That kid is a grasshopper! Metaphor development from 3 to 9 years of age.

Two major trends on children's skills to comprehend metaphors have governed the literature on the subject: the literal stage hypothesis vs. the early birds hypothesis (Falkum, 2022). We aim to contribute to this debate by testing children's capability to comprehend novel metaphors ('X is a Y') in Spanish with a child-friendly, picture selection task, while also tracking their gaze. Further, given recent findings on the development of metonymy comprehension suggesting a U-shaped developmental curve for this phenomenon (Köder & Falkum, 2020), we aimed to determine the shape of the developmental trajectory of novel metaphor comprehension, and to explore how both types of data (picture selection and gaze behavior) relate to each other. Our results suggest a linear developmental trajectory with 6-year-olds significantly succeeding in picture selection and consistently looking at the metaphorical target even after question onset.

Growth-driven displacement of protein aggregates along the cell length ensures partitioning to both daughter cells in Caulobacter crescentus.

All living cells must cope with protein aggregation, which occurs as a result of experiencing stress. In previously studied bacteria, aggregated protein is collected at the cell poles and is retained throughout consecutive cell divisions only in old pole-inheriting daughter cells, resulting in aggregation-free progeny within a few generations. In this study, we describe the in vivo kinetics of aggregate formation and elimination following heat and antibiotic stress in the asymmetrically dividing bacterium Caulobacter crescentus. Unexpectedly, in this bacterium, protein aggregates form as multiple distributed foci located throughout the cell volume. Time-lapse microscopy revealed that under moderate stress, the majority of these protein aggregates are short-lived and rapidly dissolved by the major chaperone DnaK and the disaggregase ClpB. Severe stress or genetic perturbation of the protein quality control machinery induces the formation of long-lived aggregates. Importantly, the majority of persistent aggregates neither collect at the cell poles nor are they partitioned to only one daughter cell type. Instead, we show that aggregates are distributed to both daughter cells in the same ratio at each division, which is driven by the continuous elongation of the growing mother cell. Therefore, our study has revealed a new pattern of protein aggregate inheritance in bacteria.

Psychopharmacologic treatment of children prenatally exposed to drugs of abuse.

OBJECTIVE: This pilot study compared the pharmacologic treatment history and clinical outcomes observed in pediatric outpatients with psychiatric disorders exposed to drugs of abuse in utero to those of an age-matched, sex-matched and psychiatric disorder-matched, non-drug-exposed group. METHODS: In this matched cohort study, medical records of children treated at an academic, child and adolescent psychiatry outpatient clinic were reviewed. Children with caregiver-reported history of prenatal drug exposure were compared with a non-drug-exposed control group being cared for by the same providers. Patients were rated with the Clinical Global Impressions-Severity scale (CGI-S) throughout treatment. The changes in pre-treatment and post-treatment CGI-S scores and the total number of medication trials were determined between groups. RESULTS: The drug-exposed group (n = 30) had a higher total number of lifetime medication trials compared with the non-drug-exposed group (n = 28) and were taking significantly more total medications, at their final assessment. Unlike the non-drug-exposed group, the drug-exposed group demonstrated a lack of clinical improvement. CONCLUSIONS: These results suggest that in utero drug-exposed children may be more treatment-refractory to or experience greater side effects from the pharmacologic treatment of psychiatric disorders than controls, although we cannot determine if early environment or drugs exposure drives these findings.

Linguistic markers of autism spectrum conditions in narratives: A comprehensive analysis.

Background & Aims: Narratives are regularly elicited as part of standardized assessments for autism spectrum conditions (ASC) such as the ADOS, but have rarely been utilized as linguistic data in their own right. We here aimed for a specific and comprehensive quantitative linguistic profile of such narratives across nominal, verbal, and clausal domains of grammatical organization, and error patterns. Methods: We manually transcribed and annotated narratives elicited from the ADOS from a sample of bilingual autistic Spanish-Catalan children (n = 18), matched with typically developing controls (n = 18) on vocabulary-based verbal IQ. Results: Results revealed fewer relative clauses and more frequent errors in referential specificity and non-relational content-word choice in ASC. Frequent error types are also discussed qualitatively. Conclusions & Implications: These findings, based on more finegrained linguistically defined variables, help to disentangle previous inconsistencies in the literature, and to better situate language changes in the spectrum of neurocognitive changes in this population.

Complete genome sequence of the beer spoilage organism Pediococcus claussenii ATCC BAA-344T.

Pediococcus claussenii is a common brewery contaminant. We have sequenced the chromosome and plasmids of the type strain P. claussenii ATCC BAA-344. A ropy variant was chosen for sequencing to obtain genetic information related to growth in beer, as well as exopolysaccharide and possibly biofilm formation by this organism.

Language level predicts perceptual categorization of complex reversible events in children.

