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Seizure activity leads to increases in extracellular potassium concentration ([K${}^{+}$]o), which can result in changes in neuronal passive and active membrane properties as well as in population activities. In this study, we examined how extracellular potassium modulates seizure activities using an acute 4-AP induced seizure model in the neocortex, both in vivo and in vitro. Moderately elevated [K${}^{+}$]o up to 9mM prolonged seizure durations and shortened interictal intervals as well as depolarized the neuronal resting membrane potential (RMP). However, when [K${}^{+}$]o reached higher than 9mM, seizure like events (SLEs) were blocked and neurons went into a depolarization-blocked state. Spreading depression was never observed as the blockade of ictal events could be reversed within 1–2min after the raised [K${}^{+}$]o was changed back to control levels. This concentration-dependent dual effect of [K${}^{+}$]o was observed using in vivo and in vitro mouse brain preparations as well as in human neocortical tissue resected during epilepsy surgery. Blocking the Ih current, mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, modulated the elevated [K${}^{+}$]o influence on SLEs by promoting the high [K${}^{+}$]o inhibitory actions. These results demonstrate biphasic actions of raised [K${}^{+}$]o on neuronal excitability and seizure activity.

To enable an accurate recognition of neuronal excitability in an epileptic brain for modeling or localization of epileptic zone, here the brain response to single-pulse electrical stimulation (SPES) has been decomposed into its constituent components using adaptive singular spectrum analysis (SSA). Given the response at neuronal level, these components are expected to be the inhibitory and excitatory components. The prime objective is to thoroughly investigate the nature of delayed responses (elicited between 100ms–1 s after SPES) for localization of the epileptic zone. SSA is a powerful subspace signal analysis method for separation of single channel signals into their constituent uncorrelated components. The consistency in the results for both early and delayed brain responses verifies the usability of the approach.

HIV mutations occur frequently despite the substantial success of combination antiretroviral therapy, which significantly impairs HIV progression. Failure to develop specific vaccines, the occurrence of drug-resistant strains, and the high incidence of adverse effects due to combination antiviral therapy regimens call for novel and safer antivirals. Natural products are an important source of new anti-infective agents. For instance, curcumin inhibits HIV and inflammation in cell culture assays. Curcumin, the principal constituent of the dried rhizomes of Curcuma longa L. (turmeric), is known as a strong anti-oxidant and anti-inflammatory agent with different pharmacological effects. This work aims to assess curcumin’s inhibitory effects on HIV in vitro and to explore the underpinning mechanism, focusing on CCR5 and the transcription factor forkhead box protein P3 (FOXP3). First, curcumin and the RT inhibitor zidovudine (AZT) were evaluated for their inhibitory properties. HIV-1 pseudovirus infectivity was determined by green fluorescence and luciferase activity measurements in HEK293T cells. AZT was used as a positive control that inhibited HIV-1 pseudoviruses dose-dependently, with IC50 values in the nanomolar range. Then, a molecular docking analysis was carried out to assess the binding affinities of curcumin for CCR5 and HIV-1 RNase H/RT. The anti-HIV activity assay showed that curcumin inhibited HIV-1 infection, and the molecular docking analysis revealed equilibrium dissociation constants of $-$9.8kcal/mol and $-$9.3kcal/mol between curcumin and CCR5 and HIV-1 RNase H/RT, respectively. To examine curcumin’s anti-HIV effect and its mechanism in vitro, cell cytotoxicity, transcriptome sequencing, and CCR5 and FOXP3 amounts were assessed at different concentrations of curcumin. In addition, human CCR5 promoter deletion constructs and the FOXP3 expression plasmid pRP–FOXP3 (with an EGFP tag) were generated. Whether FOXP3 DNA binding to the CCR5 promoter was blunted by curcumin was examined using transfection assays employing truncated CCR5 gene promoter constructs, a luciferase reporter assay, and a chromatin immunoprecipitation (ChIP) assay. Furthermore, micromolar concentrations of curcumin inactivated the nuclear transcription factor FOXP3, which resulted in decreased expression of CCR5 in Jurkat cells. Moreover, curcumin inhibited PI3K-AKT activation and its downstream target FOXP3. These findings provide mechanistic evidence encouraging further assessment of curcumin as a dietary agent used to reduce the virulence of CCR5-tropic HIV-1. Curcumin-mediated FOXP3 degradation was also reflected in its functions, namely, CCR5 promoter transactivation and HIV-1 virion production. Furthermore, curcumin inhibition of CCR5 and HIV-1 might constitute a potential therapeutic strategy for reducing HIV progression.

Bioleaching is the dissolution of metal sulfides like pyrite by bacterial oxidation processes. Beside desired heap or tank leaching for winning metals such as copper or gold, unwanted bioleaching causes acid mine drainage (AMD)/acid rock drainage (ARD) e.g. in during coal mining processes. Bioleaching can cause acidification of surface- and groundwater concomitant with pollution by high amounts of heavy metals. The addition of a surfactant to active leaching cultures decreases bacterial cell numbers and leaching. To investigate the inhibition effect of the surfactant in situ, a percolator system was used. Percolators were filled with pyrite containing material from a brown coal area where unwanted bacterial leaching occurs. The surfactant was added after bacterial leaching was established. The addition of the surfactant inhibited leaching within one week till the end of the experiment after 13 weeks. Based on these findings, applications for the inhibition of bacterial leaching in brown coal mining areas can be established.