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Despite extensive literature on what may be involved in making a request, there is dispute among scholars as to which linguistic formats constitute the social action of making a request proper. In this study, we examine the much-disputed declarative request format and in particular what we call "declaratives of trouble." We present evidence that in the context of a service encounter such as the shoe repair shop, this format is unproblematically and systematically treated by both customer and service provider as performing requests. The study thus enriches our understanding of action formation and ascription by examining in detail that and how utterances that in some contexts might not serve as requests in other contexts constitute a primary resource for building requests. Data are in American English. [ABSTRACT FROM AUTHOR]

This study examines the temporally unfolding activities engaged in by customers at a shoe repair shop as they move into a participation framework with the staff and initiate a requesting sequence. We find that the utterances used by the customers to initiate the requesting sequence are carefully designed to manage the time needed to get to the counter and make visible the problem articulated in their requesting utterance. We find that customers who seek help with a problem have to coordinate the timing of a) their own physical approximation to the counter, b) the shoetender's physical approximation to the counter, c) the visual availability of the to-be-repaired object, d) the inspectability of the problem for which they are seeking help, and e) the temporal trajectory of their verbal requesting utterance. • This study examines the design of requests by customers at a shoe repair shop. • Request design gives time to get to the counter and make visible the problem. • Customers have to coordinate the timing of a range of contingencies. [ABSTRACT FROM AUTHOR]

In this paper, we identify and describe a new practice for responding to unfinished requests, which we call telescoping responses, due to their being designed for telescoping the request sequence forward in the face of troubles with progressivity and in producing the request. Considering cases from an American shoe repair shop, we demonstrate that telescoping responses serve to telescope request sequences exactly because they are neither syntactically, prosodically or pragmatically fitted to the unfinished requests that they respond to. [ABSTRACT FROM AUTHOR]

Toxin-producing Clostridioides difficile infection (CDI) is the leading cause of hospital-acquired diarrhea. However, it is now recognized as a cause of diarrhea in the community. This single-center study aimed to determine the epidemiological origin of CDI cases between January 2014 and December 2019 and to compare demographic characteristics, comorbidities, risk factors, severity, and mortality of community CDI with healthcare facility-associated CDI. There were 52 CDI cases from the community (34.4%). Community patients were significantly younger (53 yo vs. 65 yo), less comorbid (Charlson Index 1.65 vs. 3.98), and less severe (only one case). The main risk factor was the use of antibiotics in the previous 90 days (65%). However, we did not find any known risk factor in 7 patients. • Patients from the community represented 34.4% of the total CDI cases. • Community patients were younger, less comorbid, and less severe. • The main risk factor was the use of antibiotics in the previous 90 days. [ABSTRACT FROM AUTHOR]

The article examines the unique biology of the bottle-shaped protozoan Toxoplasma gondii and its role in cancer therapy. Topics covered include the effectiveness of the microbe when engineered into a safe nonreplicating vaccine in breaking tumor control over the immune system, how it can promote survival and preventing cancer recurrence by unleashing potent immunity against already established cancer, and the interrelation of cancer, inflammation, and microbial infection.

In this study we explore patterns of same-turn self-repair within the word, across ten typologically and areally diverse languages. We find universal processes emerging through language-specific resources, namely: recycling is used to delay a next item due, while replacement is used to replace an inappropriate item. For example, most of our languages with prefixes or proclitics recycle those elements to delay production of the root/host, while languages with suffixes tend not to recycle just suffixes without their roots/hosts, since that would not serve to delay the production of the root/host; rather, the whole word is recycled. Replacement of affixes and clitics is rare, regardless of position. We provide several possible explanations for these facts, all based on the nature of replacement. [ABSTRACT FROM AUTHOR]

