Induction of early apoptosis and reactive oxygen species (ROS) production by Tanzanian basidiomycete (Cantharellus miomboensis)

Cantharellus miomboensis is a new basidiomycete fungus recently found in Miombo woodlands in Tanzania. In this study, crude extract was prepared from fruiting bodies of C. miomboensis and was in vitro screened for its cytotoxicity using Tetrazolium salt (3-(4,5-dimethlthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) in human cell lines namely; Hepatocellular carcinoma (HepG2), Human non-small cell lung carcinoma (H157) and Human colon adenocarcinoma (HT.29). Thereafter, pro-apoptotic effects were determined using biochemical changes in apoptotic cells. These included externalization of phospholipid phosphatidylserine (PS) using APO Percentage dye by flow cytometry and depolarization of mitochondrial membrane potential using Tetramethyl rhodamine ethyl ester perchlorate (TMRE) assay. The test extract was found to induce dose dependent PS externalization on human cell lines when treated with various concentrations (1 - 5 mg/ml) and completely depolarized the mitochondrial membrane potential after 6 hours on HepG2 cell line. When the extract was examined for ROS production using 2’,7’- dichlorofluorescin diacetate (DCFH-DA) staining, there was no ROS generation found in HepG2 cells. It is therefore concluded that C. miomboensis extract is able to induce apoptosis in HepG2 cells and PS externalization and loss of mitochondrial membrane potential in HepG2 cells appear to be independent of ROS production. © 2010 International Formulae Group. All rights reserved.Keywords: Miombo woodlands, apoptosis, basidiomycete, reactive oxygen species, carcinoma

Review of the phenotype of early-onset generalised progressive dystonia due to mutations in KMT2B

In 2016, two research groups independently identified microdeletions and pathogenic variants in the lysine-specific histone methyltransferase 2B gene, KMT2B in patients with early-onset progressive dystonia. KMT2B-dystonia (DYT28) is emerging as an important and frequent cause of childhood-onset progressive generalised dystonia and is estimated to potentially account for up to 10% of early-onset generalised dystonia. Herein, we review variants in KMT2B associated with dystonia, as well as the clinical phenotype, treatment and underlying disease mechanisms. Furthermore, in context of this newly identified condition, we summarise our approach to the genetic investigation of paediatric dystonia

Re-weighting of somatosensory inputs from the foot and the ankle for controlling posture during quiet standing following trunk extensor muscles fatigue

The present study focused on the effects of trunk extensor muscles fatigue on postural control during quiet standing under different somatosensory conditions from the foot and the ankle. With this aim, 20 young healthy adults were asked to stand as immobile as possible in two conditions of No fatigue and Fatigue of trunk extensor muscles. In Experiment 1 (n = 10), somatosensation from the foot and the ankle was degraded by standing on a foam surface. In Experiment 2 (n = 10), somatosensation from the foot and ankle was facilitated through the increased cutaneous feedback at the foot and ankle provided by strips of athletic tape applied across both ankle joints. The centre of foot pressure displacements (CoP) were recorded using a force platform. The results showed that (1) trunk extensor muscles fatigue increased CoP displacements under normal somatosensatory conditions (Experiment 1 and Experiment 2), (2) this destabilizing effect was exacerbated when somatosensation from the foot and the ankle was degraded (Experiment 1), and (3) this destabilizing effect was mitigated when somatosensation from the foot and the ankle was facilitated (Experiment 2). Altogether, the present findings evidenced re-weighting of sensory cues for controlling posture during quiet standing following trunk extensor muscles fatigue by increasing the reliance on the somatosensory inputs from the foot and the ankle. This could have implications in clinical and rehabilitative areas

Testing the paradox of enrichment along a land use gradient in a multitrophic aboveground and belowground community

