Influence of addition of plasmin or mastitic milk to cheesemilk on quality of smear-ripened cheese

peer-reviewedSmear-ripened cheese varieties are characterised by the growth of a smear culture, containing predominantly Brevibacterium linens, on the cheese surface during ripening. In such cheese, considerable zonal differences in biochemistry of ripening exist, due to moisture loss from, and growth and metabolic activity of smear microflora at, the cheese surface. In this study, the effects of adding exogenous plasmin or small amounts of mastitic milk to good quality milk on the quality of smear-ripened cheese made subsequently was examined. Addition of plasmin did not influence cheese composition immediately after manufacture, but slightly decreased the rate of moisture loss during cheese ripening. Plasmin activity decreased during the early stages of ripening, but subsequently increased towards the end of ripening, perhaps due to changing pH conditions in the cheese. Addition of plasmin increased rates of primary proteolysis in cheese, as measured by levels of pH 4.6- soluble N and urea-PAGE, although production of later products of proteolysis appeared less affected. Addition ofmastitic milk had largely similar effects to addition of exogenous plasmin, which may reflect a high content of plasmin or plasminogen activators in such milk. Overall, changes in milk quality and enzymology appear to influence the quality of smear-ripened cheese

In vivo emergence of HIV-1 highly sensitive to neutralizing antibodies.

BACKGROUND: The rapid and continual viral escape from neutralizing antibodies is well documented in HIV-1 infection. Here we report in vivo emergence of viruses with heightened sensitivity to neutralizing antibodies, sometimes paralleling the development of neutralization escape. METHODOLOGY/PRINCIPAL FINDINGS: Sequential viral envs were amplified from seven HIV-1 infected men monitored from seroconversion up to 5 years after infection. Env-recombinant infectious molecular clones were generated and tested for coreceptor use, macrophage tropism and neutralization sensitivity to homologous and heterologous serum, soluble CD4 and monoclonal antibodies IgG1b12, 2G12 and 17b. We found that HIV-1 evolves sensitivity to contemporaneous neutralizing antibodies during infection. Neutralization sensitive viruses grow out even when potent autologous neutralizing antibodies are present in patient serum. Increased sensitivity to neutralization was associated with susceptibility of the CD4 binding site or epitopes induced after CD4 binding, and mediated by complex envelope determinants including V3 and V4 residues. The development of neutralization sensitive viruses occurred without clinical progression, coreceptor switch or change in tropism for primary macrophages. CONCLUSIONS: We propose that an interplay of selective forces for greater virus replication efficiency without the need to resist neutralizing antibodies in a compartment protected from immune surveillance may explain the temporal course described here for the in vivo emergence of HIV-1 isolates with high sensitivity to neutralizing antibodies

Improved simulation of Australian climate and ENSO-related rainfall variability in a global climate model with an interactive aerosol treatment

We assess the simulation of Australian mean climate and rainfall variability in a new version of the CSIRO coupled ocean-atmosphere global climate model (GCM). The new version, called Mark 3.6 (Mk3.6), differs from its recent predecessors (Mk3.0 and Mk3.5) by inclusion of an interactive aerosol scheme, which treats sulfate, dust, sea salt and carbonaceous aerosol. Other changes include an updated radiation scheme and a modified boundary-layer treatment. Comparison of the mean summer and winter climate simulations in Mk3.6 with those in Mk3.0 and Mk3.5 shows several improvements in the new version, especially regarding winter rainfall and sea-level pressure. The improved simulation of Australian mean seasonal climate is confirmed by calculation of a non-dimensional skill score (the 'M-statistic'), using data from all four seasons. However, the most dramatic improvement occurs in the model's simulation of the leading modes of annual rainfall variability, which we assess using empirical orthogonal teleconnections (EOTs). Compared to its predecessors and several international GCMs, Mk3.6 is best able to capture the spatial pattern of the leading rainfall mode, which represents variability due to the El Nino Southern Oscillation (ENSO). Mk3.6 is also best able to capture the spatial pattern of the second rainfall mode, which corresponds to increased rainfall in the northwest, and decreased rainfall over eastern Australia. We propose a possible mechanism for the improved simulation of rainfall variability in terms of the role of interactive dust in Mk3.6. By further suppressing convection over eastern Australia during El Nino events, dust feedbacks may enhance rainfall variability there, in tune with the model's ENSO cycle. This suggests that an interactive aerosol treatment may be important in a GCM used for the study of Australian climate change and variability. Mechanistic sensitivity studies are needed to further evaluate this hypothesis

Implementing subtype-specific pre-clinical models of breast cancer to study pre-treatment aspirin effects

Backgorund: Prior data suggest pre-diagnostic aspirin use impacts breast tumour biology and patient outcome. Here, we employed faithful surgical resection models of HER2+ and triple-negative breast cancer (TNBC), to study outcome and response mechanisms across breast cancer subtypes. Method: NOD/SCID mice were implanted with HER2+ MDA-MB-231/LN/2-4/ H2N, trastuzumab-resistant HER2+ HCC1954 or a TNBC patient-derived xenograft (PDX). A daily low-dose aspirin regimen commenced until primary tumours reached ~250 mm3 and subsequently resected. MDA-MB-31/LN/2-4/H2N mice were monitored for metastasis utilising imaging. To interrogate the survival benefit of pre-treatment aspirin, 3weeks post-resection, HCC1954/TNBC animals received standard-of-care (SOC) chemotherapy for 6 weeks. Primary tumour response to aspirin was interrogated using immunohistochemistry. Results: Aspirin delayed time to metastasis in MDA-MB-231/LN/2-4/H2N xeno- grafts and decreased growth of HER2+/TNBC primary tumours. Lymphangiogenic factors and lymph vessels number were decreased in HER2+ tumours. However, no survival benefit was seen in aspirin pre-treated animals (HCC1954/TNBC) that further received adjuvant SOC, compared with animals treated with SOC alone. In an effort to study mechanisms responsible for the observed reduction in lymphangiogenesis in HER2+ BC we utilised an in vitro co-culture system of HCC1954 tumour cells and mesenchymal stromal cells (MSC). Aspirin abrogated the secretion of VEGF-C in MSCs and also decreased the lymph/angiogenic potential of the MSCs and HCC1954 by tubule formation assay. Furthermore, aspirin decreased the secretion of uPA in HCC1954 cells potentially diminishing its metastatic capability. Conclusion: Our data employing clinically relevant models demonstrate that aspirin alters breast tumour biology. However, aspirin may not represent a robust chemo-preventative agent in the HER2+ or TNBC setting.ISSN:2045-763