Degradation of the Disease-Associated Prion Protein by a Serine Protease from Lichens

The disease-associated prion protein (PrPTSE), the probable etiological agent of the transmissible spongiform encephalopathies (TSEs), is resistant to degradation and can persist in the environment. Lichens, mutualistic symbioses containing fungi, algae, bacteria and occasionally cyanobacteria, are ubiquitous in the environment and have evolved unique biological activities allowing their survival in challenging ecological niches. We investigated PrPTSE inactivation by lichens and found acetone extracts of three lichen species (Parmelia sulcata, Cladonia rangiferina and Lobaria pulmonaria) have the ability to degrade prion protein (PrP) from TSE-infected hamsters, mice and deer. Immunoblots measuring PrP levels and protein misfolding cyclic amplification indicated at least two logs of reductions in PrPTSE. Degradative activity was not found in closely related lichen species or in algae or a cyanobacterium that inhabit lichens. Degradation was blocked by Pefabloc SC, a serine protease inhibitor, but not inhibitors of other proteases or enzymes. Additionally, we found that PrP levels in PrPTSE-enriched preps or infected brain homogenates are also reduced following exposure to freshly-collected P. sulcata or an aqueous extract of the lichen. Our findings indicate that these lichen extracts efficiently degrade PrPTSE and suggest that some lichens could have potential to inactivate TSE infectivity on the landscape or be a source for agents to degrade prions. Further work to clone and characterize the protease, assess its effect on TSE infectivity and determine which organism or organisms present in lichens produce or influence the protease activity is warranted

A study of patent thickets

Report analysing whether entry of UK enterprises into patenting in a technology area is affected by patent thickets in the technology area

emm typing and validation of provisional M types for group A streptococci.

This report discusses the following issues related to typing of group A streptococci (GAS): The development and use of the 5' emm variable region sequencing (emm typing) in relation to the existing serologic typing system; the designation of emm types in relation to M types; a system for validation of new emm types; criteria for validation of provisional M types to new M-types; a list of reference type cultures for each of the M-type or emm-type strains of GAS; the results of the first culture exchange program for a quality control testing system among the national and World Health Organization collaborating centers for streptococci; and dissemination of new approaches to typing of GAS to the international streptococcal community

The L&E of Intellectual Property – Do we get maximum innovation with the current regime?

Innovation is crucial to economic growth – the essential path for lifting much of the world population out of dire poverty and for maintaining the living standard of those who already have. To stimulate innovation, the legal system has to support the means through which innovators seek to get rewarded for their efforts. Amongst these means, some, such as the first mover advantage or 'lead time,' are not directly legal; but secrets and intellectual property rights are legal institutions supported for the specific purpose of stimulating innovation. Whilst the protection of secrets has not changed very much over recent years, intellectual property (or IP) has. IP borrows some features from ordinary property rights, but is also distinct, in that, unlike physical goods, information, the object of IP, is not inherently scarce; indeed as information and communication technologies expand, the creation and distribution of information is becoming ever cheaper and in many circumstances abundant, so that selection is of the essence ('on the internet, point of view is everything'). Where rights on information extend too far, their monopolising effect may hamper innovation. The paper investigates the underlying structure of IP rights and surveys what we know empirically about the incentive effects of IP as about industries that flourish without formal IP

Population Genetics of Streptococcus dysgalactiae Subspecies equisimilis Reveals Widely Dispersed Clones and Extensive Recombination

Streptococcus dysgalactiae subspecies equisimilis (SDSE) is an emerging global pathogen that can colonize and infect humans. Although most SDSE isolates possess the Lancefield group G carbohydrate, a significant minority have the group C carbohydrate. Isolates are further sub-typed on the basis of differences within the emm gene. To gain a better understanding of their molecular epidemiology and evolutionary relationships, multilocus sequence typing (MLST) analysis was performed on SDSE isolates collected from Australia, Europe and North America.The 178 SDSE isolates, representing 37 emm types, segregate into 80 distinct sequence types (STs) that form 17 clonal complexes (CCs). Eight STs recovered from all three continents account for >50% of the isolates. Thus, a small number of STs are highly prevalent and have a wide geographic distribution. Both ST and CC strongly correlate with group carbohydrate. In contrast, eleven STs were associated with >1 emm type, suggestive of recombinational replacements involving the emm gene; furthermore, 35% of the emm types are associated with genetically distant STs. Data also reveal a history of extensive inter- and intra-species recombination involving the housekeeping genes used for MLST. Sequence analysis of single locus variants identified through goeBURST indicates that genetic change mediated by recombination occurred approximately 4.4 times more frequently than by point mutation.A few genetic lineages with an intercontinental distribution dominate among SDSE causing infections in humans. The distinction between group C and G isolates reflects recent evolution, and no long-term genetic isolation between them was found. Lateral gene transfer and recombination involving housekeeping genes and the emm gene are important mechanisms driving genetic variability in the SDSE population

