Synthesis of melanin-like pigments by Sporothrix schenckii in vitro and during mammalian infection

Melanin has been implicated in the pathogenesis of several important human fungal pathogens. Existing data suggest that the conidia of the dimorphic fungal pathogen Sporothrix schenckii produce melanin or melanin-like compounds; in this study we aimed to confirm this suggestion and to demonstrate in vitro and in vivo production of melanin by yeast cells. S. schenckii grown on Mycosel agar produced visibly pigmented conidia, although yeast cells grown in brain heart infusion and minimal medium broth appeared to be nonpigmented macroscopically. However, treatment of both conidia and yeast cells with proteolytic enzymes, denaturant, and concentrated hot acid yielded dark particles similar in shape and size to the corresponding propagules, which were stable free radicals consistent with identification as melanins. Melanin particles extracted from S. schenckii yeast cells were used to produce a panel of murine monoclonal antibodies (MAbs) which labeled pigmented conidia, yeast cells, and the isolated particles. Tissue from hamster testicles infected with S. schenckii contained fungal cells that were labeled by melanin-binding MAbs, and digestion of infected hamster tissue yielded dark particles that were also reactive. Additionally, sera from humans with sporotrichosis contained antibodies that bound melanin particles. These findings indicate that S. schenckii conidia and yeast cells can produce melanin or melanin-like compounds in vitro and that yeast cells can synthesize pigment in vivo. Since melanin is an important virulence factor in other pathogenic fungi, this pigment may have a similar role in the pathogenesis of sporotrichosis.     

Differential gene expression in ovarian carcinoma: identification of potential biomarkers

Ovarian cancer remains the fifth leading cause of cancer death for women in the United States. In this study, the gene expression of 20 ovarian carcinomas, 17 ovarian carcinomas metastatic to the omentum, and 50 normal ovaries was determined by Gene Logic Inc. using Affymetrix GeneChip HU_95 arrays containing approximately 12,000 known genes. Differences in gene expression were quantified as fold changes in gene expression in ovarian carcinomas compared to normal ovaries and ovarian carcinoma metastases. Genes up-regulated in ovarian carcinoma tissue samples compared to more than 300 other normal and diseased tissue samples were identified. Seven genes were selected for further screening by immunohistochemistry to determine the presence and localization of the proteins. These seven genes were: the beta8 integrin subunit, bone morphogenetic protein-7, claudin-4, collagen type IX alpha2, cellular retinoic acid binding protein-1, forkhead box J1, and S100 calcium-binding protein A1. Statistical analyses showed that the beta8 integrin subunit, claudin-4, and S100A1 provided the best distinction between ovarian carcinoma and normal ovary tissues, and may serve as the best candidate tumor markers among the seven genes studied. These results suggest that further exploration into other up-regulated genes may identify novel diagnostic, therapeutic, and/or prognostic biomarkers in ovarian carcinoma.     

How to Right a Wrong: Empirically Evaluating Whether Victim,Offender, and Assault Characteristics can Inform Rape Kit Testing Policies

ABSTRACT

Hundreds of thousands of previously untested sexual assault kits (SAKs) have been uncovered in police property storage facilities across the United States, representing a national failure in institutional response to sexual assault. Faced with this discovery, jurisdictions must now decide if and how they should test these kits. Some stakeholders have suggested prioritizing kits for testing by victim, offender, or assault characteristics, based on the belief that these characteristics can predict the likely utility of DNA testing. However, little research has examined the empirical merits of such prioritization. To address this gap in the literature and inform SAK testing policies, we randomly sampled 900 previously untested SAKs from Detroit, MI. The sampled SAKs were submitted for DNA testing, and eligible DNA profiles were entered into Combined DNA Index System (CODIS), the federal DNA database. Police records associated with each SAK were coded for victim, offender, and assault characteristics, and logistic regression analyses were conducted to test whether these characteristics predict which SAKs yield DNA profiles that match (“hit”) to other criminal offenses in CODIS. Testing this sample of previously-untested SAKs produced a substantial number of CODIS hits, but few of the tested variables were significant predictors of CODIS hit rate. These findings suggest that testing all previously-unsubmitted kits may generate information that is useful to the criminal justice system, while also potentially addressing the institutional betrayal victims experienced when their kits were ignored.     

A contig of non-chimaeric YACs containing the spinal muscular atrophy gene in 5q13

We have constructed a contig of non-chimaeric yeast artificialchromosomes (YACs) across the candidate region for childhoodautosomal recessive spinal muscular atrophy (SMA) In 5q13. Anovel microsatellite reduces the candidate region to approximately400kb of DNA distal to D5S435. The candidate region containsblocks of chromosome 5 specific repeats which have copies on5p as well as elsewhere on 5q. Restriction mapping of the YACsreveals at least one CpG island In the SMA gene region. TheYAC maps indicate that the contig contains minimal rearrangementsor deletions. The data show the value of screening several YAClibraries simultaneously in order to construct a set of overlappingsequences suitable for candidate gene searches and direct genomicsequencing.     

The Frequency and Context of Snacking among Children: An Objective Analysis Using Wearable Cameras

Snacking is a common eating behaviour, but there is little objective data about children’s snacking. We aimed to determine the frequency and context of children’s snacking (n = 158; mean age = 12.6 years) by ethnicity, gender, socioeconomic deprivation and body mass index (BMI) children. Participants wore wearable cameras that passively captured images of their surroundings every seven seconds. Images (n = 739,162) were coded for snacking episodes, defined as eating occasions in between main meals. Contextual factors analysed included: snacking location, food source, timing, social contact and screen use. Rates of total, discretionary (not recommended for consumption) and healthful (recommended for consumption) snacking were calculated using negative binomial regression. On average, children consumed 8.2 (95%CI 7.4, 9.1) snacks per day, of which 5.2 (95%CI 4.6, 5.9) were discretionary foods/beverages. Children consumed more discretionary snacks than healthful snacks in each setting and at all times, including 15.0× more discretionary snacks in public spaces and 2.4× more discretionary snacks in schools. Most snacks (68.9%) were sourced from home. Girls consumed more total, discretionary and healthful snacks than boys, and Māori and Pacific consumed fewer healthful snacks than New Zealand (NZ) Europeans. Results show that children snack frequently, and that most snacking involves discretionary food items. Our findings suggest targeting home buying behaviour and environmental changes to support healthy snacking choices.     

Effects of Coronavirus Disease Pandemic on Tuberculosis Notifications,Malawi

The coronavirus disease (COVID-19) pandemic might affect tuberculosis (TB) diagnosis and patient care. We analyzed a citywide electronic TB register in Blantyre, Malawi and interviewed TB officers. Malawi did not have an official COVID-19 lockdown but closed schools and borders on March 23, 2020. In an interrupted time series analysis, we noted an immediate 35.9% reduction in TB notifications in April 2020; notifications recovered to near prepandemic numbers by December 2020. However, 333 fewer cumulative TB notifications were received than anticipated. Women and girls were affected more (30.7% fewer cases) than men and boys (20.9% fewer cases). Fear of COVID-19 infection, temporary facility closures, inadequate personal protective equipment, and COVID-19 stigma because of similar symptoms to TB were mentioned as reasons for fewer people being diagnosed with TB. Public health measures could benefit control of both TB and COVID-19, but only if TB diagnostic services remain accessible and are considered safe to attend.