Natural infection of Plasmodium brasilianum in humans: Man and monkey share quartan malaria parasites in the Venezuelan Amazon

AbstractBackgroundThe quartan malaria parasite Plasmodium malariae is the widest spread and best adapted human malaria parasite. The simian Plasmodium brasilianum causes quartan fever in New World monkeys and resembles P. malariae morphologically. Since the genetics of the two parasites are nearly identical, differing only in a range of mutations expected within a species, it has long been speculated that the two are the same. However, no naturally acquired infection with parasites termed as P. brasilianum has been found in humans until now.MethodsWe investigated malaria cases from remote Yanomami indigenous communities of the Venezuelan Amazon and analyzed the genes coding for the circumsporozoite protein (CSP) and the small subunit of ribosomes (18S) by species-specific PCR and capillary based-DNA sequencing.FindingsBased on 18S rRNA gene sequencing, we identified 12 patients harboring malaria parasites which were 100% identical with P. brasilianum isolated from the monkey, Alouatta seniculus. Translated amino acid sequences of the CS protein gene showed identical immunodominant repeat units between quartan malaria parasites isolated from both humans and monkeys.InterpretationThis study reports, for the first time, naturally acquired infections in humans with parasites termed as P. brasilianum. We conclude that quartan malaria parasites are easily exchanged between humans and monkeys in Latin America. We hypothesize a lack of host specificity in mammalian hosts and consider quartan malaria to be a true anthropozoonosis. Since the name P. brasilianum suggests a malaria species distinct from P. malariae, we propose that P. brasilianum should have a nomenclatorial revision in case further research confirms our findings. The expansive reservoir of mammalian hosts discriminates quartan malaria from other Plasmodium spp. and requires particular research efforts

Ecological theory meets soil ecotoxicology: Challenge and chance.

International audienceThe degradation of soils due to various anthropogenic stress factors is alarming. Although chemicals are a major reason for soil degradation, most ecologists are not interested in studying such effects. We try to wake their interest by addressing a number of unsolved soil ecotoxicological problems that are related to disturbance ecology, biodiversity, ecosystem functioning and modelling. Features distinguishing chemical from natural stress render promising new aspects in disturbance ecology. Ecotoxicological studies are ideal models of disturbance, particularly regarding frequency, intensity or multitude of stress. Patterns of secondary succession after a major chemical damage can directly be related to the intermediate disturbance hypothesis. More knowledge on altered life history patterns following stress could support both evolutionary ecology and risk assessment. We raise the question if inherent resource competition makes communities more vulnerable to stress. Three aspects of ecotoxicological risk assessment are introduced: (1) exposure and bioavailability, which is directly connected to environmental heterogeneity; (2) tests on ecosystem functioning, suffering from major drawbacks; and (3) modelling. Here, promising approaches exist but need substantial input for being applicable to soils. Ecological modelling should put more emphasis on simulating both natural and chemical disturbances, including behavioural aspects and environmental variability. Finally, research needs for ecological risk assessment in soils are derived such as a simple system to assess the impact of chemicals on soil biodiversity, the inclusion of behavioural changes of keystone species or the consideration of density-dependent effects. Common research efforts of basic ecologists and soil ecotoxicologists could render a lot of mutual benefits

Adsorption and Orientation of the Physiological Extracellular Peptide Glutathione Disulfide on Surface Functionalized Colloidal Alumina Particles

Understanding the interrelation between surface chemistry of colloidal particles and surface adsorption of biomolecules is a crucial prerequisite for the design of materials for biotechnological and nanomedical applications. Here, we elucidate how tailoring the surface chemistry of colloidal alumina particles (d(50) = 180 nm) with amino (-NH2), carboxylate (-COOH), phosphate (-PO3H2) or sulfonate (-SO3H) groups affects adsorption and orientation of the model peptide glutathione disulfide (GSSG). GSSG adsorbed on native, -NH2-functionalized, and -SO3H-functionalized alumina but not on -COOH- and -PO3H2-functionalized particles. When adsorption occurred, the process was rapid (<= 5 min), reversible by application of salts, and followed a Langmuir adsorption isotherm dependent on the particle surface functionalization and zeta potential. The orientation of particle bound GSSG was assessed by the release of glutathione after reducing the GSSG disulfide bond and by zeta potential measurements. GSSG is likely to bind via the carboxylate groups of one of its two glutathionyl (GS) moieties onto native and -NH2-modified alumina, whereas GSSG is suggested to bind to -SO3H-modified alumina via the primary amino groups of both GS moieties. Thus, GSSG adsorption and orientation can be tailored by varying the molecular composition of the particle surface, demonstrating a step toward guiding interactions of biomolecules with colloidal particles

Long-term results of robotic radiosurgery for non brachytherapy patients with cervical cancer

