Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs

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Teratogenic effects of parthenogenetic cells from LTXBO mice,a strain which develops ovarian teratomas at high frequency

Summary LTXBO mice develop ovarian teratomas at high frequency. The phenotype of tumour tissues is unusual in that most contain trophoblast elements. Since the tumours are derived from parthenogenetically activated oocytes, they would not be expected to produce trophoblast. The developmental potential of parthenogenetic cells from these mice was tested in aggregation chimeras. No contribution to trophoblast tissues was observed. However, a high incidence of morphological abnormalities was seen, suggesting that the parthenogenetic cells exerted a teratogenic effect.     

Signals for site-specific cleavage of HSV DNA: maturation involves two separate cleavage events at sites distal to the recognition sequences

Mature Herpes Simplex Virus (HSV) genomes are cleaved from concatemeric precursors by a site-specific mechanism. These cleavage events are probably coupled to the encapsidation process. Sequences within the terminal repeat of HSV DNA are necessary for the cleavage and packaging reactions, and are also thought to be responsible for high frequency genome isomerization events. Here we present evidence to show that two viral DNA cleavage and packaging signals reside within a 250 bp subfragment of the terminal repeat, that the termini of mature viral DNA are generated by a process involving two separate DNA cleavages at sites distal to the cleavage signals, and that the sequences between these two cleavage sites are duplicated by the DNA maturation system.     

Underestimating Calorie Content When Healthy Foods Are Present: An Averaging Effect or a Reference-Dependent Anchoring Effect?

Objective

Previous studies have shown that estimations of the calorie content of an unhealthy main meal food tend to be lower when the food is shown alongside a healthy item (e.g. fruit or vegetables) than when shown alone. This effect has been called the negative calorie illusion and has been attributed to averaging the unhealthy (vice) and healthy (virtue) foods leading to increased perceived healthiness and reduced calorie estimates. The current study aimed to replicate and extend these findings to test the hypothesized mediating effect of ratings of healthiness of foods on calorie estimates.

Methods

In three online studies, participants were invited to make calorie estimates of combinations of foods. Healthiness ratings of the food were also assessed.

Results

The first two studies failed to replicate the negative calorie illusion. In a final study, the use of a reference food, closely following a procedure from a previously published study, did elicit a negative calorie illusion. No evidence was found for a mediating role of healthiness estimates.

Conclusion

The negative calorie illusion appears to be a function of the contrast between a food being judged and a reference, supporting the hypothesis that the negative calorie illusion arises from the use of a reference-dependent anchoring and adjustment heuristic and not from an ‘averaging’ effect, as initially proposed. This finding is consistent with existing data on sequential calorie estimates, and highlights a significant impact of the order in which foods are viewed on how foods are evaluated.     

Isolation, Characterization and Antifungal Activity of Proteinase Inhibitors from Capsicum chinense Jacq. Seeds

Capsicum species belong to the Solanaceae family and have great social, economic and agronomical significance. The present research presents data on the isolation and characterization of Capsicum chinense Jacq. peptides which were scrutinized in relation to their toxicity towards a diverse set of yeast species. The protein extract was separated with C18 reverse-phase chromatography in high performance liquid chromatography, resulting in three different peptide enriched fractions (PEFs) termed PEF1, PEF2 and PEF3. Tricine-SDS-PAGE of the PEF2 revealed peptides with molecular masses of approximately 5.0 and 8.5 kDa. These PEFs also exhibited strong antifungal activity against different yeasts. In the presence of the PEF2, Candida tropicalis exhibited morphological changes, including cellular agglomeration and formation of pseudohyphae. Determined N-terminal sequences of PEF2 and PEF3 were proven to be highly homologous to serine proteinase inhibitors, when analysed by comparative database sequence tools. For this reason were performed protease inhibitory activity assay. The PEFs displayed high inhibitory activity against trypsin and low inhibitory activity against chymotrypsin. PEF2 and PEF3 were considerably unsusceptible to a broad interval of pH and temperatures. Due to the myriad of application of Proteinase inhibitors (PIs) in fields ranging from plant protection against pathogens and pests to medicine such as in cancer and virus replication inhibition, the discovery of new PIs with new properties are of great interest.     

The Epidemiology of HIV and HSV-2 Infections among Women Participating in Microbicide and Vaccine Feasibility Studies in Northern Tanzania

Objectives

To prepare for future HIV prevention trials, we conducted prospective cohort studies among women working in food and recreational facilities in northern Tanzania. We examined the prevalence and incidence of HIV and HSV-2, and associated risk factors.

