Treatment with solvent/detergent is a widely used method for ensuring the virus safety of plasma products. In the present study, virus inactivation by a novel solvent/detergent combination, i.e. TnBP (tri-n-butyl phosphate) and polysorbate 20 during the manufacture of the factor VIII/VWF concentrate Optivate has been investigated. The inactivation of most enveloped viruses was rapid, i.e. > 5 l...

Protein-A or Protein-L affinity chromatography and virus inactivation are key processes for the manufacturing of therapeutic antibodies and antibody fragments. These two processes often involve exposure of therapeutic proteins to denaturing low pH conditions. Antibodies have been shown to undergo conformational changes at low pH, which can lead to irreversible damages on the final product. Here...

Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as m...

The distal short arm of the human X chromosome is of interest because it contains genes which escape X chromosome inactivation and because it is subject to frequent deletions in human patients. The steroid sulfatase gene has been particularly well studied as an example of a gene which escapes X inactivation and which is included in a number of these deletion events. For these reasons a physical...

Mammals compensate for unequal X-linked gene dosages between the sexes by inactivating one X chromosome in the female. In marsupials and in the early mouse embryo, X chromosome inactivation (XCI) is imprinted to occur selectively on the paternal X chromosome (X(P)). The mechanisms and events underlying X(P) imprinting remain unclear. Here, we find that the imprinted X(P) can be functionally div...

Germ cells have the same DNA sequence as somatic cells, but the processes that act on their chromatin are different. Germline chromatin undergoes a series of dramatic remodeling events during the life cycle of an organism. Different aspects of germline chromatin have been dissected in recent years, such as differences between the sex chromosomes and autosomes in histone variants and modificatio...

Dosage compensation in mammals occurs by X inactivation, a silencing mechanism regulated in cis by the X inactivation center (Xic). In response to developmental cues, the Xic orchestrates events of X inactivation, including chromosome counting and choice, initiation, spread, and establishment of silencing. It remains unclear what elements make up the Xic. We previously showed that the Xic is co...

The pseudoautosomal region (PAR) is a unique and specialized segment on the mammalian sex chromosomes with known functions in male meiosis and fertility. Detailed molecular studies of the region in human and mouse show dramatic differences between the 2 PARs. Recent mapping efforts in horse, dog/cat, cattle/ruminants, pig and alpaca indicate that the PAR also varies in size and gene content bet...

A good deal of sex differences in kidney disease is attributable to sex differences in the function of genes on the X chromosome. Males are uniquely vulnerable to mutations in their single copy of X-linked genes, whereas females are often mosaic, having a mixture of cells expressing different sets of X-linked genes. This cellular mosaicism created by X inactivation in females is most often adva...

In female mammals, a single X chromosome is stably and heritably silenced early in embryogenesis. The inactive X is characterized by asynchronous DNA replication and epigenetic chromatin modifications, including DNA methylation, histone H3/H4 hypoacetylation, and incorporation of a variant histone macroH2A. X inactivation is initiated by a cis-acting RNA molecule, the X-inactive specific transc...