Photosystem II for photoelectrochemical hydrogen production.

Water is a primary source of electrons and protons for photosynthetic organisms. For the production of hydrogen through the process of mimicking natural photosynthesis, photosystem II (PSII)-based hybrid photosynthetic systems have been created, both with and without an external voltage source. In the past 30 years, various PSII immobilization techniques have been proposed, and redox polymers have been created for charge transfer from PSII. This review considers the main components of photosynthetic systems, methods for evaluating efficiency, implemented systems and the ways to improve them. Recently, low-overpotential catalysts have emerged that do not contain precious metals, which could ultimately replace Pt and Ir catalysts and make water electrolysis cheaper. However, PSII competes with semiconductor analogues that are less efficient but more stable. Methods originally created for sensors also allow for the use of PSII as a component of a photoanode. To date, charge transfer from PSII remains a bottleneck for such systems. Novel data about action mechanism of artificial electron acceptors in PSII could develop redox polymers to level out mass transport limitations. Hydrogen-producing systems based on PSII have allowed to work out processes in artificial photosynthesis, investigate its features and limitations. Supplementary Information: The online version contains supplementary material available at 10.1007/s12551-023-01139-5.

Autotolerant ceruloplasmin based biocathodes for implanted biological power sources.

High-performance autotolerant bioelectrodes should be ideally suited to design implantable bioelectronic devices. Because of its high redox potential and ability to reduce oxygen directly to water, human ceruloplasmin, HCp, the only blue multicopper oxidase present in human plasma, appears to be the ultimate biocatalyst for oxygen biosensors and also biocathodes in biological power sources. In comparison to fungal and plant blue multicopper oxidases, e.g. Myrothecium verrucaria bilirubin oxidase and Rhus vernicifera laccase, respectively, the inflammatory response to HCp in human blood is significantly reduced. Partial purification of HCp allowed to preserve the native conformation of the enzyme and its biocatalytic activity. Therefore, electrochemical studies were carried out with the partially purified enzyme immobilised on nanostructured graphite electrodes at physiological pH and temperature. Amperometric investigations revealed low reductive current densities, i.e. about 1.65 µA cm-2 in oxygenated electrolyte and in the absence of any mediator, demonstrating nevertheless direct electron transfer based O2 bioelectroreduction by HCp for the first time. The reductive current density obtained in the mediated system was about 12 µA cm-2. Even though the inflammatory response of HCp is diminished in human blood, inadequate bioelectrocatalytic performance hinders its use as a cathodic bioelement in a biofuel cell.

Olfactory ability in normal pressure hydrocephalus as compared to Alzheimer's disease and healthy controls.

OBJECTIVES: Normal pressure hydrocephalus (NPH) is a treatable neurological disorder that appears in older adults, lacks specific diagnostic criteria, and resembles symptoms seen in Alzheimer's disease (AD). Presently, differentiating NPH from AD in the early stages of symptom presentation remains difficult. This study established whether olfactory testing may be useful in this regard. In addition, we determined whether olfactory function of NPH patients differed before and after extended lumbar drainage (ELD), as well as six months after surgical implantation of a ventriculoperitoneal (VP) shunt. PATIENTS AND METHODS: Twenty-two NPH patients (mean age=77.6yrs), 14 age- and gender-matched healthy controls (mean age=79.9yrs), and 7 AD patients (mean age=75.5yrs) were administered the 40-item University of Pennsylvania Smell Identification Test (UPSIT). Eighteen of the 22 NPH patients were also tested following ELD and 8 patients were tested six months following implantation of VP shunt. RESULTS: Prior to ELD, patients with NPH scored significantly higher on the UPSIT than those with AD [respective means (SDs)=26.9 (7.1) & 14.1 (4.7)]. While the mean NPH score was significantly below that of the matched controls [control mean (SD)=32.7 (6.7)], their test scores were nonetheless within the general normal range, as determined from published normative data (48th percentile). The UPSIT scores did not differ significantly among the three longitudinal time points in the NPH patients. CONCLUSION: Olfactory testing may be useful in differentiating between patients with NPH and patients with AD. Odor identification test scores of NPH patients are not influenced by the release of intracranial pressure via ELD or six months following implantation of a VP shunt.

The effects of histone deacetylase inhibitors on glioblastoma-derived stem cells.

