bluuebunny/crossref_metadata_2025 huggingface dataset:
Kisspeptin in functional hypothalamic amenorrhea: Pathophysiology and therapeutic potential
Authors: Patel Aaran H. , Koysombat Kanyada , Pierret Aureliane , Young Megan , Comninos Alexander N. , Dhillo Waljit S. , Abbara Ali
Published: September 2024

Functional hypothalamic amenorrhea (FHA) is one of the most common causes of secondary amenorrhea, resulting in anovulation and infertility, and is a low estrogen state that increases the risk of cardiovascular disease and impairs bone health. FHA is characterized by acquired suppression of physiological pulsatile gonadotropin‐releasing hormone (GnRH) release by the hypothalamus in the absence of an identifiable structural cause, resulting in a functional hypogonadotropic hypogonadism. FHA results from either decreased energy intake and/or excessive exercise, leading to low energy availability and weight loss—often in combination with psychological stress on top of a background of genetic susceptibility. The hypothalamic neuropeptide kisspeptin is a key component of the GnRH pulse generator, tightly regulating pulsatile GnRH secretion and the downstream reproductive axis. Here, we review the physiological regulation of pulsatile GnRH secretion by hypothalamic kisspeptin neurons and how their activity is modulated by signals of energy status to affect reproductive function. We explore endocrine factors contributing to the suppression of GnRH pulsatility in the pathophysiology of FHA and how hypothalamic kisspeptin neurons likely represent a final common pathway through which these factors affect GnRH pulse generation. Finally, we discuss the therapeutic potential of kisspeptin as a novel treatment for women with FHA.
Rethinking City Population Growth: How Reclassification Matters
Authors: Alessandrini Alfredo , Deuster Christoph , Dijkstra Lewis , Ghio Daniela , Natale Fabrizio
Published: September 2024

City populations grow due to natural change, migration, and areas that are reclassified as part of a city. Because a time series of city boundaries was not available, most analyses ignore reclassification. This paper measures reclassification in a harmonized and transparent manner by applying a new harmonized definition of cities, towns, and rural areas, called the degree of urbanization, to gridded population data between 1980 and 2020. Ignoring reclassification would attribute city population growth equally to natural change and migration. Including the effects of reclassification reveals that two‐thirds of the growth is due to natural change, followed by reclassification (29 percent), and the remainder to migration (4 percent). This demonstrates the importance of accounting for reclassification. It also underlines that discouraging migration to cities will not significantly reduce city population growth.
Editorial comments on “Multiarray screening identifies plasma proteins associated with Th17 cell differentiation and viral defense in coincident asthma and obesity”
Authors: Cavaleiro Rufo João , Chauhan Jitesh , Kalayci Ömer , Eigenmann Philippe
Published: September 2024

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Identification of risk loci for postpartum depression in a genome‐wide association study
Authors: Li Xue , Takahashi Nagahide , Narita Akira , Nakamura Yukako , Sakurai‐Yageta Mika , Murakami Keiko , Ishikuro Mami , Obara Taku , Kikuya Masahiro , Ueno Fumihiko , Metoki Hirohito , Ohseto Hisashi , Takahashi Ippei , Nakamura Tomohiro , Warita Noriko , Shoji Tomoka , Yu Zhiqian , Ono Chiaki , Kobayashi Natsuko , Kikuchi Saya , Matsuki Tasuku , Nagami Fuji , Ogishima Soichi , Sugawara Junichi , Hoshiai Tetsuro , Saito Masatoshi , Fuse Nobuo , Kinoshita Kengo , Yamamoto Masayuki , Yaegashi Nobuo , Ozaki Norio , Tamiya Gen , Kuriyama Shinichi , Tomita Hiroaki
Published: September 2024

Aim

Genome‐wide association studies (GWAS) of postpartum depression (PPD) based on accumulated cohorts with multiple ethnic backgrounds have failed to identify significantly associated loci. Herein, we conducted a GWAS of Japanese perinatal women along with detailed confounding information to uncover PPD‐associated loci.

Methods

The first and second cohorts (n = 9260 and n = 8582 perinatal women enrolled in the Tohoku Medical Megabank Project) and the third cohort (n = 997), recruited at Nagoya University, underwent genotyping. Of them, 1421, 1264, and 225 were classified as PPD based on the Edinburgh Postnatal Depression Scale 1 month after delivery. The most influential confounding factors of genetic liability to PPD were selected, and logistic regression analyses were performed to evaluate genetic associations with PPD after adjusting for confounders.

