Development of KISS1 knockout pigs is characterized by hypogonadotropic hypogonadism, normal growth, and reduced skatole.

Kisspeptin is a major regulator of gonadotropin secretion in pigs. Previously, CRISPR/Cas9 knockout of KISS1 was used to develop a mosaic parental line of pigs to generate offspring that would not need castration due to loss of kisspeptin. The current goal was to characterize growth and reproductive development of F1 pigs from this parental line. Body weights, gonadotropin concentrations and gonadal development were measured from birth through development (boars to 220 d of age, n = 42; gilts to 160 d of age, n = 36). Testosterone, skatole, and androstenone were also measured in boars. Blood samples were collected by jugular venipuncture for quantification of serum hormones, gonadal tissues collected for gross morphology and histology, and a fat biopsy collected (boars) for skatole and androstenone analysis. Body weight did not differ with genotype. There were no differences between KISS1+/+ and heterozygote KISS1+/- animals for most parameters measured. Gonadotropin concentrations were reduced in KISS1-/- boars and gilts compared with KISS1+/+ and KISS1+/- animals (P < 0.05). Concentrations of testosterone in serum and both androstenone and skatole in adipose were less in KISS1-/- boars than in KISS1+/+ and KISS1+/- boars (P < 0.05). Hypogonadism was in all KISS1-/- gilts and boars. These data indicate that knocking out KISS1 causes hypogonadotropic hypogonadism but does not negatively affect growth in pigs. Only one KISS1 allele is needed for normal gonadotropin secretion and gonadal development, and accumulation of compounds in adipose leading to boar taint.

Alternative double strand break repair pathways shape the evolution of high recombination in the honey bee, Apis mellifera.

Social insects, particularly honey bees, have exceptionally high genomic frequencies of genetic recombination. This phenomenon and underlying mechanisms are poorly understood. To characterise the patterns of crossovers and gene conversion in the honey bee genome, a recombination map of 187 honey bee brothers was generated by whole-genome resequencing. Recombination events were heterogeneously distributed without many true hotspots. The tract lengths between phase shifts were bimodally distributed, indicating distinct crossover and gene conversion events. While crossovers predominantly occurred in G/C-rich regions and seemed to cause G/C enrichment, the gene conversions were found predominantly in A/T-rich regions. The nucleotide composition of sequences involved in gene conversions that were associated with or distant from crossovers corresponded to the differences between crossovers and gene conversions. These combined results suggest two types of DNA double-strand break repair during honey bee meiosis: non-canonical homologous recombination, leading to gene conversion and A/T enrichment of the genome, and the canonical homologous recombination based on completed double Holliday Junctions, which can result in gene conversion or crossover and is associated with G/C bias. This G/C bias may be selected for to balance the A/T-rich base composition of eusocial hymenopteran genomes. The lack of evidence for a preference of the canonical homologous recombination for double-strand break repair suggests that the high genomic recombination rate of honey bees is mainly the consequence of a high rate of double-strand breaks, which could in turn result from the life history of honey bees and their A/T-rich genome.

Bridging the transition from homelessness: Developing an occupational therapy framework.

BACKGROUND: Occupational therapists support individuals experiencing homelessness in traditional roles, and occupational therapy positions focussed specifically on homelessness appear to be growing. OBJECTIVES: To develop and refine a framework to guide occupational therapy practice and research in homelessness. METHOD: We developed a framework and refined it through a stakeholder consultation process conducted with 17 international occupational therapy experts using an online survey. In this survey, we presented an initial framework and requested qualitative feedback. We analyzed this qualitative data using content analysis. RESULTS: Stakeholder feedback was categorized into eight recommendations: (1) Revision to the 'four processes'; (2) Emphasizing social justice and systems-level advocacy; (3) Reflecting intersectionality; (4) Emphasizing meaningful activity; (5) Emphasizing peer support; (6) Incorporating a focus on independent living skills; (7) Increasing a focus on an activity for addressing substance misuse; and (8) Acknowledging cognitive and physical health. Each of these recommendations was incorporated into a refined version of this framework. These recommendations and a refined version of the framework are presented in this paper. CONCLUSIONS: We have developed and refined a framework aimed at guiding practice and research in occupational therapy in homelessness that will be evaluated in future research. SIGNIFICANCE: Though a range of frameworks exists for guiding the practice of occupational therapists more generally, this framework represents the first that is focussed specifically on guiding occupational therapy practice and research with individuals who experience homelessness. Research and practice implications are discussed.

Role of gonadotropin-releasing hormone-II and its receptor in swine reproduction.

