Immunotherapy for Malignant Gliomas: A Roadmap for the Future

status: publishe

Variation in methanotroph-related proxies in peat deposits from Misten Bog, Hautes-Fagnes, Belgium

Methane emissions from peat bogs are strongly reduced by aerobic methane oxidising bacteria (methanotrophs) living in association with Sphagnum spp. Field studies and laboratory experiments have revealed that, with increasing water level and temperature, methanotrophic activity increases. To gain a better understanding of how longer term changes in methanotrophic activity are reflected in methanotroph biomarkers, a peat record (0–100 cm) from the Hautes-Fagnes (Belgium) encompassing the past 1500 years, was analysed for methanotroph-specific intact bacteriohopanepolyols (BHPs) and the carbon isotopic composition of diploptene. A predominance of aminobacteriohopanetetrol (aminotetrol) over aminobacteriohopanepentol (aminopentol) indicated the prevalence of type II methanotrophs. Relatively high methanotrophic activity was indicated by all methanotroph markers between 20 and 45 cm depth, around the present oxic–anoxic boundary, most likely representing the currently active methanotrophic community. Comparing methanotrophic markers in the deeper part of the peat profile with environmental variables afforded, however, no clear correlation between change in water level and methanotrophic activity. This is potentially caused by a predominance of type II methanotrophs, a combination of sources for methanotrophic biomarkers or insufficient variation in climatic changes. A proposed way forward would include a study of a core covering a longer timescale, thereby involving greater variability

Individual Behavioral differences and health of golden-headed lion tamarins, Leontopithecus chrysomelas

Individual behavioral differences may influence how animals cope with altered environments. Depending on their behavioral traits, individuals may thus vary in how their health is affected by environmental conditions. We investigated the relationship between individual behavior of free-living golden-headed lion tamarins (Leontopithecus chrysomelas) responding to a novel object (to assess exploration-avoidance), and their habitat use and health status (endoparasitism; clinical measures: biometric data, heart rate, respiratory frequency, and temperature; fecal glucocorticoid metabolites). As parasite transmission can be affected by individual variation in social contact and social grooming, we also evaluated whether more sociable individuals show higher endoparasite loads compared with less sociable animals. Four groups living in landscapes with different levels of human disturbance were investigated: two in degraded forest fragments in an agricultural matrix (DFAM-higher disturbance), and two in a cocoa agroforestry system (cabruca-lower disturbance) in the Atlantic forest of South Bahia, Brazil. Using a subjective ratings approach, highly correlated adjective descriptors were combined to produce z-score ratings of one derived variable ("confidence"), which was selected to characterize the tamarins' exploration/avoidance responses during a novel object test. The higher the confidence score, the longer female tamarins spent foraging for prey independent of landscape, and the greater their body mass independent of sex and landscape. Only DFAM individuals showed intestinal parasite infection. Endoparasite loads were positively correlated with the number of grooming partners, suggesting an association between social grooming and transmission (more groomers = more endoparasites). Individual behavior, including in a test situation, may thus have some predictive value for behavior in a free-living context, and for its health consequences

Safe surgery for glioblastoma: recent advances and modern challenges

One of the major challenges during glioblastoma surgery is balancing between maximizing extent of resection and preventing neurological deficits. Several surgical techniques and adjuncts have been developed to help identify eloquent areas both preoperatively (fMRI, nTMS, MEG, DTI) and intraoperatively (imaging (ultrasound, iMRI), electrostimulation (mapping), cerebral perfusion measurements (fUS)), and visualization (5-ALA, fluoresceine)). In this review, we give an update of the state-of-the-art management of both primary and recurrent glioblastomas. We will review the latest surgical advances, challenges, and approaches that define the onco-neurosurgical practice in a contemporary setting and give an overview of the current prospective scientific efforts

Indonesian Throughflow drove Australian climate from humid Pliocene to arid Pleistocene

Late Miocene to mid-Pleistocene sedimentary proxy records reveal that northwest Australia underwent an abrupt transition from dry to humid climate conditions at 5.5 million years (Ma), likely receiving year-round rainfall, but after ~3.3 Ma, climate shifted toward an increasingly seasonal precipitation regime. The progressive constriction of the Indonesian Throughflow likely decreased continental humidity and transferred control of northwest Australian climate from the Pacific to the Indian Ocean, leading to drier conditions punctuated by monsoonal precipitation. The northwest dust pathway and fully established seasonal and orbitally controlled precipitation were in place by ~2.4 Ma, well after the intensification of Northern Hemisphere glaciation. The transition from humid to arid conditions was driven by changes in Pacific and Indian Ocean circulation and regional atmospheric moisture transport, influenced by the emerging Maritime Continent. We conclude that the Maritime Continent is the switchboard modulating teleconnections between tropical and high-latitude climate systems