In the asexual stages, Toxoplasma gondii stage converts between acute phase rapidly replicating tachyzoites and chronic phase slowly dividing bradyzoites. Correspondingly, T. gondii differentially expresses two distinct genes and isoforms of the lactate dehydrogenase enzyme, expressing LDH1 exclusively in the tachyzoite stage and LDH2 preferentially in the bradyzoite stage. LDH catalyzes the interconversion of pyruvate and lactate in anaerobic growth conditions and is utilized for energy supply, however, the precise role of LDH1 and LDH2 in parasite biology in the asexual stages is still unclear. Here, we investigated the biological role of LDH1 and LDH2 in the asexual stages, and the vaccine strain potential of deletion mutants lacking LDH1, LDH2, or both genes (Δldh1, Δldh2 and Δldh1/2). Deletion of LDH1 reduced acute parasite virulence, impaired bradyzoite differentiation in vitro, and markedly reduced chronic stage cyst burdens in vivo. In contrast, deletion of LDH2 impaired chronic stage cyst burdens without affecting virulence or bradyzoite differentiation. Deletion of both LDH1 and LDH2 induced a more severe defect in chronic stage cyst burdens. These LDH mutant phenotypes were not associated with any growth defect. Vaccination of mice with a low dose of mutants deleted for LDH elicited effective protective immunity to lethal challenge infection, demonstrating the vaccine potential of LDH deletion mutants. These results suggest that lactate dehydrogenase in T. gondii controls virulence, bradyzoite differentiation, and chronic infection and reveals the potential of LDH mutants as vaccine strains. [ABSTRACT FROM AUTHOR]

Repair organization provides a powerful mechanism for handling problems of mutual understanding in natural conversation. Our study reviews past research on repair initiation and resolution practices involving embodied-visual practices, including eye gaze, facial expressions, hand gestures, and head and body movements. We charted details of theoretical background, methodology, and main findings for 31 studies. Embodiment was studied equally in connection with self- (SIR) and other-initiated repair (OIR); gaze and gestures were the most commonly studied embodied-visual practices. In OIR sequences, research has focused on upper body and gaze. In SIR sequences, more gestures were examined, but this may be specific to word search, which was predominant in SIR studies. In addition, embodied-visual practices can form gestalts independently from talk, and can occur early in the repair sequence, even pre-trouble source. Data were in Argentine Sign Language, Cha'palaa, Danish, English, Finnish, French, German, Italian, Japanese, Korean, Mandarin, Turkish, and Yélî Dnye. [ABSTRACT FROM AUTHOR]

The article examines the risk factors for suicide in older adults. Topics discussed include the rising suicide rate observed in the older population and the anticipated rate increase as the older population expands. The mental state of the patient and struggles in coping with major physical illnesses are also mentioned.

This study explores the formulation of requests in an American English-speaking shoe repair shop. Taking prior work on request formats as our starting point, we explore the two primary syntactic moods (declarative and interrogative) in our collection and two of the commonly noted subtypes of these moods, need/want-declaratives and can-interrogatives. While our findings in very general terms match those of previous studies, we also find significant grammatical variation within each of these formats, and note interactional uses for each variation. Our examination yields insight into facets of requesting that were previously undescribed. We offer an Emergent Grammar perspective on the complexity of lexicosyntax in the social action of requesting. (Requests, formats, Emergent Grammar, Conversation Analysis, American English, service encounters)* [ABSTRACT FROM AUTHOR]

Nonreplicating type I uracil auxotrophic mutants of Toxoplasma gondii possess a potent ability to activate therapeutic immunity to established solid tumors by reversing immune suppression in the tumor microenvironment. Here we engineered targeted deletions of parasite secreted effector proteins using a genetically tractable Δku80 vaccine strain to show that the secretion of specific rhoptry (ROP) and dense granule (GRA) proteins by uracil auxotrophic mutants of T. gondii in conjunction with host cell invasion activates antitumor immunity through host responses involving CD8α+ dendritic cells, the IL-12/interferon-gamma (IFN-γ) TH1 axis, as well as CD4+ and CD8+ T cells. Deletion of parasitophorous vacuole membrane (PVM) associated proteins ROP5, ROP17, ROP18, ROP35 or ROP38, intravacuolar network associated dense granule proteins GRA2 or GRA12, and GRA24 which traffics past the PVM to the host cell nucleus severely abrogated the antitumor response. In contrast, deletion of other secreted effector molecules such as GRA15, GRA16, or ROP16 that manipulate host cell signaling and transcriptional pathways, or deletion of PVM associated ROP21 or GRA3 molecules did not affect the antitumor activity. Association of ROP18 with the PVM was found to be essential for the development of the antitumor responses. Surprisingly, the ROP18 kinase activity required for resistance to IFN-γ activated host innate immunity related GTPases and virulence was not essential for the antitumor response. These data show that PVM functions of parasite secreted effector molecules, including ROP18, manipulate host cell responses through ROP18 kinase virulence independent mechanisms to activate potent antitumor responses. Our results demonstrate that PVM associated rhoptry effector proteins secreted prior to host cell invasion and dense granule effector proteins localized to the intravacuolar network and host nucleus that are secreted after host cell invasion coordinately control the development of host immune responses that provide effective antitumor immunity against established ovarian cancer. [ABSTRACT FROM AUTHOR]

