Post-translational processing targets functionally diverse proteins in Mycoplasma hyopneumoniae

© 2016 The Authors. Mycoplasma hyopneumoniae is a genome-reduced, cell wall-less, bacterial pathogen with a predicted coding capacity of less than 700 proteins and is one of the smallest self-replicating pathogens. The cell surface of M. hyopneumoniae is extensively modified by processing events that target the P97 and P102 adhesin families. Here, we present analyses of the proteome of M. hyopneumoniae-type strain J using protein-centric approaches (one- and two-dimensional GeLC-MS/MS) that enabled us to focus on global processing events in this species. While these approaches only identified 52% of the predicted proteome (347 proteins), our analyses identified 35 surface-associated proteins with widely divergent functions that were targets of unusual endopro-teolytic processing events, including cell adhesins, lipoproteins and proteins with canonical functions in the cytosol that moonlight on the cell surface. Affinity chromatography assays that separately used heparin, fibronectin, actin and host epithelial cell surface proteins as bait recovered cleavage products derived from these processed proteins, suggesting these fragments interact directly with the bait proteins and display previously unrecognized adhesive functions. We hypothesize that protein processing is underestimated as a post-translational modification in genome-reduced bacteria and prokaryotes more broadly, and represents an important mechanism for creating cell surface protein diversity

Analysis for genotyping Duffy blood group in inhabitants of Sudan, the Fourth Cataract of the Nile

<p>Abstract</p> <p>Background</p> <p>Genetic polymophisms of the Duffy antigen receptor for the chemokines (DARC) gene successfully protected against blood stage infection by <it>Plasmodium vivax </it>infection. The Fy (a-, b-) phenotype is predominant among African populations, particularly those originating from West Africa, and it is rare among non-African populations. The aim of this study was to analyse the frequency of four Duffy blood groups based on SNPs (T-33C, G125A, G298A and C5411T) in two local tribes of Sudanese Arabs, the <it>Shagia </it>and <it>Manasir</it>, which are both from the region of the Fourth Nile cataract in Sudan.</p> <p>Methods</p> <p>An analysis of polymorphisms was performed on 217 individuals (126 representatives of the <it>Shagia </it>tribe and 91 of the <it>Manasir)</it>. Real-time PCR and TaqMan Genotyping Assays were used to study the prevalence of alleles and genotypes.</p> <p>Results</p> <p>The analysis of allelic and genotype frequency in the T-33C polymorphisms demonstrated a significant dominance of the <it>C </it>allele and <it>CC </it>genotype (OR = 0.53 [0.32-0.88]; p = 0.02) in both tribes. The G125A polymorphism is associated with phenotype Fy(a-, b-) and was identified in 83% of <it>Shagia </it>and 77% of <it>Manasir</it>. With regard to G298A polymorphisms, the genotype frequencies were different between the tribes (p = 0,002) and no single <it>AA </it>homozygote was found. Based on four SNPs examined, 20 combinations of genotypes for the <it>Shagia </it>and <it>Manasir </it>tribes were determined. The genotype <it>CC/AA/GG/CT </it>occurred most often in <it>Shagia </it>tribe (45.9%) but was rare in the <it>Manasir </it>tribe (6.6%) (p < 0.001 <it>Shagia </it>versus <it>Manasir</it>). The <it>FY*A^ES</it>allele was identified in both analysed tribes. The presence of individuals with the <it>FY*A/FY*A </it>genotype was demonstrated only in the <it>Shagia </it>tribe.</p> <p>Conclusion</p> <p>This is probably the first report showing genotypically Duffy-negative people who carry both <it>FY*B^ES</it>and <it>FY*A^ES</it>. The identification of the <it>FY*A^ES</it>allele in both tribes may be due to admixture of the non-African genetic background. Taken as a whole, allele and genotype frequencies between the <it>Shagia </it>and the <it>Manasir </it>were statistically different. However, the presence of individuals with the <it>FY*A/FY*A </it>genotype was demonstrated only in the <it>Shagia </it>tribe.</p

How Immunocontraception Can Contribute to Elephant Management in Small, Enclosed Reserves: Munyawana Population as a Case Study

