Effects of glycated albumin on mesangial cells: evidence for a role in diabetic nephropathy

Nonenzymatically glycated proteins are preferentially transported across the glomerular filtration barrier, and the glomerular mesangium in diabetes is bathed with serum containing increased concentrations of glycated albumin. We investigated effects of glycated albumin on mesangial cells, which are involved in diabetic nephropathy. [³H]-thymidine incorporation was significantly inhibited when murine mesangial cells were grown in culture media containing human serum that had been nonenzymatically glycated by incubation for 4 days with 28 mM glucose. This inhibition was reversed when monoclonal antibodies that selectively react with Amadori products of glycated albumin were added to the culture media. Purified glycated albumin containing Amadori adducts of the glycation reaction induced significant inhibition of thymidine incorporation and stimulation of Type IV collagen secretion compared with cells cultured in the presence of purified nonglycated albumin. These changes were prevented when monoclonal antibodies specifically reactive with fructosyl-lysine epitopes in glycated albumin were added to the cultures. The antibodies had no effect on growth or collagen production in the presence of nonglycated albumin. The results provide the first evidence directly implicating Amadori adducts in glycated albumin in the pathogenesis of diabetic nephropathy, which is characterized by decreased cellularity in association with expansion of the mesangial matrix.     

Regional chromosomal assignment of the Kell blood group locus (KEL) to chromosome 7q33-q35 by fluorescence in situ hybridization: evidence for the polypeptide nature of antigenic variation

The gene encoding the Kell blood group polypeptide has been localized to chromosome 7q33-35 by in situ hybridization using a biotinylated 1.1-kb DNA fragment containing the 3 half of the human cDNA. This assignment is in accord with genetic localization using antigenic variation as a marker, and strongly suggests that Kell antigenic determinants are part of the polypeptide chain rather than the associated sugar molecules.     

Environmental factors influencing zooplankton species composition of lakes in north-central Ontario,Canada

To assess the relative importance of lake chemistry, morphometry and zoogeography on limnetic zooplankton, we collected zooplankton, water, and morphometric data from 132 headwater Canadian Shield lakes in 6 regions across north-central Ontario. A subset of these lakes (n = 52) were fished with gill nets. We clustered lakes based on their zooplankton species composition (presence/absence). Discriminant analysis was employed to determine how well lake characteristics could predict zooplankton community types. Correct classification of zooplankton communities for three models ranged from 72 to 91%. Lake size, lake location, and buffering capacity were ranked as the most important factors separating lake groups. Fish abundance (CPUE) was not significant in distinguishing between zooplankton communities. Though the range of lake sizes was limited (1–110 ha), larger lakes tended to support more species. Lake location (zoogeography) also influenced species composition patterns. Although Algoma lakes tended to be larger (\-x = 18.0 ha, other lakes \-x = 2.5 ha), they supported relatively depauperate zooplankton communities. Buffering capacity was ranked third in the discriminant analysis models, but pH and alkalinity were not significantly different between lake groups.     

Scatter hoarding by kangaroo rats (Dipodomys merriami) and pilferage from their caches

We observed radio-implanted Merriam's kangaroo rats disposingof 10-g bonanzas of rolled oats in 48 trials in the field. Theprincipal determinant of the initial disposition of discoveredfood was apparently its distance from the day burrow: food foundwithin about 10m was mainly larder hoarded, whereas food encounteredfarther afield was usually dispersed immediately in shallowcaches. Cache sites were newly dug for the purpose and not reused;most caches were nearer the current day burrow than was thefood source, but a few were placed far from both the cacher'sday burrow and its habitual nocturnal range. An experiment withartificial caches indicated that security from discovery increaseswith spacing and with proximity to perennial shrubs. Nine kangaroorats cached dyed food, and fecal dye traces revealed extensivepilferage from five of them, by both conspecifics and otherrodent species. Limited evidence indicates that food encounterednearer home and initially larder hoarded was more secure frompilferage than food initially scattered, and yet kangaroo ratswere observed to scatter caches soon after initial larder hoarding.A kangaroo rat whose dyed stores escaped pilferage fed fromthem at intervals for at least 12 days. Even cachers who incurredpilferage made as much, or more, use of their caches as anythief, suggesting that scattering caches may be a defense againstcatastrophic losses.     

