Immunisation with Transgenic Expressing Gamma Glutamyl Cysteine Synthetase from Pathogenic Species Protected against and Infection in a Murine Model.

Leishmaniasis is a protozoan disease responsible for significant morbidity and mortality. There is no recommended vaccine to protect against infection. In this study, transgenic expressing gamma glutamyl cysteine synthetase (γGCS) from three pathogenic species were produced and their ability to protect against infection determined using models of cutaneous and visceral leishmaniasis.

Absence of DEATH kinesin is fatal for Leishmania mexicana amastigotes.

Kinesins are motor proteins present in organisms from protists to mammals playing important roles in cell division, intracellular organisation and flagellum formation and maintenance. Leishmania mexicana is a protozoan parasite of the order Kinetoplastida causing human cutaneous leishmaniasis. Kinetoplastida genome sequence analyses revealed a large number of kinesins showing sequence and structure homology to eukaryotic kinesins.

Mapping Cell Viability Quantitatively and Independently From Cell Density in 3D Gels Noninvasively.

Objective: In biomanufacturing there is a need for quantitative methods to map cell viability and density inside 3D bioreactors to assess health and proliferation over time. Recently, noninvasive MRI readouts of cell density have been achieved. However, the ratio of live to dead cells was not varied.

Spermatic cord liposarcomas incidentally found during hernia surgery: is histology of any lipoma mandatory? A review of the literature.

Liposarcomas found incidentally during open or laparoscopic inguinal hernia surgery are extremely rare. It is unclear, whether any adipose tissue being removed during inguinal hernia surgery must be sent for histology due to the potential risk of liposarcoma of the spermatic cord. This study aims to evaluate the frequency of liposarcomas incidentally found in the inguinal canal during hernia surgery and tries to derive evidence-based recommendations regarding the optimal management of any fatty tissue found in the inguinal canal.

Efficient Concentration of an Amino Acid Using Reactive Extraction Coupled with Bipolar Electrodialysis.

One intention of the PRODIAS (processing diluted aqueous systems) project is to develop and establish a toolbox of innovative and tailored separation technologies applicable to design energy-efficient water removal and product recovery techniques. Within this project, the recovery of -aminobutyric acid (GABA) was investigated. Using both synthetic as well as fermented solutions, reactive extraction of GABA with the solvent di-(2-ethylhexyl)phosphoric acid + isododecane was performed.

Leishmania donovani 90 kD Heat Shock Protein - Impact of Phosphosites on Parasite Fitness, Infectivity and Casein Kinase Affinity.

Leishmania parasites are thought to control protein activity at the post-translational level, e.g. by protein phosphorylation.

Noninvasive Quantification of Cell Density in Three-Dimensional Gels by MRI.

Objective: For tissue engineering, there is a need for quantitative methods to map cell density inside three-dimensional (3-D) bioreactors to assess tissue growth over time. The current cell mapping methods in 2-D cultures are based on optical microscopy. However, optical methods fail in 3-D due to increased opacity of the tissue.

Continuous hyperpolarization with parahydrogen in a membrane reactor.

Hyperpolarization methods entail a high potential to boost the sensitivity of NMR. Even though the "Signal Amplification by Reversible Exchange" (SABRE) approach uses para-enriched hydrogen, p-H, to repeatedly achieve high polarization levels on target molecules without altering their chemical structure, such studies are often limited to batch experiments in NMR tubes. Alternatively, this work introduces a continuous flow setup including a membrane reactor for the p-H, supply and consecutive detection in a 1 T NMR spectrometer.

An Arginine Deprivation Response Pathway Is Induced in Leishmania during Macrophage Invasion.

Amino acid sensing is an intracellular function that supports nutrient homeostasis, largely through controlled release of amino acids from lysosomal pools. The intracellular pathogen Leishmania resides and proliferates within human macrophage phagolysosomes. Here we describe a new pathway in Leishmania that specifically senses the extracellular levels of arginine, an amino acid that is essential for the parasite.

Sorption Behavior of Compressed CO2 and CH4 on Ultrathin Hybrid Poly(POSS-imide) Layers.

Sorption of compressed gases into thin polymeric films is essential for applications including gas sensors and membrane based gas separation. For glassy polymers, the sorption behavior is dependent on the nonequilibrium status of the polymer. The uptake of molecules by a polymer is generally accompanied by dilation, or swelling, of the polymer material.

Transgenic analysis of the Leishmania MAP kinase MPK10 reveals an auto-inhibitory mechanism crucial for stage-regulated activity and parasite viability.

Protozoan pathogens of the genus Leishmania have evolved unique signaling mechanisms that can sense changes in the host environment and trigger adaptive stage differentiation essential for host cell infection. The signaling mechanisms underlying parasite development remain largely elusive even though Leishmania mitogen-activated protein kinases (MAPKs) have been linked previously to environmentally induced differentiation and virulence. Here, we unravel highly unusual regulatory mechanisms for Leishmania MAP kinase 10 (MPK10).

Scenario planning for community development in Vietnam: a new tool for integrated health approaches?

Background: Like many countries in Southeast Asia, Vietnam's rapid population and economic growth has met challenges in infrastructure development, especially sanitation in rural areas.