Language plays a well-documented role in perceptual object categorization, but little is known about its role in the categorization of complex events. We explored this here with a perspective from age or developmentally appropriate language capacities in neurotypical children between the ages of two and four years (N = 21), and from delayed language development in a clinical group of children (N = 20), whose verbal mental ages (VMA) often fell far below their chronological ages (CAs). All participants watched two demonstrations of a series of transitive events (e.g. tiger jumps over a girl). The toy agents were then moved out of sight, and participants had to act out the same event type, based on a different tiger and girl that were selected among two distractors. We aimed to determine how mastery of this task relates to CA in the neurotypical group, and whether task performance in the clinical group was predicted by VMA and a standardized measure of grammatical comprehension. Results from a series of logistic mixed-effect regression models showed that neurotypical children start to perform correctly on this task with a chance of around 50% during their third year of CA but reach ceiling performance only during their fourth. A similar pattern emerged for VMA in the clinical group, despite a wide range of CAs and diagnoses. In addition, grammatical comprehension predicted performance. These patterns suggest that language competence plays a role in the perceptual categorization and encoding of complex reversible events.

Patatin-like phospholipase CapV in Escherichia coli - morphological and physiological effects of one amino acid substitution.

In rod-shaped bacteria, morphological plasticity occurs in response to stress, which blocks cell division to promote filamentation. We demonstrate here that overexpression of the patatin-like phospholipase variant CapVQ329R, but not CapV, causes pronounced sulA-independent pyridoxine-inhibited cell filamentation in the Escherichia coli K-12-derivative MG1655 associated with restriction of flagella production and swimming motility. Conserved amino acids in canonical patatin-like phospholipase A motifs, but not the nucleophilic serine, are required to mediate CapVQ329R phenotypes. Furthermore, CapVQ329R production substantially alters the lipidome and colony morphotype including rdar biofilm formation with modulation of the production of the biofilm activator CsgD, and affects additional bacterial traits such as the efficiency of phage infection and antimicrobial susceptibility. Moreover, genetically diverse commensal and pathogenic E. coli strains and Salmonella typhimurium responded with cell filamentation and modulation in colony morphotype formation to CapVQ329R expression. In conclusion, this work identifies the CapV variant CapVQ329R as a pleiotropic regulator, emphasizes a scaffold function for patatin-like phospholipases, and highlights the impact of the substitution of a single conserved amino acid for protein functionality and alteration of host physiology.

The Protein Quality Control Network in Caulobacter crescentus.

The asymmetric life cycle of Caulobacter crescentus has provided a model in which to study how protein quality control (PQC) networks interface with cell cycle and developmental processes, and how the functions of these systems change during exposure to stress. As in most bacteria, the PQC network of Caulobacter contains highly conserved ATP-dependent chaperones and proteases as well as more specialized holdases. During growth in optimal conditions, these systems support a regulated circuit of protein synthesis and degradation that drives cell differentiation and cell cycle progression. When stress conditions threaten the proteome, most components of the Caulobacter proteostasis network are upregulated and switch to survival functions that prevent, revert, and remove protein damage, while simultaneously pausing the cell cycle in order to regain protein homeostasis. The specialized physiology of Caulobacter influences how it copes with proteotoxic stress, such as in the global management of damaged proteins during recovery as well as in cell type-specific stress responses. Our mini-review highlights the discoveries that have been made in how Caulobacter utilizes its PQC network for regulating its life cycle under optimal and proteotoxic stress conditions, and discusses open research questions in this model.

The Chaperonin GroESL Facilitates Caulobacter crescentus Cell Division by Supporting the Functions of the Z-Ring Regulators FtsA and FzlA.

The highly conserved chaperonin GroESL performs a crucial role in protein folding; however, the essential cellular pathways that rely on this chaperone are underexplored. Loss of GroESL leads to severe septation defects in diverse bacteria, suggesting the folding function of GroESL may be integrated with the bacterial cell cycle at the point of cell division. Here, we describe new connections between GroESL and the bacterial cell cycle using the model organism Caulobacter crescentus Using a proteomics approach, we identify candidate GroESL client proteins that become insoluble or are degraded specifically when GroESL folding is insufficient, revealing several essential proteins that participate in cell division and peptidoglycan biosynthesis. We demonstrate that other cell cycle events, such as DNA replication and chromosome segregation, are able to continue when GroESL folding is insufficient. We further find that deficiency of two FtsZ-interacting proteins, the bacterial actin homologue FtsA and the constriction regulator FzlA, mediate the GroESL-dependent block in cell division. Our data show that sufficient GroESL is required to maintain normal dynamics of the FtsZ scaffold and divisome functionality in C. crescentus In addition to supporting divisome function, we show that GroESL is required to maintain the flow of peptidoglycan precursors into the growing cell wall. Linking a chaperone to cell division may be a conserved way to coordinate environmental and internal cues that signal when it is safe to divide.IMPORTANCE All organisms depend on mechanisms that protect proteins from misfolding and aggregation. GroESL is a highly conserved molecular chaperone that functions to prevent protein aggregation in organisms ranging from bacteria to humans. Despite detailed biochemical understanding of GroESL function, the in vivo pathways that strictly depend on this chaperone remain poorly defined in most species. This study provides new insights into how GroESL is linked to the bacterial cell division machinery, a crucial target of current and future antimicrobial agents. We identify a functional interaction between GroESL and the cell division proteins FzlA and FtsA, which modulate Z-ring function. FtsA is a conserved bacterial actin homologue, suggesting that as in eukaryotes, some bacteria exhibit a connection between cytoskeletal actin proteins and chaperonins. Our work further defines how GroESL is integrated with cell wall synthesis and illustrates how highly conserved folding machines ensure the functioning of fundamental cellular processes during stress.

