The use of phylogeny to interpret cross-cultural patterns in plant use and guide medicinal plant discovery: an example from Pterocarpus (Leguminosae)

The study of traditional knowledge of medicinal plants has led to discoveries that have helped combat diseases and improve healthcare. However, the development of quantitative measures that can assist our quest for new medicinal plants has not greatly advanced in recent years. Phylogenetic tools have entered many scientific fields in the last two decades to provide explanatory power, but have been overlooked in ethnomedicinal studies. Several studies show that medicinal properties are not randomly distributed in plant phylogenies, suggesting that phylogeny shapes ethnobotanical use. Nevertheless, empirical studies that explicitly combine ethnobotanical and phylogenetic information are scarce.In this study, we borrowed tools from community ecology phylogenetics to quantify significance of phylogenetic signal in medicinal properties in plants and identify nodes on phylogenies with high bioscreening potential. To do this, we produced an ethnomedicinal review from extensive literature research and a multi-locus phylogenetic hypothesis for the pantropical genus Pterocarpus (Leguminosae: Papilionoideae). We demonstrate that species used to treat a certain conditions, such as malaria, are significantly phylogenetically clumped and we highlight nodes in the phylogeny that are significantly overabundant in species used to treat certain conditions. These cross-cultural patterns in ethnomedicinal usage in Pterocarpus are interpreted in the light of phylogenetic relationships.This study provides techniques that enable the application of phylogenies in bioscreening, but also sheds light on the processes that shape cross-cultural ethnomedicinal patterns. This community phylogenetic approach demonstrates that similar ethnobotanical uses can arise in parallel in different areas where related plants are available. With a vast amount of ethnomedicinal and phylogenetic information available, we predict that this field, after further refinement of the techniques, will expand into similar research areas, such as pest management or the search for bioactive plant-based compounds

Mycobacterium tuberculosis Induces an Atypical Cell Death Mode to Escape from Infected Macrophages

BACKGROUND: Macrophage cell death following infection with Mycobacterium tuberculosis plays a central role in tuberculosis disease pathogenesis. Certain attenuated strains induce extrinsic apoptosis of infected macrophages but virulent strains of M. tuberculosis suppress this host response. We previously reported that virulent M. tuberculosis induces cell death when bacillary load exceeds approximately 20 per macrophage but the precise nature of this demise has not been defined. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the characteristics of cell death in primary murine macrophages challenged with virulent or attenuated M. tuberculosis complex strains. We report that high intracellular bacillary burden causes rapid and primarily necrotic death via lysosomal permeabilization, releasing hydrolases that promote Bax/Bak-independent mitochondrial damage and necrosis. Cell death was independent of cathepsins B or L and notable for ultrastructural evidence of damage to lipid bilayers throughout host cells with depletion of several host phospholipid species. These events require viable bacteria that can respond to intracellular cues via the PhoPR sensor kinase system but are independent of the ESX1 system. CONCLUSIONS/SIGNIFICANCE: Cell death caused by virulent M. tuberculosis is distinct from classical apoptosis, pyroptosis or pyronecrosis. Mycobacterial genes essential for cytotoxicity are regulated by the PhoPR two-component system. This atypical death mode provides a mechanism for viable bacilli to exit host macrophages for spreading infection and the eventual transition to extracellular persistence that characterizes advanced pulmonary tuberculosis

Chronic hepatitis caused by persistent parvovirus B19 infection

<p>Abstract</p> <p>Background</p> <p>Human infection with parvovirus B19 may lead to a diverse spectrum of clinical manifestations, including benign erythema infectiosum in children, transient aplastic crisis in patients with haemolytic anaemia, and congenital hydrops foetalis. These different diseases represent direct consequences of the ability of parvovirus B19 to target the erythroid cell lineage. However, accumulating evidence suggests that this virus can also infect other cell types resulting in diverse clinical manifestations, of which the pathogenesis remains to be fully elucidated. This has prompted important questions regarding the tropism of the virus and its possible involvement in a broad range of infectious and autoimmune medical conditions.</p> <p>Case Presentation</p> <p>Here, we present an unusual case of persistent parvovirus B19 infection as a cause of chronic hepatitis. This patient had persistent parvovirus B19 viraemia over a period of more than four years and displayed signs of chronic hepatitis evidenced by fluctuating elevated levels of ALAT and a liver biopsy demonstrating chronic hepatitis. Other known causes of hepatitis and liver damage were excluded. In addition, the patient was evaluated for immunodeficiency, since she had lymphopenia both prior to and following clearance of parvovirus B19 infection.</p> <p>Conclusions</p> <p>In this case report, we describe the current knowledge on the natural history and pathogenesis of parvovirus B19 infection, and discuss the existing evidence of parvovirus B19 as a cause of acute and chronic hepatitis. We suggest that parvovirus B19 was the direct cause of this patient's chronic hepatitis, and that she had an idiopathic lymphopenia, which may have predisposed her to persistent infection, rather than bone marrow depression secondary to infection. In addition, we propose that her liver involvement may have represented a viral reservoir. Finally, we suggest that clinicians should be aware of parvovirus B19 as an unusual aetiology of chronic hepatitis, when other causes have been ruled out.</p

