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Kisspeptin, encoded by Kiss1 gene, regulates reproduction via the hypothalamic-pituitary-gonadal axis. While kisspeptin treatment promotes follicular development in Tan sheep, its direct action on ovarian granulosa cells remains unclear. For this, we first detected the expression of Kiss1 and its receptor Kiss1r in primary ovarian granulosa cells of Tan sheep. Second, the effect of kisspeptin on steroid hormone secretion, proliferation and apoptosis of ovarian granulosa cells was investigated. Third, the signaling pathway of kisspeptin regulating steroid hormone secretion was revealed by western bolting in ovarian granulosa cells. The results showed that the Kiss1 and Kiss1r genes were present in ovarian granulosa cells of Tan-sheep, and 500 nM dose of kisspeptin significantly stimulated steroids hormone secretion (P < 0.05), and up-regulated StAR, HSD17B2, CPY19A1, FSHR, LHR, ERβ, PGR and p-ERK1/2 proteins expression (P < 0.05). Moreover, this treatment significantly promoted cell proliferation and increased the proportion of cells in S phase (P < 0.05), and significantly suppressed granulosa cell apoptosis (P < 0.05). Additionally, the stimulatory effects of kisspeptin on estradiol and progesterone secretion were blocked by inhibitors of the Mitogen-activated Protein Kinase (MAPK) signaling pathway (including PKA inhibitor, PLC inhibitor, PKC inhibitor, and Ca2+inhibitor). Western blot analysis confirmed that kisspeptin regulates steroid hormone secretion primarily through the MAPK-ERK signaling pathway. Our results demonstrate that kisspeptin can directly act on ovarian granulosa cells to promote steroidogenesis, proliferation, and inhibit apoptosis, providing a foundational basis for developing novel kisspeptin-mediated techniques to regulate reproduction in Tan sheep.
Infants with CHD who undergo cardiopulmonary bypass surgery are at risk of impaired growth and neurodevelopment. However, few studies have thoroughly investigated the risk factors for growth and neurodevelopmental impairments, particularly with respect to the timing of the initial surgical intervention.
Methods:
We retrospectively analysed term singleton infants with CHD who underwent cardiopulmonary bypass surgery at a Japanese tertiary centre between 2015 and 2021. Neurodevelopment was assessed at 18–22 months of age using the Kyoto Scale of Psychological Development. We compared outcomes by CHD type (univentricular [UV] vs. biventricular [BV]) and analysed risk factors for growth impairment (weight and height < tenth percentile) and neurodevelopmental impairment (developmental quotient [DQ] < 85), including birth weight, sex, the type of CHD (UV or BV), and timing of the initial cardiopulmonary bypass surgery (<28 days or ≥28 days).
Results:
Of the 108 eligible children, 29 had UV physiology and 79 had BV physiology. Both groups showed impaired growth, with significantly lower body weights in the UV group. Neurodevelopmental scores (total DQ) were significantly lower in the UV group. Neurodevelopmental impairment (total DQ < 85) was observed in 44/108 (40.7%) children, and after adjustment, UV repair was significantly associated with neurodevelopmental impairment (adjusted odds ratio [OR] 3.11, 95% confidence interval [CI] 1.27–7.65). Timing of the initial cardiopulmonary bypass surgery was not associated with outcomes.
Conclusion:
Infants with CHD in Japan exhibit impaired growth and neurodevelopment at 18–22 months following cardiopulmonary bypass surgery, especially those with UV physiology.
The organisation and financing of services dominate long-term care policy and research. This article argues for reorientation towards the social determinants of long-term care and the inequalities they generate. Building on Dahlgren and Whitehead’s influential equivalent for health, the article offers a framework for understanding how inequalities in long-term care need, access and experience are shaped by social networks, living and working conditions, services and policies, social norms, and political, economic and environmental conditions. International evidence on inequalities in need, access and experience is reviewed, and new analysis is presented for England, based on analysis of the Health Survey for England and the Adult Social Care Survey. Socio-economic inequalities are associated with steep gradients in need. Combined with unequal access to formal services, this results in more unmet need among disadvantaged people and a greater weight of responsibility on their family and friends. The final section explores the implications of a social determinants’ perspective for long-term care: addressing ‘upstream’ drivers of need (including social protection, housing and neighbourhood regeneration); inclusion and empowerment agendas; and ensuring that services effectively compensate for, rather than re-enforce, inequalities.