Global discovery of human-infective RNA viruses: A modelling analysis

RNA viruses are a leading cause of human infectious diseases and the prediction of where new RNA viruses are likely to be discovered is a significant public health concern. Here, we geocoded the first peer-reviewed reports of 223 human RNA viruses. Using a boosted regression tree model, we matched these virus data with 33 explanatory factors related to natural virus distribution and research effort to predict the probability of virus discovery across the globe in 2010–2019. Stratified analyses by virus transmissibility and transmission mode were also performed. The historical discovery of human RNA viruses has been concentrated in eastern North America, Europe, central Africa, eastern Australia, and north-eastern South America. The virus discovery can be predicted by a combination of socio-economic, land use, climate, and biodiversity variables. Remarkably, vector-borne viruses and strictly zoonotic viruses are more associated with climate and biodiversity whereas non-vector-borne viruses and human transmissible viruses are more associated with GDP and urbanization. The areas with the highest predicted probability for 2010–2019 include three new regions including East and Southeast Asia, India, and Central America, which likely reflect both increasing surveillance and diversity of their virome. Our findings can inform priority regions for investment in surveillance systems for new human RNA viruses.     

Classification of Achromobacter genogroups 2, 5, 7 and 14 as Achromobacter insuavis sp. nov., Achromobacter aegrifaciens sp. nov., Achromobacter anxifer sp. nov. and Achromobacter dolens sp. nov., respectively

The phenotypic and genotypic characteristics of seventeen Achromobacter strains representing MLST genogroups 2, 5, 7 and 14 were examined. Although genogroup 2 and 14 strains shared a DNA–DNA hybridization level of about 70%, the type strains of both genogroups differed in numerous biochemical characteristics and all genogroup 2 and 14 strains could by distinguished by nitrite reduction, denitrification and growth on acetamide. Given the MLST sequence divergence which identified genogroups 2 and 14 as clearly distinct populations, the availability of nrdA sequence analysis as a single locus identification tool for all Achromobacter species and genogroups, and the differential phenotypic characteristics, we propose to formally classify Achromobacter genogroups 2, 5, 7 and 14 as four novel Achromobacter species for which we propose the names Achromobacter insuavis sp. nov. (with strain LMG 26845^T [= CCUG 62426^T] as the type strain), Achromobacter aegrifaciens sp. nov. (with strain LMG 26852^T [= CCUG 62438^T] as the type strain), Achromobacter anxifer sp. nov. (with strain LMG 26857^T [= CCUG 62444^T] as the type strain), and Achromobacter dolens sp. nov. (with strain LMG 26840^T [= CCUG 62421^T] as the type strain).     

