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The current study aimed to investigate the validity and reliability of the Hungarian version of the brief Work-Family Conflict Questionnaire (Conflicto Trabajo – Familia, CCTF) using both homogeneous (social care workers, N = 206) and heterogeneous (N = 586) occupational samples. In order to examine construct validity, we explored both two-factor and bifactor models. Our findings provided greater support for the two-factor model (homogeneous sample: χ2 = 14.032, p = .379, df = 13; CFI = 0.999; NNFI = 0.998; RMSEA = 0.020 [0.000–0.051]; heterogeneous sample: χ2 = 40.213, p < .001 df = 13; CFI = 0.993; NNFI = 0.985; RMSEA = 0.060 [0.023–0.079]). Our results demonstrated good reliability (ω = 0.797–0.911) and predictive validity, which we tested by exploring the relation of the construct with burnout and psychosomatic symptoms. Our results suggest that the Hungarian version of the CCTF is a reliable and valid instrument for measuring both work-to-family and family-to-work conflict.

Ancylostoma caninum is an important zoonotic gastrointestinal nematode of dogs worldwide and a close relative of human hookworms. We recently reported that racing greyhound dogs in the USA are infected with A. caninum that are commonly resistant to multiple anthelmintics. Benzimidazole resistance in A. caninum in greyhounds was associated with a high frequency of the canonical F167Y(TTC>TAC) isotype-1 β-tubulin mutation. In this work, we show that benzimidazole resistance is remarkably widespread in A. caninum from domestic dogs across the USA. First, we identified and showed the functional significance of a novel benzimidazole isotype-1 β-tubulin resistance mutation, Q134H(CAA>CAT). Several benzimidazole resistant A. caninum isolates from greyhounds with a low frequency of the F167Y(TTC>TAC) mutation had a high frequency of a Q134H(CAA>CAT) mutation not previously reported from any eukaryotic pathogen in the field. Structural modeling predicted that the Q134 residue is directly involved in benzimidazole drug binding and that the 134H substitution would significantly reduce binding affinity. Introduction of the Q134H substitution into the C. elegans β-tubulin gene ben-1, by CRISPR-Cas9 editing, conferred similar levels of resistance as a ben-1 null allele. Deep amplicon sequencing on A. caninum eggs from 685 hookworm positive pet dog fecal samples revealed that both mutations were widespread across the USA, with prevalences of 49.7% (overall mean frequency 54.0%) and 31.1% (overall mean frequency 16.4%) for F167Y(TTC>TAC) and Q134H(CAA>CAT), respectively. Canonical codon 198 and 200 benzimidazole resistance mutations were absent. The F167Y(TTC>TAC) mutation had a significantly higher prevalence and frequency in Western USA than in other regions, which we hypothesize is due to differences in refugia. This work has important implications for companion animal parasite control and the potential emergence of drug resistance in human hookworms.

Whole-genome sequencing is being rapidly applied to the study of helminth genomes, including de novo genome assembly, population genetics, and diagnostic applications. Although late-stage juvenile and adult parasites typically produce sufficient DNA for molecular analyses, these parasitic stages are almost always inaccessible in the live host; immature life stages found in the environment for which samples can be collected non-invasively offer a potential alternative; however, these samples typically yield very low quantities of DNA, can be environmentally resistant, and are susceptible to contamination, often from bacterial or host DNA. Here, we have tested five low-input DNA extraction protocols together with a low-input sequencing library protocol to assess the feasibility of whole-genome sequencing of individual immature helminth samples. These approaches do not use whole-genome amplification, a common but costly approach to increase the yield of low-input samples. We first tested individual parasites from two species spotted onto FTA cards—egg and L1 stages of Haemonchus contortus and miracidia of Schistosoma mansoni—before further testing on an additional five species—Ancylostoma caninum, Ascaridia dissimilis, Dirofilaria immitis, Strongyloides stercoralis, and Trichuris muris—with an optimal protocol. A sixth species—Dracunculus medinensis—was included for comparison. Whole-genome sequencing followed by analyses to determine the proportion of on- and off-target mapping revealed successful sample preparations for six of the eight species tested with variation both between species and between different life stages from some species described. These results demonstrate the feasibility of whole-genome sequencing of individual parasites, and highlight a new avenue toward generating sensitive, specific, and information-rich data for the diagnosis and surveillance of helminths.

