Stochastic modelling of the invasion process of nematodes in fly larvae

Stochastic models based on Markov birth processes are constructed to describe the process of invasion of a fly larva by entomopathogenic nematodes. Various forms for the birth (invasion) rates are proposed. These models are then fitted to data sets describing the observed numbers of nematodes that have invaded a fly larval after a fixed period of time. Non-linear birthrates are required to achieve good fits to these data, with their precise form leading to different patterns of invasion being identified for three populations of nematodes considered. One of these (Nemasys) showed the greatest propensity for invasion. This form of modelling may be useful more generally for analysing data that show variation which is different from that expected from a binomial distribution.

Deoxycytidine glyoxal:Lesion induction and evidence of repair following vitamin C supplementation in vivo

Oxidative DNA damage is postulated to be involved in carcinogenesis, and as a consequence, dietary antioxidants have received much interest. A recent report indicates that vitamin C facilitates the decomposition of hydroperoxides in vitro, generating reactive aldehydes. We present evidence for the in vivo generation of glyoxal, an established product of lipid peroxidation, glucose/ascorbate autoxidation, or free radical attack of deoxyribose, following supplementation of volunteers with 400 mg/d vitamin C. Utilizing a monoclonal antibody to a deoxycytidine-glyoxal adduct (gdC), we measured DNA lesion levels in peripheral blood mononuclear cells. Supplementation resulted in significant (p = .001) increases in gdC levels at weeks 11, 16, and 21, with corresponding increases in plasma malondialdehyde levels and, coupled with previous findings, is strongly suggestive of a pro-oxidative effect. However, continued supplementation revealed a highly significant (p = .0001) reduction in gdC levels. Simultaneous analysis of cyclobutane thymine dimers revealed no increase upon supplementation but, as with gdC, levels decreased. Although no single mechanism is identified, our data demonstrate a pro-oxidant event in the generation of reactive aldehydes following vitamin C supplementation in vivo. These results are also consistent with our hypothesis for a role of vitamin C in an adaptive/repair response and indicate that nucleotide excision repair specifically may be affected. © 2003 Elsevier Science Inc.

Functional neuroanatomy and behavioural correlates of the basal ganglia:evidence from lesion studies

Introduction: The basal ganglia are interconnected with cortical areas involved in behavioural, cognitive and emotional processes, in addition to movement regulation. Little is known about which of these functions are associated with individual basal ganglia substructures. Methods: Pubmed was searched for literature related to behavioural, cognitive and emotional symptoms associated with focal lesions to basal ganglia structures in humans. Results: Six case-control studies and two case reports were identified as relevant. Lesion sites included the caudate nucleus, putamen and globus pallidus. These were associated with a spectrum of behavioural and cognitive symptoms, including abulia, poor working memory and deficits in emotional recognition. Discussion: It is often difficult to precisely map associations between cognitive, emotional or behavioural functions and particular basal ganglia substructures, due to the non-specific nature of the lesions. However, evidence from lesion studies shows that most symptoms correspond with established non-motor frontal-subcortical circuits. © 2013-IOS Press and the authors. All rights reserved.

Instability of CTG Repeats is Governed by the Position of a DNA Base Lesion through Base Excision Repair

Trinucleotide repeat (TNR) expansions and deletions are associated with human neurodegeneration and cancer. However, their underlying mechanisms remain to be elucidated. Recent studies have demonstrated that CAG repeat expansions can be initiated by oxidative DNA base damage and fulfilled by base excision repair (BER), suggesting active roles for oxidative DNA damage and BER in TNR instability. Here, we provide the first evidence that oxidative DNA damage can induce CTG repeat deletions along with limited expansions in human cells. Biochemical characterization of BER in the context of (CTG)20 repeats further revealed that repeat instability correlated with the position of a base lesion in the repeat tract. A lesion located at the 59-end of CTG repeats resulted in expansion, whereas a lesion located either in the middle or the 39-end of the repeats led to deletions only. The positioning effects appeared to be determined by the formation of hairpins at various locations on the template and the damaged strands that were bypassed by DNA polymerase b and processed by flap endonuclease 1 with different efficiency. Our study indicates that the position of a DNA base lesion governs whether TNR is expanded or deleted through BER.

