Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing and Potentially Promotes Neoplasia.

Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions, wounds that undergo protracted cycles of healing, and re-injury over years of chronic infection. We show that O. viverrini secreted proteins accelerated wound resolution in human cholangiocytes, an outcome that was compromised following silencing of expression of the fluke-derived gene encoding the granulin-like growth factor, Ov-GRN-1. Recombinant Ov-GRN-1 induced angiogenesis and accelerated mouse wound healing. Ov-GRN-1 was internalized by human cholangiocytes and induced gene and protein expression changes associated with wound healing and cancer pathways. Given the notable but seemingly paradoxical properties of liver fluke granulin in promoting not only wound healing but also a carcinogenic microenvironment, Ov-GRN-1 likely holds marked potential as a therapeutic wound-healing agent and as a vaccine against an infection-induced cancer of major public health significance in the developing world

AA and DHA are Decreased in Paediatric AD/HD and Inattention is Ameliorated by Increased Plasma DHA

The purpose of this study was to assess long chain polyunsaturated fatty acid (LCPUFA) status in relation to socio-behavioral outcomes in children with Attention Deficit/Hyperactivity Disorder (AD/HD). In a case-control design, plasma phospholipid fatty acid content was assessed in children aged 5–12 years with AD/HD and in typically functioning children. Dietary intakes of LCPUFAs arachidonic acid (AA; 20:4n6) and docosahexaenoic acid (DHA; 22:6n3) were quantified using a four-day food record, polymorphisms were determined in FADS1 and FADS2, and socio-behavioral outcomes were assessed using the Conners 3 Parent Rating Scales in a cross section of children with AD/HD. Compared to typically functioning children, plasma AA and DHA were 40% lower in children with AD/HD. Median intake of AA, but not DHA, was higher in children with AD/HD compared to typically functioning children. Polymorphisms in FADS1 (rs174546) and FADS2 (174575) were associated with higher plasma linoleic acid (LA; 18:2n6) level. Plasma DHA level was inversely associated with inattention score. Despite having an elevated intake of AA, children diagnosed with AD/HD have a reduction in plasma AA level which may be due in part to polymorphisms in the fatty acid desaturase (FADS) gene cluster or increased conversion to AA-derived metabolites. Increasing intake of DHA may ameliorate symptoms of inattention in AD/HD

Zebrafish behavioural profiling identifies GABA and serotonin receptor ligands related to sedation and paradoxical excitation.

Anesthetics are generally associated with sedation, but some anesthetics can also increase brain and motor activity-a phenomenon known as paradoxical excitation. Previous studies have identified GABAA receptors as the primary targets of most anesthetic drugs, but how these compounds produce paradoxical excitation is poorly understood. To identify and understand such compounds, we applied a behavior-based drug profiling approach. Here, we show that a subset of central nervous system depressants cause paradoxical excitation in zebrafish. Using this behavior as a readout, we screened thousands of compounds and identified dozens of hits that caused paradoxical excitation. Many hit compounds modulated human GABAA receptors, while others appeared to modulate different neuronal targets, including the human serotonin-6 receptor. Ligands at these receptors generally decreased neuronal activity, but paradoxically increased activity in the caudal hindbrain. Together, these studies identify ligands, targets, and neurons affecting sedation and paradoxical excitation in vivo in zebrafish

Cryptic, sympatric diversity in Tegu lizards of the Tupinambis teguixin Group (Squamata, Sauria, Teiidae) and the description of three new species

Tegus of the genera Tupinambis and Salvator are the largest Neotropical lizards and the most exploited clade of Neotropical reptiles. For three decades more than 34 million tegu skins were in trade, about 1.02 million per year. The genus Tupinambis is distributed in South America east of the Andes, and currently contains four recognized species, three of which are found only in Brazil. However, the type species of the genus, T. teguixin, is known from Bolivia, Brazil, Colombia, Ecuador, French Guyana, Guyana, Peru, Suriname, Trinidad and Tobago, and Venezuela (including the Isla de Margarita). Here we present molecular and morphological evidence that this species is genetically divergent across its range and identify four distinct clades some of which are sympatric. The occurrence of cryptic sympatric species undoubtedly exacerbated the nomenclatural problems of the past. We discuss the species supported by molecular and morphological evidence and increase the number of species in the genus Tupinambis to seven. The four members of the T. teguixin group continue to be confused with Salvator merianae, despite having a distinctly different morphology and reproductive mode. All members of the genus Tupinambis are CITES Appendix II. Yet, they continue to be heavily exploited, under studied, and confused in the minds of the public, conservationists, and scientists

