Crystal Structure of 2′,3′-Di-O-Acetyl-5′-Deoxy-5-Fluorocytidine with N–H···(O,F) Proton Donor Bifurcated and (C,N)–H···O Bifurcated Acceptor Dual Three-Center Hydrogen Bond Configurations

The title compound, C13H16O6N3F, features a central furan ring containing four carbon atom chiral centers with a 4-amino-5-fluoro-2-oxopyrimidine group, two acetyl groups and a methyl group bonded at the 2,3,4,5 positions, each in an absolute R configuration (2R,3R,4R,5R). It crystallizes in the monoclinic space group C2 with unit cell parameters a = 14.5341(3), b = 7.26230(10), c = 16.2197(3) Å, β = 116.607(2)°, Z = 4. An extensive array of intra and inter molecular hydrogen bond interactions dominate crystal packing in the unit cell highlighted by a relatively rare three-center proton-bifurcated donor N–H···(O,F) hydrogen bond interaction in cooperation with a second, (C,N)–H···O bifurcated acceptor three-center hydrogen bond in a supportive fashion. Additional weak Cg π-ring inter molecular interactions between a fluorine atom and the 4-amino-5-fluoro-2-oxopyrimidine ring in concert with multiple donor and acceptor hydrogen bonds significantly influence the bond distances, bond angles and torsion angles of the deoxy-5-fluorocytidine group. Comparison to a MOPAC computational calculation provides support to these observations

Comprehensive Brain MRI Segmentation in High Risk Preterm Newborns

Most extremely preterm newborns exhibit cerebral atrophy/growth disturbances and white matter signal abnormalities on MRI at term-equivalent age. MRI brain volumes could serve as biomarkers for evaluating the effects of neonatal intensive care and predicting neurodevelopmental outcomes. This requires detailed, accurate, and reliable brain MRI segmentation methods. We describe our efforts to develop such methods in high risk newborns using a combination of manual and automated segmentation tools. After intensive efforts to accurately define structural boundaries, two trained raters independently performed manual segmentation of nine subcortical structures using axial T2-weighted MRI scans from 20 randomly selected extremely preterm infants. All scans were re-segmented by both raters to assess reliability. High intra-rater reliability was achieved, as assessed by repeatability and intra-class correlation coefficients (ICC range: 0.97 to 0.99) for all manually segmented regions. Inter-rater reliability was slightly lower (ICC range: 0.93 to 0.99). A semi-automated segmentation approach was developed that combined the parametric strengths of the Hidden Markov Random Field Expectation Maximization algorithm with non-parametric Parzen window classifier resulting in accurate white matter, gray matter, and CSF segmentation. Final manual correction of misclassification errors improved accuracy (similarity index range: 0.87 to 0.89) and facilitated objective quantification of white matter signal abnormalities. The semi-automated and manual methods were seamlessly integrated to generate full brain segmentation within two hours. This comprehensive approach can facilitate the evaluation of large cohorts to rigorously evaluate the utility of regional brain volumes as biomarkers of neonatal care and surrogate endpoints for neurodevelopmental outcomes

Radiotherapeutic alternatives for previously irradiated recurrent gliomas

Re-irradiation for recurrent gliomas has been discussed controversially in the past. This was mainly due to only marginal palliation while being associated with a high risk for side effects using conventional radiotherapy

Concerns about anti-angiogenic treatment in patients with glioblastoma multiforme

BACKGROUND: The relevance of angiogenesis inhibition in the treatment of glioblastoma multiforme (GBM) should be considered in the unique context of malignant brain tumours. Although patients benefit greatly from reduced cerebral oedema and intracranial pressure, this important clinical improvement on its own may not be considered as an anti-tumour effect. DISCUSSION: GBM can be roughly separated into an angiogenic component, and an invasive or migratory component. Although this latter component seems inert to anti-angiogenic therapy, it is of major importance for disease progression and survival. We reviewed all relevant literature. Published data support that clinical symptoms are tempered by anti-angiogenic treatment, but that tumour invasion continues. Unfortunately, current imaging modalities are affected by anti-angiogenic treatment too, making it even harder to define tumour margins. To illustrate this we present MRI, biopsy and autopsy specimens from bevacizumab-treated patients. Moreover, while treatment of other tumour types may be improved by combining chemotherapy with anti-angiogenic drugs, inhibiting angiogenesis in GBM may antagonise the efficacy of chemotherapeutic drugs by normalising the blood-brain barrier function. SUMMARY: Although angiogenesis inhibition is of considerable value for symptom reduction in GBM patients, lack of proof of a true anti-tumour effect raises concerns about the place of this type of therapy in the treatment of GBM

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Not AvailablePlants have evolved several adaptive strategies through physiological changes in response to herbivore attacks. Plant secondary metabolites (PSMs) are synthesized to provide defensive functions and regulate defense signaling pathways to safeguard plants against herbivores. Herbivore injury initiates complex reactions which ultimately lead to synthesis and accumulation of PSMs. The biosynthesis of these metabolites is regulated by the interplay of signaling molecules comprising phytohormones. Plant volatile metabolites are released upon herbivore attack and are capable of directly inducing or priming hormonal defense signaling pathways. Secondary metabolites enable plants to quickly detect herbivore attacks and respond in a timely way in a rapidly changing scenario of pest and environment. Several studies have suggested that the potential for adaptation and/or resistance by insect herbivores to secondary metabolites is limited. These metabolites cause direct toxicity to insect pests, stimulate antixenosis mechanisms in plants to insect herbivores, and, by recruiting herbivore natural enemies, indirectly protect the plants. Herbivores adapt to secondary metabolites by the up/down regulation of sensory genes, and sequestration or detoxification of toxic metabolites. PSMs modulate multi-trophic interactions involving host plants, herbivores, natural enemies and pollinators. Although the role of secondary metabolites in plant-pollinator interplay has been little explored, several reports suggest that both plants and pollinators are mutually benefited. Molecular insights into the regulatory proteins and genes involved in the biosynthesis of secondary metabolites will pave the way for the metabolic engineering of biosynthetic pathway intermediates for improving plant tolerance to herbivores. This review throws light on the role of PSMs in modulating multi-trophic interactions, contributing to the knowledge of plant-herbivore interactions to enable their management in an eco-friendly and sustainable manner.Not Availabl