Timing and Pacing of Indonesian Throughflow Restriction and Its Connection to Late Pliocene Climate Shifts

drier conditions. This shift fundamentally reorganized Earth\u27s climate from the Miocene state toward conditions similar to the present. During the Pliocene, the progressive restriction of the Indonesian Throughflow (ITF) is suggested to have enhanced this shift toward stronger meridional thermal gradients. Reduced ITF, caused by the northward movement of Australia and uplift of Indonesia, impeded global thermohaline circulation, also contributing to late Pliocene Northern Hemisphere cooling via atmospheric and oceanographic teleconnections. Here we present an orbitally tuned high‐resolution sediment geochemistry, calcareous nannofossil, and X‐ray fluorescence record between 3.65 and 2.97 Ma from the northwest shelf of Australia within the Leeuwin Current. International Ocean Discovery Program Site U1463 provides a record of local surface water conditions and Australian climate in relation to changing ITF connectivity. Modern analogue‐based interpretations of nannofossil assemblages indicate that ITF configuration culminated ~3.54 Ma. A decrease in warm, oligotrophic taxa such as Umbilicosphaera sibogae, with a shift from Gephyrocapsa sp. to Reticulofenestra sp., and an increase of mesotrophic taxa (e.g., Umbilicosphaera jafari and Helicosphaera spp.) suggest that tropical Pacific ITF sources were replaced by cooler, fresher, northern Pacific waters. This initial tectonic reorganization enhanced the Indian Oceans sensitivity to orbitally forced cooling in the southern high latitudes culminating in the M2 glacial event (~3.3 Ma). After 3.3 Ma the restructured ITF established the boundary conditions for the inception of the Sahul‐Indian Ocean Bjerknes mechanism and increased the response to glacio‐eustatic variability

Proceedings of the second "international Traveling Workshop on Interactions between Sparse models and Technology" (iTWIST'14)

The implicit objective of the biennial "international - Traveling Workshop on Interactions between Sparse models and Technology" (iTWIST) is to foster collaboration between international scientific teams by disseminating ideas through both specific oral/poster presentations and free discussions. For its second edition, the iTWIST workshop took place in the medieval and picturesque town of Namur in Belgium, from Wednesday August 27th till Friday August 29th, 2014. The workshop was conveniently located in "The Arsenal" building within walking distance of both hotels and town center. iTWIST'14 has gathered about 70 international participants and has featured 9 invited talks, 10 oral presentations, and 14 posters on the following themes, all related to the theory, application and generalization of the "sparsity paradigm": Sparsity-driven data sensing and processing; Union of low dimensional subspaces; Beyond linear and convex inverse problem; Matrix/manifold/graph sensing/processing; Blind inverse problems and dictionary learning; Sparsity and computational neuroscience; Information theory, geometry and randomness; Complexity/accuracy tradeoffs in numerical methods; Sparsity? What's next?; Sparse machine learning and inference.Comment: 69 pages, 24 extended abstracts, iTWIST'14 website: http://sites.google.com/site/itwist1

Global comparison of awake and asleep mapping procedures in glioma surgery: an international multicenter survey

Background Mapping techniques are frequently used to preserve neurological function during glioma surgery. There is, however, no consensus regarding the use of many variables of these techniques. Currently, there are almost no objective data available about potential heterogeneity between surgeons and centers. The goal of this survey is therefore to globally identify, evaluate and analyze the local mapping procedures in glioma surgery. Methods The survey was distributed to members of the neurosurgical societies of the Netherlands (Nederlandse Vereniging voor Neurochirurgie-NVVN), Europe (European Association of Neurosurgical Societies-EANS), and the United States (Congress of Neurological Surgeons-CNS) between December 2020 and January 2021 with questions about awake mapping, asleep mapping, assessment of neurological morbidity, and decision making. Results Survey responses were obtained from 212 neurosurgeons from 42 countries. Overall, significant differences were observed for equipment and its settings that are used for both awake and asleep mapping, intraoperative assessment of eloquent areas, the use of surgical adjuncts and monitoring, anesthesia management, assessment of neurological morbidity, and perioperative decision making. Academic practices performed awake and asleep mapping procedures more often and employed a clinical neurophysiologist with telemetric monitoring more frequently. European neurosurgeons differed from US neurosurgeons regarding the modality for cortical/subcortical mapping and awake/asleep mapping, the use of surgical adjuncts, and anesthesia management during awake mapping. Discussion This survey demonstrates the heterogeneity among surgeons and centers with respect to their procedures for awake mapping, asleep mapping, assessing neurological morbidity, and decision making in glioma patients. These data invite further evaluations for key variables that can be optimized and may therefore benefit from consensus

Dynamic stroma reorganization drives blood vessel dysmorphia during glioma growth

Glioma growth and progression are characterized by abundant development of blood vessels that are highly aberrant and poorly functional, with detrimental consequences for drug delivery efficacy. The mechanisms driving this vessel dysmorphia during tumor progression are poorly understood. Using longitudinal intravital imaging in a mouse glioma model, we identify that dynamic sprouting and functional morphogenesis of a highly branched vessel network characterize the initial tumor growth, dramatically changing to vessel expansion, leakage, and loss of branching complexity in the later stages. This vascular phenotype transition was accompanied by recruitment of predominantly pro-inflammatory M1-like macrophages in the early stages, followed by in situ repolarization to M2-like macrophages, which produced VEGF-A and relocate to perivascular areas. A similar enrichment and perivascular accumulation of M2 versus M1 macrophages correlated with vessel dilation and malignancy in human glioma samples of different WHO malignancy grade. Targeting macrophages using anti-CSF1 treatment restored normal blood vessel patterning and function. Combination treatment with chemotherapy showed survival benefit, suggesting that targeting macrophages as the key driver of blood vessel dysmorphia in glioma progression presents opportunities to improve efficacy of chemotherapeutic agents. We propose that vessel dysfunction is not simply a general feature of tumor vessel formation, but rather an emergent property resulting from a dynamic and functional reorganization of the tumor stroma and its angiogenic influences