Results

A meta‐analysis of GWAS results from the three cohorts identified significant associations between PPD and the following loci (P < 5 × 10−8) by integrating the number of deliveries and the number of family members living together as the most influential confounders: rs377546683 at DAB1, rs11940752 near UGT8, rs141172317, rs117928019, rs76631412, rs118131805 at DOCK2, rs188907279 near ZNF572, rs504378, rs690150, rs491868, rs689917, rs474978, rs690118, rs690253 near DIRAS2, rs1435984417 at ZNF618, rs57705782 near PTPRM, and rs185293917 near PDGFB. Pathway analyses indicated that SNPs suggestively associated with PPD were mostly over‐represented in categories including long‐term depression, GnRH signaling, glutamatergic synapse, oxytocin signaling, and Rap1 signaling.

Conclusion

The current GWAS study identified eight loci significantly associated with PPD, which may clarify the genetic structure underlying its pathogenesis.
Zetetic supererogation
Authors: Hirvelä Jaakko
Published: September 2024

Several authors have recently argued that knowledge is not the aim of inquiry since it can make sense to inquire into a question even though one knows the answer. I argue that this a faulty diagnostic for determining whether one has met the constitutive standard of success of an activity type. The constitutive standards of success tell us when an activity is successful, but such standards can be exceeded and exceeding them can be reasonable. To back this up I develop an account of zetetic supererogation and argue that subjects who continue to inquire into a question while knowing the answer do what is zetetically supererogatory.
Structural encroachment
Authors: Barranco Lopez Aliosha
Published: September 2024

Moral encroachment states that moral factors can make a difference to what we are epistemically justified in believing. I present two motivating cases that resemble a common example in the moral encroachment literature to show that the agent's commitments and beliefs, and not the moral factors of the situation, influence epistemic justification. I call this view Structural Encroachment.
Mutation of KAP, which encodes a keratin‐associated protein, affects grain size and yield production in rice
Authors: Chen Chunpeng , Cheng Weimin , Jiang Hongrui , Fang Cheng , Li Wenhao , Peng Lingling , Tao Liangzhi , Zhan Yue , Wu Yuejin , Huang Xianzhong , Liu Binmei , Ye Yafeng
Published: September 2024

Grain size and shape are critical agronomic traits that directly impact rice grain yield. Identifying genes that control these traits can provide new strategies for yield improvement. In this study, we characterized a rice mutant, reduced grain length (rgl), which exhibited decreased grain length due to reduced cell proliferation. Map‐based cloning identified a base deletion in OsRGL2, a gene encoding a keratin‐associated protein (KAP), as the cause of the mutant phenotype. CRISPR‐Cas9‐generated OsRGL2 knockout mutants also displayed reduced grain length, confirming its role. OsRGL2 transcripts were detected in various tissues, with relative higher gene expression in young panicles, and OsRGL2 was localized to the plasma membrane. Overexpression of OsRGL2 increased grain size by promoting cell proliferation in the spikelet hull and significantly enhanced grain yield per plant. Importantly, OsRGL2 was found to interact with RGB1, indicating that OsRGL2 positively regulates grain size and yield through its interaction with RGB1. Additionally, OsRGL2 regulated the expression of cell cycle‐related genes, further elucidating its role in grain development. These findings demonstrate that OsRGL2 is a positive regulator of grain size in rice, and manipulating its expression may offer a novel strategy for enhancing rice grain yield.
A Plant biostimulant prepared from Ascophyllum nodosum Induces Flowering by Regulating the MIR156‐mediated Age Pathway in Arabidopsis
Authors: Bahmani Ramin , Prithiviraj Balakrishnan
Published: September 2024