Ancylostoma caninum is an important zoonotic gastrointestinal nematode of dogs worldwide and a close relative of human hookworms. We recently reported that racing greyhound dogs in the USA are infected with A. caninum that are commonly resistant to multiple anthelmintics. Benzimidazole resistance in A. caninum in greyhounds was associated with a high frequency of the canonical F167Y(TTC>TAC) isotype-1 β-tubulin mutation. In this work, we show that benzimidazole resistance is remarkably widespread in A. caninum from domestic dogs across the USA. First, we identified and showed the functional significance of a novel benzimidazole isotype-1 β-tubulin resistance mutation, Q134H(CAA>CAT). Several benzimidazole resistant A. caninum isolates from greyhounds with a low frequency of the F167Y(TTC>TAC) mutation had a high frequency of a Q134H(CAA>CAT) mutation not previously reported from any eukaryotic pathogen in the field. Structural modeling predicted that the Q134 residue is directly involved in benzimidazole drug binding and that the 134H substitution would significantly reduce binding affinity. Introduction of the Q134H substitution into the C. elegans β-tubulin gene ben-1, by CRISPR-Cas9 editing, conferred similar levels of resistance as a ben-1 null allele. Deep amplicon sequencing on A. caninum eggs from 685 hookworm positive pet dog fecal samples revealed that both mutations were widespread across the USA, with prevalences of 49.7% (overall mean frequency 54.0%) and 31.1% (overall mean frequency 16.4%) for F167Y(TTC>TAC) and Q134H(CAA>CAT), respectively. Canonical codon 198 and 200 benzimidazole resistance mutations were absent. The F167Y(TTC>TAC) mutation had a significantly higher prevalence and frequency in Western USA than in other regions, which we hypothesize is due to differences in refugia. This work has important implications for companion animal parasite control and the potential emergence of drug resistance in human hookworms. Author summary: Although increasingly common in livestock, no reports of widespread anthelmintic resistance are confirmed in any companion animal or human gastrointestinal nematode parasite to date. The canine hookworm is a common intestinal zoonotic parasite of dogs with severe clinical impacts in young dogs, and for which control is dependent on regular anthelmintic use. We recently reported multiple anthelmintic drug resistance in A. caninum isolates from greyhounds derived from multiple locations in the USA likely caused by long standing intensive treatment regimens in kennels. In this study, we investigated benzimidazole resistance in A. caninum in pet dogs across the USA. We also identified and showed the functional significance of a novel benzimidazole isotype-1 β-tubulin resistance mutation in A. caninum from greyhounds that has not been previously reported in the field for any organism. We then determined that this novel mutation, as well as a previously characterized resistance mutation, were present, often at high frequency, in many A. caninum populations across the USA. This study reports the first evidence of widespread drug resistance for any parasitic nematode of companion animals and illustrates the power of molecular approaches to rapidly assess anthelmintic resistance in a region. [ABSTRACT FROM AUTHOR]

The current study aimed to investigate the validity and reliability of the Hungarian version of the brief Work-Family Conflict Questionnaire (Conflicto Trabajo - Familia, CCTF) using both homogeneous (social care workers, N = 206) and heterogeneous (N = 586) occupational samples. In order to examine construct validity, we explored both two-factor and bifactor models. Our findings provided greater support for the two-factor model (homogeneous sample: χ² = 14.032, p = .379, df = 13; CFI = 0.999; NNFI = 0.998; RMSEA = 0.020 [0.000-0.051]; heterogeneous sample: χ² = 40.213, p < .001 df = 13; CFI = 0.993; NNFI = 0.985; RMSEA = 0.060 [0.023-0.079]). Our results demonstrated good reliability (ω = 0.797-0.911) and predictive validity, which we tested by exploring the relation of the construct with burnout and psychosomatic symptoms. Our results suggest that the Hungarian version of the CCTF is a reliable and valid instrument for measuring both work-tofamily and family-to-work conflict. [ABSTRACT FROM AUTHOR]

While previous studies have debated the extent to which Sarah Scott's Millenium Hall values the disabled, this article argues that the novel's treatment of disability cannot be separated from its treatment of gender and old age. Operating at the nexus of disability studies and aging studies, this article situates Scott's novel as a key text in the history of disability. Writing in a century that was fascinated by the vagaries of human aging, Scott radically revises her culture's principal assumptions about female old age. Whereas other eighteenth-century authors cast female aging as a process of undesirable deformation, Scott suggests that old age and disability benefit her heroines by bringing them into contact with the timeless realm of the divine. The novel therefore enriches our understanding of disability in the eighteenth century and beyond, demonstrating the powerful ways in which disability, gender, and temporality intersect. [ABSTRACT FROM AUTHOR]

A powerful strategy to obtain complex supramolecular materials is the bottom-up construction of noncovalently bound materials by hierarchical self-assembly. This assembly process involves step wise, uniform increases to the architectural complexity of a substrate, starting from discrete precursors and growing in dimensionality through controlled reactivity to a final product. Herein, two orthogonal processes are exploited: coordination-driven self-assembly and hydrogen bonding. The former relies on the predictable formation of metal-ligand bonds wherein the directionalities of the rigid precursors used determines the structural outcome. The latter uses 2-ureido-4-pyrimidinone interfaces that are structurally robust by virtue of the quadruple hydrogen bonding that can occur between subunits. By combining these two processes into a single system, it is possible to generate hierarchical materials that preserve the attractive tunability associated with discrete supra molecular coordination complexes. For instance, the synthesis of a one-dimensional chain comprising linked metalla-rhomboids is readily adapted to a 2D cross-linked hexagonal network by simply selecting a different metal acceptor precursor as an assembly component. The specific interactions between subunits, in this case platinum(ll)-pyridyl bonds and the quadruple H-bonding of ureidopyrimidinone, are unchanged, establishing a unique strategy to obtain supramolecular polymers with marked topological differences with minimal synthetic redesign. In addition, the structural rigidity imposed by the inclusion of the platinum metallacycles serves to minimize the formation of cyclic oligomers, increasing the efficacy of formation and improving the properties of the resultant materials. Furthermore, this study taps the potential of organoplatinum(ll) metallacycles in materials science. [ABSTRACT FROM AUTHOR]

Abstract  It has become increasingly clear that the investigation of vascular development is best considered in the context of a whole tissue environment since in vivo endothelial cells interact closely with other cell types. Murine embryoid bodies have been used as a model for the early development of a vascular network and are amenable to genetic manipulation and treatment with soluble modulators. However, quantifying morphological changes in these complex three-dimensional structures is challenging. In this paper we describe protocols to culture embryoid bodies on a large scale to study vascular development together with methods to quantify changes seen when antiangiogenic agents or endothelial cell-specific transgenes are introduced. [ABSTRACT FROM AUTHOR]

Reports on the similarities of the properties of coupling of adenosine triphosphates (ATP) hydrolysis to electron transfer in nitrogeneses to nucleotide-dependent switch proteins. What is an essential feature of nitrogenase mechanism; Dependence of nucleotide hydrolysis on the association of the ATP binding agent; What preliminary ideas about the nature of ATP hydrolysis were based on.