Glioblastoma multiforme (GBM) is the most malignant brain tumor with limited effective treatment options. Cancer stem cells (CSCs), a subpopulation of cancer cells with stem cell properties found in GBMs, have been shown to be extremely resistant to radiation and chemotherapeutic agents and have the ability to readily reform tumors. Therefore, the development of therapeutic agents targeting CSCs is extremely important. In this study, we isolated glioblastoma-derived stem cells (GDSCs) from GBM tissue removed from patients during surgery and analyzed their gene expression using quantitative real-time PCR and immunocytochemistry. We examined the effects of histone deacetylase inhibitors trichostatin A (TSA) and valproic acid (VPA) on the proliferation and gene expression profiles of GDSCs. The GDSCs expressed significantly higher levels of both neural and embryonic stem cell markers compared to GBM cells expanded in conventional monolayer cultures. Treatment of GDSCs with histone deacetylase inhibitors, TSA and VPA, significantly reduced proliferation rates of the cells and expression of the stem cell markers, indicating differentiation of the cells. Since differentiation into GBM makes them susceptible to the conventional cancer treatments, we posit that use of histone deacetylase inhibitors may increase efficacy of the conventional cancer treatments for eliminating GDSCs.

Involvement of notch signaling pathway in amyloid precursor protein induced glial differentiation.

The amyloid precursor protein (APP) has been mainly studied in its role in the production of amyloid ß peptides (Aß), because Aß deposition is a hallmark of Alzheimer's disease. Although several studies suggest APP has physiological functions, it is still controversial. We previously reported that APP increased glial differentiation of neural progenitor cells (NPCs). In the current study, NPCs transplanted into APP23 transgenic mice primarily differentiated into glial cells. In vitro treatment with secreted APP (sAPP) dose-dependently increased glial fibrillary acidic protein (GFAP) immuno-positive cells in NPCs and over expression of APP caused most NPCs to differentiate into GFAP immuno-positive cells. Treatment with sAPP also dose-dependently increased expression levels of GFAP in NT-2/D1 cells along with the generation of Notch intracellular domain (NICD) and expression of Hairy and enhancer of split 1 (Hes1). Treatment with γ-secretase inhibitor suppressed the generation of NICD and reduced Hes1 and GFAP expressions. Treatment with the N-terminal domain of APP (APP 1-205) was enough to induce up regulation of GFAP and Hes1 expressions, and application of 22 C11 antibodies recognizing N-terminal APP suppressed these changes by sAPP. These results indicate APP induces glial differentiation of NPCs through Notch signaling.

Amyloid-ß precursor protein induces glial differentiation of neural progenitor cells by activation of the IL-6/gp130 signaling pathway.

Although amyloid precursor protein (APP) due to the cytotoxicity of Aß peptides, has been intensively studied, the physiological role of APP still remains wrapped up in veil. In this article, we propose that α-cleaved ectodomain of APP (sAPPα) stimulates the IL-6/gp130 signaling pathway for induction of gliogenesis within neural progenitor cells (NPCs). In our previous study, a high dose of APP differentiated NPCs into glial fibrillary acidic protein (GFAP) positive cells. In order to elucidate the mechanism of APP-induced glial differentiation, we examined the effects of sAPPα on the IL-6/gp130 signaling pathway. Application of sAPPα promoted mRNA expression of gp130, ciliary neurotrophic factor (CNTF), and Janus kinase 1 (JAK1). sAPPα stimulated the glial differentiation by upregulating the expression and phosphorylation of gp130. While mRNA expression of STAT3 was unchanged, phosphorylation of STAT3-Tyr705 gradually increased. Application of small interference RNA (siRNA) for STAT3 suppressed GFAP expression even in the presence of APP. Treatment with siRNA or inhibitor, AG490, of JAK1 efficiently suppressed STAT3 phosphorylation and GFAP expression. Upregulation of CNTF was observed in either short- or long-term treatment with sAPPα. RNA's interference of CNTF dose-dependently inhibited GFAP expression upregulated by treatment with sAPPα. This study suggests that the IL-6/gp130 signaling pathway is involved in sAPPα-induced glial differentiation of NPCs. Although further investigation is needed, this study may provide insight into the mechanism of glial differentiation of NPCs under pathological conditions in Alzheimer's disease or Down syndrome.

Receptor channel TRPC6 is a key mediator of Notch-driven glioblastoma growth and invasiveness.

Glioblastoma multiforme (GBM) is the most frequent and incurable type of brain tumor of adults. Hypoxia has been shown to direct GBM toward a more aggressive and malignant state. Here we show that hypoxia increases Notch1 activation, which in turn induces the expression of transient receptor potential 6 (TRPC6) in primary samples and cell lines derived from GBM. TRPC6 is required for the development of the aggressive phenotype because knockdown of TRPC6 expression inhibits glioma growth, invasion, and angiogenesis. Functionally, TRPC6 causes a sustained elevation of intracellular calcium that is coupled to the activation of the calcineurin-nuclear factor of activated T-cell (NFAT) pathway. Pharmacologic inhibition of the calcineurin-NFAT pathway substantially reduces the development of the malignant GBM phenotypes under hypoxia. Clinically, expression of TRPC6 was elevated in GBM specimens in comparison with normal tissues. Collectively, our studies indicate that TRPC6 is a key mediator of tumor growth of GBM in vitro and in vivo and that TRPC6 may be a promising therapeutic target in the treatment of human GBM.