A Ronkin type function for coamoebas

The Ronkin function plays a fundamental role in the theory of amoebas. We introduce an analogue of the Ronkin function in the setting of coamoebas. It turns out to be closely related to a certain toric arrangement known as the shell of the coamoeba and we use our Ronkin type function to obtain some properties of it

A Ronkin type function for coamoebas

The Ronkin function plays a fundamental role in the theory of amoebas. We introduce an analogue of the Ronkin function in the setting of coamoebas. It turns out to be closely related to a certain toric arrangement known as the shell of the coamoeba and we use our Ronkin type function to obtain some properties of it

The anti-asthmatic drug, montelukast, modifies the neurogenic potential in the young healthy and irradiated brain

Brain tumors are the most common form of solid tumors in children. Due to the increasing number of survivors, it is of importance to prevent long-term treatment-induced side effects. Montelukast, a leukotriene receptor antagonist, may have the desired neuroprotective properties. The aim of the study was to determine whether montelukast could reduce adverse effects of cranial irradiation (CIR) to the young brain. Daily injections of montelukast or vehicle was given to young mice for 4 or 14 days in combination with CIR or under normal conditions. Montelukast treatment for 4 days protected against cell death with 90% more cell death in the vehicle group compared to the montelukast group 24 h after CIR. It also resulted in less microglia activation 6 h after CIR, where montelukast lowered the levels of CD68 compared to the vehicle groups. Interestingly, the animals that received montelukast for 14 days had 50% less proliferating cells in the hippocampus irrespective of receiving CIR or not. Further, the total number of neurons in the granule cell layer was altered during the sub-acute phase. The number of neurons was decreased by montelukast treatment in control animals (15%), but the opposite was seen after CIR, where montelukast treatment increased the number of neurons (15%). The results show beneficial effects by montelukast treatment after CIR in some investigated parameters during both the acute phase and with longer drug treatment. However, it also resulted in lower proliferation in the hippocampus under normal conditions, indicating that the effects of montelukast can be either beneficial or unfavorable, depending on the circumstances

C3 deficiency ameliorates the negative effects of irradiation of the young brain on hippocampal development and learning

Radiotherapy in the treatment of pediatric brain tumors is often associated with debilitating late-appearing adverse effects, such as intellectual impairment. Areas in the brain harboring stem cells are particularly sensitive to irradiation (IR) and loss of these cells may contribute to cognitive deficits. It has been demonstrated that IR-induced inflammation negatively affects neural progenitor differentiation. In this study, we used mice lacking the third complement component (C3-/-) to investigate the role of complement in a mouse model of IR-induced injury to the granule cell layer (GCL) of the hippocampus. C3-/- and wild type (WT) mice received a single, moderate dose of 8 Gy to the brain on postnatal day 10. The C3-/- mice displayed 55 % more microglia (Iba-1+) and a trend towards increase in proliferating cells in the GCL compared to WT mice 7 days after IR. Importantly, months after IR C3-/- mice made fewer errors than WT mice in a reversal learning test indicating better learning capacity in C3-/- mice after IR. Notably, months after IR C3-/- and WT mice had similar GCL volumes, survival of newborn cells (BrdU), microglia (Iba-1) and astrocyte (S100β) numbers in the GCL. In summary, our data show that the complement system contributes to IR-induced loss of proliferating cells and maladaptive inflammatory responses in the acute phase after IR, leading to impaired learning capacity in adulthood. Targeting the complement system is hence promising for future strategies to reduce the long-term adverse consequences of IR in the young brain

Hannibal's trek across the alps: Geomorphological Analysis of sites of geoarchaeological interest

International audienceA ~2200 year-old question related to Hannibal's invasion route across the Alps into Italia, has been argued by classicists without recovery of material evidence. A comparison of topographical descriptions in the ancient literature with environmental parameters in the Alps, attempted here for the first time, provides a database against which various pathways can be assessed. Identification of sites using geological, geomorphological, astronomical, chemical and petrological methods leads to the exclusion of certain transit points and targeting of others where geoarchaeological excavation might yield important evidence related to the military culture of ancient Carthage

Serum concentrations of the axonal injury marker neurofilament light protein are not influenced by blood-brain barrier permeability

A blood biomarker to monitor individual susceptibility to neuronal injury from cranial radiotherapy could potentially help to individualize radiation treatment and thereby reduce the incidence and severity of late effects. An important feature of such a blood biomarker is that its concentration is not confounded by varying degrees of release from the brain into the blood across the blood-brain barrier (BBB). In this study, we investigated serum neurofilament light protein (NFL) concentrations in 21-day old mice following a single dose of cranial irradiation (8 Gy). Cranial irradiation resulted in acute cell injury measured as a 12.9-fold increase in caspase activity 6 h after irradiation; activation of inflammation measured by levels of CCL2 and increased BBB permeability measured by 14C-sucrose concentration ratios in brain and cerebrospinal fluid (CSF). Serum levels of NFL peaked at 6 h after both anesthesia and cranial irradiation, but no timely correlation of serum NFL concentration with BBB permeability was found. Further, three groups of patients with different degrees of BBB impairment (measured as the CSF/serum albumin ratio) were investigated. There was no correlation between serum NFL concentration and CSF/serum albumin ratio (r = 0.139, p = 0.3513), however a strong correlation was found for NFL concentration in serum and NFL concentration in CSF (r = 0.6303, p < 0.0001). In conclusion, serum NFL appears to be a reliable blood biomarker for neuronal injury, and its concentration is not confounded by BBB permeability