Flowering, the change from vegetative development to the reproductive phase, represents a crucial and intricate stage in the life cycle of plants, which is tightly controlled by both internal and external factors. In this study, we investigated the effect of Ascophyllum nodosum extract (ANE) on the flowering time of Arabidopsis. We found that a 0.1% concentration of ANE induced flowering in Arabidopsis, accompanied by the upregulation of key flowering time genes: FT (FLOWERING LOCUS T), SOC1 (SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1), and LFY (LEAFY). Further investigation showed that ANE specifically promotes flowering through the MIR156‐mediated age pathway. ANE treatment resulted in the repression of negative regulator genes, MIR156, while simultaneously enhancing the expression of positive regulator genes, including SPLs and MIR172. This, in turn, led to the downregulation of AP2‐like genes, which are known as floral repressors. It is worth noting that ANE did not alleviate the late flowering phenotype of MIR156‐overexpressing plants and spl mutants. Furthermore, ANE‐derived fucoidan mimics the function of sugars in regulating MIR156, closely mirroring the effects induced by ANE treatments. It suppresses the transcript levels of MIR156 and AP2‐like genes while inducing those of SPLs and MIR172, thereby reinforcing the involvement of fucoidan in the control of flowering by ANE. In summary, our results demonstrate that ANE induces flowering by modulating the MIR156‐SPL module within the age pathway, and this effect is mediated by fucoidan.
Roles of big data analytics and organizational culture in developing innovation capabilities: a hybrid PLS‐fsQCA approach
Authors: Foroughi Behzad , Iranmanesh Mohammad , Hajli Nick , Ling Lee Shih , Ghobakhloo Morteza , Nikbin Davoud
Published: September 2024

Big data analytics creates and consolidates competitive advantage by providing insights on data with enormous variety, velocity, and volume to firms. However, many companies' investments in big data analytics were unsuccessful, and they could not gain full advantage of these technologies. This study investigates the impacts of big data analytics capabilities on innovation quality and speed by considering organizational learning culture as a moderator. The study's data are obtained from a survey of 221 managers in the manufacturing industry. We integrate the Partial Least Squares (PLS) technique and fuzzy‐set Qualitative Comparative Analysis (fsQCA) to perform the analysis. The findings of PLS indicated that big data analytics capabilities positively influence both innovation quality and speed. However, innovation quality influences both market performance and financial performance, and innovation speed only affects market performance. Organizational learning culture negatively moderates the impacts of big data analytics on innovation speed and quality. fsQCA uncovered four solutions with varied combinations of factors that predict the high market and financial performance. The theoretical and practical implications are explained at the end of the paper.
Salt tolerance of native trees relevant to the restoration of degraded landscapes in the Monte region, Argentina
Authors: Meglioli Pablo A. , Alvarez Juan A. , Lana Nerina B. , Cony Mariano A. , Villagra Pablo E.
Published: September 2024

Afforestation with native trees can enhance the conversion of degraded saline lands into productive landscapes with considerable economic and environmental benefits. To identify the native salt‐resistant species for restoration, we investigated how salinity affects the growth and water status of sapling from two Neltuma species from the Monte region. We produced Neltuma flexuosa and Neltuma chilensis saplings using seeds harvested from native forests with multiple provenances (Fiambalá, Chilecito, Mogna, Pipanaco, Talampaya, and Andalgalá). We conducted a greenhouse trial in which 810 saplings of different species/provenance combination received one of three saline irrigations, that is, sodium chloride solutions of 0.01 (no stress), 0.10 (moderate stress), and 0.25 M (severe stress). We found that Neltuma saplings exhibited varying degrees of reduction in their growth (plant height and aboveground biomass) and water status (e.g., stomatal conductance and leaf water potential) traits with increasing salt stress. N. flexuosa‐Fiambalá and N. flexuosa‐Chilecito were the most tolerant and sensitive, respectively, while all provenances of N. chilensis showed intermediate tolerance to salinity. These results suggest that N. flexuosa displays highly variable plasticity to salt stress compared to N. chilensis, emphasizing the need to select appropriate provenances for afforestation in saline‐degraded areas.
Benefits of chest wall mobilization on respiratory efficiency and functional exercise capacity in people with severe chronic obstructive pulmonary disease (COPD): A randomized controlled trial
Authors: Tsui Amy Ying Yu , Cheing Gladys Lai Ying , Chau Rosanna Mei Wa , Mok Thomas Yun Wing , Ling Sai On , Kwan Candy Hoi Yee , Tsang Sharon Man Ha
Published: September 2024

Background

Coexistence of chest wall hypomobility and lung hyperinflation compromises respiratory muscle function and respiratory efficiency in people with severe chronic obstructive pulmonary disease (COPD). This study aimed to investigate the effect of chest wall mobilization on functional exercise capacity, respiratory muscle activity and respiratory muscle tissue oxygen saturation for people with severe COPD.

