Occurrence of enterotoxic Staphylococcus aureus in raw milk from yaks and cattle in Mongolia.

Staphylococcal food poisoning is considered one of the leading foodborne illnesses in humans worldwide and is associated with contaminated foods of animal origin, such as milk and dairy products. In this study, we investigated the occurrence of staphylococci and the enterotoxigenic properties of Staphylococcus aureus isolated from raw milk from yaks (Bos mutus) and cattle in Mongolia. Staphylococci were isolated from 72 (74%) of the 97 raw milk samples. Of the samples containing staphylococci, 69% (50 of 72) were from yaks and 30.5% (22 of 72) were from cattle. S. aureus was detected in 10% of yak (7 of 72) and 21% of cattle (15 of 72) milk samples. Staphylococcal enterotoxin C was detected in 23% (5 of 22) of the S. aureus strains investigated, based on the reverse passive latex agglutination technique. Three of the five enterotoxigenic strains were from yaks and two were from cattle. None of the S. aureus strains tested produced staphylococcal enterotoxins A, B, or D. To our knowledge, this is the first report of the occurrence of staphylococci and enterotoxigenic S. aureus in milk from yaks and cattle in Mongolia

Recent advances in understanding Cushing disease: resistance to glucocorticoid negative feedback and somatic USP8 mutations

Cushing’s disease is a rare disease with a characteristic phenotype due to significant hypercortisolism driven by over-secretion of adrenocorticotropic hormone and to high morbidity and mortality if untreated. It is caused by a corticotroph adenoma of the pituitary, but the exact mechanisms leading to tumorigenesis are not clear. Recent advances in molecular biology such as the discovery of somatic mutations of the ubiquitin-specific peptidase 8 (USP8) gene allow new insights into the pathogenesis, which could be translated into exciting and much-needed therapeutic applications

Molecular detection of Cyclospora in water, soil, vegetables and humans in southern Italy signals a need for improved monitoring by health authorities

To date, in Europe, there is scant information on the occurrence of Cyclospora in water from treatment plants and in humans, and no data are available on soil or fresh plant products. Here, we undertook the first molecular survey of Cyclospora in multiple biological matrices collected from the Apulia region of southern Italy. Samples of irrigation water from four municipal treatment plants, eight different types of vegetables or fruit (cucumber, lettuce, fennel, celery, tomato, melon, endive and chicory) and soil from the same farms on which these plants were grown, as well as faecal samples from humans living in the same region were tested by qPCR-coupled single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. Cyclospora was detected in 15.5% of all 213 samples tested. Specifically, this protist was detected in (i) treated water (21.3% of 94 samples), well water (6.2% of 16), but not drinking water (0% of 3); (ii) soil (11.8% of 51 samples) and vegetables (12.2% of 49),with the highest prevalence (18.7%) on fennel; and (iii) human stools (27.5% of 40 samples). In environmental and food samples, Cyclosporawas detectedmainly in autumn and was significantly more prevalent in the faeces from humans of 40–50 years of age. This is the first comprehensive molecular survey of Cyclospora in environmental, food and human faecal samples in Europe. These data suggest that irrigation water, soil and vegetables might be contaminated by Cyclospora cayetanensis, which might represent a source of infection to humans in the study area and calls for monitoring by health authorities

Toxoplasma gondii lineages circulating in slaughtered industrial pigs and potential risk for consumers

Toxoplasma gondii is a cosmopolitan zoonotic protozoan parasite, and the consumption of raw or undercooked pig meat is one of the most important sources of T. gondii infection. Three predominant lineages, types I, II, and III, are widespread in Europe. Although still poorly understood, a relationship between each type and the severity of illness represents a public health issue. To gain further knowledge of the genotypes in circulation and of the potential risk for consumers, one heart sample and one diaphragm sample (206 total) were taken from each of 103 pig carcasses at an abattoir in Italy. Then, we used 529-bp repetitive element PCR and a B1 real-time PCR high-resolution melting assay coupled with sequencing to detect and genotype T. gondii isolates. T. gondii DNA was detected in 14 pigs (13.6%, 95% confidence interval ¼ 7 to 20.2%), and types I (3.9%), II (5.8%), and III (3.9%) were identified. We found that heart tissue had a significantly higher PCR positivity rate for T. gondii than did diaphragm tissue. This is Europe’s largest study on genotyping of T. gondii from pigs, and it demonstrates that all three main lineages are present in carcasses of industrially reared pigs in Italy. There is a potential risk to consumers of infection with any or all of the three lineages, and the related clinical consequences should be taken into account. This study suggests that monitoring of T. gondii types in meat is essential, especially in meat that is traditionally eaten raw or that is minimally processed

Protein/DNA interactions in complex DNA topologies: expect the unexpected

DNA supercoiling results in compacted DNA structures that can bring distal sites into close proximity. It also changes the local structure of the DNA, which can in turn influence the way it is recognised by drugs, other nucleic acids and proteins. Here, we discuss how DNA supercoiling and the formation of complex DNA topologies can affect the thermodynamics of DNA recognition. We then speculate on the implications for transcriptional control and the three-dimensional organisation of the genetic material, using examples from our own simulations and from the literature. We introduce and discuss the concept of coupling between the multiple length-scales associated with hierarchical nuclear structural organisation through DNA supercoiling and topology

Verocytotoxin-Producing Escherichia coli O26 in raw water buffalo (Bubalus bubalis) milk products in Italy

