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Purpose: Define a simple and efficient method to allocate costs and benefits in energy communities, and characterize some of its key properties. Design/methodology/approach: The approach is theoretical. We define an algorithm to allocate costs and benefits in energy communities, and derive some of its formal properties using mathematical reasoning. We also compare the proposed algorithm with several alternatives. Findings: The proposed algorithm is simple and it ensures that the resulting distribution of costs and benefits is (i) beneficial for every member of the community, (ii) efficient, (iii) fair (in a formally defined sense), (iv) smooth (small changes in the consumption or in the generation of energy cannot lead to big changes in the allocation of costs and benefits), and (v) environmentally friendly in the sense that the individual allocated cost is a strictly increasing function of individual consumption. Research limitations/implications: The properties of the proposed algorithm are satisfied for a specific type of energy community that is defined in the paper. Practical implications: The algorithm is easy to implement in any energy community. Social implications: The algorithm is highly relevant for any community of prosumers who are willing to exchange energy internally. It guarantees a number of desirable properties that are formally defined in the paper. Originality/value: We prove that a simple algorithm to allocate costs and benefits in energy communities guarantees the fulfilment of several desirable properties. [ABSTRACT FROM AUTHOR]

We consider population games played by procedurally rational players who, when revising their current strategy, test each of their available strategies independently in a series of random matches –i.e., a battery of tests–, and then choose the strategy that performed best in this battery of tests. This revision protocol leads to the so-called payoff-sampling dynamics (aka test-all Best Experienced Payoff dynamics). In this paper we characterize the support of all the rest points of these dynamics in any game and analyze the asymptotic stability of the faces to which they belong. We do this by defining strategy sets closed under payoff sampling , and by proving that the identification of these sets can be made in terms of simple comparisons between some of the payoffs of the game. [ABSTRACT FROM AUTHOR]

Some southern member states have undertaken the reform of their vocational education and training (VET) systems so as to promote dual apprenticeship, such as that which is promoted in Germany. During this process, the European Union (EU) has exercised an extensive influence. This paper advances the analysis of the role exercised by the EU in this stage of cross-national attraction by analysing the model of VET governance promoted by European institutions. The methodology consists of a reflexive thematic analysis of the EU VET texts. A total of 35 texts from the EU institutions was analysed by using NVivo. This produced three themes under the overarching theme of fostering a more pluralistic governance system: promoting cooperation among stakeholders in the design, management and financing of the system, enhancing social dialogue and strengthening responsiveness to change in the world of work. This analysis concludes that the EU, as an agent of the policy transfer process, encourages the implementation of a cooperative governance model of VET systems, such as that present in the dual VET systems of certain member states with collective skill formation governance regimens such as Germany, Austria and Denmark. [ABSTRACT FROM AUTHOR]

In recent years, tourism literature has been incorporating tourist satisfaction as a determinant of competitiveness and expenditure in destinations. It was expected a direct relationship between the variables: the better the experience, the greater the expenditure. However, previous literature has not found a strong relationship between them. This study attempts to address this gap by analysing a data survey from Calp, a consolidated destination on the Spanish Mediterranean coastline, using a static comparative exercise between different tourism seasons. As a novel theoretical contribution, seasonality and the different items of expenditure are included in the analysis. In accordance with the previous literature, the result obtained does not confirm a close relationship between satisfaction and expenditure. Some managerial implications are also suggested. [ABSTRACT FROM AUTHOR]

ABED is free and open-source software for simulating evolutionary game dynamics in finite populations. We explain how ABED can be used to simulate a wide range of dynamics considered in the literature and many novel dynamics. In doing so, we introduce a general model of revisions for dynamic evolutionary models, one that decomposes strategy updates into selection of candidate strategies, payoff determination, and choice among candidates. Using examples, we explore ways in which simulations can complement theory in increasing our understanding of strategic interactions in finite populations. [ABSTRACT FROM AUTHOR]

Like any other microorganism, pathogenic protozoan parasites rely heavily on glycoconjugates and glycan binding proteins to protect themselves from the environment and to interact with their diverse hosts. A thorough comprehension of how glycobiology contributes to the survival and virulence of these organisms may reveal unknown aspects of their biology and may open much needed avenues for the design of new strategies against them. In the case of Plasmodium falciparum , which causes the vast majority of malaria cases and deaths, the restricted variety and the simplicity of its glycans seemed to confer limited significance to the role played by glycoconjugates in the parasite. Nonetheless, the last 10 to 15 years of research are revealing a clearer and more defined picture. Thus, the use of new experimental techniques and the results obtained provide new avenues for understanding the biology of the parasite, as well as opportunities for the development of much required new tools against malaria. • Malaria parasite glycans seem to be of a few kinds, simple and with low variability. • Yet, most of them are critical for parasite development and/or transmission. • Glycans modify important malaria vaccine antigens in different parasite stages. • Still, lifecycle and glycan biosynthesis complexity hinder a better insight. • Despite recent progress, key questions on specific life stages and processes remain. [ABSTRACT FROM AUTHOR]

Objective. The following report presents the adaptation of an existing technique of intrastromal corneal ring (ICRS) implantation enabling repositioning of the ring position postoperatively to manage a refractive failure in two patients with keratoconus. Methods. In two cases, KeraRing and Ferrara nomograms had suggested different ring positions. To manage with the differences between the two nomograms, a longer corneal tunnel was created followed by the classic intervention to move the ring through the initial intrastromal corneal tunnel according to the topographic values. Once the first ring position has failed, the ring segment was repositioned along the longer corneal tunnel according to the postoperative outcome. Results. Significant improvement in both cases was observed in the best corrected visual acuity (BCVA), uncorrected visual acuity (UCVA), and root mean square (RMS) measured with Scheimpflug imaging (Pentacam; Oculus GmBH, Wetzlar, Germany). The participants were followed for one year. Conclusion. In patients with keratoconus which exhibit significant differences between KeraRing and Ferrara nomograms, a longer tunnel should be created to enable repositioning of the ring postoperatively if necessary, to avoid extracting the ring or changing it. [ABSTRACT FROM AUTHOR]

Artificial Economics is one of the fastest growing approaches to analyse complex socio-economic systems. In this paper we present our views on the distinguishing features of Artificial Economics and on its relation with Theoretical Economics - the field that in our opinion lies closest to Artificial Economics. In this context, we discuss various reasons why conducting research on Artificial Economics may be worthwhile, and provide general guidelines on how to go about it. Our view is that Artificial Economics and Theoretical Economics share the same goals, do not differ conceptually as much as it is sometimes perceived, and their approaches are certainly complementary. [ABSTRACT FROM AUTHOR]

A study was conducted in order to identify the training gaps regarding the managerial capacity; the current situation in institutions, organizations and projects with regards to the determination of the demand of capacity building on entrepreneurial culture and management in the farming sector; as well as the actors with possibilities of undertaking work as promoters, facilitators and trainers, who would respond to a training program proposed for years 2015-2017. For compiling the information surveys were applied to actors associated to the farming sector, in institutions and projects at national and territorial level; and workshops were also carried out. The demanders stated that 60% of their needs are framed in the logistics and infrastructure area, followed by capacity building to assume the transformations of the surroundings and the new ways to manage economic activities and people. However, for the providers, the equipment and capacity building on topics related to entrepreneurial culture and management constitute the relevant aspects. Fifty-five new economic activities were identified, from which 39 are related to providing services of technical advisory, introduction of technologies and talent formation. This determines the need to develop, in the actors of the institutions and contexts, the necessary capacities to guarantee the success of the new enterprises. In this sense, demanders as well as providers stated that the biggest efforts should be aimed at the advanced management of people and capacity building to promote innovation in the institutions. The work alerts about the importance of developing training programs on entrepreneurial culture, which are not only referred to the formation of enterprises and business plans, but also create values and expectations in people; so that they are receptors of the changes and also participants, in a such a way that they can respond to the constant transformations that are developed in the Cuban context at present. [ABSTRACT FROM AUTHOR]