DNA Blocks the Lethal Effect of Human Beta-Defensin 2 Against Neisseria meningitidis.

Neisseria meningitidis is a gram-negative bacterium that often asymptomatically colonizes the human nasopharyngeal tract. These bacteria cross the epithelial barrier can cause life-threatening sepsis and/or meningitis. Antimicrobial peptides are one of the first lines of defense against invading bacterial pathogens. Human beta-defensin 2 (hBD2) is an antimicrobial peptide with broad antibacterial activity, although its mechanism of action is poorly understood. Here, we investigated the effect of hBD2 on N. meningitidis. We showed that hBD2 binds to and kills actively growing meningococcal cells. The lethal effect was evident after 2 h incubation with the peptide, which suggests a slow killing mechanism. Further, the membrane integrity was not changed during hBD2 treatment. Incubation with lethal doses of hBD2 decreased the presence of diplococci; the number and size of bacterial microcolonies/aggregates remained constant, indicating that planktonic bacteria may be more susceptible to the peptide. Meningococcal DNA bound hBD2 in mobility shift assays and inhibited the lethal effect of hBD2 in a dose-dependent manner both in suspension and biofilms, supporting the interaction between hBD2 and DNA. Taken together, the ability of meningococcal DNA to bind hBD2 opens the possibility that extracellular DNA due to bacterial lysis may be a means of N. meningitidis to evade immune defenses.

The prevalence of gene duplications and their ancient origin in Rhodobacter sphaeroides 2.4.1.

BACKGROUND: Rhodobacter sphaeroides 2.4.1 is a metabolically versatile organism that belongs to α-3 subdivision of Proteobacteria. The present study was to identify the extent, history, and role of gene duplications in R. sphaeroides 2.4.1, an organism that possesses two chromosomes. RESULTS: A protein similarity search (BLASTP) identified 1247 orfs (~29.4% of the total protein coding orfs) that are present in 2 or more copies, 37.5% (234 gene-pairs) of which exist in duplicate copies. The distribution of the duplicate gene-pairs in all Clusters of Orthologous Groups (COGs) differed significantly when compared to the COG distribution across the whole genome. Location plots revealed clusters of gene duplications that possessed the same COG classification. Phylogenetic analyses were performed to determine a tree topology predicting either a Type-A or Type-B phylogenetic relationship. A Type-A phylogenetic relationship shows that a copy of the protein-pair matches more with an ortholog from a species closely related to R. sphaeroides while a Type-B relationship predicts the highest match between both copies of the R. sphaeroides protein-pair. The results revealed that ~77% of the proteins exhibited a Type-A phylogenetic relationship demonstrating the ancient origin of these gene duplications. Additional analyses on three other strains of R. sphaeroides revealed varying levels of gene loss and retention in these strains. Also, analyses on common gene pairs among the four strains revealed that these genes experience similar functional constraints and undergo purifying selection. CONCLUSIONS: Although the results suggest that the level of gene duplication in organisms with complex genome structuring (more than one chromosome) seems to be not markedly different from that in organisms with only a single chromosome, these duplications may have aided in genome reorganization in this group of eubacteria prior to the formation of R. sphaeroides as gene duplications involved in specialized functions might have contributed to complex genomic development.

Protein aggregation in bacteria.

Protein aggregation occurs as a consequence of perturbations in protein homeostasis that can be triggered by environmental and cellular stresses. The accumulation of protein aggregates has been associated with aging and other pathologies in eukaryotes, and in bacteria with changes in growth rate, stress resistance and virulence. Numerous past studies, mostly performed in Escherichia coli, have led to a detailed understanding of the functions of the bacterial protein quality control machinery in preventing and reversing protein aggregation. However, more recent research points toward unexpected diversity in how phylogenetically different bacteria utilize components of this machinery to cope with protein aggregation. Furthermore, how persistent protein aggregates localize and are passed on to progeny during cell division and how their presence impacts reproduction and the fitness of bacterial populations remains a controversial field of research. Finally, although protein aggregation is generally seen as a symptom of stress, recent work suggests that aggregation of specific proteins under certain conditions can regulate gene expression and cellular resource allocation. This review discusses recent advances in understanding the consequences of protein aggregation and how this process is dealt with in bacteria, with focus on highlighting the differences and similarities observed between phylogenetically different groups of bacteria.