The pig represents the only livestock mammal capable of producing a functional protein for the second mammalian form of gonadotropin-releasing hormone (GnRH-II) and its receptor (GnRHR-II). To examine the role of GnRH-II and its receptor in pig reproduction, we produced a unique swine line with ubiquitous knockdown of endogenous GnRHR-II levels (GnRHR-II knockdown [KD]), which is largely the focus of this review. In mature GnRHR-II KD males, circulating testosterone concentrations were 82% lower than littermate control boars, despite similar luteinizing hormone (LH) levels. In addition, nine other gonadal steroids were reduced in the serum of GnRHR-II KD boars, whereas adrenal steroids (except 11-deoxycortisol) did not differ between lines. Interestingly, testes from GnRHR-II KD males had fewer, hypertrophic Leydig cells and fewer, enlarged seminiferous tubules than control testes. As expected, downstream reproductive traits such as androgen-dependent organ weights and semen characteristics were also significantly reduced in GnRHR-II KD versus control boars. Next, we explored the importance of this novel ligand/receptor complex in female reproduction. Transgenic gilts had fewer, but heavier, corpora lutea with smaller luteal cells than littermate control females. Although the number of antral follicles were similar between lines, the diameter of antral follicles tended to be larger in GnRHR-II KD females. In regard to steroidogenesis, circulating concentrations of progesterone and 17ß-estradiol were lower in transgenic compared to control gilts, even though serum levels of follicle-stimulating hormone and LH were similar. Thus, GnRH-II and GnRHR-II represent a potential avenue to enhance fertility and promote the profitability of pork producers.

Spectral degradation influences phonological memory in typically hearing adults.

Phonological processing is a fundamental component of language, can be impaired in people with hearing loss, and involves several confounded subprocesses. The purpose of this study was to systematically examine several phonological subprocesses - i.e., the spectral quality of auditory input and phonological short-term and long-term memory - in order to better understand how they interact with one another in basic linguistic tasks. Using an experimental, within-subjects design, 30 typically-hearing adults completed nonword repetition (NWR) and auditory lexical decision (ALD) tasks varying in spectral quality (normal versus spectrally-degraded), consonant age of acquisition (CAoA; i.e. early-acquired versus late-acquired consonants), syllable length (NWR task), and lexical status (ALD task). In NWR, spectral degradation muted the word length effect, though performance differed depending on how familiar participants were with the degraded stimuli. ALD findings showed that the magnitude of the degradation effect varied between stimuli comprising early-acquired versus late-acquired consonants. The robust effect of spectral degradation on phonological short-term and long-term memory provides a model of the interactive nature of these subprocesses in typical adults. Future work with populations with hearing loss can provide a comparison to help understand how the typical and clinical phonological systems differ.

Coronavirus disease 2019 in the pediatric emergency department: unique considerations in preparation and response.

PURPOSE OF REVIEW: Pediatric Emergency Departments (PEDs) have experienced unique considerations throughout the coronavirus disease 2019 (COVID-19) pandemic. We review the adaptations and challenges surrounding the preparation and response for pediatric emergency patients, with a specific focus on operational modifications, evolving personal protected equipment (PPE) needs, protected resuscitation responses, clinical characteristics in children, and the unintended effects on children and youth. RECENT FINDINGS: COVID-19 has thus far proven to have a milder course in children, with manifestations ranging from asymptomatic carriage or typical viral symptoms, to novel clinical entities such as 'COVID toes' and multisystem inflammatory syndrome in children (MIS-C), the latter associated with potentially significant morbidity. It has had an important effect on primary prevention, injury rates, reduced presentations for emergency care, and increased mental health, abuse and neglect rates in children and youth. PEDs have prepared successfully. The most significant adjustments have occurred with screening, testing, and consistent and effective use of PPE, along with protected responses to resuscitation, adaptations to maintain family-centered care, and technological advances in communication and virtual care. Simulation has been key to the successful implementation of many of these strategies. SUMMARY: COVID-19 has pushed PEDs to rapidly adapt to evolving clinical and societal needs, with both resultant challenges and positive advances. Further experience and research will guide how in the face of a global pandemic we can further optimize the clinical and operational care of children and youth, ensure robust educational training programs, and maintain provider safety and wellness.

Assessing and promoting the use of implementation intentions in clinical practice.