In this study we explore request sequences at an American shoe repair shop. We investigate the methods through which customers at the shop present objects for repair or alteration, focusing on the fine interplay between their verbal requests and their manual manipulation of these objects. Our analysis shows that customers coming to the shoe repair shop enact an epistemic stance toward the object they have brought in for repair. We argue that the verbal utterances and manual manipulations are fitted to one another with regard to the epistemic stance individual customers display: Customers whose requests are formulated, for instance, as problem descriptions or as inquiries into the repairability of an object manipulate the object only very minimally, if at all; whereas customers whose requests are formulated as solution specifications manipulate the object in ways that also evidence the problem and/or its solution. The data are in American English. [ABSTRACT FROM PUBLISHER]

In early work within Conversation Analysis, utterances within a request sequence which inquire regarding some of the preconditions of granting the request (such as having the item or having the ability to perform the action) are analyzed as pre-requests. Levinson, in an extended discussion of the organization of pre-requests and request sequences, treats utterances such as ‘do you have X?’, ‘can I have X?’ or ‘can you X for me?’ as inquiring about preconditions that could prevent the recipient from granting the request. By checking on preconditions, the requester works to avoid producing a request which will be declined, which is a dispreferred action. In other words, pre-requests, like other pre-sequences, function to project that another action will be produced if a favorable response is given; if not, that projected action may not be produced. In this view, then, they work to maintain the preference organization. This study uses requesting in service encounters to re-examine the evidence for an analysis of such utterances as pre-requests and finds that alternative analyses are more suited in these requesting activities. [ABSTRACT FROM AUTHOR]

Highlights: [•] Immunotherapy based on avirulent Toxoplasma reverses tumor-associated immune suppression. [•] Toxoplasma activates tumor-specific CD8+ T cell responses. [•] Toxoplasma immunotherapy regresses established solid tumors. [Copyright &y& Elsevier]

Reversing tumor-associated immunosuppression seems necessary to stimulate effective therapeutic immunity against lethal epithelial tumors. Here, we show this goal can be addressed using cps, an avirulent, nonreplicating uracil auxotroph strain of the parasite Toxoplasma gondii (T. gondii), which preferentially invades immunosuppressive CD11c+ antigen-presenting cells in the ovarian carcinoma microenvironment. Tumor-associated CD11c+ cells invaded by cps were converted to immunostimulatory phenotypes, which expressed increased levels of the T-cell receptor costimulatory molecules CD80 and CD86. In response to cps treatment of the immunosuppressive ovarian tumor environment, CD11c+ cells regained the ability to efficiently cross-present antigen and prime CD8+ T-cell responses. Correspondingly, cps treatment markedly increased tumor antigen-specific responses by CD8+ T cells. Adoptive transfer experiments showed that these antitumor T-cell responses were effective in suppressing solid tumor development. Indeed, intraper-itoneal cps treatment triggered rejection of established ID8-VegfA tumors, an aggressive xenograft model of ovarian carcinoma, also conferring a survival benefit in a related aggressive model (ID8-Defb29/Vegf-A). The therapeutic benefit of cps treatment relied on expression of IL-12, but it was unexpectedly independent of MyD88 signaling as well as immune experience with T. gondii. Taken together, our results establish that cps preferentially invades tumor-associated antigen-presenting cells and restores their ability to trigger potent antitumor CD8+ T-cell responses. Immunochemotherapeutic applications of cps might be broadly useful to reawaken natural immunity in the highly immunosuppressive microenvironment of most solid tumors. [ABSTRACT FROM AUTHOR]