Methods

Thirty male adults (age: 75 ± 6) diagnosed with severe COPD completed a 6‐week programme (twice/week) according to intervention randomization (chest wall mobilization group, CWMG, n = 15; control group, CG, n = 15). Both groups received standardized education and walking exercise, while CWMG also received chest wall and thoracic spine mobilization. Electromyography of the essential and accessory respiratory muscles and tissue oxygen saturation of the intercostal muscle (StO2, measured by near‐infrared spectroscopy) during incremental cycle exercise test were measured and compared between the two groups at pre‐programme, post‐programme and 3‐month follow‐up.

Results

Patients in CWMG demonstrated a significant increase in exercise tolerance from <3 METS to 4–6 METS (p = 0.000) after intervention. A significant decrease in activity of scalene, sternocleidomastoids and intercostal muscle during exercise test (p < 0.01) was found in CWMG, as compared to CG. A significant decrease in StO2 (p < 0.05) and greater decline in the slope of oxygenation dissociation (p = 0.000) were seen in CWMG during exercise test. These positive results were maintained at 3‐month follow‐up in CWMG.

Conclusion

Improvements in exercise tolerance, respiratory muscle efficiency and oxygenation extraction ability in CWMG suggest a potential clinical benefit of integrating chest wall and thoracic spine mobilization for rehabilitation of people with severe COPD.

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Inverse scattering transform for continuous and discrete space‐time‐shifted integrable equations
Authors: Ablowitz Mark J. , Musslimani Ziad H. , Ossi Nicholas J.
Published: September 2024

Nonlocal integrable partial differential equations possessing a spatial or temporal reflection have constituted an active research area for the past decade. Recently, more general classes of these nonlocal equations have been proposed, wherein the nonlocality appears as a combination of a shift (by a real or a complex parameter) and a reflection. This new shifting parameter manifests itself in the inverse scattering transform (IST) as an additional phase factor in an analogous way to the classical Fourier transform. In this paper, the IST is analyzed in detail for several examples of such systems. Particularly, time, space, and space‐time‐shifted nonlinear Schrödinger (NLS) and space‐time‐shifted modified Korteweg‐de Vries equations are studied. Additionally, the semidiscrete IST is developed for the time, space, and space‐time‐shifted variants of the Ablowitz–Ladik integrable discretization of the NLS. One‐soliton solutions are constructed for all continuous and discrete cases.
Interpretability and clinical utility of the strength and stressors in parenting questionnaire
Authors: Burge Sara , Hallin Anna Eva , Miniscalco Carmela , Sand Anders , Strömbergsson Sofia
Published: September 2024

This study aimed to enhance the interpretability and clinical utility of the strength and stressors in parenting (SSF) questionnaire, a parent‐reported questionnaire designed to assess strength, stress and associated risks of mental ill‐health in parents of children with developmental disabilities. Responses to the SSF and a demographic questionnaire were collected from 576 parents of children with (n = 203) and without (n = 373) developmental disabilities. To enhance the interpretability of the SSF, a subset of 129 parents were invited to complete an additional questionnaire consisting of three free‐text questions regarding recent help‐seeking behavior, experiences of mental ill‐health and experiences of parenthood. Parents' responses to the free‐text questions were then categorized as indicative of higher or lower degrees of stress and compared to their SSF score distribution to derive empirical cut‐offs for strength, stress and risk of mental ill‐health as measured by the SSF. The credibility of these cut‐offs was evaluated by comparing the cut‐offs with SSF scores collected from the other 447 parents. Finally, SSF scores from parents of children without developmental disabilities (n = 373) were used to generate percentile values for the SSF to enable a standardized interpretation of SSF scores. To increase the utility of the SSF, we examined a recurring pattern of missing answers to items 23 and 33–38, noted in previous studies of the SSF and repeated in the present study. These items were excluded from further analysis since our examination revealed that they were not missing at random but rather constituted real differences in parental experiences, such as receiving a healthcare allowance, or caring for more than one child. The proposed empirical cut‐offs performed well in discriminating between the two groups and yielded a specificity of 77–89% and a sensitivity of 68–76% for the strength, stress and risk of mental ill‐health subscales of the SSF. This study also presents a conversion chart associating each SSF score with a corresponding percentile value. We propose modifications to the SSF, whereby items 23 and 33–38 are excluded, which will enable a more reliable assessment of parental experiences. This will, together with the empirical cut‐offs and percentile values, enhance the interpretability and clinical utility of the SSF.
The role of White identity in anti‐racist allyship
Authors: Yantis Caitlyn
Published: September 2024

