The Clp chaperones and proteases of the human malaria parasite Plasmodium falciparum

The Clp chaperones and proteases play an important role in protein homeostasis in the cell. They are highly conserved across prokaryotes and found also in the mitochondria of eukaryotes and the chloroplasts of plants. They function mainly in the disaggregation, unfolding and degradation of native as well as misfolded proteins. Here, we provide a comprehensive analysis of the Clp chaperones and proteases in the human malaria parasite Plasmodium falciparum. The parasite contains four Clp ATPases, which we term PfClpB1, PfClpB2, PfClpC and PfClpM. One PfClpP, the proteolytic subunit, and one PfClpR, which is an inactive version of the protease, were also identified. Expression of all Clp chaperones and proteases was confirmed in blood-stage parasites. The proteins were localized to the apicoplast, a non-photosynthetic organelle that accommodates several important metabolic pathways in P. falciparum, with the exception of PfClpB2 (also known as Hsp101), which was found in the parasitophorous vacuole. Both PfClpP and PfClpR form mostly homoheptameric rings as observed by size-exclusion chromatography, analytical ultracentrifugation and electron microscopy. The X-ray structure of PfClpP showed the protein as a compacted tetradecamer similar to that observed for Streptococcus pneumoniae and Mycobacterium tuberculosis ClpPs. Our data suggest the presence of a ClpCRP complex in the apicoplast of P. falciparum.     

Bandoniozyma gen. nov., a Genus of Fermentative and Non-Fermentative Tremellaceous Yeast Species

Background

Independent surveys across the globe led to the proposal of a new basidiomycetous yeast genus within the Bulleromyces clade of the Tremellales, Bandoniozyma gen. nov., with seven new species.

Methodology/Principal Findings

The species were characterized by multiple methods, including the analysis of D1/D2 and ITS nucleotide sequences, and morphological and physiological/biochemical traits. Most species can ferment glucose, which is an unusual trait among basidiomycetous yeasts.

Conclusions/Significance

In this study we propose the new yeast genus Bandoniozyma, with seven species Bandoniozyma noutii sp. nov. (type species of genus; CBS 8364^T  =  DBVPG 4489^T), Bandoniozyma aquatica sp. nov. (UFMG-DH4.20^T  =  CBS 12527^T  =  ATCC MYA-4876^T), Bandoniozyma complexa sp. nov. (CBS 11570^T  =  ATCC MYA-4603^T  =  MA28a^T), Bandoniozyma fermentans sp. nov. (CBS 12399^T  =  NU7M71^T  =  BCRC 23267^T), Bandoniozyma glucofermentans sp. nov. (CBS 10381^T  =  NRRL Y-48076^T  =  ATCC MYA-4760^T  =  BG 02-7-15-015A-1-1^T), Bandoniozyma tunnelae sp. nov. (CBS 8024^T  =  DBVPG 7000^T), and Bandoniozyma visegradensis sp. nov. (CBS 12505^T  =  NRRL Y-48783^T  =  NCAIM Y.01952^T).     

Communities of culturable yeasts and yeast-like fungi in oligotrophic hypersaline coastal waters of the Arabian Gulf surrounding Qatar

This report is the first investigation of yeast biodiversity from the oligotrophic hypersaline coastal waters of the Arabian Gulf surrounding Qatar. Yeasts and yeast-like fungi, were cultured from seawater sampled at 13 coastal areas surrounding Qatar over a period of 2 years (December 2013–September 2015). Eight hundred and forty-two isolates belonging to 82 species representing two phyla viz., Ascomycota (23 genera) and Basidiomycota (16 genera) were identified by molecular sequencing. The results indicated that the coastal waters of the Qatari oligotrophic marine environment harbor a diverse pool of yeast species, most of which have been reported from terrestrial, clinical and aquatic sources in various parts of the world. Five species, i.e., Candida albicans, C. parapsilosis, C. tropicalis, Pichia kudriavzevii and Meyerozyma guilliermondii (n?=?252/842; 30% isolates) are known as major opportunistic human pathogens. Fifteen species belonging to nine genera (n?=?498/842; 59%) and 12 species belonging to seven genera (n?=?459/842; 55%) are hydrocarbon degrading yeast and pollution indicator yeast species, respectively. Ascomycetous yeasts were predominant (66.38%; 559/842) as compared to their basidiomycetous counterparts (33.6%; 283/842). The most isolated yeast genera were Candida (28%; 236/842) (e.g., C. aaseri, C. boidinii, C. glabrata, C. intermedia, C. oleophila, C. orthopsilosis, C. palmioleophila, C. parapsilosis, C. pseudointermedia, C. rugopelliculosa, C. sake, C. tropicalis and C. zeylanoides), Rhodotorula (12.7%; 107/842), Naganishia (8.4%; 71/842), Aureobasidium (7.4%; 62/842), Pichia (7.3%; 62/842), and Debaryomyces (6.4%; 54/842). A total of eleven yeast species ( n = 38) isolated in this study are reported for the first time from the marine environment. Chemical testing demonstrated that seven out of the 13 sites had levels of total petroleum hydrocarbons (TPH) ranging from 200 to 900 µg/L, whereas 6 sites showed higher TPH levels (>?1000–21000 µg/L). The results suggest that the yeast community structure and density are impacted by various physico-chemical factors, namely total organic carbon, dissolved organic carbon and sulphur.

