities; however, there was some residual weakness predominantly in the proximal hip flexors bilaterally.

Short-Course Radiation plus Temozolomide in Elderly Patients with Glioblastoma.

BACKGROUND: Glioblastoma is associated with a poor prognosis in the elderly. Survival has been shown to increase among patients 70 years of age or younger when temozolomide chemotherapy is added to standard radiotherapy (60 Gy over a period of 6 weeks). In elderly patients, more convenient shorter courses of radiotherapy are commonly used, but the benefit of adding temozolomide to a shorter course of radiotherapy is unknown. METHODS: We conducted a trial involving patients 65 years of age or older with newly diagnosed glioblastoma. Patients were randomly assigned to receive either radiotherapy alone (40 Gy in 15 fractions) or radiotherapy with concomitant and adjuvant temozolomide. RESULTS: A total of 562 patients underwent randomization, 281 to each group. The median age was 73 years (range, 65 to 90). The median overall survival was longer with radiotherapy plus temozolomide than with radiotherapy alone (9.3 months vs. 7.6 months; hazard ratio for death, 0.67; 95% confidence interval [CI], 0.56 to 0.80; P<0.001), as was the median progression-free survival (5.3 months vs. 3.9 months; hazard ratio for disease progression or death, 0.50; 95% CI, 0.41 to 0.60; P<0.001). Among 165 patients with methylated O6-methylguanine-DNA methyltransferase (MGMT) status, the median overall survival was 13.5 months with radiotherapy plus temozolomide and 7.7 months with radiotherapy alone (hazard ratio for death, 0.53; 95% CI, 0.38 to 0.73; P<0.001). Among 189 patients with unmethylated MGMT status, the median overall survival was 10.0 months with radiotherapy plus temozolomide and 7.9 months with radiotherapy alone (hazard ratio for death, 0.75; 95% CI, 0.56 to 1.01; P=0.055; P=0.08 for interaction). Quality of life was similar in the two trial groups. CONCLUSIONS: In elderly patients with glioblastoma, the addition of temozolomide to short-course radiotherapy resulted in longer survival than short-course radiotherapy alone. (Funded by the Canadian Cancer Society Research Institute and others; ClinicalTrials.gov number, NCT00482677 .).

A phase I study of vistusertib (dual mTORC1/2 inhibitor) in patients with previously treated glioblastoma multiforme: a CCTG study.

The PI3K/AKT/mTOR pathway activation plays a central role in glioblastoma multiforme (GBM) development and progression, and in resistance to anti-cancer therapies. Inhibition of the PI3K pathway has been shown to sensitize cultured glioma cells and tumor xenografts to the effects of temozolomide (TMZ) and radiation. Vistusertib is an oral inhibitor of mTORC1/2 complexes. The primary objective of this Canadian Cancer Trials Group phase I study was to determine the recommended phase II dose (RP2D) of vistusertib in patients with GBM receiving TMZ at first progression following primary treatment. Vistusertib was administered at a starting dose of 100 mg bid 2 days on/5 days off weekly with TMZ 150 mg/m2 daily for 5 days/28-days cycle. Dose escalation was according to a 3 + 3 design. Secondary objectives included assessment of vistusertib safety and toxicity profile, and preliminary efficacy. 15 patients were enrolled in the study (median age 66 (range 51-77), females 8). Vistusertib 125 mg BID in combination with TMZ 150 mg/m2 daily for 5 days was well tolerated. Vistusertib treatment-related adverse events were generally grade 1-2, with the most frequently reported being fatigue, gastrointestinal symptoms, and rash. Of 13 response evaluable patients, 1 patient (8%) had a partial response ongoing at 7.6 months of follow-up, and 5 patients had stable disease (38%) as best response (median duration 9.6 months, range 3.7-not yet reached). Six-month progression-free survival (PFS) rate was 26.6%. Combination of vistusertib with TMZ in GBM patients at first recurrence demonstrated a favorable safety profile at the tested dose levels.

Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study.