The so-called 'Win-Continue, Lose-Reverse' (WCLR) rule is a simple iterative procedure that can be used to choose a value for any numeric variable (e.g., setting a price or a production level). The rule dictates that one should evaluate the effect on profits of the last adjustment made to the value (e.g., a price variation), and keep on changing the value in the same direction if the adjustment led to greater profits, or reverse the direction of change otherwise. Somewhat surprisingly, this simple rule has been shown to lead to collusive outcomes in Cournot oligopolies, even though its application requires no information about the other firms' profits or choices. In this paper, we show that the convergence of the WCLR rule toward collusive outcomes can be very sensitive to small independent perturbations in the cost functions or in the income functions of the firms. These perturbations typically push the process toward the Nash equilibrium of the one-shot game. We also explore the behavior of WCLR against other strategies and demonstrate that WCLR is easily exploitable. We then conduct a similar analysis of the WCLR rule in a differentiated Bertrand model, where firms compete in prices. [ABSTRACT FROM AUTHOR]

Trypanosoma brucei is the causative agent of human African sleeping sickness and the cattle disease nagana. Trypanosoma brucei is dependent on glycoproteins for its survival and infectivity throughout its life cycle. Here we report the functional characterization of TbGT3, a glycosyltransferase expressed in the bloodstream and procyclic form of the parasite. Bloodstream and procyclic form TbGT3 conditional null mutants were created and both exhibited normal growth under permissive and nonpermissive conditions. Under nonpermissive conditions, the normal glycosylation of the major glycoprotein of bloodstream form T. brucei, the variant surface glycoprotein and the absence of major alterations in lectin binding to other glycoproteins suggested that the major function of TbGT3 occurs in the procyclic form of the parasite. Consistent with this, the major surface glycoprotein of the procyclic form, procyclin, exhibited a marked reduction in molecular weight due to changes in glycosylphosphatidylinositol (GPI) anchor side chains. Structural analysis of the mutant procyclin GPI anchors indicated that TbGT3 encodes a UDP-Gal: β-GlcNAc-GPI β1-3 Gal transferase. Despite the alterations in GPI anchor side chains, TbGT3 conditional null mutants remained infectious to tsetse flies under nonpermissive conditions. [ABSTRACT FROM AUTHOR]

Research from the Beagle Channel (Tierra del Fuego) offers a rich ethnographic and historical record produced by the late inclusion of Tierra del Fuego in the industrial world (the Beagle Channel was discovered by R. Fitz- Roy in 1830). This is an interesting frame for using new techniques (social simulation by Agent Based Modelling (ABM)) to generate new hypotheses in archaeology. In this case, the hypothesis is focused on the role of social cooperation in Yámana hunter-fisher-gatherer society. [ABSTRACT FROM AUTHOR]

This paper illustrates how a deterministic approximation of a stochastic process can be usefully applied to analyse the dynamics of many simple simulation models. To demonstrate the type of results that can be obtained using this approximation, we present two illustrative examples which are meant to serve as methodological references for researchers exploring this area. Finally, we prove some convergence results for simulations of a family of evolutionary games, namely, intra-population imitation models in n-player games with arbitrary payoffs. [ABSTRACT FROM AUTHOR]

We recently presented a model for site-specific protein N-glycosylation in Trypanosoma brucei whereby the TbSTT3A oligosaccharyltransferase (OST) first selectively transfers biantennary Man5GlcNAc2 from the lipid-linked oligosaccharide (LLO) donor Man5GlcNAc2-PP-Dol to N-glycosylation sequons in acidic to neutral peptide sequences and TbSTT3B selectively transfers triantennary Man9GlcNAc2 to any remaining sequons. In this paper, we investigate the specificities of the two OSTs for their preferred LLO donors by glycotyping the variant surface glycoprotein (VSG) synthesized by bloodstream-form T. brucei TbALG12 null mutants. The TbALG12 gene encodes the α1-6-mannosyltransferase that converts Man7GlcNAc2-PP-Dol to Man8GlcNAc2-PP-Dol. The VSG synthesized by the TbALG12 null mutant in the presence and the absence of α-mannosidase inhibitors was characterized by electrospray mass spectrometry both intact and as pronase glycopetides. The results show that TbSTT3A is able to transfer Man7GlcNAc2 as well as Man5GlcNAc2 to its preferred acidic glycosylation site at Asn263 and that, in the absence of Man9GlcNAc2-PP-Dol, TbSTT3B transfers both Man7GlcNAc2 and Man5GlcNAc2 to the remaining site at Asn428, albeit with low efficiency. These data suggest that the preferences of TbSTT3A and TbSTT3B for their LLO donors are based on the c-branch of the Man9GlcNAc2 oligosaccharide, such that the presence of the c-branch prevents recognition and/or transfer by TbSTT3A, whereas the presence of the c-branch enhances recognition and/or transfer by TbSTT3B. [ABSTRACT FROM PUBLISHER]

The replicator-mutator dynamics is a set of differential equations frequently used in biological and socioeconomic contexts to model evolutionary processes subject to mutation, error or experimentation. The replicator-mutator dynamics generalizes the widely used replicator dynamics, which appears in this framework as the extreme case where replication is perfectly precise. This paper studies the influence of strictly dominated strategies on the location of the rest points of the replicator-mutator dynamics, at the limit where the mutation terms become arbitrarily small. It can be proved that such limit rest points for small mutation are Nash equilibria, so strictly dominated strategies do not occur at limit stationary points. However, we show through a simple case how strictly dominated strategies can have an influence on the location of the limit rest points for small mutation. Consequently, the characterization of the limit rest points of the replicator-mutator dynamics cannot in general proceed safely by readily eliminating strictly dominated strategies. [ABSTRACT FROM AUTHOR]

Abstract: Conditional dissociation, i.e. the option to leave an interacting partner in response to his behaviour, is a mechanism that has been shown to promote cooperation in several settings, but the fundamental features that make conditional dissociation work in this way are not yet fully understood. This paper identifies some of the key conditions that make conditional dissociation lead to high levels of cooperation, explains how this mechanism can support the evolutionary coexistence of cooperative and non-cooperative behaviour typically observed in nature, and provides an analytical formula to estimate the expected degree of cooperation thus achieved. Our model involves a population of individuals who are paired to play an iterated prisoner’s dilemma. All individuals share the same capacity to react to the action previously chosen by their partner and, without any other a priori constraint or exclusion, they may use any behavioural rule that is compatible with this capacity. The dynamic evolution of the population eventually enters either a non-cooperative or a partially cooperative regime, depending mainly on the expected lifetime of individuals. Whenever the partially cooperative regime materializes, the cornerstone of its long-run stability is the coexistence of defectors and “Out-for-Tat” strategists, the latter being those who start cooperating and respond to defection by merely leaving. We find, therefore, that conditional dissociation is the essential disciplinary device supporting cooperation, whilst other conditional strategies (such as Tit-for-Tat) remain present only in small population shares. These conclusions are obtained both by extensive numerical simulations and through analytical mean-field methods that approximate the stochastic simulation dynamics and deliver accurate predictions for general parameter configurations. [ABSTRACT FROM AUTHOR]

