Screening donors for xenotransplantation: The potential for xenozoonoses

Xenotransplantation is a potential solution to the current donor shortage for solid organ transplantation. The transmission of infectious agents from donor organs or bone marrow to the recipient is a well-recognized phenomenon following allotransplantation. Thus the prospect of xenotransplantation raises the issue of xenozoonoses-i.e., the transmission of animal infections to the human host. Anticipating an increasing number of baboon to human transplants, 31 adult male baboons (Papio cynocephalus) from a single colony in the United States were screened for the presence of antibody to microbial agents (principally viral) that may pose a significant risk of infection. Antibody to simian cytomegalovirus, simian agent 8 and Epstein-Barr virus, was found in 97% of animals tested. Antibody to simian retroviruses and Toxoplasma gondii was found in 30% and 32% respectively. Discordant results were found when paired samples were examined by two primate laboratories. This was particularly noted when methodologies were based on cross-reaction with human viral antigens. These results highlight the need to develop specific antibody tests against the species used for xenotransplantation. © 1994 Williams & Wilkins

Detergent and sanitizer stresses decrease the thermal resistance of Enterobacter sakazakii in infant milk formula

Infant milk formula has been identified as a potential source of Enterobacter sakazakii. This bacterium can cause a severe form of neonatal meningitis and necrotizing entercolitis. This study determined the effect of acid, alkaline, chlorine and ethanol stresses on the thermal inactivation of E. sakazakii in infant milk formula. Stressed cells were mixed with reconstituted powdered infant milk formula (PIMF) at temperatures between 52 and 58°C for various time periods or mixed with PFMF prior to reconstitution with water at temperatures between 50 and 100°C. The D- and z-values of the cells were determined using linear regression analysis. Detergent and sanitizer stresses decreased the thermal resistance of E. sakazakii in powdered and reconstituted infant milk formula. The values for Z)- acid, alkaline, chlorine and ethanol stressed E. sakazakii at 52-58°C were 14.57-0.54, 12.07-0.37, 10.08-0.40 and 11.61-0.50 min, respectively. The values of alkaline, chlorine and ethanol stressed cells were significantly lower than those of unstressed cells. Only the z-value (4.4°C) of ethanol stressed E. sakazakii was significantly different than that of unstressed cells (4.12°C). Reconstitution at 60°C did not significantly reduce the number of pre-stressed E. sakazakii cells compared with unstressed control cells, whereas significant decreases were obtained at 70°C. Using water at 70°C during the preparation of reconstituted PIMF before feeding infants, may be a suitable and applicable means of reducing the risk of E. sakazakii in the formula. The results of this study may be of use to regulatory agencies, infant milk producers and infant caregivers to design heating processes to eliminate E. sakazakii that may be present in infant milk formula

Sperm Swimming Velocity Predicts Competitive Fertilization Success in the Green Swordtail Xiphophorus helleri

Sperm competition is expected to favour the evolution of traits that influence the performance of sperm when they compete to fertilize a female's eggs. While there is considerable evidence that selection favours increases in sperm numbers, much less is known about how sperm quality contributes towards competitive fertilization success. Here, we determine whether variation in sperm quality influences competitive fertilization success in the green swordtail Xiphophorus helleri, a highly promiscuous livebearing fish. We use artificial insemination as a method of controlled sperm delivery and show that sperm swimming velocity is the primary determinant of fertilization success when ejaculates from two males compete to fertilize a female's eggs. By contrast, we found no evidence that sperm length had any effect on siring success. We also found no evidence that pre- and postcopulatory sexual traits were phenotypically integrated in this species, suggesting that the previous observation that reproductive skew favours males with high mating rates is unlikely to be due to any direct association between sperm quality and male sexual ornamentation

Ejaculate Economics: Testing the Effects of Male Sexual History on the Trade-Off between Sperm and Immune Function in Australian Crickets

Trade-offs between investment into male sexual traits and immune function provide the foundation for some of the most prominent models of sexual selection. Post-copulatory sexual selection on the male ejaculate is intense, and therefore trade-offs should occur between investment into the ejaculate and the immune system. Examples of such trade-offs exist, including that between sperm quality and immunity in the Australian cricket, Teleogryllus oceanicus. Here, we explore the dynamics of this trade-off, examining the effects that increased levels of sexual interaction have on the viability of a male's sperm across time, and the concomitant effects on immune function. Males were assigned to a treatment, whereby they cohabited with females that were sexually immature, sexually mature but incapable of copulation, or sexually mature and capable of copulation. Sperm viability of each male was then assessed at two time points: six and 13 days into the treatment, and immune function at day 13. Sperm viability decreased across the time points, but only for males exposed to treatment classes involving sexually mature females. This decrease was similar in magnitude across both sexually mature classes, indicating that costs to the expression of high sperm viability are incurred largely through levels of pre-copulatory investment. Males exposed to immature females produced sperm of low viability at both time points. Although we confirmed a weak negative association between sperm viability and lytic activity (a measure of immune response to bacterial infection) at day 13, this relationship was not altered across the mating treatment. Our results highlight that sperm viability is a labile trait, costly to produce, and subject to strategic allocation in these crickets

