The Andean bear alopecia syndrome may be caused by social housing

The Andean bear alopecia syndrome is a progressive and chronic condition documented in ex situ populations. Recent advances focus on treating symptoms, not preventing future cases. We therefore explored the epidemiology of this syndrome through an analysis of husbandry and veterinary conditions of 63 Andean bears (26M:37F) housed in North and South American zoos and other ex situ circumstances. We had the most complete information for the North American population and found that 29% of females (n = 24) were affected. No males (n = 26) were affected. An analysis of generalized linear models indicated that three models were competitive in describing the occurrence of the condition (i.e., ΔAIC_c ≤ 2): the model including only the individual's sex (χ² = 13.41, df = 1, p < .001), the model including both individual sex and social housing status (χ² = 1.36, df = 2, p < .001), and the model including both individual sex and the expression of stereotypical behaviors (χ² = 13.82, df = 2, p = .001). Stereotypical behaviors were common among both males (50%, n = 26) and females (51.9%, n = 27) whether or not they were affected, but the syndrome was seen only in females who had been socially housed. Therefore, we suggest that the Andean bear alopecia syndrome is a symptomatic response to the long‐term social housing of bears that would otherwise not live socially. To prevent new cases, we recommend that female Andean bears be housed with adult conspecifics only when females choose to cohabitate.     

Rasagiline derivatives combined with histamine H3 receptor properties

The irreversible monoamine oxidase B (MAO B) inhibitor rasagiline has been described with multiple disease modifying effects in vitro on models of Parkinson’s disease. The combination of this established drug to recently developed histamine H₃ receptor (H₃R) antagonist elements gives new impetus to the design of multitargeting ligands. Surprisingly, the 5-substituted 3-piperidinopropyloxy rasagiline derivative 1 was more potent on both targets than its 6-substituted isomer. It showed nanomolar affinities at the desired targets (MAO B IC₅₀ = 256 nM; hH₃R K_i = 2.6 nM) with a high preference over monoamine oxidase A (MAO A) and negligible affinity at histamine H₁, H₄, dopamine D₂, D₃ receptors or acetyl-/butyrylcholinesterases.     

Collagen biomaterial doped with colominic acid for cell culture applications with regard to peripheral nerve repair

Colominic acid (CA) is a homopolymer of sialic acid residues and is solely composed of polymerised units of alpha-2,8-linked N-acetylneuraminic acid. CA is a specific derivative of polysialic acid (PSA), produced as the capsular polysaccharide of Escherichia coli K1 derived molecule of PSA. PSA in vivo plays a significant role in synaptic plasticity and neural development. The use of collagen materials doped with defined CA is presented for the cultivation of various cell lines relevant for possible applications in Tissue Engineering. First, the release behaviour under culture conditions of the collagen-based (C-CA) materials was investigated by thiobarbituric acid assay. Additionally, the established cell lines, PC-12 and immortalised Schwann cells (ISC), used for neurobiological and neurochemical studies and the model liver cell line Hep-G2 as indicator for biocompatibility testing, were cultured on the C-CA matrix. Cell proliferation (MTT-test) and cell adhesion (DAPI-staining) of the cell lines on the matrices were observed. Likewise, gene expression of the marker genes thyrosine hydroxylase for the PC-12 cells, and albumin, transferrin and CYP3A4 for the Hep-G2 cells was evaluated via RT-PCR. The results indicate that CA integration in established biomaterial constructs enhances cell proliferation and offers promising features as conduits additive in regarding peripheral nerve regeneration.     

Effects of fibroblasts and microenvironment on epidermal regeneration and tissue function in long-term skin equivalents

In vitro generated skin models find growing interest as promising tools in basic research and clinical application in regenerative medicine. Here, we present further details of an improved long-term skin equivalent (SE) enabling mechanistic studies on skin reconstruction and epidermal function. Growth conditions of fibroblasts in a 3D scaffold were analysed to optimise the dermal microenvironment by providing an authentic dermal matrix for regular tissue reconstruction and function of cocultured keratinocytes. These SEs demonstrate sustained epidermal viability - over 12 weeks - with regular differentiation as substantiated by in vivo-like patterns of all differentiation products, exemplified here by the cornified envelope components loricrin and repetin. The continuous expression of all major tight junction components in the granular layer, shown here for ZO-1 in coherence with the presence of epidermal barrier lipids, and ultrastructural accumulation of lamellar bodies, collectively indicate proper epidermal barrier structures. Remarkably, cocultured keratinocytes exerted an ongoing proliferation-stimulating effect on fibroblasts colonising the scaffold comparable to a cocktail of fibroblast growth factors. Consequently, precultivation of dermal equivalents (DEs) in basal or growth factor-enriched media had only minor effects on the quality of epidermal regeneration in cocultures. As to the role of fibroblast numbers, complete absence of dermal cells resulted in atrophic epithelia but the effect of cell numbers as low as 5 x 10(4)cells/cm(2) on epidermal tissue quality equalled that of the standard density (2 x 10(5)cells/cm(2)). Surprisingly, precultivation of fibroblasts in the DEs for 7 days (standard) showed no better effect on epidermal tissue reformation as compared to 2 days whereas a precultivation period of 14 days resulted in atrophic epidermal and dermal tissue development. These data demonstrate, (i) the strict dependence of epidermal tissue regeneration on the presence of fibroblasts, (ii) the mutual keratinocyte-fibroblast interactions for cell proliferation and organogenesis, and (iii) the importance of the proper microenvironment for epidermal tissue function and supposedly for establishment of a stem cell niche in vitro.     