The ROP16 kinase of Toxoplasma gondii is injected into the host cell cytosol where it activates signal transducer and activator of transcription (STAT)-3 and STAT6. Here, we generated a ROP16 deletion mutant on a Type I parasite strain background, as well as a control complementation mutant with restored ROP16 expression. We investigated the biological role of the ROP16 molecule during T. gondii infection. Infection of mouse bone marrow-derived macrophages with rop16- deleted (Δ ROP16) parasites resulted in increased amounts of IL-12p40 production relative to the ROP16-positive RH parental strain. High level IL-12p40 production in ΔROP16 infection was dependent on the host cell adaptor molecule MyD88, but surprisingly was independent of any previously recognized T. gondii triggered pathway linking to MyD88 (TLR2, TLR4, TLR9, TLR11, IL-1β and IL-18). In addition, ROP16 was found to mediate the suppressive effects of Toxoplasma on LPS-induced cytokine synthesis in macrophages and on IFN-γ-induced nitric oxide production by astrocytes and microglial cells. Furthermore, ROP16 triggered synthesis of host cell arginase-1 in a STAT6-dependent manner. In fibroblasts and macrophages, failure to induce arginase-1 by ΔROP16 tachyzoites resulted in resistance to starvation conditions of limiting arginine, an essential amino acid for replication and virulence of this parasite. ΔROP16 tachyzoites that failed to induce host cell arginase-1 displayed increased replication and dissemination during in vivo infection. We conclude that encounter between Toxoplasma ROP16 and the host cell STAT signaling cascade has pleiotropic downstream effects that act in multiple and complex ways to direct the course of infection. [ABSTRACT FROM AUTHOR]

This article explores the distribution and use of a relatively new grammatical format in English, it’s like + enactment. We propose that it’s like utterances are used to enact thoughts, feelings and attitudes which are internal and affect-laden assessments of a prior utterance or event, produced as assessments that anyone in the same situation might have had. As such they tend to occur within stories, typically during the closing of a story. The enactments are often ‘response cries’ (Goffman, 1978) such as oh, mm, wow, and man. Because of the highly indexical nature of this grammatical format, it represents a fascinating site for participants to work out a ‘world known in common’ (Goodwin, personal communication). [ABSTRACT FROM PUBLISHER]

Abstract: This paper presents the results of a quantitative analysis of recycle and replacement self-repairs in English, Hebrew and German. The analysis revealed patterns of similarities and differences across the languages. Beginning with patterns of difference, we found first that English and Hebrew speakers engage in simple recycling about two-thirds of the time, while German speakers make less frequent use of simple recycling. Second, we found that English speakers frequently recycle back to the subject pronoun of a clause, while Hebrew and German speakers make much less use of subject pronoun as a destination of recycling. Third, we found that Hebrew and German speakers recycle back to prepositions much more frequently than do English speakers. With regard to similarities across the three languages, we noted that all three languages used function words as destinations of recycling more often than content words, while replacing content words at a disproportionately high rate. We claimed that entrenched word order patterns play a crucial role in explaining the facts we have observed; patterns of morphological dependence across collocates also shape self-repair practices in these languages. This study is thus further evidence of the shaping role that morpho-syntactic resources have on the self-repair practices of a speech community. [Copyright &y& Elsevier]

Abstract: New treatments need to be developed for the significant human diseases of toxoplasmosis and malaria to circumvent problems with current treatments and drug resistance. Apicomplexan parasites causing these lethal diseases are deficient in pyrimidine salvage, suggesting that selective inhibition of de novo pyrimidine biosynthesis can lead to a severe loss of uridine 5′-monophosphate (UMP) and thymidine 5′-monophosphate (dTMP) pools, thereby inhibiting parasite RNA and DNA synthesis. Disruption of Toxoplasma gondii carbamoyl phosphate synthetase II (CPSII) induces a severe uracil auxotrophy with no detectable parasite replication in vitro and complete attenuation of virulence in mice. Here we show that a CPSII cDNA minigene efficiently complements the uracil auxotrophy of CPSII-deficient mutants, restoring parasite growth and virulence. Our complementation assays reveal that engineered mutations within, or proximal to, the catalytic triad of the N-terminal glutamine amidotransferase (GATase) domain inactivate the complementation activity of T. gondii CPSII and demonstrate a critical dependence on the apicomplexan CPSII GATase domain in vivo. Surprisingly, indels present within the T. gondii CPSII GATase domain as well as the C-terminal allosteric regulatory domain are found to be essential. In addition, several mutations directed at residues implicated in allosteric regulation in Escherichia coli CPS either abolish or markedly suppress complementation and further define the functional importance of the allosteric regulatory region. Collectively, these findings identify novel features of T. gondii CPSII as potential parasite-selective targets for drug development. [Copyright &y& Elsevier]

This paper is a usage-based study of the grammar of that set of English Relative Clauses with which a relativizer has been described as optional. We argue that the regularities in the use of relativizers in English can be seen as systematically arising from pragmatic-prosodic factors, creating frequency effects, resulting in some cases highly grammaticized formats: the more the Main Clause and the Relative Clause are integrated with each other, that is, approach monoclausal status, the more likely we are to find no relativizer used; conversely, the more separate the two clauses are, the more likely we are to find an overt relativizer. These findings have led us to suggest that the more monoclausal combinations have become unitary storage and processing chunks. We thus see these findings as a contribution not only to our understanding of Relative Clauses, but to our understanding of syntactic organization in general and of the nature of the grammatical practices in which speakers engage in everyday interactions. [ABSTRACT FROM AUTHOR]