Whole genome sequencing reveals high clonal diversity of Escherichia coli isolated from patients in a tertiary care hospital in Moshi, Tanzania

Abstract Background Limited information regarding the clonality of circulating E. coli strains in tertiary care hospitals in low and middle-income countries is available. The purpose of this study was to determine the serotypes, antimicrobial resistance and virulence genes. Further, we carried out a phylogenetic tree reconstruction to determine relatedness of E. coli isolated from patients in a tertiary care hospital in Tanzania. Methods E. coli isolates from inpatients admitted at Kilimanjaro Christian Medical Centre between August 2013 and August 2015 were fully genome-sequenced at KCMC hospital. Sequence analysis was done for identification of resistance genes, Multi-Locus Sequence Typing, serotyping, and virulence genes. Phylogeny reconstruction using CSI Phylogeny was done to ascertain E. coli relatedness. Stata 13 (College Station, Texas 77,845 USA) was used to determine Cohen’s kappa coefficient of agreement between the phenotypically tested and whole genome sequence predicted antimicrobial resistance. Results Out of 38 E. coli isolates, 21 different sequence types (ST) were observed. Eight (21.1%) isolates belonged to ST131; of which 7 (87.5.%) were serotype O25:H4. Ten (18.4%) isolates belonged to ST10 clonal complex; of these, four (40.0%) were ST617 with serotype O89:H10. Twenty-eight (73.7%) isolates carried genes encoding beta-lactam resistance enzymes. On average, agreement across all drugs tested was 83.9%. Trimethoprim/sulphamethoxazole (co-trimoxazole) showed moderate agreement: 45.8%, kappa =15% and p = 0.08. Amoxicillin-clavulanate showed strongest agreement: 87.5%, kappa = 74% and p = 0.0001. Twenty-two (57.9%) isolates carried virulence factors for host cells adherence and 25 (65.7%) for factors that promote E. coli immune evasion by increasing survival in serum. The phylogeny analysis showed that ST131 clustering close together whereas ST10 clonal complex had a very clear segregation of the ST617 and a mix of the rest STs. Conclusion There is a high diversity of E. coli isolated from patients admitted to a tertiary care hospital in Tanzania. This underscores the necessity to routinely screen all bacterial isolates of clinical importance in tertiary health care facilities. WGS use for laboratory-based surveillance can be an effective early warning system for emerging pathogens and resistance mechanisms in LMICs

Mother Positivity and Family Adjustment in Households with Children with a Serious Disability

Only limited attention has been given to parent coping resources in the positive adjustment of families of children with a disability. This study is the first to explore maternal positivity as a psychological coping resource related to family adjustment in these families. Consistent with broaden-and-build theory and prior positivity research, positivity was operationalized through a ratio of positive to negative affect scores. We employed longitudinal tracking over a 1 year interval. Children’s diagnostic categories included developmental conditions or impairments, mental health disorders, complex health conditions, physical/motor conditions or impairments, sensory impairments, and provisionally diagnosed conditions or impairments. We used a computer assisted telephone survey to gather psychological, family, and demographic information from 152 mothers in Alberta, Canada. Hierarchical regression analysis indicated mothers’ level of positivity and age, when controlled for family adjustment at Time 1, accounted for 46% of the variance in family adjustment at Time 2. That is, older mothers with higher positivity scores were found to live in households with higher levels of family adjustment after 1 year. These findings provide promising support for broaden-and-build theory, which posits that positive experienced emotions can offset and diminish the negative health and relationship impacts of chronic stress. Study findings support the salience of mothers’ positivity as a psychological coping resource, which is related to enhanced family adjustment in situations of childhood disability