Cathepsin B is essential for regeneration of scratch-wounded normal human epidermal keratinocytes

Migration, proliferation and differentiation of keratinocytes are important processes during tissue regeneration and wound healing of the skin. Here, we focussed on proteases that contribute to extracellular matrix (ECM) remodeling as a prerequisite of keratinocyte migration. In particular, we assessed the significance of the mammalian cysteine peptidase cathepsin B for human keratinocytes during regeneration from scratch wounding. We describe the construction of a scratch apparatus that allows applying scratches of defined length, width and depth to cultured cells in a reproducible fashion. The rationale for our approach derived from our previous work where we have shown that HaCaT keratinocytes secrete cathepsin B into the extracellular space during spontaneous and induced migration. Here, we observed rapid removal of type IV collagen from underneath lamellipodial extensions of keratinocytes at the advancing fronts of regenerating monolayers, indicating that proteolytic ECM remodeling starts upon initiation of keratinocyte migration. Furthermore, we verified our previous results with HaCaT cells by using normal human epidermal keratinocytes (NHEK) and show that non-cell-permeant cathepsin B-specific inhibitors delayed full regeneration of the monolayers from scratch wounding in both cell systems, HaCaT and NHEK. Application of a single dose of cathepsin B inhibitor directly after scratch wounding of keratinocytes demonstrated that cathepsin B is essential during initial stages of wound healing, while its contribution to the subsequent processes of proliferation and differentiation of keratinocytes was of less significance. This notion was supported by our observation that the cathepsin B inhibitors used in this study did not affect proliferation rates of keratinocytes of regenerating cultures. Thus, we conclude that cathepsin B is indeed involved in ECM remodeling after its secretion from migrating keratinocytes. Cathepsin B might directly cleave ECM constituents or it may initiate proteolytic cascades that involve other proteases with the ability to degrade ECM components. Because cathepsin B is important for enabling migration of both, HaCaT cells and NHEK, our results support the notion that HaCaT keratinocytes represent an excellent cell culture model for analysis of human epidermal skin keratinocyte migration.     

Measurement of pancreatic islet cell proliferation by heavy water labeling

We describe a sensitive technique for measuring long-term islet cell proliferation rates in vivo in rats. Pancreatic islets were isolated and the incorporation of deuterium ((2)H) from heavy water ((2)H(2)O) into the deoxyribose moiety of DNA was measured by GC-MS. The results of heavy water labeling and BrdU staining were compared. The two methods were highly correlated (r = 0.9581, P < 0.001). Based on long-term heavy water labeling, approximately 50% of islet cells divided in rats between 8 and 15 wk of age. Of interest, long-term BrdU administration suppressed proliferation of islet cells significantly, but not of bone marrow cells. Physiological evidence further supported the validity of the method: older animals (24 wk old) had 60% lower islet cell proliferation rates than younger rats (5 wk old), and partial (50%) pancreatectomy increased proliferation by 20%. In addition, cholecystokinin-8 treatment significantly stimulated proliferation in pancreatectomized rats only. In summary, heavy water labeling is a quantitative approach for measuring islet cell proliferation and testing therapeutic agents.     

An Approaching Motor Boat Induces Stress-Related Behaviors in Proboscis Monkeys (Nasalis larvatus) Living in a Riparian Area

International Journal of Primatology - Primate ecotourism is a fast-growing tourism sector that may have a negative effect on wildlife. In riparian areas, tourists can conveniently reach primates...     

Tannic Acid Attenuates Peripheral and Brain Changes in a Preclinical Rat Model of Glioblastoma by Modulating Oxidative Stress and Purinergic Signaling

Neurochemical Research - Glioblastoma (GB) is a highly aggressive and invasive brain tumor; its treatment remains palliative. Tannic acid (TA) is a polyphenol widely found in foods and possesses...     

Novel meriolin derivatives as rapid apoptosis inducers

3-(Hetero)aryl substituted 7-azaindoles possessing multikinase inhibitor activity are readily accessed in a one-pot Masuda borylation-Suzuki coupling sequence. Several promising derivatives were identified as apoptosis inducers and, emphasizing the multikinase inhibition potential, as sphingosine kinase 2 inhibitors. Our measurements provide additional insights into the structure-activity relationship of meriolin derivatives, suggesting derivatives bearing a pyridine moiety with amino groups in 2-position as most active anticancer compounds and thus as highly promising candidates for future in vivo studies.