BACKGROUND: Outcome of low-grade glioma (WHO grade II) is highly variable, reflecting molecular heterogeneity of the disease. We compared two different, single-modality treatment strategies of standard radiotherapy versus primary temozolomide chemotherapy in patients with low-grade glioma, and assessed progression-free survival outcomes and identified predictive molecular factors. METHODS: For this randomised, open-label, phase 3 intergroup study (EORTC 22033-26033), undertaken in 78 clinical centres in 19 countries, we included patients aged 18 years or older who had a low-grade (WHO grade II) glioma (astrocytoma, oligoastrocytoma, or oligodendroglioma) with at least one high-risk feature (aged >40 years, progressive disease, tumour size >5 cm, tumour crossing the midline, or neurological symptoms), and without known HIV infection, chronic hepatitis B or C virus infection, or any condition that could interfere with oral drug administration. Eligible patients were randomly assigned (1:1) to receive either conformal radiotherapy (up to 50·4 Gy; 28 doses of 1·8 Gy once daily, 5 days per week for up to 6·5 weeks) or dose-dense oral temozolomide (75 mg/m2 once daily for 21 days, repeated every 28 days [one cycle], for a maximum of 12 cycles). Random treatment allocation was done online by a minimisation technique with prospective stratification by institution, 1p deletion (absent vs present vs undetermined), contrast enhancement (yes vs no), age (<40 vs ≥40 years), and WHO performance status (0 vs ≥1). Patients, treating physicians, and researchers were aware of the assigned intervention. A planned analysis was done after 216 progression events occurred. Our primary clinical endpoint was progression-free survival, analysed by intention-to-treat; secondary outcomes were overall survival, adverse events, neurocognitive function (will be reported separately), health-related quality of life and neurological function (reported separately), and correlative analyses of progression-free survival by molecular markers (1p/19q co-deletion, MGMT promoter methylation status, and IDH1/IDH2 mutations). This trial is closed to accrual but continuing for follow-up, and is registered at the European Trials Registry, EudraCT 2004-002714-11, and at ClinicalTrials.gov, NCT00182819. FINDINGS: Between Sept 23, 2005, and March 26, 2010, 707 patients were registered for the study. Between Dec 6, 2005, and Dec 21, 2012, we randomly assigned 477 patients to receive either radiotherapy (n=240) or temozolomide chemotherapy (n=237). At a median follow-up of 48 months (IQR 31-56), median progression-free survival was 39 months (95% CI 35-44) in the temozolomide group and 46 months (40-56) in the radiotherapy group (unadjusted hazard ratio [HR] 1·16, 95% CI 0·9-1·5, p=0·22). Median overall survival has not been reached. Exploratory analyses in 318 molecularly-defined patients confirmed the significantly different prognosis for progression-free survival in the three recently defined molecular low-grade glioma subgroups (IDHmt, with or without 1p/19q co-deletion [IDHmt/codel], or IDH wild type [IDHwt]; p=0·013). Patients with IDHmt/non-codel tumours treated with radiotherapy had a longer progression-free survival than those treated with temozolomide (HR 1·86 [95% CI 1·21-2·87], log-rank p=0·0043), whereas there were no significant treatment-dependent differences in progression-free survival for patients with IDHmt/codel and IDHwt tumours. Grade 3-4 haematological adverse events occurred in 32 (14%) of 236 patients treated with temozolomide and in one (<1%) of 228 patients treated with radiotherapy, and grade 3-4 infections occurred in eight (3%) of 236 patients treated with temozolomide and in two (1%) of 228 patients treated with radiotherapy. Moderate to severe fatigue was recorded in eight (3%) patients in the radiotherapy group (grade 2) and 16 (7%) in the temozolomide group. 119 (25%) of all 477 patients had died at database lock. Four patients died due to treatment-related causes: two in the temozolomide group and two in the radiotherapy group. INTERPRETATION: Overall, there was no significant difference in progression-free survival in patients with low-grade glioma when treated with either radiotherapy alone or temozolomide chemotherapy alone. Further data maturation is needed for overall survival analyses and evaluation of the full predictive effects of different molecular subtypes for future individualised treatment choices. FUNDING: Merck Sharpe & Dohme-Merck & Co, Canadian Cancer Society, Swiss Cancer League, UK National Institutes of Health, Australian National Health and Medical Research Council, US National Cancer Institute, European Organisation for Research and Treatment of Cancer Cancer Research Fund.