The penetration strategy of hypersonic vehicles in hostile environments is a critical factor in determining their effectiveness in completing reconnaissance or strike missions. Reinforcement learning (RL), as an end-to-end method, exhibits inherent advantages in addressing complex problems. However, existing research indicates that to enhance the efficiency of RL-based strategies, further advancements are necessary to reduce training costs and improve generalisation capabilities. This paper introduces a RL-based cooperative guidance law for multi-hypersonic vehicles, incorporating the estimated remaining time-of-flight and the absolute value of the bank angle obtained through a predictor-corrector method. The observation space and reward function are specifically designed to simplify the complex decision-making problem into a single-value decision problem, thereby reducing computational complexity and training costs. The proposed guidance law integrates the observation space, reward function and action space within the reinforcement learning framework to control flight trajectories, flight time and penetration of no-fly zones, ensuring compliance with multiple constraints. Model training and simulation tests conducted under multiple constraints demonstrate that the proposed approach reduces the training iterations required for the reinforcement learning agent and improves decision-making efficiency. Furthermore, simulations under different no-fly zone distributions confirm the proposed guidance approach’s high generalisation ability.
This essay reflects on my research and teaching on the history of gender and education, specifically with respect to the schooling history of Chinese women in the colonial world. In doing so, it aims to propose an alternate way of seeing the silent and missing figures in the colonial archives: the subordinated, marginalized, feminine colonial subjects. Commonly framed as orphaned, wounded, and diseased bodies in the historical research on the colonial era, these women were rendered as part of the “problem” that the colonial government ought to fix. It was through “them,” the disenfranchised Chinese females, that the missionary and the colonial state found their meaning and purpose. By the early twentieth century, although Chinese women’s education in the colonial context shifted from a discourse of evangelization to one of modernization, the function of women’s schooling remained constant: The feminine figure was still a platform through which the colonial government projected much of its civilizing ambition and desires for modernity. However, if one reads beyond the colonial archives and the paradigm of colonial subject as “recipient” and focuses instead on the archives of everyday life, one can see Chinese feminine figures as the triumphant masters of modern life. This essay traces this paradigm shift and argues that “gender” is an analytical tool capable of unearthing the hidden figures of modernity.
Let $M^{({k})}_{d}(n)$ be the manifold of n-tuples $(x_1,\ldots,x_n)\in(\mathbb{R}^d)^n$ having non-k-equal coordinates. We show that, for $d\geq2$, $M^{({3})}_{d}(n)$ is rationally formal if and only if $n\leq6$. This stands in sharp contrast with the fact that all classical configuration spaces $M^{({2})}_d(n)=\text{Conf}(\mathbb{R}^d,n)$ are rationally formal, just as are all complements of arrangements of arbitrary complex subspaces with geometric lattice of intersections. The rational non-formality of $M^{({3})}_{d}(n)$ for $n \gt 6$ is established via detection of non-trivial triple Massey products, which are assessed geometrically through Poincaré duality.
A 9200-year-long Holocene record of pollen, magnetic susceptibility (MS), and sedimentation rates from Pup Lake, northern Lower Michigan, USA, along with comparative pollen data from regional paleoecological sites and optically stimulated luminescence dates from inland sand dunes across the Great Lakes region, reveals emerging relationships among climate, vegetation, and erosion. Tsuga (hemlock) pollen was used to track local- and regional-scale hydroclimate variability owing to the taxon’s moisture sensitivity and close association with modern lake-effect snowfall gradients. Two periods of elevated MS and Tsuga values, 6800–5200 cal yr BP and 3200–800 cal yr BP, are interpreted as millennial-scale phases of greater effective moisture that drove key changes in forest composition and resulted in accelerated erosion. Overall, the lake’s MS record broadly tracks changes in Tsuga pollen frequencies and sedimentation rates, particularly during the Late Holocene, suggesting the emergence of a well-defined lake-effect climate system between 5200 and 1000 cal yr BP. Additionally, Pup Lake’s MS record exhibits notable connections with widely recognized hemispheric-scale climate deterioration episodes, including the 9.2, 8.2, and 5.2 ka BP events.