Thyroparathyroidectomy procedures and thyroxine levels in the chinchilla.

Thyroid and embedded parathyroid glands were surgically removed (thyroparathyroidectomized) from adult chinchillas (Chinchilla laniger) to create an animal model of hypothyroidism. Thyroxine (T4) levels were measured at the time of surgery and one or two times after surgery from 10 thyroparathyroidectomized chinchillas and five sham controls to establish baseline serum T4 levels and to assess the degree and duration of hypothyroidism in this animal model. Baseline T4 levels ranged from 3.4 to 6.4 microg/dl (mean +/- 1 standard deviation, 5.25 +/- 0.84 microg/dl), with no differences between male and female chinchillas (5.4 +/- 0.6 microg/dl versus 5.2 +/- 1.0 microg/dl, respectively). T4 levels were significantly reduced in 80% of thyroparathyroidectomized chinchillas when measured 6 to 14 days after surgery, but reductions were variable, ranging from 9 to 89% in individual animals. There was rapid regrowth of thyroid tissue and a return of T4 levels to the baseline range in five of the seven animals followed for 1 to 2 months after surgery. T4 levels increased significantly in the sham-operated chinchillas, indicating a nonspecific effect of surgery. The results establish surgical procedures for creating a model of variable, transient hypothyroidism in the chinchilla. We also summarize published basal T4 values for various laboratory animals, to provide a convenient reference.

Fiber type composition of the human quadratus plantae muscle: a comparison of the lateral and medial heads.

BACKGROUND: The human quadratus plantae muscle has been attributed a variety of functions, however no consensus has been reached on its significance to foot functioning. The architecture of the human quadratus plantae consists of an evolutionarily conserved lateral head, and a medial head thought to be unique to Man. Surveys of human anatomy have demonstrated the absence of either the medial or lateral head in 20% of the population, which may have implications for foot functioning if each muscle head performs a discrete function. METHODS: We investigated the quadratus plantae from eleven formalin-embalmed specimens with a mean age of 84 ± 9 years. Immunohistochemical methods were used to determine the percentage of Type I and Type II muscle fibers in the medial and lateral heads of the quadratus plantae from these specimens. RESULTS: Results showed striking homogeneity in fiber type composition within an individual, with an average difference in Type I fiber content of 4.1% between lateral and medial heads. Between individuals, however, the ratio of fiber types within the quadratus plantae was highly variable, with Type I fiber percentages ranging from 19.1% to 91.6% in the lateral head, and 20.4% to 97.0% within the medial head. CONCLUSIONS: Our finding of similar fiber type composition of lateral and medial heads within an individual supports the hypothesis that the two heads have a singular function.

Aproximación al lenguaje en el trastorno del espectro autista / An approach to language in austim / Aproximació al llenguatge en el trastorn de l’espectre autista

Este artículo examina y reconsidera el papel del lenguaje en el trastorno de espectro autista (TEA). Aunque las anomalías lingüísticas no constituyen una categoría específica para el diagnóstico del TEA, no han pasado nunca desapercibidas. Es más, se observan en todo el espectro, son un indicador del grado de afectación y tienen un valor muy importante para el pronóstico. Un estudio detallado del lenguaje aportaría más información del perfil cognitivo y mejoras en el diagnóstico y tratamiento. Facilitaría además el diseño de terapias que actuaran sobre el lenguaje. El papel de la mentalización en la etiología de la conducta violenta

This article surveys and re-assesses the role of language in autism spectrum disorder (ASD). Although language abnormalities are not a specific category of ASD diagnosis, they have never gone unnoticed. Moreover, they are observable across the entirety of the spectrum and are an indicator of severity levels and highly relevant for prognosis. A detailed study of language can provide us with more information about the cognitive profile and improvements in diagnosis and treatment. In addition, it can promote therapy designs that would have an effect on language

Aquest article examina i reconsidera el paper del llenguatge en el trastorn de l’espectre autista (TEA). Tot i que les anomalies lingüístiques no constitueixen una categoria específica per al diagnòstic del TEA, mai no han passat desapercebudes. És més, s’observen en tot l’espectre, són un indi­cador del grau d’afectació i tenen un valor molt important per al pronòstic. Un estudi detallat del llenguatge aportaria més informació del perfil cognitiu i millores en el diagnòstic i tractament. Facilitaria, a més, el disseny de teràpies que actuaran sobre el llenguatge