Methods

Women aged 18–44 years working in food and recreational facilities were screened to determine their eligibility for the studies. Between 2008–2010, HIV-negative women were enrolled and followed for 12 months. At enrolment and 3-monthly, we collected socio-demographic and behavioural data, and performed clinical examinations for collection of biological specimens that were tested for reproductive tract infections. Risk factors for HIV and HSV-2 incidence were investigated using Poisson regression models.

Results

We screened 2,229 and enrolled 1,378 women. The median age was 27 years (interquartile range, IQR 22, 33), and median duration working at current facility was 2 years. The prevalences of HIV at screening and HSV-2 at enrolment were 16% and 67%, respectively. Attendance at the 12-month visit was 86%. HIV and HSV-2 incidence rates were 3.7 (95% confidence interval, CI: 2.8,5.1) and 28.6 (95% CI: 23.5,35.0)/100 person-years, respectively. Women who were separated, divorced, or widowed were at increased risk of HIV (adjusted incidence rate ratio, aRR = 6.63; 95% CI: 1.97,22.2) and HSV-2 (aRR = 2.00; 95% CI: 1.15,3.47) compared with married women. Women reporting ≥3 partners in the past 3 months were at higher HIV risk compared with women with 0–1 partner (aRR = 4.75; 95% CI: 2.10,10.8), while those who had reached secondary education or above were at lower risk of HSV-2 compared with women with incomplete primary education (aRR = 0.42; 95% CI: 0.22,0.82).

Conclusions

HIV and HSV-2 rates remain substantially higher in this cohort than in the general population, indicating urgent need for effective interventions. These studies demonstrate the feasibility of conducting trials to test new interventions in this highly-mobile population.     

Increased recombination frequency showing evidence of loss of interference is associated with abnormal testicular histopathology

Nondisjunction leading to aneuploid gametes has been linked genetically to both increases and decreases in recombination frequency on the aneuploid chromosome. In the present study, we present physical evidence of increased frequency of recombination nodules as measured by Mut-S-like homologue-1 (MLH1) foci on pachytene chromosomes from sterile male mice homozygous for a mutation in the protein phosphatase 1cgamma (PP1cgamma) gene. The pattern of elevated recombination frequency in PP1cgamma mutant spermatocytes is consistent with a loss of interference. Previous studies demonstrated: (1) spermiogenesis is impaired starting at step 8 with a severe reduction in elongating and condensed spermatids; (2) spermatids and sperm exhibit elevated rates of DNA fragmentation; and (3) haploid gametes exhibit elevated levels of aneuploidy. Morphometric analysis of developing testes revealed that the first wave of meiosis proceeds at a normal rate in mutant testes, a surprising result given that the PP1 inhibitor okadaic acid has been shown to accelerate progression of spermatocytes from pachytene to the first meiotic division (MI). Evidence of abnormal testicular histopathology is apparent at 3 weeks, before the appearance of haploid gametes, eliminating the possibility that the mutant phenotype is caused by the presence of abnormal spermatids, but coincident with the appearance of the first set of mid to late pachytene spermatocytes. These observations lead us to conclude that the PP1cgamma mutation causes a complex phenotype, including subtle adverse effects on meiosis, possibly mediated by defective signaling between germ cells and Sertoli cells.     

The novel retinoid AHPN/CD437 induces a rapid but incomplete apoptotic response in human myeloma cells

The synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN/CD437) appears to possess an apoptotic activity superior to classical retinoids in vitro as in vivo. Numerous studies have shown that CD437-induced apoptosis is independent of its nuclear receptor activity, suggesting that CD437 might have a unique mechanism of action. The purpose of this study was to compare CD437- and all-trans retinoic acid (atRA)-induced cell death. CD437 provoked a rapid apoptotic phenotype immediately followed by secondary necrosis in RPMI 8226, U266 and L363 human myeloma cell lines. Nuclear apoptotic features were observed upon both CD437 and atRA treatments. In contrast, membrane blebbing and the subsequent formation of apoptotic bodies, a classical apoptotic event, was only observed upon atRA treatment. In addition, CD437, contrary to atRA, was unable to induce tissue transglutaminase (tTG), an intracellular enzyme involved in the formation of cross-linked protein polymers contributing to apoptotic morphological changes. Taken together, these data suggest that CD437 induces rapid but incomplete apoptotic phenotype in human myeloma cells.