This article explores the principles of interaction that shape grammatical practices of conversational speech cross-linguistically. Seven such principles are explored, and the grammatical practices they give rise to are illustrated. The role of these principles in shaping non-linguistic behavior is also touched on. [ABSTRACT FROM AUTHOR]

The present study was designed to examine longitudinal predictors of moral courage in late adolescence. Supportive, responsive parenting, which was measured through home observations and family reports in the fifth grade year, predicted girls’ willingness in late adolescence to speak up or take action when they witnessed or experienced injustice or harm. In contrast, parenting that was harsh and restrictive predicted both girls’ and boys’ later reticence in those circumstances. Further, the effects of earlier parenting were mediated by individual and peer-related factors. Specifically, social competence with peers in fifth grade and self-esteem in twelfth grade mediated the effects of parenting on both moral courage and moral reticence for late adolescent girls, and self-esteem in fifth grade mediated the effects of parenting on moral reticence for late adolescent boys. [ABSTRACT FROM AUTHOR]

Abstract: Several studies suggest that a dopamine transporter uptake inhibitor that has a slower onset and longer duration of action than cocaine in animal behavioral measures and decreases cocaine self-administration would be useful as an indirect dopamine agonist pharmacotherapy to treat cocaine addiction. In the present study, we compared five 3-phenyltropane analogs administered orally in locomotor activity in mice and drug discrimination in rats to gain information concerning relative potency, onset, and duration of action. The compounds were also evaluated for reduction of cocaine self-administration in rats after oral administration. In general, the compounds had a slower onset of action than cocaine and reduced cocaine self-administration. 3β-(4-Chlorophenyl)-2β-(3-(4′-methylphenyl)-isoxazol-5-yl)tropane (RTI-336) was the most potent in locomotor activity and drug discrimination; it was less stimulatory than cocaine in the first hour and had the slowest onset and longest duration of action. It also reduced self-administration of two infusion doses of cocaine in the rat. [Copyright &y& Elsevier]

Two separate carbamoyl phosphate synthetase activities are required for the de novo synthesis of pyrimidines and arginine in most eukaryotes. Toxoplasma gondii is novel in possessing a single carbamoyl phosphate synthetase II gene that corresponds to a glutamine-dependent form required for pyrimidine biosynthesis. We therefore examined arginine acquisition in T. gondii to determine whether the single carbamoyl phosphate synthetase II activity could provide both pyrimidine and arginine biosynthesis. We found that arginine deprivation efficiently blocks the replication of intracellular T. gondii, yet has little effect on long-term parasite viability. Addition of citrulline, but not ornithine, rescues the growth defect observed in the absence of exogenous arginine. This rescue with citrulline is ablated when parasites are cultured in a human citrullinemia fibroblast cell line that is deficient in argininosuccinate synthetase activity. These results reveal the absence of genes and activities of the arginine biosynthetic pathway and demonstrate that T. gondii is an arginine auxotroph. Arginine starvation was also found to efficiently trigger differentiation of replicative tachyzoites into bradyzoites contained within stable cyst-like structures. These same parasites expressing bradyzoite antigens can be efficiently switched back to rapidly proliferating tachyzoites several weeks after arginine starvation. We hypothesise that the absence of gene activities that are essential for the biosynthesis of arginine from carbamoyl phosphate confers a selective advantage by increasing bradyzoite switching during the host response to T. gondii infection. These findings are consistent with a model of host–parasite evolution that allowed host control of bradyzoite induction by trading off virulence for increased transmission. [Copyright &y& Elsevier]

Index Descriptors and Abbreviations: DHFR–TS/m2m3, high-level pyrimethamine resistant dihydrofolate reductase (EC 1.5.1.3)-thymidylate synthase (EC 2.1.1.45); FLAG, FLAG epitope; pyrR, high-level pyrimethamine resistance; SERA, serine repeat antigen [Copyright &y& Elsevier]