Although White allies attempt to support racial justice movements, their behaviors can be interpreted as performative rather than genuine by racially minoritized individuals. In the current work, I discuss how White individuals' personal connection to their racial identity and the power it confers—White identity form—shapes their allyship behaviors. Specifically, moving beyond conceptualizations of White identity as centrality, I call for a study of White identity that incorporates power‐relevant ideologies, understanding how White individuals make meaning of their unearned privilege and incorporate it into their self‐concept. I suggest that a power‐cognizant identity form, which involves personally connecting the self to Whiteness and unearned power, is necessary for White individuals to engage in genuine anti‐racist allyship. I discuss White identity measurement issues as well as potential interventions for promoting a power‐cognizant identity form.
Not ready to make nice: Congressional candidates’ emotional appeals on Twitter
Authors: Russell Annelise , Evans Heather K. , Gervais Bryan
Published: September 2024

Objective

Congressional candidates use digital platforms to bolster and define their political reputation, and political stalemates over inflation, reproductive rights, and the lasting impact of Trump politics are fueling candidates’ emotionally charged rhetoric on Twitter, especially for women. Against the backdrop of President Donald Trump's presidency and the #MeToo movement, previous research has shown that women running for Congress are leading with angry rhetoric on Twitter. In this article, we ask whether anger is a persistent feature of women's digital appeals on Twitter over time.

Method

Using a data set of tweets by candidates for the U.S. House from 2016 to 2022, we highlight the escalating anger in the emotional appeals candidates make on Twitter and the resiliency of angry rhetoric as a modern feature of political Twitter.

Results

We find that women, most notably Democratic candidates, are more likely to convey angry emotions on Twitter, not only matching male colleagues but defying gendered social stereotypes to turn frustration into a valuable political asset. Across the four last congressional elections, women have averaged more angry words in their digital appeals, with that anger as a consistent facet of how women engage online. Women are leaning into angry emotional appeals and adopting a negative appeal in their digital engagement that highlights their policy and political frustrations for voters.
Genre‐based writing in the German classroom in the age of generative AI
Authors: Redmann Jennifer
Published: September 2024

Genre, defined as a “staged goal‐oriented social process” (Martin, 2009), has long stood as a key principle in second‐language writing instruction. This article presents the principles underpinning genre theory as it relates to the language curriculum and the five phases of genre‐based L2 writing pedagogy. This pedagogy provides the foundation for a case study in which students in an intermediate, fifth‐semester German class at a small liberal arts college received instruction in the film review genre. Student products written prior to classroom work with film reviews are compared with those written after students had gained an awareness and understanding of the film review genre, revealing the positive effects of genre‐based instruction on student writing. In light of the future impact of generative artificial intelligence (AI) on writing pedagogy, the final section addresses how ChatGPT and similar platforms can potentially enhance genre‐based pedagogies. The article suggests ways in which generative AI can be incorporated into each phase of genre‐based second language writing instruction. As technologies such as ChatGPT become established in language classrooms, it is clear that the writing process must share the stage with written products, both in instruction and assessments.
Semilinear clannish algebras
Authors: Bennett‐Tennenhaus Raphael , Crawley‐Boevey William
Published: September 2024

We define a class of associative algebras generalizing ‘clannish algebras’, as introduced by the second author, but also incorporating semilinear structure, like a skew polynomial ring. Clannish algebras generalize the well‐known ‘string algebras’ introduced by Butler and Ringel. Our main result is the classification of finite‐dimensional indecomposable modules for these new algebras.
ПОЛУЧЕНИЕ В КЛЕТКАХ БАКТЕРИЙ ESCHERICHIA COLI РЕКОМБИНАНТНОГО ЧЕЛОВЕЧЕСКОГО БЕЛКА Р62
Authors: Сауткина Н.В. , Матчан И.Д. , Пластинина О.В. , Прокулевич В.А.
Published: September 2024