Immunocontraception has been widely used as a management tool to reduce population growth in captive as well as wild populations of various fauna. We model the use of an individual-based rotational immunocontraception plan on a wild elephant, Loxodonta africana, population and quantify the social and reproductive advantages of this method of implementation using adaptive management. The use of immunocontraception on an individual, rotational basis stretches the inter-calving interval for each individual female elephant to a management-determined interval, preventing exposing females to unlimited long-term immunocontraception use (which may have as yet undocumented negative effects). Such rotational immunocontraception can effectively lower population growth rates, age the population, and alter the age structure. Furthermore, such structured intervention can simulate natural process such as predation or episodic catastrophic events (e.g., drought), which regulates calf recruitment within an abnormally structured population. A rotational immunocontraception plan is a feasible and useful elephant population management tool, especially in a small, enclosed conservation area. Such approaches should be considered for other long-lived, social species in enclosed areas where the long-term consequences of consistent contraception may be unknown

Duffy blood group gene polymorphisms among malaria vivax patients in four areas of the Brazilian Amazon region

<p>Abstract</p> <p>Background</p> <p>Duffy blood group polymorphisms are important in areas where <it>Plasmodium vivax </it>predominates, because this molecule acts as a receptor for this protozoan. In the present study, Duffy blood group genotyping in <it>P. vivax </it>malaria patients from four different Brazilian endemic areas is reported, exploring significant associations between blood group variants and susceptibility or resistance to malaria.</p> <p>Methods</p> <p>The <it>P. vivax </it>identification was determined by non-genotypic and genotypic screening tests. The Duffy blood group was genotyped by PCR/RFLP in 330 blood donors and 312 malaria patients from four Brazilian Amazon areas. In order to assess the variables significance and to obtain independence among the proportions, the Fisher's exact test was used.</p> <p>Results</p> <p>The data show a high frequency of the <it>FYA/FYB </it>genotype, followed by <it>FYB/FYB, FYA/FYA</it>, <it>FYA/FYB-33 </it>and <it>FYB/FYB-33</it>. Low frequencies were detected for the <it>FYA/FY</it>^<it>X</it>, <it>FYB/FY</it>^<it>X</it>, <it>FYX/FY</it>^{<it>X </it>}and <it>FYB-33/FYB-33 </it>genotypes. Negative Duffy genotype (<it>FYB-33/FYB-33</it>) was found in both groups: individuals infected and non-infected (blood donors). No individual carried the <it>FY</it>^<it>X</it><it>/FYB-33 </it>genotype. Some of the Duffy genotypes frequencies showed significant differences between donors and malaria patients.</p> <p>Conclusion</p> <p>The obtained data suggest that individuals with the <it>FYA/FYB </it>genotype have higher susceptibility to malaria. The presence of the <it>FYB-33 </it>allele may be a selective advantage in the population, reducing the rate of infection by <it>P. vivax </it>in this region. Additional efforts may contribute to better elucidate the physiopathologic differences in this parasite/host relationship in regions endemic for <it>P. vivax </it>malaria, in particular the Brazilian Amazon region.</p

Characterising the growth in palliative care prescribing 2011-2015: Analysis of national medical and non-medical activity

YesThe role of non-medical prescribers working in palliative care has been expanding in recent years and prescribers report improvements in patient care, patient safety, better use of health professionals’ skills and more flexible team working. Despite this, there is a lack of empirical evidence to demonstrate its clinical and economic impact, limiting our understanding of the future role of non-medical prescribers within a healthcare system serving an increasing number of people with palliative care needs. We developed a unique methodology to establish the level of non-medical prescribers’ activity in palliative care across England and consider the likely overall contribution these prescribers are making at a national level in this context in relation to medical prescribing. All prescriptions for 10 core palliative care drugs prescribed by general practitioners, nurses and pharmacists in England and dispensed in the community between April 2011 and April 2015 were extracted from the Prescribing Analysis Cost Tool system. The data were broken down by prescriber and basic descriptive analysis of prescription frequencies by opioid, non-opioids and total prescriptions by year were undertaken. To evaluate the yearly growth of non-medical prescribers, the total number of prescriptions was compared by year for each prescribing group. Non-medical prescribers issued prescriptions rose by 28% per year compared to 9% in those issued by medical prescribers. Despite this, the annual growth in non-medical prescribers prescriptions was less than 1% a year in relation to total community palliative care prescribing activity in England. Impact on medical prescribing is therefore minimal