Developmental Hippocampal Neuroplasticity in a Model of Nicotine Replacement Therapy during Pregnancy and Breastfeeding

The influence of developmental nicotine exposure on the brain represents an important health topic in light of the popularity of nicotine replacement therapy (NRT) as a smoking cessation method during pregnancy.In this study, we used a model of NRT during pregnancy and breastfeeding to explore the consequences of chronic developmental nicotine exposure on cerebral neuroplasticity in the offspring. We focused on two dynamic lifelong phenomena in the dentate gyrus (DG) of the hippocampus that are highly sensitive to the environment: granule cell neurogenesis and long-term potentiation (LTP).Pregnant rats were implanted with osmotic mini-pumps delivering either nicotine or saline solutions. Plasma nicotine and metabolite levels were measured in dams and offspring. Corticosterone levels, DG neurogenesis (cell proliferation, survival and differentiation) and glutamatergic electrophysiological activity were measured in pups.Juvenile (P15) and adolescent (P41) offspring exposed to nicotine throughout prenatal and postnatal development displayed no significant alteration in DG neurogenesis compared to control offspring. However, NRT-like nicotine exposure significantly increased LTP in the DG of juvenile offspring as measured in vitro from hippocampal slices, suggesting that the mechanisms underlying nicotine-induced LTP enhancement previously described in adult rats are already functional in pups.These results indicate that synaptic plasticity is disrupted in offspring breastfed by dams passively exposed to nicotine in an NRT-like fashion

Cross-Protective Peptide Vaccine against Influenza A Viruses Developed in HLA-A*2402 Human Immunity Model

Background: The virus-specific cytotoxic T lymphocyte (CTL) induction is an important target for the development of a broadly protective human influenza vaccine, since most CTL epitopes are found on internal viral proteins and relatively conserved. In this study, the possibility of developing a strain/subtype-independent human influenza vaccine was explored by taking a bioinformatics approach to establish an immunogenic HLA-A24 restricted CTL epitope screening system in HLAtransgenic mice. Methodology/Principal Findings: HLA-A24 restricted CTL epitope peptides derived from internal proteins of the H5N1 highly pathogenic avian influenza A virus were predicted by CTL epitope peptide prediction programs. Of 35 predicted peptides, six peptides exhibited remarkable cytotoxic activity in vivo. More than half of the mice which were subcutaneously vaccinated with the three most immunogenic and highly conserved epitopes among three different influenza A virus subtypes (H1N1, H3N2 and H5N1) survived lethal influenza virus challenge during both effector and memory CTL phases. Furthermore, mice that were intranasally vaccinated with these peptides remained free of clinical signs after lethal virus challenge during the effector phase. Conclusions/Significance: This CTL epitope peptide selection system can be used as an effective tool for the development of a cross-protective human influenza vaccine. Furthermore this vaccine strategy can be applicable to the development o

Association between neighborhood socioeconomic status and screen time among pre-school children: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Sedentary behavior is considered a separate construct from physical activity and engaging in sedentary behaviors results in health effects independent of physical activity levels. A major source of sedentary behavior in children is time spent viewing TV or movies, playing video games, and using computers. To date no study has examined the impact of neighborhood socioeconomic status (SES) on pre-school children's screen time behavior.</p> <p>Methods</p> <p>Proxy reports of weekday and weekend screen time (TV/movies, video games, and computer use) were completed by 1633 parents on their 4-5 year-old children in Edmonton, Alberta between November, 2005 and August, 2007. Postal codes were used to classified neighborhoods into low, medium or high SES. Multiple linear and logistic regression models were conducted to examine relationships between screen time and neighborhood SES.</p> <p>Results</p> <p>Girls living in low SES neighborhoods engaged in significantly more weekly overall screen time and TV/movie minutes compared to girls living in high SES neighborhoods. The same relationship was not observed in boys. Children living in low SES neighborhoods were significantly more likely to be video game users and less likely to be computer users compared to children living in high SES neighborhoods. Also, children living in medium SES neighborhoods were significantly less likely to be computer users compared to children living in high SES neighborhoods.</p> <p>Conclusions</p> <p>Some consideration should be given to providing alternative activity opportunities for children, especially girls who live in lower SES neighborhoods. Also, future research should continue to investigate the independent effects of neighborhood SES on screen time as well as the potential mediating variables for this relationship.</p