Протеостаз включает внутриклеточные биологические пути, контролирующие биогенез, фолдинг, перенос и деградацию белков, присутствующих внутри и вне клетки. Эффективный протеостаз имеет решающее значение для поддержания соматического гомеостаза, а его снижение во время старения приводит к клеточной дисфункции и заболеваниям. Селективная аутофагия представляет собой форму аутофагии, опосредованную рецепторами, которые нацелены на специфические субстраты для деградации, и является важным процессом для поддержания протеостаза.
Белок секвестосома-1 (p62/SQSTM1) известен как убиквитин-связывающий белок p62 с доменной организацией. Он является классическим селективным рецептором аутофагии, но также выполняет определенные функции в убиквитин-протеасомной системе, клеточном метаболизме, передаче сигналов и апоптозе. Белок p62 играет решающую роль во множестве клеточных процессов, включая реакцию на повреждение ДНК, старение, инфекцию и иммунитет, хроническое воспаление и канцерогенез, зависящий от аутофагии или независимый от нее. Потеря p62 приводит к ускоренному старению клеток из-за снижения протеостаза, нарушения регуляции сигнальных путей и неспособности реагировать на окислительный стресс.
Целью работы является клонирование и экспрессия рекомбинантного человеческого белка p62 в клетках бактерий E. coli.
В процессе разработки дизайна гена, обозначенного как p62, определяли нуклеотидную последовательность путем обратной трансляции соответствующей первичной структуры белка p62 из базы данных UniProt, затем оптимизировали для усиления экспрессии в клетках бактерий E. coli до значения CAI=0,8. На 5’-конце фрагмента вводили сайт узнавания эндонуклеазы NdeI, на 3’-конце – сайт узнавания эндонуклеазы EcoRI и стоп-кодоны.
Ген p62 по соответствующим сайтам рестрикции вводили в состав вектора рЕТ-24b(+) (Novagen) под контролем промотора бактериофага Т7 и клонировали в клетках штамма E. coli XL1-Blue. Результаты клонирования проверяли ПЦР-анализом трансформантов с использованием праймеров, фланкирующих полилинкерную область вектора, а также рестрикционным анализом рекомбинантных плазмид.
Индуцировали экспрессию гена p62 в клетках штамма E. coli BL21-Gold(DEЗ) синтетическим аналогом лактозы – ИПТГ (0,5 ммоль/л) при 37 °С в течение 4 часов. Эффективность экспрессии анализировали при помощи SDS-PAGE электрофореза, результаты которого показали, что целевой белок массой около 48 кДа накапливается в бактериальных клетках.
Таким образом, получен бактериальный продуцент, в клетках которого рекомбинантный многофункциональный человеческий белок p62 синтезируется в количестве около 25 % от общего клеточного белка при стандартных условиях индукции экспрессии, рекомендованных производителями плазмид серии рЕТ.
3D Study of Cloud Cavitation on a Circular Leading-Edge Hydrofoil Using RANS Approaches
Authors: Puga Gallegos Diana , Luo Xianwu
Published: September 2024

In spite of the improvements in computational fluid dynamics (CFD) techniques, engineering problems still need robust models that can ensure accuracy at low cost in the prediction of complex phenomena such as cavitating turbulent flows. In the present study, cavitation over a circular leading-edge hydrofoil imitating the leading-edge geometry of centrifugal pump impeller blades was analyzed for different cavitation numbers ranging from 2 to 2.7 and Reynolds numbers of 1.3 × 106 and 1.6 × 106. The unsteady simulations were conducted by using the RANS method with the Zwart-Gerber-Belamri (ZGB) cavitation model. To capture the features of cavitating turbulent flow, three turbulence models i.e. the MSST PANS, k-ε FBDCM and k-ω FBDCM were evaluated to determine the suitable turbulence model for simulating cloud cavitation over a hydrofoil. The numerical results were compared with the experimental data obtained by Bohm and the sequence of images recorded by Dular. The results showed that the MSST PANS can reproduce better the cavitation phenomenon than the k-ε FBDCM and k-ω FBDCM turbulence models when the shedding frequency and the cavitating structures were analyzed and compared with the experiment.
Toward monitoring submarine glacier melt using hydroacoustics: The role of timescale in the signal of bubble release
Authors: Grossman Shayna , Johnson Hayden , Stokes Dale , Deane Grant
Published: September 2024