Results of an isotope tracer experiment with arctic deep-sea nematodes

A stable isotope (13C)-labeling experiment was performed to quantify the importance of bacterial carbon as a food source for an Arctic deep-sea nematode community. Bacterial functional groups were isotopically enriched with 13C-glucose, 13C-acetate, 13C- bicarbonate, and 13C-amino acids injected into sediments collected from 1280 m depth at 79uN, 6uE, west of Svalbard. Incorporation of the 13C label into bacterial phospholipid-derived fatty acids (PLFAs) and nematodes in the top 5 cm of the sediment was monitored over a 7-d period. The 13C dynamics of nematodes was fitted with a simple isotope turnover model to derive the importance of the different bacterial functional groups as carbon sources for the nematodes. The different substrates clearly labeled different bacterial groups as evidenced by differential labeling of the PLFA patterns. The deep-sea nematode community incorporated a very limited amount of the label, and the isotope turnover model showed that the dynamics of the isotope transfer could not be attributed to bacterivory. The low enrichment of nematodes suggests a limited passive uptake of injected 13C-labeled substrates. The lack of accumulation suggests that the injected 13C-labeled dissolved organic carbon compounds are not important as carbon sources for deep-sea nematodes. Since earlier studies with isotopically enriched algae also found limited uptake by nematodes, the food sources of deep-sea nematodes remain unclear.

Interactions between nematodes, potato and soil-borne micro-organisms and their effect on the management of potato cyst nematodes

Potato cyst nematodes (PCN) cause significant damage to the potato crop worldwide and growers experience economic losses related to yield loss and the cost of control measures. Experiments were set up to further elucidate the complex tritrophic PCNpotato-soil bacteria relationship. Bacterial strains isolated from the sugar beet rhizosphere were shown to be hatch active towards Globodera pallida and to be capable of successfully colonising the sugar beet rhizosphere when applied exogenously. A trap-crop system, based on these isolates, was proposed. Ridge and bulk soil taken from a commercial potato field were incubated with sterile potato root leachate (sPRL) and subsequent in vitro hatching assays showed that PCN hatch was influenced by microorganisms present in the ridge, but not in the bulk soil. Community level physiological profiling (CLPP) of ridge and bulk soil, using BIOLOG EcoplatesTM, demonstrated differences in bacterial functional diversity between the two soil types. An investigation of the inter-species competition between G. pallida and G. rostochiensis showed that G. pallida performed significantly better, in terms of multiplication rate, in competition with G. rostochiensis compared to its multiplication rate in single-species populations. Effectively removing the early hatch of G. rostochiensis in pot trials led to the removal of this competitive advantage of G. pallida suggesting that this advantage was due, at least in part, to morphological changes to the root caused by the early hatching of G. rostochiensis.

Unraveling flp-11/flp-32 dichotomy in nematodes

FMRFamide-like peptide (FLP) signalling systems are core to nematode neuromuscular function. Novel drug discovery efforts associated with nematode FLP/FLP receptor biology are advanced through the accumulation of basic biological data that can reveal subtle complexities within the neuropeptidergic system. This study reports the characterisation of FMRFamide-like peptide encoding gene-11 (flp-11) and FMRFamide-like peptide encoding gene-32 (flp-32), two distinct flp genes which encode the analogous peptide, AMRN(A/S)LVRFamide, in multiple nematode species - the only known example of this phenomenon within the FLPergic system of nematodes. Using bioinformatics, in situ hybridisation, immunocytochemistry and behavioural assays we show that: (i) flp-11 and -32 are distinct flp genes expressed individually or in tandem across multiple nematode species, where they encode a highly similar peptide; (ii) flp-11 does not appear to be the most widely expressed flp in Caenorhabditis elegans; (iii) in species expressing both flp-11 and flp-32, flp-11 displays a conserved, restricted expression pattern across nematode clades and lifestyles; (iv) in species expressing both flp-11 and flp-32, flp-32 expression is more widespread and less conserved than flp-11; (v) in species expressing only flp-11, the flp-11 expression profile is more similar to the flp-32 profile observed in species expressing both; and (vi) FLP-11 peptides inhibit motor function in multiple nematode species. The biological significance and evolutionary origin of flp-11 and -32 peptide duplication remains unclear despite attempts to identify a common ancestor; this may become clearer as the availability of genomic data improves. This work provides insight into the complexity of the neuropeptidergic system in nematodes, and begins to examine how nematodes may compensate for structural neuronal simplicity. From a parasite control standpoint this work underscores the importance of basic biological data, and has wider implications for the utility of C. elegans as a model for parasite neurobiology.