Rapid Spectroscopic Liquid Biopsy for the Universal Detection of Brain Tumours

Background: To support the early detection and diagnosis of brain tumours we have developed a rapid, cost-effective and easy to use spectroscopic liquid biopsy based on the absorbance of infrared radiation. We have previously reported highly sensitive results of our approach which can discriminate patients with a recent brain tumour diagnosis and asymptomatic controls. Other liquid biopsy approaches (e.g., based on tumour genetic material) report a lower classification accuracy for early-stage tumours. In this manuscript we present an investigation into the link between brain tumour volume and liquid biopsy test performance. Methods: In a cohort of 177 patients (90 patients with high-grade glioma (glioblastoma (GBM) or anaplastic astrocytoma), or low-grade glioma (astrocytoma, oligoastrocytoma and oligodendroglioma)) tumour volumes were calculated from magnetic resonance imaging (MRI) investigations and patients were split into two groups depending on MRI parameters (T1 with contrast enhancement or T2/FLAIR (fluid-attenuated inversion recovery)). Using attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy coupled with supervised learning methods and machine learning algorithms, 90 tumour patients were stratified against 87 control patients who displayed no symptomatic indications of cancer, and were classified as either glioma or non-glioma. Results: Sensitivities, specificities and balanced accuracies were all greater than 88%, the area under the curve (AUC) was 0.98, and cancer patients with tumour volumes as small as 0.2 cm3 were correctly identified. Conclusions: Our spectroscopic liquid biopsy approach can identify gliomas that are both small and low-grade showing great promise for deployment of this technique for early detection and diagnosis.</jats:p

An environment for relation mining over richly annotated corpora: the case of GENIA

BACKGROUND: The biomedical domain is witnessing a rapid growth of the amount of published scientific results, which makes it increasingly difficult to filter the core information. There is a real need for support tools that 'digest' the published results and extract the most important information. RESULTS: We describe and evaluate an environment supporting the extraction of domain-specific relations, such as protein-protein interactions, from a richly-annotated corpus. We use full, deep-linguistic parsing and manually created, versatile patterns, expressing a large set of syntactic alternations, plus semantic ontology information. CONCLUSION: The experiments show that our approach described is capable of delivering high-precision results, while maintaining sufficient levels of recall. The high level of abstraction of the rules used by the system, which are considerably more powerful and versatile than finite-state approaches, allows speedy interactive development and validation

Stratifying Brain Tumour Histological Sub-Types: The Application of ATR-FTIR Serum Spectroscopy in Secondary Care

Patients living with brain tumours have the highest average years of life lost of any cancer, ultimately reducing average life expectancy by 20 years. Diagnosis depends on brain imaging and most often confirmatory tissue biopsy for histology. The majority of patients experience non-specific symptoms, such as headache, and may be reviewed in primary care on multiple occasions before diagnosis is made. Sixty-two per cent of patients are diagnosed on brain imaging performed when they deteriorate and present to the emergency department. Histological diagnosis from invasive surgical biopsy is necessary prior to definitive treatment, because imaging techniques alone have difficulty in distinguishing between several types of brain cancer. However, surgery itself does not necessarily control tumour growth, and risks morbidity for the patient. Due to their similar features on brain scans, glioblastoma, primary central nervous system lymphoma and brain metastases have been known to cause radiological confusion. Non-invasive tests that support stratification of tumour subtype would enhance early personalisation of treatment selection and reduce the delay and risks associated with surgery for many patients. Techniques involving vibrational spectroscopy, such as attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, have previously demonstrated analytical capabilities for cancer diagnostics. In this study, infrared spectra from 641 blood serum samples obtained from brain cancer and control patients have been collected. Firstly, we highlight the capability of ATR-FTIR to distinguish between healthy controls and brain cancer at sensitivities and specificities above 90%, before defining subtle differences in protein secondary structures between patient groups through Amide I deconvolution. We successfully differentiate several types of brain lesions (glioblastoma, meningioma, primary central nervous system lymphoma and metastasis) with balanced accuracies >80%. A reliable blood serum test capable of stratifying brain tumours in secondary care could potentially avoid surgery and speed up the time to definitive therapy, which would be of great value for both neurologists and patients

