Abundance and accessibility of forage for reindeer in forests of Northern Sweden: Impacts of landscape and winter climate regime

The survival of reindeer during winter, their period of greatest food stress, depends largely on the abundance and accessibility of forage in their pastures. In Northern Sweden, realized availability of forage is notably affected by snow conditions and the impacts of forestry. While these factors have been examined in isolation, their combined effect has, to the best of our knowledge to date, not been researched. In this study, vegetation surveys and analysis of snow conditions were undertaken in forest stands at various stages of recovery from clear‐cutting. The variation in abundance and growth of understory species edible by reindeer, such as lichen, was noted as forests matured. The barrier effect of ice lenses in the snow was also measured in these stands. Lichen biomass was significantly affected by a combination of stand maturity, understory vegetation height, and lichen height. Soil disturbance from the processes of felling and competition in the vegetation communities recovering from this disturbance were identified as key drivers of change in lichen biomass. Overall, clear‐cut forests had some of the greatest prevalence of ice lenses in the snow column, and forage availability at these sites was up to 61% less than in mature stands over 58 years in age. It is suggested that alternative silviculture methods are investigated for use in this reindeer herding region, as frequent clear‐cutting and consequent reduction in the average forest stand age and maturity class may be detrimental to reindeer grazing, reducing both abundance of forage, and access to it during winter.     

Serum-free cryopreservation of porcine hepatocytes

The use of porcine hepatocytes in xenotransplantation, bioartificial liver support or pharmacological approaches demands serum-free cryopreservation protocols yielding high quality, viable, functional hepatocytes. Here, primary porcine hepatocytes were frozen without serum in liquid nitrogen by the use of a computer-assisted freezing device. After thawing, more than 90% of the initial hepatocytes were lost, in part because of damage to genomic DNA. When cryoprotectants were used, the loss was lowered to 70% of the initial cell number; 90% of the remaining cells excluded trypan blue indicating a high degree of viability. Cells were seeded serum-free onto collagen-coated plastic dishes to determine proliferation and retainment of specific functions representing prominent features of hepatocytes in vivo. Whereas no cells adhered to the substratum effectively in conventional culture medium, the addition of conditioned medium derived from hepatic non-parenchymal cells improved attachment. Cells proliferated, retained hepatocyte-specific functions, such as urea production and cytochrome P450 activity, and expressed liver-specific genes to levels observed in non-cryopreserved hepatocytes. Thus, serum-free cryopreserved primary porcine hepatocytes may serve as a valid source of cells for downstream applications. The cells seem to function adequately when an appropriate environment is chosen for recovery after cryopreservation, an ultimate demand for the clinical application of human hepatocytes.     

Doxorubicin prodrug on the basis of tert-butyl cephalosporanate sulfones

Doxorubicin-cephalosporin prodrug adapted to the development of elastases for the liberation of parent drug was synthesized on the basis of cephalosporanate sulfone esters.     

Therapy-induced antibodies against the antiviral and antiproliferative effects of interferons in patients with chronic hepatitis C virus infection

Sera from 86 patients with chronic hepatitis C virus (HCV) infection treated with recombinant interferons-alpha (rIFN-alpha) were screened for IFN-binding and antiviral effect-neutralizing antibodies. Out of the 61 patients treated with rIFN-alpha2b, 46% had binding and 28% had neutralizing antibodies. 44% of the 25 patients treated with rIFN-alpha2a developed binding antibodies and 24% had neutralizing antibodies. Contradictory data were observed concerning the appearance of anti-IFN antibodies and the outcome of IFN therapy. A significantly higher number of the patients with a sustained response to rIFN-alpha2b therapy formed antibodies than the number among the non-responder patients. At the same time, in the patients treated with rIFN-alpha2a, opposite data were found. The activity of the antibodies in some sera was studied against the antiproliferative effect of IFNs on Daudi cells by measuring the [3H]thymidine incorporation. The binding antibodies without neutralization of the antiviral effect of the IFNs inhibited the antiproliferative activity of the rIFNs, similarly to antibodies having both IFN-binding and antiviral effect-neutralizing capacities. At the same time, the antiproliferative effect of the natural IFN was less affected. It is suggested that the antiproliferative assay is more sensitive than the antiviral method for demonstration of the presence of antibodies exerting an inhibitory effect on the biological activities of IFN.     

Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome

Kindler syndrome is an autosomal recessive disorder characterized by neonatal blistering, sun sensitivity, atrophy, abnormal pigmentation, and fragility of the skin. Linkage and homozygosity analysis in an isolated Panamanian cohort and in additional inbred families mapped the gene to 20p12.3. Loss-of-function mutations were identified in the FLJ20116 gene (renamed “KIND1” [encoding kindlin-1]). Kindlin-1 is a human homolog of the Caenorhabditis elegans protein UNC-112, a membrane-associated structural/signaling protein that has been implicated in linking the actin cytoskeleton to the extracellular matrix (ECM). Thus, Kindler syndrome is, to our knowledge, the first skin fragility disorder caused by a defect in actin-ECM linkage, rather than keratin-ECM linkage.     

Diethyldithiocarbamate inhibits the catalytic activity of xanthine oxidase

We sought to determine the effects of the superoxide dismutase (SOD) inhibitor diethyldithiocarbamate (DETC) on vascular superoxide production. Rat aortic rings treated with DETC (10 mM) showed no change of superoxide generation (5 microM lucigenin). Likewise, DETC did not change the expression and activity of vascular soluble guanylyl cyclase, an enzyme known to be extremely sensitive to superoxide. In striking contrast, DETC completely inhibited the superoxide production induced by 6-anilino-5,8-quinolinedione (LY83583) and abolished the catalytic activity of xanthine oxidase (XO). Thus, DETC inhibits vascular superoxide production by blocking oxidoreductase enzymes such as XO and those reducing LY83583 in rat aorta.     

GRACILE syndrome,a lethal metabolic disorder with iron overload,is caused by a point mutation in BCS1L

GRACILE (growth retardation, aminoaciduria, cholestasis, iron overload, lactacidosis, and early death) syndrome is a recessively inherited lethal disease characterized by fetal growth retardation, lactic acidosis, aminoaciduria, cholestasis, and abnormalities in iron metabolism. We previously localized the causative gene to a 1.5-cM region on chromosome 2q33-37. In the present study, we report the molecular defect causing this metabolic disorder, by identifying a homozygous missense mutation that results in an S78G amino acid change in the BCS1L gene in Finnish patients with GRACILE syndrome, as well as five different mutations in three British infants. BCS1L, a mitochondrial inner-membrane protein, is a chaperone necessary for the assembly of mitochondrial respiratory chain complex III. Pulse-chase experiments performed in COS-1 cells indicated that the S78G amino acid change results in instability of the polypeptide, and yeast complementation studies revealed a functional defect in the mutated BCS1L protein. Four different mutations in the BCS1L gene have been reported elsewhere, in Turkish patients with a distinctly different phenotype. Interestingly, the British and Turkish patients had complex III deficiency, whereas in the Finnish patients with GRACILE syndrome complex III activity was within the normal range, implying that BCS1L has another cellular function that is uncharacterized but essential and is putatively involved in iron metabolism.     

The molecular diagnostics of viruses

For many years data of cancer research indicated that viruses can cause cancer. Virus infections induce cancer by different mechanisms. To predict the significance of a viral DNA fragment in human cells we have to be aware of the changes the particular virus is able to induce there.However, no matter which mechanisms of viral carcinogenesis are utilized, generally other factors (environmental, chemical, immunodeficiency, etc.) are also needed to induce invasive cancer in human. Before the introduction of nucleic acid based detection technique virus identification was a long and cumbersome process. This has been eliminated by the invention of recombinant gene technology and polymerase chain reaction. Virus nucleic acid can be detected without amplification using Southern, Northern and in situ hybridization. Techniques for target (polymerase chain reaction)or signal (hybrid capture, tyramine) amplification improved the sensitivity of detection. In the meantime, for the successful use of the arsenal of new methods we have to consider the characteristic feature of molecular virus research. A major achievement of molecular virus detection is that it proved the pathological significance of viruses in human cancers even in those where this was not expected. Hopefully these informations will increase the effort for elimination of oncogene virus infections.