RATIONALE: Striving for goals is a key part of psychological therapy, but people often struggle to translate their goals into action. Prior evidence has found that forming if then plans (or 'implementation intentions') is an effective way to bridge the gap between goals and action. However, it is unclear if therapists naturally prompt their clients to form implementation intentions and, if not, whether training would be feasible. METHOD AND RESULTS STUDY 1: Researchers coded the behavior change techniques used in 40 sessions of therapy for depression using a Cognitive Behavioral Therapy approach and a Person-Centered Experiential Therapy approach and found that therapists do not typically prompt their clients to form implementation intentions in either therapeutic approach. METHOD AND RESULTS STUDIES 2 AND 3: The aim was to develop and evaluate a training program for therapists on implementation intentions. Training was delivered face-to-face to 69 cognitive-behavioral therapists (Study 2), and online to 87 therapists working across models (Study 3) and therapists completed self-report measures of their use and knowledge of implementation intentions before training, post-training, and follow-up. The training significantly increased therapists' use and knowledge of implementation intentions. CONCLUSIONS: Taken together, these findings suggest therapists can be trained in the use of implementation intentions and that appropriate content might be integrated into training programs.

Genomic correlates of recombination rate and its variability across eight recombination maps in the western honey bee (Apis mellifera L.).

BACKGROUND: Meiotic recombination has traditionally been explained based on the structural requirement to stabilize homologous chromosome pairs to ensure their proper meiotic segregation. Competing hypotheses seek to explain the emerging findings of significant heterogeneity in recombination rates within and between genomes, but intraspecific comparisons of genome-wide recombination patterns are rare. The honey bee (Apis mellifera) exhibits the highest rate of genomic recombination among multicellular animals with about five cross-over events per chromatid. RESULTS: Here, we present a comparative analysis of recombination rates across eight genetic linkage maps of the honey bee genome to investigate which genomic sequence features are correlated with recombination rate and with its variation across the eight data sets, ranging in average marker spacing ranging from 1 Mbp to 120 kbp. Overall, we found that GC content explained best the variation in local recombination rate along chromosomes at the analyzed 100 kbp scale. In contrast, variation among the different maps was correlated to the abundance of microsatellites and several specific tri- and tetra-nucleotides. CONCLUSIONS: The combined evidence from eight medium-scale recombination maps of the honey bee genome suggests that recombination rate variation in this highly recombining genome might be due to the DNA configuration instead of distinct sequence motifs. However, more fine-scale analyses are needed. The empirical basis of eight differing genetic maps allowed for robust conclusions about the correlates of the local recombination rates and enabled the study of the relation between DNA features and variability in local recombination rates, which is particularly relevant in the honey bee genome with its exceptionally high recombination rate.

A structured population model suggests that long life and post-reproductive lifespan promote the evolution of cooperation.

Social organization correlates with longevity across animal taxa. This correlation has been explained by selection for longevity by social evolution. The reverse causality is also conceivable but has not been sufficiently considered. We constructed a simple, spatially structured population model of asexually reproducing individuals to study the effect of temporal life history structuring on the evolution of cooperation. Individuals employed fixed strategies of cooperation or defection towards all neighbours in a basic Prisoner's Dilemma paradigm. Individuals aged and transitioned through different life history stages asynchronously without migration. An individual's death triggered a reproductive event by one immediate neighbour. The specific neighbour was chosen probabilistically according to the cumulative payoff from all local interactions. Varying the duration of pre-reproductive, reproductive, and post-reproductive life history stages, long-term simulations allowed a systematic evaluation of the influence of the duration of these specific life history stages. Our results revealed complex interactions among the effects of the three basic life history stages and the benefit to defect. Overall, a long post-reproductive stage promoted the evolution of cooperation, while a prolonged pre-reproductive stage has a negative effect. In general, the total length of life also increased the probability of the evolution of cooperation. Thus, our specific model suggests that the timing of life history transitions and total duration of life history stages may affect the evolution of cooperative behaviour. We conclude that the causation of the empirically observed association of life expectancy and sociality may be more complex than previously realized.

Oxygen tension changes the rate of migration of human skin keratinocytes in an age-related manner.

Migration of keratinocytes to re-epithelialize wounds is a key step in dermal wound healing. In aged human skin, wound healing rates decrease and cellular damage by reactive oxygen species (ROS) accumulates. The relationship between age, ROS and human skin keratinocyte migration is not clearly understood. In this study, 4% and 21% oxygen tensions were used to modify levels of ROS produced by metabolism to model low and high oxidative stress conditions. When migration of keratinocytes from young and old primary skin was compared using an in vitro scratch assay, old keratinocytes migrated faster in high oxygen tension than did young keratinocytes, whereas young keratinocytes migrated faster in low oxygen tension. Although all young and old cells at the scratch margins showed intense increases in dihydroethidium oxidation immediately after scratching, the old keratinocytes grown at 21% oxygen demonstrated a greater decrease in the DHE oxidation following scratching and migrated the fastest. These results show that old and young keratinocytes respond to oxygen tension differently and support the hypothesis that keratinocyte migration is affected by the capacity to remove ROS.