Glucosinolate and Desulfo-glucosinolate Metabolism by a Selection of Human Gut Bacteria.

Glucosinolate (GSL) hydrolysis is mediated by the enzyme myrosinase which together with specifier proteins can give rise to isothiocyanates (ITCs), thiocyanates, and nitriles (NITs) in cruciferous plants. However, little is known about the metabolism of GSLs by the human gut flora. The aim of the work was to investigate the metabolic fates of sinigrin (SNG), glucotropaeolin (GTP), gluconasturtiin (GNT), and their corresponding desulfo-GSLs (DS-GSLs). Three human gut bacterial strains, Enterococcus casseliflavus CP1, Lactobacillus agilis R16, and Escherichia coli VL8, were chosen for this study. GNT was metabolized to completion within 24 h to phenethyl ITC and phenethyl NIT (PNIT) by all bacteria, except for L. agilis R16 which produced only PNIT. At least 80 % of GTP and SNG were metabolized by all bacteria within 24 h to the corresponding ITCs and NITs. The pH of media over time gradually became acidic for both L. agilis R16 and E. coli VL8, while for E. casseliflavus CP1 the media became slightly alkaline with NIT and ITC production occurring between pH 3.0 and 7.5. ITC production peaked between 4 and 10 h in most cases and gradually declined while NIT production increased and remained relatively constant over time. The total percentage products accounted for 3-53 % of the initial GSL. NITs were produced from DS-GSLs suggesting an alternative metabolism via desulfation for the food based GSLs. The metal ion dependency for NIT production for GNT and its DS form was investigated where it was shown that Fe(2+) increased NIT production, while Mg(2+) stimulated the formation of ITC.

Death of a 29-Year-Old Male from Undifferentiated Sepsis.

Tumour necrosis factor alpha inhibitors, such as infliximab, and other biologic agents are associated with increased risk of opportunistic infection, including tuberculosis. Tuberculosis infections associated with infliximab tend to present atypically and can be difficult to diagnose, as they are more likely to manifest as extrapulmonary or disseminated disease. The authors report a case involving a 29-year-old male patient who died following 16 days of treatment for undifferentiated sepsis and who was found on autopsy to have widespread disseminated tuberculosis. Prior to the onset of illness, the patient had received infliximab for the treatment of Crohn's disease. Following discussion of the case, the authors review the definition of adverse events, provide a root cause analysis of the cognitive errors and breakdowns in the health care system that contributed to the reported outcome, and identify opportunities to address these breakdowns and improve patient safety measures for future cases.

Drought alters interactions between root and foliar herbivores.

Drought can alter plant quality and the strength of trophic interactions between herbivore groups, and is likely to increase in occurrence and severity under climate change. We hypothesized that changes in plant chemistry due to root herbivory and drought stress would affect the performance of a generalist and a specialist aphid species feeding on a Brassica plant. High drought stress increased the negative effect of root herbivory on the performance of both aphid species (30% decrease in fecundity and 15% reduction in intrinsic rate of increase). Aphid performance was greatest at moderate drought stress, though the two species differed in which treatment combination maximized performance. Nitrogen concentration was greatest in high and moderately drought-stressed plants without root herbivores and moderately drought-stressed plants under low root herbivore density, and correlated positively with aphid fecundity for both species. Glucosinolate concentrations increased 62% under combined drought stress and root herbivory, and were positively correlated with extended aphid development time. Root herbivory did not influence relative water content and foliar biomass under normal water regimes but they decreased 24 and 63%, respectively, under high drought stress. This study shows that drought can alter the strength of interactions between foliar and root herbivores, and that plant chemistry is key in mediating such interactions. The two aphid species responded in a broadly similar way to root herbivore and drought-stress treatments, which suggests that generalized predictions of the effects of abiotic factors on interactions between above- and below-ground species may be possible.

Clinical Neuropathology practice guide 6-2013: morphology and an appropriate immunohistochemical screening panel aid in the identification of synovial sarcoma by neuropathologists.