In the light of ongoing land use changes, it is important to understand how multitrophic communities perform at different land use intensities. The paradox of enrichment predicts that fertilization leads to destabilization and extinction of predator-prey systems. We tested this prediction for a land use intensity gradient from natural to highly fertilized agricultural ecosystems. We included multiple aboveground and belowground trophic levels and land use-dependent searching efficiencies of insects. To overcome logistic constraints of field experiments, we used a successfully validated simulation model to investigate plant responses to removal of herbivores and their enemies. Consistent with our predictions, instability measured by herbivore-induced plant mortality increased with increasing land use intensity. Simultaneously, the balance between herbivores and natural enemies turned increasingly towards herbivore dominance and natural enemy failure. Under natural conditions, there were more frequently significant effects of belowground herbivores and their natural enemies on plant performance, whereas there were more aboveground effects in agroecosystems. This result was partly due to the “boom-bust” behavior of the shoot herbivore population. Plant responses to herbivore or natural enemy removal were much more abrupt than the imposed smooth land use intensity gradient. This may be due to the presence of multiple trophic levels aboveground and belowground. Our model suggests that destabilization and extinction are more likely to occur in agroecosystems than in natural communities, but the shape of the relationship is nonlinear under the influence of multiple trophic interactions.

Dietary elimination of children with food protein induced gastrointestinal allergy – micronutrient adequacy with and without a hypoallergenic formula?

Background: The cornerstone for management of Food protein-induced gastrointestinal allergy (FPGIA) is dietary exclusion; however the micronutrient intake of this population has been poorly studied. We set out to determine the dietary intake of children on an elimination diet for this food allergy and hypothesised that the type of elimination diet and the presence of a hypoallergenic formula (HF) significantly impacts on micronutrient intake. Method: A prospective observational study was conducted on children diagnosed with FPIGA on an exclusion diet who completed a 3 day semi-quantitative food diary 4 weeks after commencing the diet. Nutritional intake where HF was used was compared to those without HF, with or without a vitamin and mineral supplement (VMS). Results: One-hundred-and-five food diaries were included in the data analysis: 70 boys (66.7%) with median age of 21.8 months [IQR: 10 - 67.7]. Fifty-three children (50.5%) consumed a HF and the volume of consumption was correlated to micronutrient intake. Significantly (p <0.05) more children reached their micronutrient requirements if a HF was consumed. In those without a HF, some continued not to achieve requirements in particular for vitamin D and zinc, in spite of VMS. Conclusion: This study points towards the important micronutrient contribution of a HF in children with FPIGA. Children, who are not on a HF and without a VMS, are at increased risk of low intakes in particular vitamin D and zinc. Further studies need to be performed, to assess whether dietary intake translates into actual biological deficiencies

Disruption of the Key Ca2+ Binding Site in the Selectivity Filter of Neuronal Voltage-Gated Calcium Channels Inhibits Channel Trafficking

Voltage-gated calcium channels are exquisitely Ca2+ selective, conferred primarily by four conserved pore-loop glutamate residues contributing to the selectivity filter. There has been little previous work directly measuring whether the trafficking of calcium channels requires their ability to bind Ca2+ in the selectivity filter or to conduct Ca2+. Here, we examine trafficking of neuronal CaV2.1 and 2.2 channels with mutations in their selectivity filter and find reduced trafficking to the cell surface in cell lines. Furthermore, in hippocampal neurons, there is reduced trafficking to the somatic plasma membrane, into neurites, and to presynaptic terminals. However, the CaV2.2 selectivity filter mutants are still influenced by auxiliary α2δ subunits and, albeit to a reduced extent, by β subunits, indicating the channels are not grossly misfolded. Our results indicate that Ca2+ binding in the pore of CaV2 channels may promote their correct trafficking, in combination with auxiliary subunits. Furthermore, physiological studies utilizing selectivity filter mutant CaV channels should be interpreted with caution

The beta-Secretase Substrate Seizure 6-Like Protein (SEZ6L) Controls Motor Functions in Mice

The membrane protein seizure 6–like (SEZ6L) is a neuronal substrate of the Alzheimer’s disease protease BACE1, and little is known about its physiological function in the nervous system. Here, we show that SEZ6L constitutive knockout mice display motor phenotypes in adulthood, including changes in gait and decreased motor coordination. Additionally, SEZ6L knockout mice displayed increased anxiety-like behaviour, although spatial learning and memory in the Morris water maze were normal. Analysis of the gross anatomy and proteome of the adult SEZ6L knockout cerebellum did not reveal any major differences compared to wild type, indicating that lack of SEZ6L in other regions of the nervous system may contribute to the phenotypes observed. In summary, our study establishes physiological functions for SEZ6L in regulating motor coordination and curbing anxiety-related behaviour, indicating that aberrant SEZ6L function in the human nervous system may contribute to movement disorders and neuropsychiatric diseases

