Harnessing IGF-1 and IL-2 as biomarkers for calcineurin activity to tailor optimal FK506 dosage in α-synucleinopathies.

Rise in Calcium (Ca) and hyperactive Ca-dependent phosphatase calcineurin represent two key determinants of a-synuclein (a-syn) pathobiology implicated in Parkinson's Disease (PD) and other neurodegenerative diseases. Calcineurin activity can be inhibited with FK506, a Food and Drug Administration (FDA)-approved compound. Our previous work demonstrated a protective effect of low doses of FK506 against a-syn pathology in various models of a-syn related pathobiology.

Octopamine metabolically reprograms astrocytes to confer neuroprotection against α-synuclein.

Octopamine is a well-established invertebrate neurotransmitter involved in fight or flight responses. In mammals, its function was replaced by epinephrine. Nevertheless, it is present at trace amounts and can modulate the release of monoamine neurotransmitters by a yet unidentified mechanism.

Herpesviruses assimilate kinesin to produce motorized viral particles.

Neurotropic alphaherpesviruses initiate infection in exposed mucosal tissues and, unlike most viruses, spread rapidly to sensory and autonomic nerves where life-long latency is established. Recurrent infections arise sporadically from the peripheral nervous system throughout the life of the host, and invasion of the central nervous system may occur, with severe outcomes. These viruses directly recruit cellular motors for transport along microtubules in nerve axons, but how the motors are manipulated to deliver the virus to neuronal nuclei is not understood.

Comparison of 66 chemical element contents in normal and benign hyperplastic prostate.

Objective: The aim of this study was to clarify the differences between the prostatic levels of chemical elements in patients with benign prostatic hyperplasia (BPH) and healthy male.

Methods: We evaluated the prostatic level of 66 chemical elements in 43 patients with BPH and 37 healthy males. Measurements were performed using five instrumental analytical methods.

Associations between age and 50 trace element contents and relationships in intact thyroid of males.

Background: It is unclear why a prevalence of thyroid dysfunction is higher in the elderly as compared to the younger population. An excess or deficiency of trace element contents in thyroid may play important role in goitre- and carcinogenesis of gland.

Aim: To examine the variation with age of the mass fraction of 50 trace elements in intact (normal) male thyroid.

FKBP12 contributes to α-synuclein toxicity by regulating the calcineurin-dependent phosphoproteome.

Calcineurin is an essential Ca-dependent phosphatase. Increased calcineurin activity is associated with α-synuclein (α-syn) toxicity, a protein implicated in Parkinson's Disease (PD) and other neurodegenerative diseases. Calcineurin can be inhibited with Tacrolimus through the recruitment and inhibition of the 12-kDa proline isomerase FK506-binding protein (FKBP12).

Allele-specific interaction between glutathione peroxidase 1 and manganese superoxide dismutase affects the levels of Bcl-2, Sirt3 and E-cadherin.

Manganese superoxide dismutase (MnSOD) is a mitochondrial-resident enzyme that reduces superoxide to hydrogen peroxide (HO), which can be further reduced to water by glutathione peroxidase (GPX1). Data from human studies have indicated that common polymorphisms in both of these proteins are associated with the risk of several cancers, including breast cancer. Moreover, polymorphisms in MnSOD and GPX1 were shown to interact to increase the risk of breast cancer.

The role of Ca signaling in Parkinson's disease.

Across all kingdoms in the tree of life, calcium (Ca) is an essential element used by cells to respond and adapt to constantly changing environments. In multicellular organisms, it plays fundamental roles during fertilization, development and adulthood. The inability of cells to regulate Ca can lead to pathological conditions that ultimately culminate in cell death.

Selenium levels in human breast carcinoma tissue are associated with a common polymorphism in the gene for SELENOP (Selenoprotein P).

Selenium supplementation of the diets of rodents has consistently been shown to suppress mammary carcinogenesis and some, albeit not all, human epidemiological studies have indicated an inverse association between selenium and breast cancer risk. In order to better understand the role selenium plays in breast cancer, 30 samples of tumor tissue were obtained from women with breast cancer and analyzed for selenium concentration, the levels of several selenium-containing proteins and the levels of the MnSOD anti-oxidant protein. Polymorphisms within the genes for these same proteins were determined from DNA isolated from the tissue samples.