AIMS: Pathologists are under increasing pressure to accurately subclassify sarcomas, yet neuropathologists have limited collective experience with rare sarcoma types such as synovial sarcoma. We reviewed 9 synovial sarcomas affecting peripheral nerve diagnosed by neuropathologists and explored the morphologic and immunohistochemical differences between these and MPNST. Our goal was to make practical recommendations for neuropathologists regarding which spindle cell tumors affecting nerve should be sent for SYT-SSX testing. METHODS: Clinical records and genetics were reviewed retrospectively and central pathology review of 9 synovial sarcomas and 6 MPNST included immunohistochemistry for SOX10, S100, BAF47, CK (lmw, pan, CK7, CK19), EMA, CD34, bcl2, CD99, and neurofilament. RESULTS: Common synovial sarcoma sites were brachial plexus, spinal and femoral nerve, none were "intra-neural", all had the SYTSSX1 translocation, and 6/9 were monophasic with myxoid stroma and distinct collagen. Half of the monophasic synovial sarcomas expressed CK7, CK19 or panCK in a "rare positive cells pattern", 8/9 (89%) expressed EMA, and all were SOX10 immunonegative with reduced but variable BAF47 expression. CONCLUSIONS: We recommend that upon encountering a cellular spindle cell tumor affecting nerve neuropathologists consider the following: 1) SYT-SSX testing should be performed on any case with morphology suspicious for monophasic synovial sarcoma including wiry or thick bands of collagen and relatively monomorphous nuclei; 2) neuropathologists should employ a screening immunohistochemical panel including one of CK7, panCK or CK19, plus EMA, S100 and SOX10, and 3) SYT-SSX testing should be performed on any spindle cell tumor with CK and/or EMA immunopositivity if SOX10 immunostaining is negative or only labels entrapped nerve elements.

Sparsely Granulated Corticotroph Pituitary Macroadenoma Presenting With Pituitary Apoplexy Resulting in Remission of Hypercortisolism.

Objective: Pituitary corticotroph macroadenomas, which account for 7% to 23% of corticotroph adenomas, rarely present with apoplexy. This report aimed to describe a patient with a sparsely granulated corticotroph tumor (SGCT) presenting with apoplexy and remission of hypercortisolism. Case Report: A 33-year-old male patient presented via ambulance with sudden onset of severe headache and nausea/vomiting. Physical examination revealed bitemporal hemianopsia, diplopia from right-sided third cranial nerve palsy, abdominal striae, facial plethora, and dorsal and supraclavicular fat pads. Magnetic resonance imaging demonstrated a 3.2-cm mass arising from the sella turcica with hemorrhage compressing the optic chiasm, extension into the sphenoid sinus and cavernous sinus. Initial investigations revealed a plasma cortisol level of 64.08 (reference range [RR], 2.36-17.05) mcg/dL. He underwent emergent transsphenoidal surgery. Pathology was diagnostic of SGCT. Postoperatively, the following laboratory findings were found: (1) cortisol level, <1.8 ug/dL (RR, 2.4-17); (2) adrenocorticotropic hormone level, 36 pg/mL (RR, 0-81); (3) thyroid-stimulating hormone level, 0.07 uIU/mL (RR, 0.36-3.74); (4) free thyroxine level, 1 ng/dL (RR, 0.8-1.5); (5) luteinizing hormone level, <1 mIU/mL (RR, 1-12); (6) follicle-stimulating hormone level, 1 mIU/mL (RR, 1-12); and (7) testosterone level, 28.8 ng/dL (RR, 219.2-905.6), with ongoing requirement for hydrocortisone, levothyroxine, testosterone replacement, and continued follow-up. Discussion: Corticotroph adenomas are divided into densely granulated, sparsely granulated, and Crooke cell tumors. Sparsely granulated pattern is associated with a larger tumor size and decreased remission rate after surgery. Conclusion: This report illustrates a rare case of hypercortisolism remission due to apoplexy of an SGCT with subsequent central adrenal insufficiency, hypothyroidism, and hypogonadism.

Molecular Cloning, Expression and Characterisation of a Bacterial Myrosinase from Citrobacter Wye1.