Asparagine-linked glycosylation is catalysed by oligosaccharyltransferase (OTase). In Trypanosoma brucei OTase activity is catalysed by single-subunit enzymes encoded by three paralogous genes of which TbSTT3B and TbSTT3C can complement a yeast Δstt3 mutant. The two enzymes have overlapping but distinct peptide acceptor specificities, with TbSTT3C displaying an enhanced ability to glycosylate sites flanked by acidic residues. TbSTT3A and TbSTT3B, but not TbSTT3C, are transcribed in the bloodstream and procyclic life cycle stages of T. brucei. Selective knockdown and analysis of parasite protein N-glycosylation showed that TbSTT3A selectively transfers biantennary Man5GlcNAc2 to specific glycosylation sites whereas TbSTT3B selectively transfers triantennary Man9GlcNAc2 to others. Analysis of T. brucei glycosylation site occupancy showed that TbSTT3A and TbSTT3B glycosylate sites in acidic to neutral and neutral to basic regions of polypeptide, respectively. This embodiment of distinct specificities in single-subunit OTases may have implications for recombinant glycoprotein engineering. TbSTT3A and TbSTT3B could be knocked down individually, but not collectively, in tissue culture. However, both were independently essential for parasite growth in mice, suggesting that inhibiting protein N-glycosylation could have therapeutic potential against trypanosomiasis. [ABSTRACT FROM AUTHOR]

Trypanosoma brucei expresses complex glycoproteins throughout its life cycle. A review of its repertoire of glycosidic linkages suggests a minimum of 38 glycosyltransferase activities. Of these, five have been experimentally related to specific genes and a further nine can be associated with candidate genes. The remaining linkages have no obvious candidate glycosyltransferase genes; however, the T. brucei genome contains a family of 21 putative UDP sugar-dependent glycosyltransferases of unknown function. One representative, TbGT8, was used to establish a functional characterization workflow. Bloodstream and procyclic-form TbGT8 null mutants were created and both exhibited normal growth. The major surface glycoprotein of the procyclic form, the procyclin, exhibited a marked reduction in molecular weight due to changes in the procyclin glycosylphosphatidylinositol (GPI) anchor side-chains. Structural analysis of the mutant procyclin GPI anchors indicated that TbGT8 encodes a UDP-GlcNAc: β-Gal-GPI β1-3 GlcNAc transferase. This is only the second GPI-modifying glycosyltransferase to have been identified from any organism. The glycosylation of the major glycoprotein of bloodstream-form T. brucei, the variant surface glycoprotein, was unaffected in the TbGT8 mutant. However, changes in the lectin binding of other glycoproteins suggest that TbGT8 influences the processing of the poly N-acetyllactosamine-containing asparagine-linked glycans of this life cycle stage. [ABSTRACT FROM AUTHOR]

This paper compares two approaches in complex systems modeling: agent-based modeling and system dynamics. The comparison is undertaken within the general framework of the process of scientific modeling. We argue that the most important difference between the two approaches appears when the modeler builds an abstraction of the target system to develop a formal model from it. This initial difference extends to the following stages of the modeling process, making the two approaches clearly distinctive. Finally, we outline the main general factors that may make one approach more suitable than the other; nevertheless, we also emphasize that modeling the same target system using both techniques seems to be a fruitful and worthy activity. [ABSTRACT FROM AUTHOR]

Agent-based modeling is being increasingly used to simulate socio-techno-ecosystems that involve social dynamics. Humans face constraints that they sometimes wish to challenge, and when they do so, they often trigger changes at the scale of the social group too. Including such adaptation dynamics explicitly in our models would allow simulation of the endogenous emergence of rule changes. This paper discusses such an approach in an institutional framework and develops a sequence that allows modeling of endogenous rule changes. Parts of this sequence are implemented in a NetLogo KISS model to provide some illustrative results. [ABSTRACT FROM AUTHOR]

Abstract: Reinforcement learners tend to repeat actions that led to satisfactory outcomes in the past, and avoid choices that resulted in unsatisfactory experiences. This behavior is one of the most widespread adaptation mechanisms in nature. In this paper we fully characterize the dynamics of one of the best known stochastic models of reinforcement learning [Bush, R., Mosteller, F., 1955. Stochastic Models of Learning. Wiley & Sons, New York] for 2-player 2-strategy games. We also provide some extensions for more general games and for a wider class of learning algorithms. Specifically, it is shown that the transient dynamics of Bush and Mosteller''s model can be substantially different from its asymptotic behavior. It is also demonstrated that in general—and in sharp contrast to other reinforcement learning models in the literature—the asymptotic dynamics of Bush and Mosteller''s model cannot be approximated using the continuous time limit version of its expected motion. [Copyright &y& Elsevier]

The protozoan parasite Trypanosoma brucei causes human African sleeping sickness in sub-Saharan Africa. The parasite makes several essential glycoproteins, which has led to the investigation of the sugar nucleotides and glycosyltransferases required to synthesize these structures. Fucose is a common sugar in glycoconjugates from many organisms; however, the sugar nucleotide donor GDP-fucose was only recently detected in T. brucei, and the importance of fucose metabolism in this organism is not known. In this paper, we identified the genes encoding functional GDP-fucose biosynthesis enzymes in T. brucei and created conditional null mutants of TbGMD, the gene encoding the first enzyme in the pathway from GDP-mannose to GDP-fucose, in both bloodstream form and procyclic form parasites. Under nonpermissive conditions, both life cycle forms of the parasite became depleted in GDP-fucose and suffered growth arrest, demonstrating that fucose metabolism is essential to both life cycle stages. In procyclic form parasites, flagellar detachment from the cell body was also observed under nonpermissive conditions, suggesting that fucose plays a significant role in flagellar adhesion. Fluorescence microscopy of epitope-tagged TbGMD revealed that this enzyme is localized in glycosomes, despite the absence of PTS-1 or PTS-2 target sequences. [ABSTRACT FROM AUTHOR]

The effect of adding sucrose (5–25% w/w) and aspartame (0.04–0.16% w/w) on the compression resistance of three hydrocolloid gelled systems: κ-carrageenan, gellan gum and κ-carrageenan/locust bean gum at three different concentrations (0.3, 0.75 and 1.2% w/w) was studied. Sucrose addition increased true rupture stress in the three-gelled systems, this effect being stronger in gellan gels. The deformability modulus increased with sucrose concentration in gellan gels, but not in the other systems. Rupture stress and deformability modulus increased with the addition of sucrose only in the harder gels (0.75 and 1.2% w/w). The effect of sucrose addition on the true rupture strain was significant but, in general, not important, mainly for lower gum concentrations. Aspartame addition did not affect the compression parameters. [ABSTRACT FROM AUTHOR]