Spatiotemporal progression of ubiquitin-proteasome system inhibition after status epilepticus suggests protective adaptation against hippocampal injury

BACKGROUND: The ubiquitin-proteasome-system (UPS) is the major intracellular pathway leading to the degradation of unwanted and/or misfolded soluble proteins. This includes proteins regulating cellular survival, synaptic plasticity and neurotransmitter signaling; processes controlling excitability thresholds that are altered by epileptogenic insults. Dysfunction of the UPS has been reported to occur in a brain region- and cell-specific manner and contribute to disease progression in acute and chronic brain diseases. Prolonged seizures, status epilepticus, may alter UPS function but there has been no systematic attempt to map when and where this occurs in vivo or to determine the consequences of proteasome inhibition on seizure-induced brain injury. METHOD: To determine whether seizures lead to an impairment of the UPS, we used a mouse model of status epilepticus whereby seizures are triggered by an intra-amygdala injection of kainic acid. Status epilepticus in this model causes cell death in selected brain areas, in particular the ipsilateral CA3 subfield of the hippocampus, and the development of epilepsy after a short latent period. To monitor seizure-induced dysfunction of the UPS we used a UPS inhibition reporter mouse expressing the ubiquitin fusion degradation substrate ubiquitin(G76V)-green fluorescent protein. Treatment with the specific proteasome inhibitor epoxomicin was used to establish the impact of proteasome inhibition on seizure-induced pathology. RESULTS AND CONCLUSIONS: Our studies show that status epilepticus induced by intra-amygdala kainic acid causes select spatio-temporal UPS inhibition which is most evident in damage-resistant regions of the hippocampus, including CA1 pyramidal and dentate granule neurons then appears later in astrocytes. In support of this exerting a beneficial effect, injection of mice with the proteasome inhibitor epoxomicin protected the normally vulnerable hippocampal CA3 subfield from seizure-induced neuronal death in the model. These studies reveal brain region- and cell-specific UPS impairment occurs after seizures and suggest UPS inhibition can protect against seizure-induced brain damage. Identifying networks or pathways regulated through the proteasome after seizures may yield novel target genes for the treatment of seizure-induced cell death and possibly epilepsy

Duffy blood group genotypes among malaria patients in Rondônia, Western Brazilian Amazon Genótipos do sistema sanguíneo Duffy em pacientes maláricos de Rondônia, Amazônia Ocidental Brasileira

We have compared Duffy blood group genotype distribution, as determined by polymerase chain reaction with allele-specific primers, in 68 Plasmodium vivax-infected patients and 59 non-vivax malaria controls from Rondônia, Brazil. Homozygosity for the allele Fy, which abolishes Duffy antigen expression on erythrocytes, was observed in 12% non-vivax controls but in no P. vivax patient. However, no significant association was found between Fy heterozygosity and protection against P. vivax. The Fy x allele, which has recently been associated with very weak erythrocyte expression of Duffy antigen, was not found in local P. vivax patients.<br>Compara-se neste trabalho a distribuição de genótipos do sistema sangüíneo Duffy, determinados através de reação em cadeia da polimerase com oligonucleotídeos iniciadores alelo-específicos, em 68 pacientes com infecção por Plasmodium vivax e em 59 controles com malária não-vivax de Rondônia, Brasil. Nenhum paciente infectado com P. vivax, mas 12% dos controles não-vivax, eram homozigotos para o alelo Fy, que abole a expressão do antígeno Duffy em hemácias. No entanto, não se observou evidência de proteção significativa contra P. vivax entre indivíduos heterozigotos para Fy. O alelo Fy x, que tem sido recentemente associado com a expressão eritrocitária muito fraca do antígeno Duffy, não foi encontrado entre pacientes locais com infecção por P. vivax