Glucosinolates are plant natural products which on degradation by myrosinases give rise to the beneficial bioactive isothiocyanates. Recently, a myrosinase activity was detected in a Citrobacter strain isolated from soil. This enzyme was purified enabling its amino acid sequence and gene sequence (cmyr) to be determined. In order to study this myrosinase it was necessary to establish an expression system that would enable future work such as a structural determination of the protein to be carried out. The myrosinase gene was amplified, cloned and expressed in Escherichia coli with a 6XHis-tag. The heterologous expression of cmyr enabled relatively large amounts of myrosinase to be produced (3.4 mg cmyr/100 ml culture). Myrosinase activity was determined by mixing substrate and enzyme and determining glucose release. Optimum pH and temperature were determined to be pH 6.0 and 25 °C for the Ni-NTA purified protein. The kinetic parameters of the purified myrosinase were determined using sinigrin as a substrate. Km and Vmax were estimated as 0.18 mM and 0.033 mmol/min/mg respectively for sinigrin under optimum conditions and compared to other kinetic data for myrosinases. The substrate specificity of myrosinase was determined having the highest affinity for sinigrin followed by glucoiberin, progoitrin, glucoerucin, glucoraphanin and glucotropaeolin.

Plant nutrient supply determines competition between phytophagous insects.

Indirect competition is often mediated by plant responses to herbivore feeding damage and is common among phytophagous insect species. Plant-mediated responses may be altered by abiotic conditions such as nutrient supply, which can affect plant growth, morphology, and the concentration of primary and secondary metabolites. Nutrient supply can be manipulated by the type and amount of fertilizer applied to a plant. Brassica oleracea plants were grown in several types of fertilizer, including those commonly used in sustainable and conventional agricultural systems. The occurrence of indirect competition between two phytophagous species from different feeding guilds (a phloem-feeder and leaf-chewer) was assessed. The leaf-chewer reduced aphid populations on plants growing in most fertilizer treatments, but not on those in the ammonium nitrate fertilizer treatment, which caused the highest concentration of foliar nitrogen. The potential consequences of our findings are discussed for phytophagous species in conventional and sustainable agricultural systems.

Oilseed rape seeds with ablated defence cells of the glucosinolate-myrosinase system. Production and characteristics of double haploid MINELESS plants of Brassica napus L.

Oilseed rape and other crop plants of the family Brassicaceae contain a unique defence system known as the glucosinolate-myrosinase system or the 'mustard oil bomb'. The 'mustard oil bomb' which includes myrosinase and glucosinolates is triggered by abiotic and biotic stress, resulting in the formation of toxic products such as nitriles and isothiocyanates. Myrosinase is present in specialist cells known as 'myrosin cells' and can also be known as toxic mines. The myrosin cell idioblasts of Brassica napus were genetically reprogrammed to undergo controlled cell death (ablation) during seed development. These myrosin cell-free plants have been named MINELESS as they lack toxic mines. This has led to the production of oilseed rape with a significant reduction both in myrosinase levels and in the hydrolysis of glucosinolates. Even though the myrosinase activity in MINELESS was very low compared with the wild type, variation was observed. This variability was overcome by producing homozygous seeds. A microspore culture technique involving non-fertile haploid MINELESS plants was developed and these plants were treated with colchicine to produce double haploid MINELESS plants with full fertility. Double haploid MINELESS plants had significantly reduced myrosinase levels and glucosinolate hydrolysis products. Wild-type and MINELESS plants exhibited significant differences in growth parameters such as plant height, leaf traits, matter accumulation, and yield parameters. The growth and developmental pattern of MINELESS plants was relatively slow compared with the wild type. The characteristics of the pure double haploid MINELESS plant are described and its importance for future biochemical, agricultural, dietary, functional genomics, and plant defence studies is discussed.

Chitin nanofibers trigger membrane bound defense signaling and induce elicitor activity in plants.