NOS1-derived nitric oxide promotes NF-κB transcriptional activity through inhibition of suppressor of cytokine signaling-1.

The NF-κB pathway is central to the regulation of inflammation. Here, we demonstrate that the low-output nitric oxide (NO) synthase 1 (NOS1 or nNOS) plays a critical role in the inflammatory response by promoting the activity of NF-κB. Specifically, NOS1-derived NO production in macrophages leads to proteolysis of suppressor of cytokine signaling 1 (SOCS1), alleviating its repression of NF-κB transcriptional activity.

Differences between chemical element contents in hyperplastic and nonhyperplastic prostate glands investigated by neutron activation analysis.

In order to clarify the differences between Ag, Br, Ca, Co, Cr, Fe, Hg, K, Mg, Mn, Na, Rb, Sb, Sc, Se, and Zn contents in hyperplastic (patients with benign prostate hyperplasia (BPH), n = 32) and nonhyperplastic (control group of healthy male inhabitants, n = 32) prostates, an instrumental neutron activation analysis was performed. Mean values (M ± SΕΜ) for mass fraction (mg/kg, dry mass basis) of chemical elements in glands of patients with BPH were the following: Ag, 0.0346 ± 0.

The Ca, Cl, Mg, Na, and P mass fractions in human bone affected by Ewing's sarcoma.

The Ca, Cl, Mg, Na, and P contents and Ca/P, Ca/Mg, Ca/Na, Cl/Ca, and Cl/Na ratios in samples of intact bone, inflamed bone, and Ewing's sarcoma tissue were investigated by neutron activation analysis with high-resolution spectrometry of short-lived radionuclides. In Ewing's sarcoma tissue, the mass fractions of Cl and Na are higher and the mass fractions of Ca and Mg are lower than those of both normal and inflamed bone tissues. It was shown that the levels of Ca and Cl mass fractions and also levels of the Ca/Cl and Cl/Na ratios can be used as an additional test for differential diagnosis between inflamed (or normal) bone and Ewing's sarcoma.

INAA application in the assessment of chemical element mass fractions in adult and geriatric prostate glands.

The variation with age of the mass fraction of 37 chemical elements in intact nonhyperplastic prostate of 65 healthy 21-87 year old males was investigated by instrumental neutron activation analysis with high resolution spectrometry of short- and long-lived radionuclides. Mean values (M±SΕΜ) for mass fractions (mg kg(-1), dry mass basis) of the chemical elements studied were: Ag-0.055±0.

Relations of the Al, B, Ba, Br, Ca, Cl, Cu, Fe, K, Li, Mg, Mn, Na, P, S, Si, Sr, and Zn mass fractions to morphometric parameters in pediatric and nonhyperplastic young adult prostate glands.

The variation with age of the 18 trace element mass fractions and some histological characteristics of intact prostate glands of 50 subjects aged 0-30 years was investigated by instrumental neutron activation analysis, inductively coupled plasma atomic emission spectrometry, and a quantitative morphometric analysis. Mean values ± standard error of the mean (M ± SΕΜ) for the mass fractions (in milligrams per kilogram wet tissue) of these trace elements in pre-puberty were: Al 28.5 ± 9.

Relations of bromine, iron, rubidium, strontium, and zinc content to morphometric parameters in pediatric and nonhyperplastic young adult prostate glands.

The variation with age of the Br, Fe, Rb, Sr, and Zn mass fractions and some histological characteristics of intact prostate glands of 50 subjects aged 0-30 years was investigated by an energy-dispersive X-ray fluorescence and a quantitative morphometric analysis. Mean values ± standard error of the mean (M ± SΕΜ) for the mass fractions (in milligrams per kilogram wet-mass basis) of these trace elements in pre-puberty were: Br-10.5 ± 1.

NAA-SLR and ICP-AES application in the assessment of mass fraction of 19 chemical elements in pediatric and young adult prostate glands.