Intellectual property management and technological entrepreneurship

This paper investigates the distinctive technology protection strategies of entrepreneurial technology firms. In contrast with much popular opinion, it is reported that intellectual property features more prominently in the business of small entrepreneurial firms than it does in the business of large, established mature firms. The intellectual property portfolios of technology firms of all sizes and ages exhibit a rich array of instruments in addition to patents for protecting technology, including trade secrets, trademarks and copyright, together with licenses to externally sourced technology. The intellectual property profiles of technology firms appear to be influenced by their context, organizational profiles and corporate goals and by the character of their technology

Health-related quality of life in patients with β-thalassemia: Data from the phase 3 BELIEVE trial of luspatercept

BACKGROUND: Patients with transfusion-dependent (TD) β-thalassemia require long-term red blood cell transfusions (RBCTs) that lead to iron overload, impacting health-related quality of life (HRQoL). METHODS: The impact of luspatercept, a first-in-class erythroid maturation agent, versus placebo on HRQoL of patients with TD β-thalassemia was evaluated in the phase 3 BELIEVE trial. HRQoL was assessed at baseline and every 12 weeks using the 36-item Short Form Health Survey (SF-36) and Transfusion-dependent Quality of Life questionnaire (TranQol). Mean change in HRQoL was evaluated from baseline to week 48 for patients receiving luspatercept + best supportive care (BSC) and placebo + BSC and between luspatercept responders and non-responders. RESULTS: Through week 48, for both groups, mean scores on SF-36 and TranQol domains were stable over time and did not have a clinically meaningful change. At week 48, more patients who achieved clinical response (≥50% reduction in RBCT burden over 24 weeks) in the luspatercept + BSC group had improvement in SF-36 Physical Function compared with placebo + BSC (27.1% vs. 11.5%; p = .019). CONCLUSIONS: Luspatercept + BSC reduced transfusion burden while maintaining patients' HRQoL. HRQoL domain improvements from baseline through 48 weeks were also enhanced for luspatercept responders

Transmission of Chronic Wasting Disease Identifies a Prion Strain Causing Cachexia and Heart Infection in Hamsters

Chronic wasting disease (CWD) is an emerging prion disease of free-ranging and captive cervids in North America. In this study we established a rodent model for CWD in Syrian golden hamsters that resemble key features of the disease in cervids including cachexia and infection of cardiac muscle. Following one to three serial passages of CWD from white-tailed deer into transgenic mice expressing the hamster prion protein gene, CWD was subsequently passaged into Syrian golden hamsters. In one passage line there were preclinical changes in locomotor activity and a loss of body mass prior to onset of subtle neurological symptoms around 340 days. The clinical symptoms included a prominent wasting disease, similar to cachexia, with a prolonged duration. Other features of CWD in hamsters that were similar to cervid CWD included the brain distribution of the disease-specific isoform of the prion protein, PrPSc, prion infection of the central and peripheral neuroendocrine system, and PrPSc deposition in cardiac muscle. There was also prominent PrPSc deposition in the nasal mucosa on the edge of the olfactory sensory epithelium with the lumen of the nasal airway that could have implications for CWD shedding into nasal secretions and disease transmission. Since the mechanism of wasting disease in prion diseases is unknown this hamster CWD model could provide a means to investigate the physiological basis of cachexia, which we propose is due to a prion-induced endocrinopathy. This prion disease phenotype has not been described in hamsters and we designate it as the ‘wasting’ or WST strain of hamster CWD