Escherichia coli 026 is known as a verocytotoxin-producing E. coli (VTEC) organism that causes severe foodborne diseases such as hemorrhagic colitis and hemolytic uremic syndrome. Although cattle are the most important reservoir of VTEC, only a few reports on the role of water buffalo (Bubalus bubalis) as a reservoir of VTEC and on the presence of these organisms in their milk are available. However, in Southern Italy, where water buffalo are intensively reared, an outbreak of hemolytic uremic syndrome due to E. coli 026 has recently been reported, in which the consumption of typical dairy products was considered to be a common risk factor. The aims of this work were to assess the prevalence of E. coli 026 in raw water buffalo milk, to characterize the virulence gene profiles of the isolates, and to evaluate their phenotypic antimicrobial resistance pattern. Of 160 analyzed samples, 1 (0.6%) tested positive for E. coli 026, and the isolate showed the stx1+ lstx2+leae-lhlyA+ genotypic profile. The strain showed resistance against glycopeptides, macrolides, and penicillins. The presence of VTEC organisms in raw water buffalo milk could be considered to be a potential threat to consumers; however, the strict adherence to the processes used in the preparation of the most common buffalo dairy products could strongly mitigate the foodborne risk. To our knowledge, this article reports the first isolation and characterization of E. coli 026 VTEC in raw water buffalo milk. Copyright ©, International Association for Food Protectio

Targeting cancer metabolism: a therapeutic window opens

Genetic events in cancer activate signalling pathways that alter cell metabolism. Clinical evidence has linked cell metabolism with cancer outcomes. Together, these observations have raised interest in targeting metabolic enzymes for cancer therapy, but they have also raised concerns that these therapies would have unacceptable effects on normal cells. However, some of the first cancer therapies that were developed target the specific metabolic needs of cancer cells and remain effective agents in the clinic today. Research into how changes in cell metabolism promote tumour growth has accelerated in recent years. This has refocused efforts to target metabolic dependencies of cancer cells as a selective anticancer strategy.Burroughs Wellcome FundSmith Family FoundationStarr Cancer ConsortiumDamon Runyon Cancer Research FoundationNational Institutes of Health (U.S.

COVID-19 epidemic strongly affected cancer research in Italy: a survey of the Italian Cancer Society (SIC)

Background: Italy was among the first countries hit by the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The application of strict lockdown measures disproportionately affected both cancer patient care as well as basic and translational cancer research. Materials and methods: The Italian Cancer Society (SIC) conducted a survey on the effect of lockdown on laboratories involved in cancer research in Italy. The survey was completed by 570 researchers at different stages of their career, working in cancer centers, research institutes and universities from 19 Italian regions. Results: During the lockdown period, the impact of the COVID-19 pandemic emergency on face-to-face research activities was high, with a complete (47.7%) or partial (36.1%) shutdown of the laboratories. In the post-lockdown period, research activities were resumed in most of the respondents’ institutions (80.4%), though with some restrictions (77.2%). COVID-19 testing was offered to research personnel only in ~50% of research institutions. Overall, the response to the pandemic was fragmented as in many cases institutions adopted different strategies often aimed at limiting possible infections without a clearly defined contingency plan. Nevertheless, research was able to provide the first answers and possible ways out of the pandemic, also with the contribution of many cancer researchers that sacrificed their research programs to help overcome the pandemic by offering their knowledge and technologies. Conclusions: Given the current persistence of an emergency situation in many European countries, a more adequate organization of research centers will be urgent and necessary to ensure the continuity of laboratory activities in a safe environment

Synergistic effects of various Her inhibitors in combination with IGF-1R, C-MET and Src targeting agents in breast cancer cell lines

Introduction: Overexpression of the receptor tyrosine kinase HER2 has been reported in around 25% of human breast cancers, usually indicating a poor prognosis. As a result, HER2 has become a popular target for therapy. However, despite recent advances in HER2 targeted therapy, many patients still experience primary and secondary resistance to such treatments. It is therefore important to understand the underlying mechanism of resistance and to develop more effective therapeutic interventions for breast cancer. Methods: The sensitivity of a panel of seven breast cancer cell lines to treatment with various types HER-family inhibitors alone, or in combination with a selection of other tyrosine kinase inhibitors (TKIs) or chemotherapeutic agents was determined using the Sulforhodamine B colorimetric assay. Receptor expression, cell-cycle distribution, cell signalling and cell migration were determined using flow cytometry, Western blot and Incucyte Zoom Live-Cell Analysis System respectively. Results: Overall, breast cancer cells were more sensitive to treatment with the irreversible pan-HER family inhibitors, particularly afatinib and neratinib, than treatment with the first-generation reversible inhibitors. Of three HER-2 overexpressing cell lines in this panel, SKBr3 and BT474 were highly sensitive to treatment with HER-family inhibitors (IC50s as low as 3 nM), while MDA-MB-453 was relatively resistant (lowest IC50 = 0.11 μM). When the HER-family inhibitors were combined with other agents such as NVP-AEW541 (an IGF-1R inhibitor), dasatinib (a Src inhibitor) or crizotinib (a c-Met/ALK inhibitor), such combination produced synergistic effects in some of the cell lines examined. Interestingly, co-targeting of Src and HER-family members in MDA-MB-453 cells led to synergistic growth inhibition, suggesting the importance of Src in mediating resistance to HER2-targeting agents. Finally, treatment with the irreversible HER family blockers and dasatinib were also most effective at inhibiting the migration of breast cancer cells. Conclusion: We concluded that the irreversible inhibitors of HER-family members are generally more effective at inhibiting growth, downstream signalling and migration compared with reversible inhibitors, and that combining HER-family inhibitors with other TKIs such as dasatinib may have therapeutic advantages in certain breast cancer subtypes and warrants further investigation