The Straw Nicotine Oral Delivery System is a novel form of nicotine replacement therapy designed to provide not only nicotine but also oral and manual stimulation and ease of dosing. The Straw is a single-use drinking straw containing loose nicotine bitartrate particles that are ingested with the first sip of a beverage. This article describes single- and repeated-dose pharmacokinetics and tolerability of The Straw in a group of 24 smokers. The subjects were randomized to receive 12, 8, or 4 mg nicotine or placebo via The Straw following overnight abstinence from smoking. On one occasion, subjects took only one dose of nicotine; a week later they took eight doses, one every 1.5 hr. The orally ingested nicotine was well tolerated with single and repeated dosing. Plasma levels of nicotine peaked between 1 and 2 hr after a single dose at levels ranging from 6 ng/ml (4-mg dose) to 20 ng/ml (8- and 12-mg doses). Nicotine levels were not different between the 8-mg and 12-mg doses, possibly related to individual variability. Dosing repeatedly with The Straw led to greater nicotine levels that continued to increase with additional dosing. Levels achieved were comparable with or greater than those of other replacement products. [ABSTRACT FROM AUTHOR]

Carbamoyl phosphate synthetase II encodes the first enzymic step of de novo pyrimidine biosynthesis. Carbamoyl phosphate synthetase II is essential for Toxoplasma gondii replication and virulence. In this study, we characterised the primary structure of a 28 kb gene encoding Toxoplasma gondii carbamoyl phosphate synthetase II. The carbamoyl phosphate synthetase II gene was interrupted by 36 introns. The predicted protein encoded by the 37 carbamoyl phosphate synthetase II exons was a 1,687 amino acid polypeptide with an N-terminal glutamine amidotransferase domain fused with C-terminal carbamoyl phosphate synthetase domains. This bifunctional organisation of carbamoyl phosphate synthetase II is unique, so far, to protozoan parasites from the phylum Apicomplexa (Plasmodium, Babesia, Toxoplasma) or zoomastigina (Trypanosoma, Leishmania). Apicomplexan parasites possessed the largest carbamoyl phosphate synthetase II enzymes due to insertions in the glutamine amidotransferase and carbamoyl phosphate synthetase domains that were not present in the corresponding gene segments from bacteria, plants, fungi and mammals. The C-terminal allosteric regulatory domain, the carbamoyl phosphate synthetase linker domain and the oligomerisation domain were also distinct from the corresponding domains in other species. The novel C-terminal regulatory domain may explain the lack of activation of Toxoplasma gondii carbamoyl phosphate synthetase II by the allosteric effector 5-phosphoribosyl 1-pyrophosphate. Toxoplasma gondii growth in vitro was markedly inhibited by the glutamine antagonist acivicin, an inhibitor of glutamine amidotransferase activity typically associated with carbamoyl phosphate synthetase II, guanosine monophosphate synthetase, or CTP synthetase. [Copyright &y& Elsevier]

Index Descriptors and Abbreviations: Plasmodium falciparum serine repeat antigen (SERA); Parasite-inhibitory epitope(s); Glutathione-S-transferase (GST) fusion proteins; Epitope mapping. [Copyright &y& Elsevier]

Examines the requirement for virulence on Toxoplasma gondii. Discussions on de novo pyrimidine biosynthesis; Aspects of obligate intracellular replication and pathogenesis for protozoan parasites; Evaluation on long-term protective immunity to toxoplasmosis.

Focuses on language as an embodied practice. Role of prosody and gesture in turn-taking.

Describes a cross-age reading program called Storymates which connected school and home literacy experiences of children through storybook reading to younger siblings, relatives and neighborhood friends. Features of the program; Examples of the storybooks that learners enjoyed; Explanation of the results and reaction to the program.

Presents letters to the editor referencing articles and topics discussed in previous issues. "The Thinking of Students: Revisiting the Sum of Odd Natural Numbers," which focused on odd numbers; Divisibility rule for the number 11 created by a sixth grade student; "Menu of Problems," which discussed problem solving in mathematics.

The article discusses a research conducted in a single local education agency that delineated the professional role responsibilities of four categories of school system personnel in conjunction with the implementation of Public Law 94-142. The legislation states that local education agencies responsible for the implementation of such policies must often make arrangements for the provision of services to clients not previously served. Agencies must assure that the full range of entitlements are available to those already on record as beneficiaries of special service programs.