Abstract: Floating point arithmetic is a subject all too often ignored, yet, for agent-based models in particular, it has the potential to create misleading results, and even to influence emergent outcomes of the model. Using a simple demonstration model, this paper illustrates the problems that accumulated floating point errors can cause, and compares a number of techniques that might be used to address them. We show that inexact representation of parameter values, imprecision in calculation results, and differing implementations of mathematical expressions can significantly influence the behaviour of the model, and create issues for replicating results, though they do not necessarily do so. None of the techniques offer a failsafe approach that can be applied in any situation, though interval arithmetic is the most promising. [Copyright &y& Elsevier]

The core lipopolysaccharide (LPS) of Klebsiella pneumoniae is characterized by the presence of disaccharide αGlcN-(1,4)-αGalA attached by an α1,3 linkage to L-glycero-D-manno-heptopyranose II (LD-HeppII). Previously it has been shown that the WabH enzyme catalyzes the incorporation of GlcNAc from UDP-GlcNAc to outer core LPS. The presence of GlcNAc instead of GlcN and the lack of UDP-GlcN in bacteria indicate that an additional enzymatic step is required. In this work we identified a new gene (wabN) in the K. pneumoniae core LPS biosynthetic cluster. Chemical and structural analysis of K. pneumoniae non-polar wabN mutants showed truncated core LPS with GlcNAc instead of GlcN. In vitro assays using LPS truncated at the level of D-galacturonic acid (GalA) and cell-free extract containing WabH and WabN together led to the incorporation of GlcN, whereas none of them alone were able to do it. This result suggests that the later enzyme (WabN) catalyzes the deacetylation of the core LPS containing the GlcNAc residue. Thus, the incorporation of the GlcN residue to core LPS in K. pneumoniae requires two distinct enzymatic steps. WabN homologues are found in Serratia marcescens and some Proteus strains that show the same disaccharide αGlcN-(1,4)-αGalA attached by an α1,3 linkage to LD-HeppII. [ABSTRACT FROM AUTHOR]

Up to now only one major type of core oligosaccharide has been found in the lipopolysaccharide of all Klebsiella pneumoniae strains analyzed. Applying a different screening approach, we identified a novel Klebsiella pneumoniae core (type 2). Both Klebsiella core types share the same inner core and the outer-core-proximal disaccharide, GlcN-(1,4)-GalA, but they differ in the GlcN substituents. In core type 2, the GlcpN residue is substituted at the O-4 position by the disaccharide β-Glcp(1–6)-α-Glcp(1, while in core type 1 the GlcpN residue is substituted at the O-6 position by either the disaccharide α-Hep(1–4)-α-Kdo(2 or a Kdo residue (Kdo is 3-deoxy-o-manno-octulosonic acid). This difference correlates with the presence of a three-gene region in the corresponding core biosynthetic clusters. Engineering of both core types by interchanging this specific region allowed studying the effect on virulence. The replacement of Klebsiella core type 1 in a highly type 2 virulent strain (52145) induces lower virulence than core type 2 in a murine infection model. [ABSTRACT FROM AUTHOR]

A methodology developed to estimate with accuracy the instantaneous specific rock energy using corrected downthe-hole (DTH) drill monitoring data is presented. A specific rock energy profile can be generated for every hole, and thus a drilling site can be mapped for this index. A special data acquisition system was developed to measure and register the following operational variables: penetration rate, torque, hole depth, pull-down force, air pressure, revolutions per minute (rpm) and the hammer percussion frequency, the latter obtained by sound recording and signal processing. The measured data are fed into two simulation models that estimate the power absorbed by the rock through impact, and then the specific rock energy index. The first of these models simulates the thermodynamic cycle of the DTH hammer, rendering the piston kinetic energy at impact, impact velocity as well as impact frequency. The second model is used for stress wave propagation analysis to estimate the effective energy delivered to the rock. Correlations were found between the specific rock energy and penetration rate, and between the specific rock energy and impact frequency, as well as between the penetration rate and applied torque, and between the penetration rate and impact frequency. [ABSTRACT FROM AUTHOR]

To determine the function of the wabG gene in the biosynthesis of the core lipopolysaccharide (LPS) of Klebsiella pneumoniae, we constructed wabG nonpolar mutants. Data obtained from the comparative chemical and structural analysis of LPS samples obtained from the wild type, the mutant strain, and the complemented mutant demonstrated that the wabG gene is involved in attachment to α-L-glycero-D-manno-heptopyranose II (L,D-HeppII) at the O-3 position of an α-D-galactopyranosyluronic acid (α-D-GalAp) residue. K. pneumoniae nonpolar wabG mutants were devoid of the cell-attached capsular polysaccharide but were still able to produce capsular polysaccharide. Similar results were obtained with K. pneumoniae nonpolar waaC and waaF mutants, which produce shorter LPS core molecules than do wabG mutants. Other outer core K. pneumoniae nonpolar mutants in the waa gene cluster were encapsulated. K. pneumoniae waaC, waaF, and wabG mutants were avirulent when tested in different animal models. Furthermore, these mutants were more sensitive to some hydrophobic compounds than the wild-type strains. All these characteristics were rescued by reintroduction of the waaC, waaF, and wabG genes from K. pneumoniae. [ABSTRACT FROM AUTHOR]

A recombinant clone encoding enzymes for Klebsiella pneumoniae O12-antigen iipopolysaccharide (LPS) was found when we screened for serum resistance of a cosmid-based genomic library of K, pneumoniae KT776 (O12:K80) introduced into Escherichia coli DH5α. A total of eight open reading frames (ORFs) (wb[sub O12] gene cluster) were necessary to produce K. pneumoniae O12-antigen LPS in E. coli K-12. A complete analysis of the K. pneumoniae wb[sub O12] cluster revealed an interesting coincidence with the wb[sub O4] cluster of Serratia marcescens from ORF5 to ORF8 (or WbbL to WbbA). This prompted us to generate mutants of K. pneumoniae strain KT776 (O12) and to study complementation between the two enterobacterial wb clusters using mutants of S. marcescens N28b (O4) obtained previously. Both wb gene clusters are examples of ABC 2 transporter-dependent pathways for O-antigen heteropolysaccharides. The wzm-wzt genes and the wbbA or wbbB genes were not interchangeable between the two gene clusters despite their high level of similarity. However, introduction of three cognate genes (wzm-wzt-wbbA or wzm-wzt-wbbB) into mutants unable to produce O antigen allowed production of the specific O antigen. The K. pneumoniae O12 WbbL protein performs the same function as WbbL from S. marcescens O4 in either the S. marcescens O4 or E. coli K-12 genetic background. [ABSTRACT FROM AUTHOR]

Vibrio cholerae WavB protein showed some similarity to WaaE of Klebsiella pneumoniae and Serratia marcescens. From previous data obtained by us and by chemical analyses of a K. pneumoniae non-polar waaE mutant from strain 889 (08:K69), its lipopolysaccharide (LPS) core structure has recently been elucidated. We demonstrated that WaaE is a β-1,4-glucosyltransferase involved in the transfer of a glucose residue to the L-glycero-D-manno-heptose I in the LPS inner core. Complementation of this K. pneumoniae non-polar waaE mutant with gene wavB obtained, either from V. cholerae or V. mimicus, showed a full complementation either by chemical studies or by a biological test (susceptibility to non-immune serum). The V. cholerae wavB gene is located in a putative core oligosaccharide (OS) gene cluster and the V. cholerae OS core structure showed the same β-1,4-glucose residue attached to Hep I as is observed for the K. pneumoniae 889 OS core structure. No other glucose residue is found in the ligosaccharide core structure of K. pneumoniae 889. We concluded that WavB protein is able to perform the same function as WaaE. [Copyright &y& Elsevier]