Background Consolidation brachytherapy is a critical treatment component for cervical cancer patients undergoing primary chemoradiation. Some patients are unsuitable for brachytherapy for a variety of reasons. The use of alternatives (LINAC-based stereotactic radiosurgery or external beam boosts) compromise oncologic results in cervical cancer patients. Thus, we evaluated the value of brachytherapy-like doses prescriptions using robotic radiosurgery (CyberKnife (R), CR, Acuuray, Sunnyvale, CA, USA). Methods From 06/2011 to 06/2015, 31 patients (median age 53 years; range 30-77 years) with histologically proven FIGO stages IB-IVB cervical cancer underwent primary chemoradiation. All patients were either not suitable for intracervical brachytherapy for a variety of reasons or refused the brachytherapy. To achieve an adequate dose within the tumor, a CK boost was applied after fiducial implantation. In 29 patients, a dose of either five times 6Gy or five times 5Gy was prescribed to the target volume. Two patients received three times 5Gy. The target dose was prescribed to the 70% isodose. Treatment toxicity was documented once weekly regarding vaginal mucositis, bladder, and bowel irritation according to CTCAE v. 4.03. If possible 3 months after completion of treatment intracervical curettage was performed to exclude residual tumor and the patients were followed up clinically. Sparing of organs at risk (OAR) and outcome in terms of local control (LC), overall survival (OS), and progression-free survival (PFS) were assessed. Results Of the 31 patients, 30 have completed CK boost therapy. The median follow-up time was 40 months (range 5-84 months). General treatment tolerability was good. Except for 1 patient, who had diarrhea grade 3, no treatment related side effects above grade 2 were reported. Sparing of OAR was excellent. The 1-, 3-, and 5-year OS rates were 89, 60, and 57% respectively across all stages. Seven patients showed progression (28%), only two of them with local relapse (8%), resulting in an LC rate of 92% after 3 and 5 years. Mean PFS was 41 months (range 2-84 months). Patients with local recurrence had PFS of 5 and 8 months. Five patients developed distant metastases. Fifteen patients (48%) underwent intracervical curettage 3 months after completion of treatment of which 14 (93%) had complete pathologic response. Conclusion Brachytherapy remains the standard of care for patients diagnosed with cervical cancer and indication for primary chemoradiation. In terms of local control, CyberKnife (R)-based boost concepts provide excellent local control. It can be an alternative for patients who cannot receive adequate brachytherapy. Distant relapse still remains a challenge in this context

Interaction of the Physiological Tripeptide Glutathione with Colloidal Alumina Particles

Understanding of the molecular interactions of alumina particles with biomolecules is fundamental for a variety of biotechnological processes. To study the interactions of polypeptides with alumina particles, we have investigated the adsorption and desorption behavior of the physiologically relevant tripeptide glutathione (GSH, γ-glutamylcysteinylglycine) onto colloidal α-alumina particles (CPs). The adsorption of GSH to positively charged alumina particles was rapid, increased proportionally to the concentration of CPs, and shifted the isoelectric point of the CP to a less alcaline pH. Desorption of particle-bound GSH was achieved by increasing the ionic strength after adding salt to the suspension, suggesting that adsorption of GSH to alumina is governed by electrostatic interactions. The presence of negatively charged and GSH-structurally related molecules such as glutamate, γ-glutamylcysteine, γ-glutamylglutamate, or methyl-S-GSH prevented the binding of GSH to the positively charged alumina surface in a concentration dependent manner, while positively charged and net-uncharged molecules and GSH esters did not affect GSH adsorption to alumina CPs. These data suggest that exclusively electrostatic interaction via the carboxylate groups of GSH governs its binding to alumina particles

Adsorption and Orientation of the Physiological Extracellular Peptide Glutathione Disulfide on Surface Functionalized Colloidal Alumina Particles

Understanding the interrelation between surface chemistry of colloidal particles and surface adsorption of biomolecules is a crucial prerequisite for the design of materials for biotechnological and nanomedical applications. Here, we elucidate how tailoring the surface chemistry of colloidal alumina particles (<i>d</i>₅₀ = 180 nm) with amino (−NH₂), carboxylate (−COOH), phosphate (−PO₃H₂) or sulfonate (−SO₃H) groups affects adsorption and orientation of the model peptide glutathione disulfide (GSSG). GSSG adsorbed on native, −NH₂-functionalized, and −SO₃H-functionalized alumina but not on −COOH- and −PO₃H₂-functionalized particles. When adsorption occurred, the process was rapid (≤5 min), reversible by application of salts, and followed a Langmuir adsorption isotherm dependent on the particle surface functionalization and ζ potential. The orientation of particle bound GSSG was assessed by the release of glutathione after reducing the GSSG disulfide bond and by ζ potential measurements. GSSG is likely to bind via the carboxylate groups of one of its two glutathionyl (GS) moieties onto native and −NH₂-modified alumina, whereas GSSG is suggested to bind to −SO₃H-modified alumina via the primary amino groups of both GS moieties. Thus, GSSG adsorption and orientation can be tailored by varying the molecular composition of the particle surface, demonstrating a step toward guiding interactions of biomolecules with colloidal particles

Immune Response to Third and Fourth COVID-19 Vaccination in Hemodialysis Patients and Kidney Transplant Recipients

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a serious hazard for hemodialysis (HD) patients and kidney transplant (KTX) recipients as they suffer from an impaired immune response to SARS-CoV-2 vaccination. In addition, a definition of SARS-CoV-2 IgG titer that indicates a sufficient immune response, especially against new omicron variants, is urgently needed. In the present study, the immune response to either a third or a fourth dose of a mRNA vaccine was investigated in 309 dialysis and 36 KTX patients. SARS-CoV-2 IgG titer thresholds indicating neutralizing activity against wild type (WT) and the omicron variant BA.1 were quantified. After four vaccine doses, a high-neutralizing activity against WT was evidenced in HD patients, whereas the neutralizing rate against BA.1 was significant lower. Concerning KTX recipients, humoral and cellular immune responses after a third vaccination were still highly impaired. This calls for modified omicron-targeting vaccines