A method to determine the impact of visual function on lesion detection performance

There are few professions in which visual acuity is as important as it is to radiologists. The diagnostic decision making process is composed of a number of events (detection or observation, interpretation and reporting), where the detection phase is subject to a number of physical and psychological phenomena that are critical to the process. Visual acuity is one phenomenon that has often been overlooked, and there is very little research assessing the impact of reduced visual acuity on diagnostic performance. The aim of this study was to investigate the impact of reduced visual acuity on an observer’s ability to detect simulated nodules in an anthropomorphic chest phantom.

Multicentric osteolytic lesion of the middle finger of the hand. Case report

Giant cell-rich osteolytic lesions may have overlapping clinical, radiologic, and histopathologic features, with an important degree of difficulty of diagnosis and treatment. We report a case of double osteolytic lesion at the middle-finger in a young man without previous history of hand trauma. He underwent en-bloc resection of the bone lesions and reconstruction by graft of hydroxyapatite, resulting in a good morpho-functional result. Histological diagnosis was giant cell reparative granuloma (GCRG), although several features were considered atypical, including the appearance of the giant cells and the areas of the stroma that more closely resembled a giant cell tumor. GCRG is a benign rare intraosseous lesion and the true nature is controversial and unknown. The theories are that it could be a reactive lesion, a developmental anomaly or a benign neoplasm. It appears as an osteolytic lesion that must be considered in the differential diagnosis of other “critical” bone lesions similar in clinical, as well as radiologic and pathological appearance. Further characterization studies are helpful and necessary for the proper management.

Lesion detection performance: comparative analysis of low-dose CT data of the chest on two hybrid imaging systems

Incidental findings on low-dose CT images obtained during hybrid imaging are an increasing phenomenon as CT technology advances. Understanding the diagnostic value of incidental findings along with the technical limitations is important when reporting image results and recommending follow-up, which may result in an additional radiation dose from further diagnostic imaging and an increase in patient anxiety. This study assessed lesions incidentally detected on CT images acquired for attenuation correction on two SPECT/CT systems. Methods: An anthropomorphic chest phantom containing simulated lesions of varying size and density was imaged on an Infinia Hawkeye 4 and a Symbia T6 using the low-dose CT settings applied for attenuation correction acquisitions in myocardial perfusion imaging. Twenty-two interpreters assessed 46 images from each SPECT/CT system (15 normal images and 31 abnormal images; 41 lesions). Data were evaluated using a jackknife alternative free-response receiver-operating-characteristic analysis (JAFROC). Results: JAFROC analysis showed a significant difference (P < 0.0001) in lesion detection, with the figures of merit being 0.599 (95% confidence interval, 0.568, 0.631) and 0.810 (95% confidence interval, 0.781, 0.839) for the Infinia Hawkeye 4 and Symbia T6, respectively. Lesion detection on the Infinia Hawkeye 4 was generally limited to larger, higher-density lesions. The Symbia T6 allowed improved detection rates for midsized lesions and some lower-density lesions. However, interpreters struggled to detect small (5 mm) lesions on both image sets, irrespective of density. Conclusion: Lesion detection is more reliable on low-dose CT images from the Symbia T6 than from the Infinia Hawkeye 4. This phantom-based study gives an indication of potential lesion detection in the clinical context as shown by two commonly used SPECT/CT systems, which may assist the clinician in determining whether further diagnostic imaging is justified.