Sleep and Sleepiness of Fishermen on Rotating Schedules

Seafaring is a hazardous occupation with high death and injury rates, but the role of seafarer fatigue in these events is generally not well documented. The International Maritime Organization has identified seafarer fatigue as an important health and safety issue. Most research to date has focused on more regularly scheduled types of operations (e.g., merchant vessels, ferries), but there is relatively little information on commercial fishing, which often involves high day‐to‐day and seasonal variability in work patterns and workload. The present study was designed to monitor the sleep and sleepiness of commercial fishermen at home and during extended periods at sea during the peak of the hoki fishing season, with a view to developing better fatigue management strategies for this workforce. Sleep (wrist actigraphy and sleep diaries) and sleepiness (Karolinska Sleepiness Scale [KSS] before and after each sleep period) of 20 deckhands were monitored for 4–13 days at home and for 5–9 days at sea while working a nominal 12 h on/6 h off schedule. On the 12 h on/6 h off schedule, there was still a clear preference for sleep at night. Comparing the last three days at home and the first three days at sea showed that fishermen were more likely to have split sleep at sea (Wilcoxon signed ranks p<0.001), but the median sleep/24 h did not differ significantly by location (5.9 h at sea vs. 6.7 h at home). However, on 23% of days at sea, fishermen obtained<4 h total sleep/24 h, compared to 3% of days at home (p(χ²)<0.01). Sleep efficiency, mean activity counts/min sleep, and subjective ratings of sleep quality did not differ significantly between the last three days at home and the first three days at sea. However, sleepiness ratings remained higher after sleep at sea (Wilcoxon signed ranks p<0.05), with fishermen having post‐sleep KSS ratings ≥7 on 24% of days at sea vs. 9% of days at home (Wilcoxon signed ranks p<0.01). This work adds to the limited number of studies that objectively monitored the sleep of seafarers. It has the strength of operational fidelity but the weakness that large inter‐ and intra‐individual variability in sleep, combined with the small sample size, limited the power of the study to detect statistically significant differences between sleep at home and at sea. The clear preference for sleep at night during the 12 h on/6 h off schedule at sea is consistent with the expectation that this 18 h duty/rest cycle is outside the range of entrainment of the circadian pacemaker. High levels of acute sleep loss, and residual sleepiness after sleep, were much more common at sea than at home. The longer duration of trips during the peak of the fishing season increases the risk of performance impairment due to greater cumulative sleep loss than would be expected on typical three‐day trips. Key fatigue management strategies in this environment include that fishermen report to work as well rested as possible. Once at sea, the day‐to‐day variability in activities due to uncontrollable factors, such as fishing success, repairing gear, and weather conditions, mean that contingency planning is required for managing situations where the entire crew have experienced long periods of intensive work with minimum recovery opportunities.     

Horizontal transmission of the microbial symbionts Enterobacter cloacae and Mycotypha microspora to their firebrat host

The firebrat, Thermobia domestica (Packard) (Thysanura: Lepismatidae), aggregates in response to the faeces of conspecifics. This aggregation response is mediated by two microbial symbionts, the bacterium Enterobacter cloacae (Jordan) Hormaeche & Edwards (Enterobacteriaceae) and the fungus Mycotypha microspora Fenner (Mucorales). Our objective was to determine how these microbes are transmitted between firebrats. We produced fluorescently labelled E. cloacae and M. microspora and presented them to firebrats. Firebrats consumed large quantities of these labelled microbes and deposited them with their faeces where they proliferated rapidly. Firebrats did not harbour E. cloacae or M. microspora within their ovarioles or eggs, and thus cannot transmit them transovarially. Instead, firebrats acquired them horizontally whenever they fed on microbe‐contaminated material, such as faeces, faeces‐contaminated paper, or egg surfaces. Firebrats moult throughout their life, and with each moult they shed the cuticular lining of their digestive tract and likely any microbes residing therein. Because firebrats remain in close contact and live in groups of mixed age and gender, newly moulted individuals can readily re‐acquire E. cloacae or M. microspora from group members. This ensures the perpetuation of their microbial aggregation and arrestment signal.     

Neuroactive diol and acyloin metabolites from cone snail-associated bacteria

The bacterium Gordonia sp. 647 W.R.1a.05 was cultivated from the venom duct of the cone snail, Conus circumcisus. The Gordonia sp. organic extract modulated the action potential of mouse dorsal root ganglion neurons. Assay-guided fractionation led to the identification of the new compound circumcin A (1) and 11 known analogs (2–12). Two of these compounds, kurasoin B (7) and soraphinol A (8), were active in a human norepinephrine transporter assay with K_i values of 2575 and 867 nM, respectively. No neuroactivity had previously been reported for compounds in this structural class. Gordonia species have been reproducibly isolated from four different cone snail species, indicating a consistent association between these organisms.