Submarine glacier melt plays a key role in determining glacier stability and driving glacier mass loss. However, quantifying submarine melt remains challenging due to occupational hazards near glacier termini. One method that has been proposed as a low-cost long-term option for remote sensing, though remains unproven, is to use the sounds of glacier ice bubbles to study submarine melt from afar. Calculating melt rate from bubble acoustics remains complicated because different bubbles produce acoustic energy heterogeneously. This study investigates the physical factors that cause this heterogeneity. A computational method to determine time scales of acoustical excitation and acoustic energy values is proposed and utilized to analyze 203 bubble release events from glacier ice collected in Svalbard, Norway. The distributions of these variables are used to show the existence of two separate types of bubble release events. Additionally, internal pressures are determined for the subset of events with the highest acoustic energy values. No straightforward relationship between time scale of excitation and internal pressure is found. This work begins to untangle the acoustic signal of submarine glacier melt and necessitates further research into the environmental factors modulating bubble release.
Plane-wave and cylindrical-wave acoustic reflection from a marine sediment with layering representative of the New England Mud Patch
Authors: Buckingham Michael J.
Published: September 2024

An analysis is presented of reflection from a marine sediment consisting of a homogeneous mud layer overlying a sand-mud basement, the latter with an upward-refracting, inverse-square sound speed profile. Such layering is representative of the sediment at the New England Mud Patch (NEMP). By applying appropriate integral transforms and their inverses to the Helmholtz equations for the ocean and the two sediment layers, along with the boundary conditions, a Sommerfeld–Weyl type of wavenumber integral is obtained for the cylindrical-wave reflection coefficient of the sediment, R. A stationary phase evaluation of this integral yields a closed-form expression for the plane-wave reflection coefficient, R0. In the absence of attenuation, the plane-wave solution exhibits total reflection up to a critical grazing angle, ac, but when attenuation in the sediment is introduced, the region of total reflection in |R0| is replaced by a sequence of contiguous peaks. With realistic levels of sediment attenuation, the cylindrical-wave solution, |R|, exhibits a quasi-critical grazing angle, less than ac, which is strongly dependent on the source-plus-receiver height above the seabed, which is mildly dependent on the depth of the mud layer but is essentially independent of frequency. Such behavior is consistent with independent experimental observations at the NEMP.
Immediate auditory feedback regulates inter-articulator speech coordination in service to phonetic structure
Authors: Masapollo Matthew , Nittrouer Susan
Published: September 2024

Research has shown that talkers reliably coordinate the timing of articulator movements across variation in production rate and syllable stress, and that this precision of inter-articulator timing instantiates phonetic structure in the resulting acoustic signal. We here tested the hypothesis that immediate auditory feedback helps regulate that consistent articulatory timing control. Talkers with normal hearing recorded 480 /tV#Cat/ utterances using electromagnetic articulography, with alternative V (/ɑ/-/ɛ/) and C (/t/-/d/), across variation in production rate (fast-normal) and stress (first syllable stressed-unstressed). Utterances were split between two listening conditions: unmasked and masked. To quantify the effect of immediate auditory feedback on the coordination between the jaw and tongue-tip, the timing of tongue-tip raising onset for C, relative to the jaw opening-closing cycle for V, was obtained in each listening condition. Across both listening conditions, any manipulation that shortened the jaw opening-closing cycle reduced the latency of tongue-tip movement onset, relative to the onset of jaw opening. Moreover, tongue-tip latencies were strongly affiliated with utterance type. During auditory masking, however, tongue-tip latencies were less strongly affiliated with utterance type, demonstrating that talkers use afferent auditory signals in real-time to regulate the precision of inter-articulator timing in service to phonetic structure.
NetballSmart, Implementation of a National Injury Prevention Program
Authors: Belcher Suzanne , Kearney Sharon , Brughelli Matt , Hardaker Natalie , Whatman Chris
Published: September 2024