To determine the function of the waaE gene in the biosynthesis of the innercore LPS of Klebsiella pneumoniae, a waaE non-polar mutant has been constructed. Data obtained from the comparative chemical analysis of LPS samples obtained from the wild-type, the mutant strain and the complemented mutant demonstrated that the waaE gene is involved in substitution of α-L-glycero-D-manno-heptopyranose I (L,D-Heppl) at the 0-4 position by a β-D-glucopyranose (β-D-Glcp) residue. In addition, DNA amplification and nucleotide sequence determination studies revealed that waaE homologues located between the waaA and coaD genes are present in clinical isolates of Enterobacteriaceae containing the structure β-D-Glcp-(1 → 4)α-L,D-Heppl (K. pneumoniae, Proteus mirabilis and Yersinia enterocolitica), as well as in strains of Serratia marcescens and Enterobacter aerogenes of unknown LPS-core structures. Complementation studies using non-polar waaE mutants prove that all the waaE homologues perform the same function. Furthermore, K. pneumoniae, Ser. marcescens and P. mirabilis non-polar waaE mutants showed reduced adhesion and pathogenicity. In addition, the Ser. marcescens and P. murabilis waaE mutants showed reduced swarming motility and ability to form biofilms in vitro. All these characteristics were rescued by reintroduction of the waaE gene independently of its origin. An easy DNA amplification method to detect this gene was established, which also helps in finding the potential presence of this structural feature [β-D-Glcp-(1 → 4)-α-L,DHeppl] in the inner-core LPS of Enterobacteriaceae members with unknown LPS-core structures. [ABSTRACT FROM AUTHOR]

The cell surface of Toxoplasma gondii is rich in glycoconjugates which hold diverse and vital functions in the lytic cycle of this obligate intracellular parasite. Additionally, the cyst wall of bradyzoites, that shields the persistent form responsible for chronic infection from the immune system, is heavily glycosylated. Formation of glycoconjugates relies on activated sugar nucleotides, such as uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). The glucosamine-phosphate-N-acetyltransferase (GNA1) generates N-acetylglucosamine-6-phosphate critical to produce UDP-GlcNAc. Here, we demonstrate that downregulation of T. gondii GNA1 results in a severe reduction of UDP-GlcNAc and a concomitant drop in glycosylphosphatidylinositols (GPIs), leading to impairment of the parasite's ability to invade and replicate in the host cell. Surprisingly, attempts to rescue this defect through exogenous GlcNAc supplementation fail to completely restore these vital functions. In depth metabolomic analyses elucidate diverse causes underlying the failed rescue: utilization of GlcNAc is inefficient under glucose-replete conditions and fails to restore UDP-GlcNAc levels in GNA1-depleted parasites. In contrast, GlcNAc-supplementation under glucose-deplete conditions fully restores UDP-GlcNAc levels but fails to rescue the defects associated with GNA1 depletion. Our results underscore the importance of glucosamine-6-phosphate acetylation in governing T. gondii replication and invasion and highlight the potential of the evolutionary divergent GNA1 in Apicomplexa as a target for the development of much-needed new therapeutic strategies. Author summary: Toxoplasma gondii, Plasmodium, and Cryptosporidium spp., pose serious threats to human health. T. gondii, an intracellular and opportunistic pathogen, effectively avoids the host immune defences by forming long-lasting tissue cysts. Finding potent drugs to eliminate these persisting parasites remains a challenge. The glucosamine-phosphate-N-acetyltransferase (GNA1) catalyses a critical key step in the production of activated sugar nucleotides to build glycoconjugates essential for various functions in the cell. In P. falciparum, this enzyme has been identified as a potential target for antimalarial drugs. In this study, we explored the importance of this pathway in T. gondii and discovered that these sugar-containing compounds play a vital role in the parasite's ability to invade and replicate in host cells–crucial processes for its survival and ability to cause disease. Intriguingly, unlike some organisms that can bypass the pathway, T. gondii relies critically on glucosamine-6-phosphate acetylation. This reliance sheds light on the parasite's distinct metabolic properties and highlights the pathway's potential as a target for new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Atmospheric aerosols represent an important component of the Earth's climate system because they can contribute both positive and negative forcing to the energy budget. We are developing the Aerosol Radiometer for Global Observations of the Stratosphere (ARGOS) instrument to provide improved measurements of stratospheric aerosols in a compact package. ARGOS makes limb scattering measurements from space in eight directions simultaneously, using two near-IR wavelengths for each viewing direction. The combination of forward and backward scattering views along the orbit track gives additional information to constrain the aerosol phase function and size distribution. Cross-track views provide expanded spatial coverage. ARGOS will have a demonstration flight through a hosted payload provider in the fall of 2024. The instrument has completed pre-launch environmental testing and radiometric characterization tests. The hosted payload approach offers advantages in size, weight, and power margins for instrument design compared to other approaches, with significant benefits in terms of reducing infrastructure requirements for the instrument team. [ABSTRACT FROM AUTHOR]

The RTS,S/AS02A malaria vaccine is based on the Plasmodium falciparum circumsporozoite protein (PfCSP), which is O -fucosylated on the sporozoite surface. We determined whether RTS,S/AS02A-induced immunoglobulin G (IgG) antibodies recognize vaccine-like nonfucosylated PfCSP better than native-like fucosylated PfCSP. Similar to previous vaccine trials, RTS,S/AS02A vaccination induced high anti-PfCSP IgG levels associated with malaria protection. IgG recognition of nonfucosylated and fucosylated PfCSP was equivalent, suggesting that PfCSP fucosylation does not affect antibody recognition. Clinical Trials Registration. NCT00197041. [ABSTRACT FROM AUTHOR]

Background: The emergence of new SARS-CoV-2 variants and the waning of immunity raise concerns about vaccine effectiveness and protection against COVID-19. While antibody response has been shown to correlate with the risk of infection with the original variant and earlier variants of concern, the effectiveness of antibody-mediated protection against Omicron and the factors associated with protection remain uncertain. Methods: We evaluated antibody responses to SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from Wuhan and variants of concern by Luminex and their role in preventing breakthrough infections 1 year after a third dose of mRNA vaccination, in a cohort of health care workers followed since the pandemic onset in Spain (N = 393). Data were analyzed in relation to COVID-19 history, demographic factors, comorbidities, vaccine doses, brand, and adverse events. Results: Higher levels of anti-S IgG and IgA to Wuhan, Delta, and Omicron were associated with protection against vaccine breakthroughs (IgG against Omicron S antigen HR, 0.06, 95%CI, 0.26–0.01). Previous SARS-CoV-2 infection was positively associated with antibody levels and protection against breakthroughs, and a longer time since last infection was associated with lower protection. In addition, priming with BNT162b2 followed by mRNA-1273 booster was associated with higher antibody responses than homologous mRNA-1273 vaccination. Conclusions: Data show that IgG and IgA induced by vaccines against the original strain or by hybrid immunization are valid correlates of protection against Omicron BA.1 despite immune escape and support the benefits of heterologous vaccination regimens to enhance antibodies and the prioritization of booster vaccination in individuals without recent infections. [ABSTRACT FROM AUTHOR]