Quantum to Classical Transition in a Single-Ion Laser

Stimulated emission of photons from a large number of atoms into the mode of a strong light field is the principle mechanism for lasing in "classical" lasers. The onset of lasing is marked by a threshold which can be characterised by a sharp increase in photon flux as a function of external pumping strength. The same is not necessarily true for the fundamental building block of a laser: a single trapped atom interacting with a single optical radiation mode. It has been shown that such a "quantum" laser can exhibit thresholdless lasing in the regime of strong coupling between atom and radiation field. However, although theoretically predicted, a threshold at the single-atom level could not be experimentally observed so far. Here, we demonstrate and characterise a single-atom laser with and without threshold behaviour by changing the strength of atom-light field coupling. We observe the establishment of a laser threshold through the accumulation of photons in the optical mode even for a mean photon number substantially lower than for the classical case. Furthermore, self-quenching occurs for very strong external pumping and constitutes an intrinsic limitation of single-atom lasers. Moreover, we find that the statistical properties of the emitted light can be adjusted for weak external pumping, from the quantum to the classical domain. Our observations mark an important step towards fundamental understanding of laser operation in the few-atom limit including systems based on semiconductor quantum dots or molecules.Comment: 19 pages, 4 figures, 10 pages supplement, accepted by Nature Physic

Valtion aluehallintovirastot ja niiden ylijohtajat: Pohjoiseurooppalainen analogia Ranskan prefeikteille

This chapter examines the closest Finnish analogy to the French function of the prefect. In Finland, since 2010, this function has been vested in the institution of the State Regional Administrative Agency (SRAA, aluehallintovirasto, ‘AVI’). There are six SRAAs, each headed by a Chief Director (ylijohtaja) nominated by the government. The study had four main findings. First, despite ambiguity in institutional terminology, classifications, boundaries and identities concerning the SRAA, one can discern few true functional or structural deficiencies. Second, the SRAA is a hybrid between an institution of its own and a territorial representative of either government ministries or government agencies, to which is related the fact that each SRAA has both responsibilities concerning its territory and nationwide responsibilities. Third, tensions between performance and institutional legitimation prevail in the institution of the SRAA, but again without serious deficiencies. Fourth, the 2010 substitution of the SRAA for the former Province comprised a radical institutional change. The 2015–2019 Finnish government intended to abolish the SRAAs, but the subsequent government abandoned that reform, and ultimately by mid-2020 it became clear that the institution of the SRAA was here to stay after all.Peer reviewe

Sensory Electrical Stimulation Improves Foot Placement during Targeted Stepping Post-Stroke

Proper foot placement is vital for maintaining balance during walking, requiring the integration of multiple sensory signals with motor commands. Disruption of brain structures post-stroke likely alters the processing of sensory information by motor centers, interfering with precision control of foot placement and walking function for stroke survivors. In this study, we examined whether somatosensory stimulation, which improves functional movements of the paretic hand, could be used to improve foot placement of the paretic limb. Foot placement was evaluated before, during, and after application of somatosensory electrical stimulation to the paretic foot during a targeted stepping task. Starting from standing, twelve chronic stroke participants initiated movement with the non-paretic limb and stepped to one of five target locations projected onto the floor with distances normalized to the paretic stride length. Targeting error and lower extremity kinematics were used to assess changes in foot placement and limb control due to somatosensory stimulation. Significant reductions in placement error in the medial–lateral direction (p = 0.008) were observed during the stimulation and post-stimulation blocks. Seven participants, presenting with a hip circumduction walking pattern, had reductions (p = 0.008) in the magnitude and duration of hip abduction during swing with somatosensory stimulation. Reductions in circumduction correlated with both functional and clinical measures, with larger improvements observed in participants with greater impairment. The results of this study suggest that somatosensory stimulation of the paretic foot applied during movement can improve the precision control of foot placement