Objective: As an entry point, we developed scenario planning as an action-research tool in a peri-urban community to identify first steps towards improving their complex sanitation problem and to, systemically, address emerging/re-emerging infectious diseases, as these are commonly linked to unsafe water and inadequate sanitation conditions. As an integrated approach, the process of constructing scenarios allowed us to work across sectors and stakeholders to incorporate this knowledge into a common vision.

The Leishmania donovani chaperone cyclophilin 40 is essential for intracellular infection independent of its stage-specific phosphorylation status.

During its life cycle, the protozoan pathogen Leishmania donovani is exposed to contrasting environments inside insect vector and vertebrate host, to which the parasite must adapt for extra- and intracellular survival. Combining null mutant analysis with phosphorylation site-specific mutagenesis and functional complementation we genetically tested the requirement of the L. donovani chaperone cyclophilin 40 (LdCyP40) for infection.

Reducing short-stay hospital admissions by ruling out non-ST elevation myocardial infarction and estimating coronary artery disease likelihood on an emergency department observation ward.

Chest pain is an important presentation in adult patients attending emergency departments (ED). The process of ruling out an acute coronary syndrome (ACS) conventionally requires a short in-patient stay. This places a significant burden on healthcare systems.

Acute angioedema: recognition and management in the emergency department.

Angioedema is characterized by localized swelling of subcutaneous tissues or mucosa of the upper respiratory or gastrointestinal tract. Laryngeal involvement may threaten airway patency and can be fatal if not addressed promptly. There are several distinct subtypes of angioedema, caused by different pathological processes involving a range of proinflammatory mediators.

Modulation of Leishmania major aquaglyceroporin activity by a mitogen-activated protein kinase.

Leishmania major aquaglyceroporin (LmjAQP1) adventitiously facilitates the uptake of antimonite [Sb(III)], an active form of Pentostam® or Glucantime®, which are the first line of defence against all forms of leishmaniasis. The present paper shows that LmjAQP1 activity is modulated by the mitogen-activated protein kinase, LmjMPK2. Leishmania parasites coexpressing LmjAQP1 and LmjMPK2 show increased Sb(III) uptake and increased Sb(III) sensitivity.

Deletion of UDP-glucose pyrophosphorylase reveals a UDP-glucose independent UDP-galactose salvage pathway in Leishmania major.

The nucleotide sugar UDP-galactose (UDP-Gal) is essential for the biosynthesis of several abundant glycoconjugates forming the surface glycocalyx of the protozoan parasite Leishmania major. Current data suggest that UDP-Gal could arise de novo by epimerization of UDP-glucose (UDP-Glc) or by a salvage pathway involving phosphorylation of Gal and the action of UDP-glucose:alpha-D-galactose-1-phosphate uridylyltransferase as described by Leloir. Since both pathways require UDP-Glc, inactivation of the UDP-glucose pyrophosphorylase (UGP) catalyzing activation of glucose-1 phosphate to UDP-Glc was expected to deprive parasites of UDP-Gal required for Leishmania glycocalyx formation.

LmxMPK4, an essential mitogen-activated protein kinase of Leishmania mexicana is phosphorylated and activated by the STE7-like protein kinase LmxMKK5.

The essential mitogen-activated protein kinase (MAP kinase), LmxMPK4, of Leishmania mexicana is minimally active when purified following recombinant expression in Escherichia coli and was therefore unsuitable for drug screening until now. Using an E. coli protein co-expression system we identified LmxMKK5, a STE7-like protein kinase from L.

Involvement of a Leishmania thymidine kinase in flagellum formation, promastigote shape and growth as well as virulence.

Leishmania promastigote cells transmitted by their insect vector get phagocytosed by macrophages and convert into the amastigote form. In a recently performed proteomic study, a thymidine kinase (TK) was found to be preferentially expressed in amastigotes. Western blot analysis showing a marked increase in TK protein synthesis during stage differentiation from promastigotes to amastigotes confirmed this result.

Leishmania MAP kinases--familiar proteins in an unusual context.

Mitogen-activated protein kinases are well-known mediators of signal transduction of higher eukaryotes regulating important processes like proliferation, differentiation, stress response and apoptosis. In Leishmania, the typical three-tiered module of MAP kinase signal transduction pathways is present. However, typical activators like cell surface receptors and substrates such as RNA polymerase II transcription factors are missing.

Targeted gene deletion of Leishmania major UDP-galactopyranose mutase leads to attenuated virulence.

Considering the high incidence of galactofuranose (Gal(f)) in pathogens and its absence from higher eukaryotes, the enzymes involved in the biosynthesis of this unusual monosaccharide appear as attractive drug targets. However, although the importance of Gal(f) in bacterial survival or pathogenesis is established, its role in eukaryotic pathogens is still undefined. Recently, we reported the identification and characterization of the first eukaryotic UDP-galactopyranose mutases.

Interacting protein kinases involved in the regulation of flagellar length.

A striking difference of the life stages of the protozoan parasite Leishmania is a long flagellum in the insect stage promastigotes and a rudimentary organelle in the mammalian amastigotes. LmxMKK, a mitogen-activated protein (MAP) kinase kinase from Leishmania mexicana, is required for growth of a full-length flagellum. We identified LmxMPK3, a MAP kinase homologue, with a similar expression pattern as LmxMKK being not detectable in amastigotes, up-regulated during the differentiation to promastigotes, constantly expressed in promastigotes, and shut down during the differentiation to amastigotes.