Serum Corticosterone and Insulin Resistance as Early Biomarkers in the hAPP23 Overexpressing Mouse Model of Alzheimer’s Disease

Increasing epidemiological evidence highlights the association between systemic insulin resistance and Alzheimer’s disease (AD). As insulin resistance can be caused by high-stress hormone levels and since hypercortisolism appears to be an important risk factor of AD, we aimed to investigate the systemic insulin functionality and circulating stress hormone levels in a mutant humanized amyloid precursor protein (APP) overexpressing (hAPP23+/−) AD mouse model. Memory and spatial learning of male hAPP23+/− and C57BL/6 (wild type, WT) mice were assessed by a Morris Water Maze (MWM) test at the age of 4 and 12 months. The systemic metabolism was examined by intraperitoneal glucose and insulin tolerance tests (GTT, ITT). Insulin and corticosterone levels were determined in serum. In the hippocampus, parietal and occipital cortex of hAPP23+/− brains, amyloid-beta (Aβ) deposits were present at 12 months of age. MWM demonstrated a cognitive decline in hAPP23+/− mice at 12 but not at 4 months, evidenced by increasing total path lengths and deteriorating probe trials compared to WT mice. hAPP23+/− animals presented increased serum corticosterone levels compared to WT mice at both 4 and 12 months. hAPP23+/− mice exhibited peripheral insulin resistance compared to WT mice at 4 months, which stabilized at 12 months of age. Serum insulin levels were similar between genotypes at 4 months of age but were significantly higher in hAPP23+/− mice at 12 months of age. Peripheral glucose homeostasis remained unchanged. These results indicate that peripheral insulin resistance combined with elevated circulating stress hormone levels could be potential biomarkers of the pre-symptomatic phase of AD.     

Increased osteoclast-like cells formation in long-term bone marrow cultures from patients with a spinal cord injury

A simple and sensitive method for analysis of three tetracyclic antidepressants, maprotiline, mianserin, and setiptiline, in human whole blood was developed using headspace-solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS). A vial containing a blood sample, sodium hydroxide, and imipramine as an internal standard was heated at 120 degrees C. The extraction fiber of the SPME was exposed for 45 min in the headspace of the vial. The compounds absorbed on the fiber were desorbed by exposing the fiber in the injection port of a GC-MS. The calibration curves, using an internal standard method, demonstrated good linearity throughout the concentration range from 0.005 to 5.0 microg/g for mianserin and setiptiline and from 0.025 to 25 microg/g for maprotiline. No interferences were found, and the time for analysis was 60 min for one sample. In addition, this proposed method was applied to a medicolegal case in which the cause of death was suspected to be acute setiptiline poisoning. Setiptiline was detected in the left and right heart blood samples of the victim at concentrations of 1.77 and 0.78 microg/g, respectively.     

A glance into aluminum toxicity and resistance in plants

Aluminum toxicity is an important stress factor for plants in acidic environments. During the last decade considerable advances have been made in both techniques to assess the potentially toxic Al species in environmental samples, and knowledge about the mechanisms of Al toxicity and resistance in plants. After a short introduction on Al risk assessment, this review aims to give an up-to-date glance into current developments in the field of Al toxicity and resistance in plants, also providing sufficient background information for non-specialists in aluminum research. Special emphasis is paid to root growth and development as primary targets for Al toxicity. Mechanisms of exclusion of Al from sensitive root tips, as well as tolerance of high Al tissue levels are considered.     

Steroidogenesis in Peripheral and Transition Zones of Human Prostate Cancer Tissue

The peripheral zone (PZ) and transition zone (TZ) represent about 70% of the human prostate gland with each zone having differential ability to develop prostate cancer. Androgens and their receptor are the primary driving cause of prostate cancer growth and eventually castration-resistant prostate cancer (CRPC). De novo steroidogenesis has been identified as a key mechanism that develops during CRPC. Currently, there is very limited information available on human prostate tissue steroidogenesis. The purpose of the present study was to investigate steroid metabolism in human prostate cancer tissues with comparison between PZ and TZ. Human prostate cancer tumors were procured from the patients who underwent radical prostatectomy without any neoadjuvant therapy. Human prostate homogenates were used to quantify steroid levels intrinsically present in the tissues as well as formed after incubation with 2 µg/mL of 17-hydroxypregnenolone (17-OH-pregnenolone) or progesterone. A Waters Acquity ultraperformance liquid chromatography coupled to a Quattro Premier XE tandem quadrupole mass spectrometer using a C₁₈ column was used to measure thirteen steroids from the classical and backdoor steroidogenesis pathways. The intrinsic prostate tissue steroid levels were similar between PZ and TZ with dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), pregnenolone and 17-OH-pregnenolone levels higher than the other steroids measured. Interestingly, 5-pregnan-3,20-dione, 5-pregnan-3-ol-20-one, and 5-pregnan-17-ol-3,20-dione formation was significantly higher in both the zones of prostate tissues, whereas, androstenedione, testosterone, DHT, and progesterone levels were significantly lower after 60 min incubation compared to the 0 min control incubations. The incubations with progesterone had a similar outcome with 5-pregnan-3,20-dione and 5-pregnan-3-ol-20-one levels were elevated and the levels of DHT were lower in both PZ and TZ tissues. The net changes in steroid formation after the incubation were more observable with 17-OH-pregnenolone than with progesterone. In our knowledge, this is the first report of comprehensive analyses of intrinsic prostate tissue steroids and precursor-driven steroid metabolism using a sensitive liquid chromatography-mass spectrometry assay. In summary, the PZ and TZ of human prostate exhibited similar steroidogenic ability with distinction in the manner each zone utilizes the steroid precursors to divert the activity towards backdoor pathway through a complex matrix of steroidogenic mechanisms.     

Taking scholarly books into account,part II: a comparison of 19 European countries in evaluation and funding

Scientometrics - In May 2016, an article published in Scientometrics, titled ‘Taking scholarly books into account: current developments in five European countries’, introduced a...     

Measuring co-authors’ contribution to an article’s visibility

The visibility of an article depends to a large extent on its authors. We study the question how each co-author’s relative contribution to the visibility of the article can be determined and quantified using an indicator, referring to such an indicator as a CAV-indicator. A two-step procedure is elaborated, whereby one first chooses an indicator (e.g. total number of citations, h-index …) and subsequently one of two possible approaches. The case where the indicator is an h-type index is elaborated in a Lotkaian framework. Different examples illustrate the procedure and the choices involved in determining a CAV-indicator.