The present study demonstrated that chitin-based nanofibers (CNFs) trigger the chitinase genes (PGIP1 and CaChi2), while elevating salicylic acid that can protect plants against pathogens. Cross-talk between this genetic induction and salicylic-acid-mediated immune response was also observed, which may arm a plant against multiple pathovars. Crab and mushroom based CNFs were synthesized by electrospinning and ball milling techniques. Plants (mung bean, Vigna radiata) (pepper, Capsicum annuum) were pre-inoculated with CNFs and treated with the pathogens Scrolotium rolfsii for pepper and Macrophomina phaseolina for mung bean and shrimp-based CNFs were used as a control. Treated plants had elevated levels of chitinase genes in response to CNFs at inoculation concentrations <10 mg/mL both in soil and media, to protect them against the pathogenic fungal disease. After 24 h of exposure to the pathogens, qRT-PCR showed genes class II chitinase gene (CaChi2) and polygalacturonase inhibitor protein 1 (PGIP1) to be up-regulated in both root and shoot at 0.1 and 1 mg/mL of inoculation, respectively. The ball milled mushroom CNFs were sufficient to trigger the membrane based enzymes with less diameter (≥15 nm) to be most efficient versus others. In vitro analysis showed IC50 of ball milled mushroom CNFs to be most efficient in limiting the growth of fungal biomass. Further trigger-like effects were prominent in reducing pathogenic fungal spread in both species.

Varying responses of insect herbivores to altered plant chemistry under organic and conventional treatments.

The hypothesis that plants supplied with organic fertilizers are better defended against insect herbivores than those supplied with synthetic fertilizers was tested over two field seasons. Organic and synthetic fertilizer treatments at two nitrogen concentrations were supplied to Brassica plants, and their effects on the abundance of herbivore species and plant chemistry were assessed. The organic treatments also differed in fertilizer type: a green manure was used for the low-nitrogen treatment, while the high-nitrogen treatment contained green and animal manures. Two aphid species showed different responses to fertilizers: the Brassica specialist Brevicoryne brassicae was more abundant on organically fertilized plants, while the generalist Myzus persicae had higher populations on synthetically fertilized plants. The diamondback moth Plutella xylostella (a crucifer specialist) was more abundant on synthetically fertilized plants and preferred to oviposit on these plants. Glucosinolate concentrations were up to three times greater on plants grown in the organic treatments, while foliar nitrogen was maximized on plants under the higher of the synthetic fertilizer treatments. The varying response of herbivore species to these strong differences in plant chemistry demonstrates that hypotheses on defence in organically grown crops have over-simplified the response of phytophagous insects.

Removing the mustard oil bomb from seeds: transgenic ablation of myrosin cells in oilseed rape (Brassica napus) produces MINELESS seeds.

Many plant phytochemicals constitute binary enzyme-glucoside systems and function in plant defence. In brassicas, the enzyme myrosinase is confined to specific myrosin cells that separate the enzyme from its substrate; the glucosinolates. The myrosinase-catalysed release of toxic and bioactive compounds such as isothiocyanates, upon activation or tissue damage, has been termed 'the mustard oil bomb' and characterized as a 'toxic mine' in plant defence. The removal of myrosin cells and the enzyme that triggers the release of phytochemicals have been investigated by genetically modifying Brassica napus plants to remove myrosinase-storing idioblasts. A construct with the seed myrosin cell-specific Myr1.Bn1 promoter was used to express a ribonuclease, barnase. Transgenic plants ectopically expressing barnase were embryo lethal. Co-expressing barnase under the control of the Myr1.Bn1 promoter with the barnase inhibitor, barstar, under the control of the cauliflower mosaic virus 35S promoter enabled a selective and controlled death of myrosin cells without affecting plant viability. Ablation of myrosin cells was confirmed with light and electron microscopy, with immunohistological analysis and immunogold-electron microscopy analysis showing empty holes where myrosin cells normally are localized. Further evidence for a successful myrosin cell ablation comes from immunoblots showing absence of myrosinase and negligible myrosinase activity, and autolysis experiments showing negligible production of glucosinolate hydrolysis products. The plants where the myrosin defence cells have been ablated and named 'MINELESS plants'. The epithiospecifier protein profile and glucosinolate levels were changed in MINELESS plants, pointing to localization of myrosinases and a 35 kDa epithiospecifier protein in myrosin cells and a reduced turnover of glucosinolates in MINELESS plants.