Interrogation of IDH1 Status in Gliomas by Fourier Transform Infrared Spectroscopy

Mutations in the isocitrate dehydrogenase 1 (IDH1) gene are found in a high proportion of diffuse gliomas. The presence of the IDH1 mutation is a valuable diagnostic, prognostic and predictive biomarker for the management of patients with glial tumours. Techniques involving vibrational spectroscopy, e.g., Fourier transform infrared (FTIR) spectroscopy, have previously demonstrated analytical capabilities for cancer detection, and have the potential to contribute to diagnostics. The implementation of FTIR microspectroscopy during surgical biopsy could present a fast, label-free method for molecular genetic classification. For example, the rapid determination of IDH1 status in a patient with a glioma diagnosis could inform intra-operative decision-making between alternative surgical strategies. In this study, we utilized synchrotron-based FTIR microanalysis to probe tissue microarray sections from 79 glioma patients, and distinguished the positive class (IDH1-mutated) from the IDH1-wildtype glioma, with a sensitivity and specificity of 82.4% and 83.4%, respectively. We also examined the ability of attenuated total reflection (ATR)-FTIR spectroscopy in detecting the biomolecular events and global epigenetic and metabolic changes associated with mutations in the IDH1 enzyme, in blood serum samples collected from an additional 72 brain tumour patients. Centrifugal filtration enhanced the diagnostic ability of the classification models, with balanced accuracies up to ~69%. Identification of the molecular status from blood serum prior to biopsy could further direct some patients to alternative treatment strategies

HIV-1 Integrates Widely throughout the Genome of the Human Blood Fluke Schistosoma mansoni.

Schistosomiasis is the most important helminthic disease of humanity in terms of morbidity and mortality. Facile manipulation of schistosomes using lentiviruses would enable advances in functional genomics in these and related neglected tropical diseases pathogens including tapeworms, and including their non-dividing cells. Such approaches have hitherto been unavailable. Blood stream forms of the human blood fluke, Schistosoma mansoni, the causative agent of the hepatointestinal schistosomiasis, were infected with the human HIV-1 isolate NL4-3 pseudotyped with vesicular stomatitis virus glycoprotein. The appearance of strong stop and positive strand cDNAs indicated that virions fused to schistosome cells, the nucleocapsid internalized and the RNA genome reverse transcribed. Anchored PCR analysis, sequencing HIV-1-specific anchored Illumina libraries and Whole Genome Sequencing (WGS) of schistosomes confirmed chromosomal integration; \u3e8,000 integrations were mapped, distributed throughout the eight pairs of chromosomes including the sex chromosomes. The rate of integrations in the genome exceeded five per 1,000 kb and HIV-1 integrated into protein-encoding loci and elsewhere with integration bias dissimilar to that of human T cells. We estimated ~ 2,100 integrations per schistosomulum based on WGS, i.e. about two or three events per cell, comparable to integration rates in human cells. Accomplishment in schistosomes of post-entry processes essential for HIV-1replication, including integrase-catalyzed integration, was remarkable given the phylogenetic distance between schistosomes and primates, the natural hosts of the genus Lentivirus. These enigmatic findings revealed that HIV-1 was active within cells of S. mansoni, and provided the first demonstration that HIV-1 can integrate into the genome of an invertebrate

Preface: Interdisciplinary contributions from the Division on Energy, Resources and the Environment at the EGU General Assembly 2019

Since 2004, the European Geosciences Union (EGU) brings together experts from all over the world at its annual General Assembly, covering all disciplines of the earth, planetary and space sciences. With this special issue in Advances in Geosciences, we are pleased to present a collection of contributions from the Division on Energy, Resources and the Environment (ERE) which were presented at the EGU General Assembly 2019 in Vienna