The effect of age on the mass fraction of 19 chemical elements in the intact prostate of 50 apparently healthy 0-30-year-old males was investigated by neutron activation analysis with high-resolution spectrometry of short-lived radionuclides and inductively coupled plasma atomic emission spectrometry. Mean values (M ± standard error of the mean) for mass fraction (in milligrams per kilogram, on dry weight basis) of chemical elements were as follows: Al, 77 ± 17; B, 1.31 ± 0.

The effect of age on Br, Ca, Cl, K, Mg, Mn, and Na mass fraction in pediatric and young adult prostate glands investigated by neutron activation analysis.

The effect of age on chemical element mass fractions in intact prostate of 50 apparently healthy 0-30 year old males was investigated by neutron activation analysis with high resolution spectrometry of short-lived radionuclides. Mean values (M ± SΕΜ) for mass fraction (mgkg(-1), dry mass basis) of chemical elements before the time of puberty and in the period of puberty and post-puberty were: Br 46.0 ± 6.

Age-related histological and zinc content changes in adult nonhyperplastic prostate glands.

To clarify age-related histological and Zn content changes in nonhyperplastic adult prostate glands, a quantitative morphometric and energy-dispersive X-ray fluorescence analyses were performed. The prostates were obtained from autopsies of 63 subjects aged 21-70 years who died mainly from trauma. It was found that histologically normal prostate tissue undergoes substantial changes throughout aging.

The herpesvirus VP1/2 protein is an effector of dynein-mediated capsid transport and neuroinvasion.

Microtubule transport of herpesvirus capsids from the cell periphery to the nucleus is imperative for viral replication and, in the case of many alphaherpesviruses, transmission into the nervous system. Using the neuroinvasive herpesvirus, pseudorabies virus (PRV), we show that the viral protein 1/2 (VP1/2) tegument protein associates with the dynein/dynactin microtubule motor complex and promotes retrograde microtubule transport of PRV capsids. Functional activation of VP1/2 requires binding to the capsid protein pUL25 or removal of the capsid-binding domain.

Relations of morphometric parameters to zinc content in paediatric and nonhyperplastic young adult prostate glands.

To clarify age-related histological and zinc content changes in paediatric and nonhyperplastic young adult prostate glands, a quantitative morphometric and energy-dispersive X-ray fluorescence analysis (EDXRF) was performed. The prostates were obtained at autopsy from 50 subjects (European-Caucasian aged 0-30 years) who died from sudden infant death syndrome, acute pulmonary aetiologies and trauma. None of the subjects had any symptoms of prostatic disease and all prostates were classified as histologically normal.

Mass fractions of 52 trace elements and zinc/trace element content ratios in intact human prostates investigated by inductively coupled plasma mass spectrometry.

Contents of 52 trace elements in intact prostate of 64 apparently healthy 13-60-year-old men (mean age 36.5 years) were investigated by inductively coupled plasma mass spectrometry. Mean values (M ± SΕΜ) for mass fraction (in milligrams per kilogram, on dry-weight basis) of trace elements were as follows: Ag 0.

Alphaherpesviruses and the cytoskeleton in neuronal infections.

Following infection of exposed peripheral tissues, neurotropic alphaherpesviruses invade nerve endings and deposit their DNA genomes into the nuclei of neurons resident in ganglia of the peripheral nervous system. The end result of these events is the establishment of a life-long latent infection. Neuroinvasion typically requires efficient viral transmission through a polarized epithelium followed by long-distance transport through the viscous axoplasm.

Trace elements of normal, benign hypertrophic and cancerous tissues of the human prostate gland investigated by neutron activation analysis.

The Ag, Co, Cr, Fe, Hg, Rb, Sb, Sc, Se, and Zn contents in normal (n=37), benign hypertrophic (n=43), and cancerous tissues (n=60) of the human prostate gland were investigated by neutron activation analysis. Mean values (M±SΕΜ) for content (mg/kg, dry weight basis) of trace elements in the normal tissue were: Ag-0.048±0.

The effect of age on Ag, Co, Cr, Fe, Hg, Rb, Sb, Sc, Se, and Zn contents in intact human prostate investigated by neutron activation analysis.

The effect of age on trace element contents in intact prostate of 64 apparently healthy 13-60 years old men was investigated by neutron activation analysis. Mean values (M±SΕΜ) for content (mg/kg, dry weight basis) of trace elements were: Ag-0.057±0.