Background: The emergence of new SARS-CoV-2 variants and the waning of immunity raise concerns about vaccine effectiveness and protection against COVID-19. While antibody response has been shown to correlate with the risk of infection with the original variant and earlier variants of concern, the effectiveness of antibody-mediated protection against Omicron and the factors associated with protection remain uncertain. Methods: We evaluated antibody responses to SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from Wuhan and variants of concern by Luminex and their role in preventing breakthrough infections 1 year after a third dose of mRNA vaccination, in a cohort of health care workers followed since the pandemic onset in Spain (N = 393). Data were analyzed in relation to COVID-19 history, demographic factors, comorbidities, vaccine doses, brand, and adverse events. Results: Higher levels of anti-S IgG and IgA to Wuhan, Delta, and Omicron were associated with protection against vaccine breakthroughs (IgG against Omicron S antigen HR, 0.06, 95%CI, 0.26–0.01). Previous SARS-CoV-2 infection was positively associated with antibody levels and protection against breakthroughs, and a longer time since last infection was associated with lower protection. In addition, priming with BNT162b2 followed by mRNA-1273 booster was associated with higher antibody responses than homologous mRNA-1273 vaccination. Conclusions: Data show that IgG and IgA induced by vaccines against the original strain or by hybrid immunization are valid correlates of protection against Omicron BA.1 despite immune escape and support the benefits of heterologous vaccination regimens to enhance antibodies and the prioritization of booster vaccination in individuals without recent infections. [ABSTRACT FROM AUTHOR]

A proposed treatment for malaria is a combination of fosmidomycin and clindamycin. Both compounds inhibit the methylerythritol 4-phosphate (MEP) pathway, the parasitic source of farnesyl and geranylgeranyl pyrophosphate (FPP and GGPP, respectively). Both FPP and GGPP are crucial for the biosynthesis of several essential metabolites such as ubiquinone and dolichol, as well as for protein prenylation. Dietary prenols, such as farnesol (FOH) and geranylgeraniol (GGOH), can rescue parasites from MEP inhibitors, suggesting the existence of a missing pathway for prenol salvage via phosphorylation. In this study, we identified a gene in the genome of P. falciparum, encoding a transmembrane prenol kinase (PolK) involved in the salvage of FOH and GGOH. The enzyme was expressed in Saccharomyces cerevisiae, and its FOH/GGOH kinase activities were experimentally validated. Furthermore, conditional knockout parasites (Δ-PolK) were created to investigate the biological importance of the FOH/GGOH salvage pathway. Δ-PolK parasites were viable but displayed increased susceptibility to fosmidomycin. Their sensitivity to MEP inhibitors could not be rescued by adding prenols. Additionally, Δ-PolK parasites lost their capability to utilize prenols for protein prenylation. Experiments using culture medium supplemented with whole/delipidated human plasma in transgenic parasites revealed that human plasma has components that can diminish the effectiveness of fosmidomycin. Mass spectrometry tests indicated that both bovine supplements used in culture and human plasma contain GGOH. These findings suggest that the FOH/GGOH salvage pathway might offer an alternate source of isoprenoids for malaria parasites when de novo biosynthesis is inhibited. This study also identifies a novel kind of enzyme related to isoprenoid metabolism. Author summary: Falciparum malaria is a potentially fatal disease caused by the parasite Plasmodium falciparum. Antimalarials such as fosmidomycin and clindamycin target a critical pathway in the parasite, crucial for producing certain substances essential for the parasite's survival, particularly phosphorylated isoprenoids. However, the limited effectiveness of these drugs in clinical trials for malaria treatment underscores the need for further related studies. Previous in vitro experiments have demonstrated that the parasite can utilize unphosphorylated isoprenoids, namely farnesol and geranylgeraniol, if they are present in the external environment. Thus, these substances act as antidotes, rendering the parasite resistant to both fosmidomycin and clindamycin. This study reveals for the first time that geranylgeraniol naturally occurs in the human body. Additionally, we have identified a novel enzyme, prenol kinase, which enables the parasite to use these unphosphorylated isoprenoids by converting them into their metabolically active phosphorylated counterparts. Parasites lacking the prenol kinase gene remain viable but become more susceptible to the effects of fosmidomycin, even in the presence of farnesol or geranylgeraniol. These findings suggest that the scavenging of unphosphorylated isoprenoids by the parasite might supplement its isoprenoid needs when the endogenous production is inhibited by drugs like fosmidomycin or clindamycin. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ambient air pollution has been associated with COVID-19 disease severity and antibody response induced by infection. OBJECTIVES: We examined the association between long-term exposure to air pollution and vaccine-induced antibody response. METHODS: This study was nested in an ongoing population-based cohort, COVICAT, the GCAT-Genomes for Life cohort, in Catalonia, Spain, with multiple follow-ups. We drew blood samples in 2021 from 1,090 participants of 2,404 who provided samples in 2020, and we included 927 participants in this analysis. We measured immunoglobulin M (IgM), IgG, and IgA antibodies against five viral-target antigens, including receptor-binding domain (RBD), spike-protein (S), and segment spike-protein (S2) triggered by vaccines available in Spain. We estimated prepandemic (2018–2019) exposure to fine particulate matter [PM =2.5 μm in aerodynamic diameter (PM2.5)], nitrogen dioxide (NO2), black carbon (BC), and ozone (O3) using Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) models. We adjusted estimates for individual- and area-level covariates, time since vaccination, and vaccine doses and type and stratified by infection status. We used generalized additive models to explore the relationship between air pollution and antibodies according to days since vaccination. RESULTS: Among vaccinated persons not infected by SARS-CoV-2 (푛=632), higher prepandemic air pollution levels were associated with a lower vaccine antibody response for IgM (1 month post vaccination) and IgG. Percentage change in geometric mean IgG levels per interquartile range of PM2.5 (1.7 μg/m³) were -8.1 (95% CI: -15.9, 0.4) for RBD, -9.9 (-16.2, -3.1) for S, and -8.4 (-13.5, -3.0) for S2. We observed a similar pattern for NO2 and BC and an inverse pattern for O3. Differences in IgG levels by air pollution levels persisted with time since vaccination. We did not observe an association of air pollution with vaccine antibody response among participants with prior infection (푛=295). DISCUSSION: Exposure to air pollution was associated with lower COVID-19 vaccine antibody response. The implications of this association on the risk of breakthrough infections require further investigation. [ABSTRACT FROM AUTHOR]

The obligate intracellular lifestyle of Plasmodium falciparum and the difficulties in obtaining sufficient amounts of biological material have hampered the study of specific metabolic pathways in the malaria parasite. Thus, for example, the pools of sugar nucleotides required to fuel glycosylation reactions have never been studied in-depth in well-synchronized asexual parasites or in other stages of its life cycle. These metabolites are of critical importance, especially considering the renewed interest in the presence of N-, O-, and other glycans in key parasite proteins. In this work, we adapted a liquid chromatography tandem mass spectrometry (LC-MS/MS) method based on the use of porous graphitic carbon (PGC) columns and MS-friendly solvents to quantify sugar nucleotides in the malaria parasite. We report the thorough quantification of the pools of these metabolites throughout the intraerythrocytic cycle of P. falciparum. The sensitivity of the method enabled, for the first time, the targeted analysis of these glycosylation precursors in gametocytes, the parasite sexual stages that are transmissible to the mosquito vector. [ABSTRACT FROM AUTHOR]