     

Further follow up of mortality and incidence of cancer in men from the United Kingdom who participated in the United Kingdom's atmospheric nuclear weapon tests and experimental programmes.

OBJECTIVES--To study the long term effects of participation in the United Kingdom''s atmospheric nuclear weapon tests and experimental programmes and to test hypotheses generated by an earlier report, including the possibility that participation in tests caused small hazards of leukaemia and multiple myeloma. DESIGN--Follow up study of mortality and cancer incidence. SUBJECTS--21,358 servicemen and civilians from the United Kingdom who participated in the tests and a control group of 22,333 non-participants. MAIN OUTCOME MEASURES--Numbers of deaths; standardised mortality ratios; relative risks of mortality from all causes and 27 types of cancer. RESULTS--During seven further years of follow up the numbers of deaths observed in participants were fewer than expected from national rates for all causes, all neoplasms, leukaemia, and multiple myeloma (standardised mortality ratios 0.86, 0.85, 0.57, and 0.46); death rates were lower than in controls (relative risks 0.99, 0.96, 0.57, and 0.57; 90% confidence intervals all included 1.00). In the period more than 10 years after the initial participation in tests the relative risk of death in participants compared with controls was near unity for all causes (relative risk 0.99 (0.95 to 1.04) and all neoplasms (0.95 (0.87 to 1.04)); it was raised for bladder cancer (2.69 (1.42 to 5.20)) and reduced for cancers of the mouth, tongue, and pharynx (0.45 (0.22 to 0.93)) and for lung cancer (0.85 (0.73 to 0.99)). For leukaemia mortality was equal to that expected from national rates but greater than in controls for both the whole follow up period (1.75 (1.01 to 3.06)) and the period 2-25 years after the tests (3.38 (1.45 to 8.25)). CONCLUSION--Participation in nuclear weapon tests had no detectable effect on expectation of life or on subsequent risk of developing cancer or other fatal diseases. The excess of leukaemia in participants compared with controls seems to be principally due to a chance deficit in the controls, but the possibility that participation in the tests may have caused a small risk of leukaemia in the early years afterwards cannot be ruled out.     

A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks

A set of linear pathways often does not capture the full range of behaviors of a metabolic network. The concept of 'elementary flux modes' provides a mathematical tool to define and comprehensively describe all metabolic routes that are both stoichiometrically and thermodynamically feasible for a group of enzymes. We have used this concept to analyze the interplay between the pentose phosphate pathway (PPP) and glycolysis. The set of elementary modes for this system involves conventional glycolysis, a futile cycle, all the modes of PPP function described in biochemistry textbooks, and additional modes that are a priori equally entitled to pathway status. Applications include maximizing product yield in amino acid and antibiotic synthesis, reconstruction and consistency checks of metabolism from genome data, analysis of enzyme deficiencies, and drug target identification in metabolic networks.     

Identification of novel Y chromosome encoded transcripts by testis transcriptome analysis of mice with deletions of the Y chromosome long arm

Background  

The male-specific region of the mouse Y chromosome long arm (MSYq) is comprised largely of repeated DNA, including multiple copies of the spermatid-expressed Ssty gene family. Large deletions of MSYq are associated with sperm head defects for which Ssty deficiency has been presumed to be responsible.     

Fat synthesis in adipose tissue. An examination of stoichiometric constraints.

The requirement for net balance of synthesis, degradation and transport for all intermediates in the pathways from glucose to fat imposes constraints on the balance of fluxes between different pathways. Linear programming has been used to examine the interactions between these constraints on metabolism in adipocytes and the requirement for efficiency in the conversion of glucose into fat. The circumstances under which excessive ATP synthesis would accompany this conversion have been investigated.