Toxoplasma gondii is a pervasive protozoan parasite that is responsible for significant zoonoses. A wide array of vaccines using different effector molecules of T. gondii have been studied worldwide to control toxoplasmosis. None of the existing vaccines are sufficiently effective to confer protective immunity. Among the different Toxoplasma -derived effector molecules, T. gondii dense granule protein 15 from the type II strain (GRA15 (II)) was recently characterized as an immunomodulatory molecule that induced host immunity via NF-κB. Therefore, we assessed the immunostimulatory and protective efficacy of recombinant GRA15 (II) (rGRA15) against T. gondii infection in a C57BL/6 mouse model. We observed that rGRA15 treatment increased the production of IL-12p40 from mouse peritoneal macrophages in vitro. Immunization of mice with rGRA15 induced the production of anti-TgGRA15-specific IgG, IgG1 and IgG2c antibodies. The rGRA15-sensitized spleen cells from mice inoculated with the same antigen strongly promoted spleen cell proliferation and IFN-γ production. Immunization with rGRA15 significantly enhanced the survival rate of mice and dramatically decreased parasite burden in mice challenged with the Pru (type II) strain. These results suggested that rGRA15 triggered humoral and cellular immune responses to control infection. However, all of the immunized mice died when challenged with the GRA15-deficient Pru strain or the RH (type I) strain. These results suggest that GRA15 (II)-dependent immunity plays a crucial role in protection against challenge infection with the type II strain of T. gondii. This study is the first report to show GRA15 (II) as a recombinant vaccine antigen against Toxoplasma infection. [ABSTRACT FROM AUTHOR]

This study uses data from a shoe-repair shop, supplemented by data from medical and mundane contexts, to analyze three progressively minimal grammatical formats used to implement offers and requests in interaction (i.e. do you want...?, you want...?, and want...?). We argue that this cline of minimality reflects a cline of the action-initiator's stance, from relatively weak to strong (respectively), regarding their expectation that the action will be accepted or complied with. In doing so, we illustrate that, as part of the design of requests and offers, participants rely on more granular distinctions than a simple binary between interrogative and declarative morphosyntax. We conclude with a discussion of the interactional logic that undergirds the normative use of these grammatical formats, and of our findings' implications for action formation and preference organization. (Conversation analysis, interactional linguistics, offer, request, stance, grammar, morphosyntax) [ABSTRACT FROM AUTHOR]

Two metallo-β-lactamase-producing Klebsiella pneumoniae (HA30 and HA31) were isolated in a hospital in Argentina during 2018. K. pneumoniae HA30 was isolated from a rectal swab during the epidemiological surveillance for carbapenemase-producing strains, while K. pneumoniae HA31 was collected from the same patient 4 days after hospitalization. The aim of the present study was to identify the clonal relationships and resistome of these two NDM-producing K. pneumoniae strains isolated from a patient with a fatal outcome. Whole-genome sequencing (WGS) was performed using Illumina MiSeq-I, and subsequent analysis involved genome assembly, annotation, antibiotic resistance gene identification, multilocus sequence typing (MLST), and plasmid characterization using bioinformatics tools. Conjugation assays to E. coli J53 was conducted as previously described. K. pneumoniae HA30 exhibited extensively drug-resistant phenotype, while HA31 was multidrug-resistant as defined by Magiorakos et al., including both resistance to carbapenems, aminoglycosides and ciprofloxacin with blaNDM-5, blaCTX-M-15 and rmtB genes found in both strains. MLST analysis showed that both strains belonged to ST11, differing by only 4 cgSNPs, indicating that K. pneumoniae HA30 and HA31 were the same strain. Conjugation assays revealed that K. pneumoniae HA31 strain possessed a transferable plasmid to E. coli J53. Bioinformatics studies identified that the same strain colonizing an inpatient during hospital admission subsequently caused the infection leading to a fatal outcome, being the first report of blaNDM-5, rmtB and blaCTX-M-15 genes in a K. pneumoniae ST11 strain from Latin America. Our results also highlighted the importance of focusing on epidemiological surveillance programs. [ABSTRACT FROM AUTHOR]