Alzheimer-associated cerebrospinal fluid fragments of neurogranin are generated by Calpain-1 and prolyl endopeptidase

BACKGROUND: Neurogranin (Ng) is a small 7.6 kDa postsynaptic protein that has been detected at elevated concentrations in cerebrospinal fluid (CSF) of patients with Alzheimer’s disease (AD), both as a full-length molecule and as fragments from its C-terminal half. Ng is involved in postsynaptic calcium (Ca) signal transduction and memory formation via binding to calmodulin in a Ca-dependent manner. The mechanism of Ng secretion from neurons to CSF is currently unknown, but enzymatic cleavage of Ng may be of relevance. Therefore, the aim of the study was to identify the enzymes responsible for the cleavage of Ng, yielding the Ng fragment pattern of C-terminal fragments detectable and increased in CSF of AD patients. METHODS: Fluorigenic quenched FRET probes containing sequences of Ng were utilized to identify Ng cleaving activities among enzymes known to have increased activity in AD and in chromatographically fractionated mouse brain extracts. RESULTS: Human Calpain-1 and prolyl endopeptidase were identified as the candidate enzymes involved in the formation of endogenous Ng peptides present in CSF, cleaving mainly in the central region of Ng, and between amino acids 75_76 in the Ng sequence, respectively. The cleavage by Calpain-1 affects the IQ domain of Ng, which may deactivate or change the function of Ng in Ca2+/calmodulin -dependent signaling for synaptic plasticity. While shorter Ng fragments were readily cleaved in vitro by prolyl endopeptidase, the efficiency of cleavage on larger Ng fragments was much lower. CONCLUSIONS: Calpain-1 and prolyl endopeptidase cleave Ng in the IQ domain and near the C-terminus, respectively, yielding specific fragments of Ng in CSF. These fragments may give clues to the roles of increased activities of these enzymes in the pathophysiology of AD, and provide possible targets for pharmacologic intervention

Palaeoclimate inferred from δ18O and palaeobotanical indicators in freshwater tufa of Lake Äntu Sinijärv, Estonia

We investigated a 3.75-m-long lacustrine sediment record from Lake Äntu Sinijärv, northern Estonia, which has a modeled basal age >12,800 cal yr BP. Our multi-proxy approach focused on the stable oxygen isotope composition (δ18O) of freshwater tufa. Our new palaeoclimate information for the Eastern Baltic region, based on high-resolution δ18O data (219 samples), is supported by pollen and plant macrofossil data. Radiocarbon dates were used to develop a core chronology and estimate sedimentation rates. Freshwater tufa precipitation started ca. 10,700 cal yr BP, ca. 2,000 years later than suggested by previous studies on the same lake. Younger Dryas cooling is documented clearly in Lake Äntu Sinijärv sediments by abrupt appearance of diagnostic pollen (Betula nana, Dryas octopetala), highest mineral matter content in sediments (up to 90 %) and low values of δ18O (less than −12 ‰). Globally recognized 9.3- and 8.2-ka cold events are weakly defined by negative shifts in δ18O values, to −11.3 and −11.7 ‰, respectively, and low concentrations of herb pollen and charcoal particles. The Holocene thermal maximum (HTM) is palaeobotanically well documented by the first appearance and establishment of nemoral thermophilous taxa and presence of water lilies requiring warm conditions. Isotope values show an increasing trend during the HTM, from −11.5 to −10.5 ‰. Relatively stable environmental conditions, represented by only a small-scale increase in δ18O (up to 1 ‰) and high pollen concentrations between 5,000 and 3,000 cal yr BP, were followed by a decrease in δ18O, reaching the most negative value (−12.7 ‰) recorded in the freshwater tufa ca. 900 cal yr BP

Characterisation of a Desmosterol Reductase Involved in Phytosterol Dealkylation in the Silkworm, Bombyx mori

Most species of invertebrate animals cannot synthesise sterols de novo and many that feed on plants dealkylate phytosterols (mostly C29 and C28) yielding cholesterol (C27). The final step of this dealkylation pathway involves desmosterol reductase (DHCR24)-catalysed reduction of desmosterol to cholesterol. We now report the molecular characterisation in the silkworm, Bombyx mori, of such a desmosterol reductase involved in production of cholesterol from phytosterol, rather than in de novo synthesis of cholesterol. Phylogenomic analysis of putative desmosterol reductases revealed the occurrence of various clades that allowed for the identification of a strong reductase candidate gene in Bombyx mori (BGIBMGA 005735). Following PCR-based cloning of the cDNA (1.6 kb) and its heterologous expression in Saccharomyces cerevisae, the recombinant protein catalysed reduction of desmosterol to cholesterol in an NADH- and FAD- dependent reaction