Forward flow-An alternative interpretation: Comment on Gray et al. (2019).

Gray et al. (2019) proposed a new construct to predict creativity, which they called forward flow, measured as the originality of chained word associations. Chained word associations, however, do not meet the requirements of a test of originality. The items ask for only 1 response when multiple responses are needed to assess originality, and the sequential responding means that the items are not independent as required for a test. Also, the originality of the associations is questionably calculated from the starting word instead of in relation to the preceding cue word. Probably because of these problems, scores on the new construct measured in this way show only weak correlations with scores on standard measures of creativity. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Structural abnormalities in neurons are sufficient to explain the clinical disease and fatal outcome of experimental rabies in yellow fluorescent protein-expressing transgenic mice.

Under natural conditions and in some experimental models, rabies virus infection of the central nervous system causes relatively mild histopathological changes, without prominent evidence of neuronal death despite its lethality. In this study, the effects of rabies virus infection on the structure of neurons were investigated with experimentally infected transgenic mice expressing yellow fluorescent protein (YFP) in neuronal subpopulations. Six-week-old mice were inoculated in the hind-limb footpad with the CVS strain of fixed virus or were mock infected with vehicle (phosphate-buffered saline). Brain regions were subsequently examined by light, epifluorescent, and electron microscopy. In moribund CVS-infected mice, histopathological changes were minimal in paraffin-embedded tissue sections, although mild inflammatory changes were present. Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling and caspase-3 immunostaining showed only a few apoptotic cells in the cerebral cortex and hippocampus. Silver staining demonstrated the preservation of cytoskeletal integrity in the cerebral cortex. However, fluorescence microscopy revealed marked beading and fragmentation of the dendrites and axons of layer V pyramidal neurons in the cerebral cortex, cerebellar mossy fibers, and axons in brainstem tracts. At an earlier time point, when mice displayed hind-limb paralysis, beading was observed in a few axons in the cerebellar commissure. Toluidine blue-stained resin-embedded sections from moribund YFP-expressing animals revealed vacuoles within the perikarya and proximal dendrites of pyramidal neurons in the cerebral cortex and hippocampus. These vacuoles corresponded with swollen mitochondria under electron microscopy. Vacuolation was also observed ultrastructurally in axons and in presynaptic nerve endings. We conclude that the observed structural changes are sufficient to explain the severe clinical disease with a fatal outcome in this experimental model of rabies.

Selective vulnerability of dorsal root ganglia neurons in experimental rabies after peripheral inoculation of CVS-11 in adult mice.

The involvement of dorsal root ganglia was studied in an in vivo model of experimental rabies virus infection using the challenge virus standard (CVS-11) strain. Dorsal root ganglia neurons infected with CVS in vitro show prolonged survival and few morphological changes, and are commonly used to study the infection. It has been established that after peripheral inoculation of mice with CVS the brain and spinal cord show relatively few neurodegenerative changes, but detailed studies of pathological changes in dorsal root ganglia have not previously been performed in this in vivo experimental model. In this study, adult ICR mice were inoculated in the right hindlimb footpad with CVS. Spinal cords and dorsal root ganglia were evaluated at serial time points for histopathological and ultrastructural changes and for biochemical markers of cell death. Light microscopy showed multifocal mononuclear inflammatory cell infiltrates in the sensory ganglia and a spectrum of degenerative neuronal changes. Ultrastructural changes in gangliocytes included features characteristic of the axotomy response, the appearance of numerous autophagic compartments, and aggregation of intermediate filaments, while the neurons retained relatively intact mitochondria and plasma membranes. Later in the process, there were more extensive degenerative neuronal changes without typical features of either apoptosis or necrosis. The degree of degenerative neuronal changes in gangliocytes contrasts with observations in CNS neurons in experimental rabies. Hence, gangliocytes exhibit selective vulnerability in this animal model. This contrasts markedly with the fact that they are, unlike CNS neurons, highly permissive to CVS infection in vitro. Further study is needed to determine mechanisms for this selective vulnerability, which will give us a better understanding of the pathogenesis of rabies.