We evaluated the kinetics of antibody responses to Two years into the COVID‐19 pandemic and 1 year after the start of vaccination rollout, the world faced a peak of cases associated with the highly contagious Omicron variant of concern (VoC) of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike (S) and nucleocapsid (N) antigens over five cross‐sectional visits (January–November 2021), and the determinants of pre‐booster immunoglobulin levels, in a prospective cohort of vaccinated primary health care workers in Catalonia, Spain. Antibodies against S antigens after a full primary vaccination course, mostly with BNT162b2, decreased steadily over time and were higher in pre‐exposed (n = 247) than naïve (n = 200) individuals, but seropositivity was maintained at 100% (100% IgG, 95.5% IgA, 30.6% IgM) up to 319 days after the first dose. Antibody binding to variants of concern was highly maintained for IgG compared to wild type but significantly reduced for IgA and IgM, particularly for Beta and Gamma. Factors significantly associated with longer‐term antibodies included age, sex, occupation, smoking, adverse reaction to vaccination, levels of pre‐vaccination SARS‐CoV‐2 antibodies, interval between disease onset and vaccination, hospitalization, oxygen supply, post COVID and symptomatology. Earlier morning vaccination hours were associated with higher IgG responses in pre‐exposed participants. Symptomatic breakthroughs occurred in 9/447 (2.01%) individuals, all among naïve (9/200, 4.5%) and generally boosted antibody responses. Additionally, an increase in IgA and/or IgM seropositivity to variants, and N seroconversion at later time points (6.54%), indicated asymptomatic breakthrough infections, even among pre‐exposed. Seropositivity remained highly stable over almost a year after vaccination. However, gradually waning of anti‐S IgGs that correlate with neutralizing activity, coupled to evidence of an increase in breakthrough infections during the Delta and Omicron predominance, provides a rationale for booster immunization. [ABSTRACT FROM AUTHOR]

This study evaluated the persistence of IgM, IgA, and IgG to SARS-CoV-2 spike and nucleocapsid antigens up to 616 days since the onset of symptoms in a longitudinal cohort of 247 primary health care workers from Barcelona, Spain, followed up since the start of the pandemic. The study also assesses factors affecting antibody levels, including comorbidities and the responses to variants of concern as well as the frequency of reinfections. Despite a gradual and significant decline in antibody levels with time, seropositivity to five SARS-CoV-2 antigens combined was always higher than 90% over the whole study period. In a subset of 23 participants who had not yet been vaccinated by November 2021, seropositivity remained at 95.65% (47.83% IgM, 95.65% IgA, 95.65% IgG). IgG seropositivity against Alpha and Delta predominant variants was comparable to that against the Wuhan variant, while it was lower for Gamma and Beta (minority) variants and for IgA and IgM. Antibody levels at the time point closest to infection were associated with age, smoking, obesity, hospitalization, fever, anosmia/hypogeusia, chest pain, and hypertension in multivariable regression models. Up to 1 year later, just before the massive roll out of vaccination, antibody levels were associated with age, occupation, hospitalization, duration of symptoms, anosmia/hypogeusia, fever, and headache. In addition, tachycardia and cutaneous symptoms associated with slower antibody decay, and oxygen supply with faster antibody decay. Eight reinfections (3.23%) were detected in low responders, which is consistent with a sustained protective role for anti-spike naturally acquired antibodies. Stable persistence of IgG and IgA responses and cross-recognition of the predominant variants circulating in the 2020-2021 period indicate long-lasting and largely variant-transcending humoral immunity in the initial 20.5 months of the pandemic, in the absence of vaccination. [ABSTRACT FROM AUTHOR]

Background: Heterogeneity of the population in relation to infection, COVID-19 vaccination, and host characteristics is likely reflected in the underlying SARS-CoV-2 antibody responses. Methods: We measured IgM, IgA, and IgG levels against SARS-CoV-2 spike and nucleocapsid antigens in 1076 adults of a cohort study in Catalonia between June and November 2020 and a second time between May and July 2021. Questionnaire data and electronic health records on vaccination and COVID-19 testing were available in both periods. Data on several lifestyle, health-related, and sociodemographic characteristics were also available. Results: Antibody seroreversion occurred in 35.8% of the 64 participants non-vaccinated and infected almost a year ago and was related to asymptomatic infection, age above 60 years, and smoking. Moreover, the analysis on kinetics revealed that among all responses, IgG RBD, IgA RBD, and IgG S2 decreased less within 1 year after infection. Among vaccinated, 2.1% did not present antibodies at the time of testing and approximately 1% had breakthrough infections post-vaccination. In the post-vaccination era, IgM responses and those against nucleoprotein were much less prevalent. In previously infected individuals, vaccination boosted the immune response and there was a slight but statistically significant increase in responses after a 2nd compared to the 1st dose. Infected vaccinated participants had superior antibody levels across time compared to naïve-vaccinated people. mRNA vaccines and, particularly the Spikevax, induced higher antibodies after 1st and 2nd doses compared to Vaxzevria or Janssen COVID-19 vaccines. In multivariable regression analyses, antibody responses after vaccination were predicted by the type of vaccine, infection age, sex, smoking, and mental and cardiovascular diseases. Conclusions: Our data support that infected people would benefit from vaccination. Results also indicate that hybrid immunity results in superior antibody responses and infection-naïve people would need a booster dose earlier than previously infected people. Mental diseases are associated with less efficient responses to vaccination. [ABSTRACT FROM AUTHOR]

Chagas disease (CD) is caused by the parasite Trypanosoma cruzi and affects 6–7 million people worldwide. The diagnosis is still challenging, due to extensive parasite diversity encompassing seven genotypes (TcI-VI and Tcbat) with diverse ecoepidemiological, biological, and pathological traits. Chemotherapeutic intervention is usually effective but associated with severe adverse events. The development of safer, more effective therapies is hampered by the lack of biomarker(s) (BMKs) for the early assessment of therapeutic outcomes. The mammal-dwelling trypomastigote parasite stage expresses glycosylphosphatidylinositol-anchored mucins (tGPI-MUC), whose O-glycans are mostly branched with terminal, nonreducing α-galactopyranosyl (α-Gal) glycotopes. These are absent in humans, and thus highly immunogenic and inducers of specific CD anti-α-Gal antibodies. In search for α-Gal-based BMKs, here we describe the synthesis of neoglycoprotein NGP11b, comprised of a carrier protein decorated with the branched trisaccharide Galα(1,2)[Galα(1,6)]Galβ. By chemiluminescent immunoassay using sera/plasma from chronic CD (CCD) patients from Venezuela and Mexico and healthy controls, NGP11b exhibited sensitivity and specificity similar to that of tGPI-MUC from genotype TcI, predominant in those countries. Preliminary evaluation of CCD patients subjected to chemotherapy showed a significant reduction in anti-α-Gal antibody reactivity to NGP11b. Our data indicated that NGP11b is a potential BMK for diagnosis and treatment assessment in CCD patients. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection has become a global health problem specially exacerbated with the continuous appearance of new variants. Healthcare workers (HCW) have been one of the most affected sectors. Children have also been affected, and although infection generally presents as a mild disease, some have developed the Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We recruited 190 adults (HCW and cohabitants, April to June 2020) and 57 children (April 2020 to September 2021), of whom 12 developed PIMS-TS, in a hospital-based study in Spain. Using an in-house Luminex assay previously validated, antibody levels were measured against different spike and nucleocapsid SARS-CoV-2 proteins, including the receptor-binding domain (RBD) of the Alpha, Beta, Gamma, and Delta variants of concern (VoC). Seropositivity rates obtained from children and adults, respectively, were: 49.1% and 11% for IgG, 45.6% and 5.8% for IgA, and 35.1% and 7.3% for IgM. Higher antibody levels were detected in children who developed PIMS-TS compared to those who did not. Using the COVID-19 IgM/IgA ELISA (Vircell, S.L.) kit, widely implemented in Spanish hospitals, a high number of false positives and lower seroprevalences compared with the Luminex estimates were found, indicating a significantly lower specificity and sensitivity. Comparison of antibody levels against RBD-Wuhan versus RBD-VoCs indicated that the strongest positive correlations for all three isotypes were with RBD-Alpha, while the lowest correlations were with RBD-Delta for IgG, RBD-Gamma for IgM, and RBD-Beta for IgA. This study highlights the differences in antibody levels between groups with different demographic and clinical characteristics, as well as reporting the IgG, IgM, and IgA response to RBD VoC circulating at the study period. [ABSTRACT FROM AUTHOR]