We have recently reported that treatment of disseminated pancreatic cancer with an attenuatedToxoplasma gondiiuracil auxotroph vaccine promoted antitumor CD8+T cell responses and long-term survival. Here, we optimized the treatment strategy for disseminated pancreatic cancer and show that attenuatedToxoplasma gondiitherapy stimulated effective long-term immunity to pancreatic cancer through mechanisms involving CD4+T cells and pancreatic tumor-specific IgG. Our results suggest that cell-mediated immunity in conjunction with humoral antibody immunity may offer greater resistance to recurrence of highly aggressive tumors. Cancer immunotherapeutic strategies using attenuatedToxoplasma gondiivaccines merit further investigation as a novel strategy to reawaken immunity to primary pancreatic carcinoma and to generate long-lasting immunity to pancreatic cancer recurrences. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii actively invades host cells and establishes a parasitophorous vacuole (PV) that accumulates many proteins secreted by the dense granules (GRA proteins). To date, at least 23 GRA proteins have been reported, though the function(s) of most of these proteins still remains unknown. We targeted gene knockouts at ten GRA gene loci (GRA1-10) to investigate the cellular roles and essentiality of these classical GRA proteins during acute infection in the virulent type I RH strain. While eight of these genes (GRA2-9) were successfully knocked out, targeted knockouts at the GRA1 and GRA10 loci were not obtained, suggesting these GRA proteins may be essential. As expected, the Δgra2 and Δgra6 knockouts failed to form an intravacuolar network (IVN). Surprisingly, Δgra7 exhibited hyper-formation of the IVN in both normal and lipid-free growth conditions. No morphological alterations were identified in parasite or PV structures in the Δgra3, Δgra4, Δgra5, Δgra8, or Δgra9 knockouts. With the exception of the Δgra3 and Δgra8 knockouts, all of the GRA knockouts exhibited defects in their infection rate in vitro. While the single GRA knockouts did not exhibit reduced replication rates in vitro, replication rate defects were observed in three double GRA knockout strains (Δgra4Δgra6, Δgra3Δgra5 and Δgra3Δgra7). However, the virulence of single or double GRA knockout strains in CD1 mice was not affected. Collectively, our results suggest that while the eight individual GRA proteins investigated in this study (GRA2-9) are not essential, several GRA proteins may provide redundant and potentially important functions during acute infection. [ABSTRACT FROM AUTHOR]

Rationale: Despite increased education regarding its dangers, cigarette smoking remains a significant public health concern due to serious associated health consequences such as cancer and respiratory and cardiovascular diseases. Most smokers fail in their attempts to quit smoking, and current pharmacological interventions have relatively low levels of efficacy and are associated with significant adverse events. We have previously reported that combinations of metyrapone and oxazepam, administered at doses that were ineffective when delivered singly, resulted in dose-related decreases in cocaine self-administration in rats while not affecting food-maintained responding during the same sessions. Objectives: The current study was designed to test the effects of the administration of a metyrapone:oxazepam combination on nicotine self-administration in rats. Methods: Several dose combinations of metyrapone (12.5, 25 or 50 mg/kg) and oxazepam (5 or 10 mg/kg) were tested in rats trained to intravenously (IV) self-administer nicotine (0.03 mg/kg/infusion) during 1-h self-administration sessions using both fixed-ratio and progressive-ratio (PR) schedules of reinforcement. Results: The administration of low doses of metyrapone and oxazepam in combination significantly decreased IV nicotine self-administration in rats. At the lowest doses of 12.5 mg/kg of metyrapone and 5 mg/kg of oxazepam, the drugs alone did not decrease IV nicotine self-administration, but the combination was effective. Varenicline was also tested using the fixed-ratio schedule, and reductions in nicotine intake were similar to those seen with the moderate dose of the combination. Conclusions: The results of this study suggest a potential utility of the combination of metyrapone and oxazepam for smoking cessation in humans. [ABSTRACT FROM AUTHOR]

The serine repeat antigen (SERA) of Plasmodium falciparum is a blood stage malaria vaccine candidate. It has been shown that 120 kDa SERA was proteolytically processed into N-terminal 47 kDa fragment (P47), central 56 kDa fragment (P56) that was further converted to 50 kDa (P50), and C-terminal 18 kDa fragment (P18). Here, we have examined the processing of SERA and the localization of its processed fragments by using mouse antibodies directed against recombinant proteins corresponding to different domains of SERA. Western blot analysis showed that all the processing events occurred inside parasitized erythrocytes at the stage just prior to the schizont rupture, that P47 was further processed into two 25 kDa fragments and that the two fragments, which were linked to P18 through disulfide bonds, were associated with the merozoite. In contrast, P50 was completely shed into culture medium and absent from the merozoite. This observation was further supported by the results of indirect immunofluorescence assay. These results could account for the findings that antibodies against P47 were inhibitory to the parasite growth in vitro but those against P50 were not. Finally, we demonstrated that the further processing of P47 is allelic type-dependent. The results of the present study would help in vaccine designing based on SERA. [Copyright &y& Elsevier]