Learning a new language is a challenge not only because of the acquisition of grammar and vocabulary but of worldview. In teaching the Irish-Gaelic language to beginners in North America, using songs has proven central to successful language acquisition. Because Irish-Gaelic has strong regional dialects and grammatical challenges that can affect comprehension and pronunciation, teaching students to sing songs that reflect those challenges leads to the internalization of grammar and vocabulary. For some in the diaspora, Irish is a heritage language; the successful combination of song and language connects them to Ireland in ways that language study alone could not.
We obtain polylogarithmic bounds in the polynomial Szemerédi theorem when the polynomials have distinct degrees and zero constant terms. Specifically, let $P_1, \dots, P_m \in \mathbb Z[y]$ be polynomials with distinct degrees, each having zero constant term. Then there exists a constant $c = c(P_1,\dots,P_m) \gt 0$ such that any subset $A \subset \{1,2,\dots,N\}$ of density at least $(\log N)^{-c}$ contains a nontrivial polynomial progression of the form $x, x+P_1(y), \dots, x+P_m(y)$. In addition, we prove an effective “popular” version, showing that every dense subset $A$ has some non-zero $y$ such that the number of polynomial progressions in $A$ with this difference $y$ is asymptotically at least as large as in a random set of the same density as $A$.
In this article, I analyse the word-prosodic system of Drubea and Numèè, two of the rare tonal Oceanic languages. Building on Rivierre’s (1973) seminal work, I show that the word-prosodic system of these two languages can be analysed as involving only register features: an underlying downstep and a postlexical epenthetic upstep. Drubea and Numèè are thus tonal languages without tones stricto sensu. This new type of word-prosodic system has both theoretical and typological implications: (i) register features, defined as in Snider’s (1999) Register Tier Theory, need not be subordinate to or associated with tones, and may exist in the absence of tone, including in underlying representation; (ii) tonal systems come in two types: tone-based systems in which the tonal contrasts are defined paradigmatically, as in most tone languages, and register-based systems where tonal contrasts are defined syntagmatically, as in Drubea and Numèè.
The best known historical narrative of the international mental hygiene movement among English-speaking audiences locates its origins in the publication of A Mind That Found Itself, the autobiographical account of Clifford Beers (1876–1943), a Yale graduate and former psychiatric patient. The success of the book is thought to have prompted the creation of the first Society for Mental Hygiene in Connecticut in 1908. Beers’ biography, published as Advocate for the Insane in 1980, contends that mental hygiene abroad developed from seeds first sown in the USA and subsequently in Canada.
This article offers a critical reappraisal of that narrative and advances an alternative framework for understanding the history of the international mental hygiene movement during the first half of the twentieth century. It draws on a body of scholarship, emerging since the 1980s, that has sought to decentre the prevailing account, exposing the multiplicity of forces at work in a history that diverges from any straightforward, linear trajectory radiating from a single point of origin.
By tracing this decentred history, the article highlights the contested nature of the ‘international’ in the context of the mental hygiene movement. Case studies from the USA, France, Brazil, and Argentina reveal both the conflicts it engendered and the diverse meanings and significance it assumed within distinct national settings.
Drawing on attribution theory and impression management research, we investigate when and how abused employees engage in different coping strategies and what the interpersonal consequences of the coping strategies are for employees. Specifically, from an employee actor–based perspective, we develop and test a dual-path-mediated moderation model that represents the double-edged sword effect of abusive supervision. Using data from 444 front-line employees, we find that injury initiation motives attribution enhances the positive relationship between abusive supervision and revenge motivation, which in turn is positively related to intimidation, exemplification, and supplication. Conversely, performance promotion motives attribution strengthens the positive relationship between abusive supervision and motivation to reconcile, which in turn is positively associated with ingratiation, self-promotion, and exemplification. Intimidation and supplication are then related to increased interpersonal conflict with leaders, while ingratiation is related to reduced interpersonal conflict with leaders. Theoretical contributions, practical implications, and limitations are discussed.