Thromboembolic events were described in patients with Chagas disease without cardiomyopathy. We aim to confirm if there is a hypercoagulable state in these patients and to determine if there is an early normalization of hemostasis factors after antiparasitic treatment. Ninety-nine individuals from Chagas disease-endemic areas were classified in two groups: G1, with T.cruzi infection (n = 56); G2, healthy individuals (n = 43). Twenty-four hemostasis factors were measured at baseline. G1 patients treated with benznidazole were followed for 36 months, recording clinical parameters and performance of conventional serology, chemiluminescent enzyme-linked immunosorbent assay (trypomastigote-derived glycosylphosphatidylinositol-anchored mucins), quantitative polymerase chain reaction, and hemostasis tests every 6-month visits. Prothrombin fragment 1+2 (F1+2) and endogenous thrombin potential (ETP) were abnormally expressed in 77% and 50% of infected patients at baseline but returned to and remained at normal levels shortly after treatment in 76% and 96% of cases, respectively. Plasmin-antiplasmin complexes (PAP) were altered before treatment in 32% of G1 patients but normalized in 94% of cases several months after treatment. None of the patients with normal F1+2 values during follow-up had a positive qRT-PCR result, but 3/24 patients (13%) with normal ETP values did. In a percentage of chronic T. cruzi infected patients treated with benznidazole, altered coagulation markers returned into normal levels. F1+2, ETP and PAP could be useful markers for assessing sustained response to benznidazole. [ABSTRACT FROM AUTHOR]

Background: Soil-transmitted helminths (STH), Schistosoma spp. and Plasmodium falciparum are parasites of major public health importance and co-endemic in many sub-Saharan African countries. Management of these infections requires detection and treatment of infected people and evaluation of large-scale measures implemented. Diagnostic tools are available but their low sensitivity, especially for low intensity helminth infections, leaves room for improvement. Antibody serology could be a useful approach thanks to its potential to detect both current infection and past exposure. Methodology: We evaluated total IgE responses and specific-IgG levels to 9 antigens from STH, 2 from Schistosoma spp., and 16 from P. falciparum, as potential markers of current infection in a population of children and adults from Southern Mozambique (N = 715). Antibody responses were measured by quantitative suspension array Luminex technology and their performance was evaluated by ROC curve analysis using microscopic and molecular detection of infections as reference. Principal findings: IgG against the combination of EXP1, AMA1 and MSP2 (P. falciparum) in children and NIE (Strongyloides stercoralis) in adults and children had the highest accuracies (AUC = 0.942 and AUC = 0.872, respectively) as markers of current infection. IgG against the combination of MEA and Sm25 (Schistosoma spp.) were also reliable markers of current infection (AUC = 0.779). In addition, IgG seropositivity against 20 out of the 27 antigens in the panel differentiated the seropositive endemic population from the non-endemic population, suggesting a possible role as markers of exposure although sensitivity could not be assessed. Conclusions: We provided evidence for the utility of antibody serology to detect current infection with parasites causing tropical diseases in endemic populations. In addition, most of the markers have potential good specificity as markers of exposure. We also showed the feasibility of measuring antibody serology with a platform that allows the integration of control and elimination programs for different pathogens. Author summary: Parasitic worms and Plasmodium falciparum, the causal agent of malaria, are among the most relevant parasitic diseases of our time and efforts are under way for their control and, ultimately, elimination. An accurate diagnosis is relevant for case management, but also allows calculating the prevalence and evaluating the effectiveness of treatment and control measures. Unfortunately, current diagnostic methods for parasitic worms are not optimal and many infections remain undetected. As for P. falciparum, current diagnostic techniques are satisfactory but do not allow for ascertaining exposure, which is relevant for evaluating control measures. Here we investigated the utility of measuring antibodies to these parasites as a diagnostic method. Our results indicate that it is possible to detect current infection with parasitic worms and P. falciparum using antibody detection with a moderate to high accuracy. We also show that antibodies against the antigens in this study have potential as markers of exposure. Importantly, we used a platform that allows for the simultaneous detection of immunoglobulins to different parasites, which would be extremely useful as a tool to integrate control and elimination programs for several pathogens. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate changes in keratoconic corneas implanted with intrastromal corneal ring segments (ICRSs) that have been explanted because of late extrusion of the segment after >2 years. Setting: Vissum Miranza, Alicante, Spain; OftalmoSalud, Lima, Peru; Minya University Hospital, Egypt. Design: Retrospective multicenter case series. Methods: 23 keratoconic corneas that were implanted for >=2 years and explanted because of natural extrusion of the segment. Clinical measures of visual, refractive, topographic, pachymetric, and aberrometric data were analyzed. To perform exploratory factor analysis, the Kaiser-Meyer-Olkin (KMO) test was used to evaluate sampling adequacy. Factor analysis with VARIMAX rotation was used to determine the main factors of the inventory. Results: The mean time interval was 5 years. Topographic findings were reversed nearly to the baseline level after segment explantation (Km: 48.97 +/- 3.47 D pre implantation and 47.60 +/- 3.67 D after explantation, P =.374). Significant worsened in refractive cylinder was found pre-ICRS extrusion ([FIGURE DASH]2.54 +/- 3.40 D after implantation and [FIGURE DASH]3.96 +/- 1.72 before extrusion, P <.05). The main factor obtained in the preimplantation moment included keratoconus grade, keratometric readings, and visual acuities. After ICRS implantation, the most strength components were the refractive cylinder, corrected distance visual acuity, and uncorrected distance visual acuity. Corneal aberrations were the main factors in the pre-explantation analysis. Conclusions: ICRSs were safely extracted, with a reversal of the corneal topographic data to the preoperative level. A significant astigmatic change was shown in patients implanted with ICRSs before late extrusion of the segment, suggesting the role of this parameter as a prognostic factor of extrusion. [ABSTRACT FROM AUTHOR]