Design of low-cost ionic liquids for lignocellulosic biomass pretreatment

The cost of ionic liquids (ILs) is one of the main impediments to IL utilization in the cellulosic biorefinery, especially in the pretreatment step. In this study, a number of ionic liquids were synthesized with the goal of optimizing solvent cost and stability whilst demonstrating promising processing potential. To achieve this, inexpensive feedstocks such as sulfuric acid and simple amines were combined into a range of protic ionic liquids containing the hydrogen sulfate [HSO] anion. The performance of these ionic liquids was compared to a benchmark system containing the IL 1-ethyl-3-methylimidazolium acetate [CCim][OAc]. The highest saccharification yields were observed for the triethylammonium hydrogen sulfate IL, which was 75% as effective as the benchmark system. Techno-economic modeling revealed that this promising and yet to be optimized yield was achieved at a fraction of the processing cost. This study demonstrates that some ILs can compete with the cheapest pretreatment chemicals, such as ammonia, in terms of effectiveness and process cost, removing IL cost as a barrier to the economic viability of IL-based biorefineries

Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage

© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes

Menstrual cycle phase does not predict political conservatism

Recent authors have reported a relationship between women's fertility status, as indexed by menstrual cycle phase, and conservatism in moral, social and political values. We conducted a survey to test for the existence of a relationship between menstrual cycle day and conservatism. 2213 women reporting regular menstrual cycles provided data about their political views. Of these women, 2208 provided information about their cycle date, 1260 provided additional evidence of reliability in self-reported cycle date, and of these, 750 also indicated an absence of hormonal disruptors such as recent hormonal contraception use, breastfeeding or pregnancy. Cycle day was used to estimate day-specific fertility rate (probability of conception); political conservatism was measured via direct self-report and via responses to the "Moral Foundations” questionnaire. We also recorded relationship status, which has been reported to interact with menstrual cycle phase in determining political preferences. We found no evidence of a relationship between estimated cyclical fertility changes and conservatism, and no evidence of an interaction between relationship status and cyclical fertility in determining political attitudes. Our findings were robust to multiple inclusion/exclusion criteria and to different methods of estimating fertility and measuring conservatism. In summary, the relationship between cycle-linked reproductive parameters and conservatism may be weaker or less reliable than previously thought

Oncological considerations of skin-sparing mastectomy

AIM: To review evidence concerning the oncological safety of performing skin-sparing mastectomy (SSM) for invasive breast cancer and ductal carcinoma in situ (DCIS). Furthermore, the evidence concerning RT in relation to SSM and the possibility of nipple preservation was considered. METHODS: Literature review facilitated by Medline and PubMed databases. FINDINGS: Despite the lack of randomised controlled trials, SSM has become an accepted procedure in women undergoing mastectomy and immediate reconstruction for early breast cancer. Compared to non-skin-sparing mastectomy (NSSM), SSM seems to be oncologically safe in patients undergoing mastectomy for invasive tumours smaller than 5 cm, multicentric tumours, DCIS or risk-reduction. However, the technique should be avoided in patients with inflammatory breast cancer or in those with extensive tumour involvement of the skin in view of the high risk of local recurrence. SSM with nipple areola complex (NAC) preservation appears to be oncologically safe, provided the tumour is not close to the nipple and a frozen section protocol for the retro-areolar tissue is followed. Although radiotherapy (RT) does not represent a contraindication to SSM, the latter should be used with caution if postoperative RT is likely, since it detracts from the final cosmetic outcome

Subverting Decryption in AEAD

This work introduces a new class of Algorithm Substitution Attack (ASA) on Symmetric Encryption Schemes. ASAs were introduced by Bellare, Paterson and Rogaway in light of revelations concerning mass surveillance. An ASA replaces an encryption scheme with a subverted version that aims to reveal information to an adversary engaged in mass surveillance, while remaining undetected by users. Previous work posited that a particular class of AEAD scheme (satisfying certain correctness and uniqueness properties) is resilient against subversion. Many if not all real-world constructions – such as GCM, CCM and OCB – are members of this class. Our results stand in opposition to those prior results. We present a potent ASA that generically applies to any AEAD scheme, is undetectable in all previous frameworks and which achieves successful exfiltration of user keys. We give even more efficient non-generic attacks against a selection of AEAD implementations that are most used in practice. In contrast to prior work, our new class of attack targets the decryption algorithm rather than encryption. We argue that this attack represents an attractive opportunity for a mass surveillance adversary. Our work serves to refine the ASA model and contributes to a series of papers that raises awareness and understanding about what is possible with ASAs