Shame is a pervasive, multidimensional emotion influencing brain, body and social life. While shame can foster accountability, its toxic forms drive stigma, withdrawal and mental illness. We call for systemic, culturally sensitive interventions to transform phatological shame into healing, fostering empathy, accountability and psychological safety in care, education and policy.
Bovine mastitis poses a significant threat to dairy production worldwide. Among the various etiologies of mastitis, Escherichia coli is a predominant environmental pathogen. Antibiotic-resistant E. coli poses substantial challenges for treating mastitis and is a threat to public health, necessitating the exploration of alternative therapeutic strategies. We studied bacteriophages as a potential alternative therapy for bovine mastitis-associated E. coli. We isolated 37 bacteriophages infecting E. coli, and characterized them for host range, growth kinetics, morphology, stability, genome fingerprinting and genome sequencing and analysis. The phages lysed between 4% and 62% of the E. coli isolates tested. Notably, 30 phages lysed bovine mastitis-associated strains. The 10 best phages selected based on host strain specificity revealed latent periods ranging from 50 to 90 min and burst sizes between 7 and 69 PFU/mL. Based on their shorter latent period and larger burst size, seven phages were subjected to transmission electron microscopy, which revealed their myovirus and siphovirus morphologies. Restriction fragment length polymorphism (RFLP) analysis of the same seven phages indicated six different patterns. The seven phages were stable at temperatures ranging from 4°C to 50°C, and at pH values ranging from 3 to 9. Whole-genome sequencing and analysis of the six phages, which showed unique RFLP patterns, predicted a lytic lifecycle, with no sequences encoding toxins or antibiotic-resistance genes. Importantly, these six phages were able to lyse multidrug-resistant and extended β-lactamase (ESBL)-producing E. coli under in vitro conditions and mastitis-associated E. coli in milk. Additionally, three phages belonging to different genera did not exhibit toxicity to mammalian cells. This study underscores the potential of bacteriophages as alternative therapeutic agents for E. coli-associated bovine mastitis. Our study has broader implications for udder and animal health, as well as the production of quality milk and dairy products, and food safety and security.
This study examined data from 20 national genebanks in Latin America and the Caribbean, Africa, the Near East and Asia to identify similarities and differences in genebank operations and processes, funding and facilities, as well as opportunities to strengthen their contributions to the global system of crop conservation and use. Data on genebank performance metrics were collected and used to assess compliance with FAO Genebank Standards. This enabled the analysis of trends in ex situ conservation of major food crops, locally important crops and crop wild relatives across national genebanks and the identification of shared challenges and opportunities to improve genebank operations and address funding gaps. All genebanks in the study failed to meet quality management standards and performance goals for the effective management of crop collections. The most pressing challenge for all national genebanks was the management and safety duplication of highly diverse collections in both seed and field genebanks, often with limited information available to guide best conservation practices. A further critical constraint was the fluctuating and often insufficient funding to support the wide range of tasks needed to secure and use this valuable national crop germplasm.
Production of seafood has received relatively little attention in agri-food debates despite the fact that, since the 1960s, seafood production has been transformed through the industrialization of fisheries and globalization of seafood commodity chains. Intensive aquaculture emerged as a new industry in response to declining fish catches. Global commodity chains of seafood and capital accumulation processes changed tremendously, leading to complex international trade dynamics and rising inequalities. The Turkish aquaculture sector has also been transformed via government subsidies, and a few vertically integrated aquaculture companies started to produce farmed sea bass and sea bream (SBSB) in Turkish waters, while organizing their operations both upstream (processing of fish feed in Africa) and downstream (sales and distribution in Europe) in the global SBSB value chain. We adopted a single commodity approach to uncover how seafood production has been transformed via expanding commodity frontiers of capital-intensive SBSB production by focusing on the strategies of Turkish aquaculture enterprises, trade dynamics, and socio-ecological implications of SBSB production via in-depth interviews with key stakeholders and a review of legislative documents and trade data. Our analysis offers critical insights into the agrarian-change debate in Turkey by analyzing the global and regional socio-ecological inequalities created by Turkish SBSB production.