Reducing lower-limb injuries in netball, particularly anterior cruciate ligament injuries, is a priority. The Accident Compensation Corporation (a no-fault national insurance system) partnered with Netball New Zealand to create the “NetballSmart” injury prevention program. Targeted research informed the successful implementation, dissemination, and adoption of the injury prevention program. Research included a nationwide epidemiological study, video analysis investigating netball injury risk maneuvers, and intervention studies exploring the effectiveness of injury prevention program warm-up resources on physical capability in youth netball. An identified spike in ankle-knee injury incidence of school-age netball players at season start and prior to tournaments along with a high overall prevalence within these ages led to the creation of age-specific educational workshops and resources focused on effective preparation, skill transition, strengthening, and balance. Observational video analysis highlighted behaviors that potentially increased the risk of anterior cruciate ligament injury and a progressive landing skills program was developed. The NetballSmart Dynamic Warm-up and Power Warm-up significantly improved player physical capability. Consequently, time to perform the Power Warm-up before all games at a national intermediate school tournament was incorporated into competition-time, reducing workload by 25%. A targeted social media and ambassador endorsement plan increased performance of the NetballSmart Dynamic Warm-up/Power Warm-up by 14% prior to games and 15% before trainings nationally. Accident Compensation Corporation injury data between 2018 and 2022 showed a 6,050 (32%) reduction of all body site and a 2,968 (33%) decrease of combined ankle-knee injury claims. Similarly, by 2021 there was a 11% decrease in fractures/dislocations, a 13% decrease in soft tissue injuries, and a 9% decrease in anterior cruciate ligament surgical repairs. During this delivery period, Accident Compensation Corporation reported that the whole of life returns on investment was NZD$4.10, for every dollar funded to the NetballSmart Injury Prevention Programme.
DCLK1 induces a pro-tumorigenic phenotype to drive gastric cancer progression
Authors: Afshar-Sterle Shoukat , Carli Annalisa L.E. , O’Keefe Ryan , Tse Janson , Fischer Stefanie , Azimpour Alexander I. , Baloyan David , Elias Lena , Thilakasiri Pathum , Patel Onisha , Ferguson Fleur M. , Eissmann Moritz F. , Chand Ashwini L. , Gray Nathanael S. , Busuttil Rita , Boussioutas Alex , Lucet Isabelle S. , Ernst Matthias , Buchert Michael
Published: September 2024

Doublecortin-like kinase 1 (DCLK1) is a proposed driver of gastric cancer (GC) that phosphorylates serine and threonine residues. Here, we showed that the kinase activity of DCLK1 orchestrated cancer cell–intrinsic and–extrinsic processes that led to pro-invasive and pro-metastatic reprogramming of GC cells. Inhibition of the kinase activity of DCLK1 reduced the growth of subcutaneous xenograft tumors formed from MKN1 human gastric carcinoma cells in mice and decreased the abundance of the stromal markers α-Sma, vimentin, and collagen. Similar effects were seen in mice with xenograft tumors formed from MKN1 cells expressing a kinase-inactive DCLK1 mutant (MKN1
D511N
). MKN1
D511N
cells also had reduced in vitro migratory potential and stemness compared with control cells. Mice orthotopically grafted with MKN1 cells overexpressing DCLK1 (MKN1
DCLK1
) showed increased invasiveness and had a greater incidence of lung metastases compared with those grafted with control MKN1 cells. Mechanistically, we showed that the chemokine CXCL12 acted downstream of DCLK1 in cultured MKN1 cells and in mice subcutaneously implanted with gastric tumors formed by MKN1
DCLK1
cells. Moreover, inhibition of the kinase activity of DCLK1 or the expression of DCLK1
D511N
reversed the pro-tumorigenic and pro-metastatic phenotype. Together, this study establishes DCLK1 as a broadly acting and potentially targetable promoter of GC.
Prospectively predicting BPaMZ phase IIb/III trial outcomes using a translational mouse-to-human platform
Authors: Goh Janice J. N. , Wang Qianwen , Zhang Nan , de Castro Suarez Niurys , Bustion Annamarie E. , Nuermberger Eric L. , Savic Rada
Published: September 2024

Despite known treatments, tuberculosis (TB) remains the world’s top infectious killer, highlighting the pressing need for new drug regimens. To prioritize the most efficacious drugs for clinical testing, we previously developed a PK-PD translational platform with bacterial dynamics that reliably predicted short-term monotherapy outcomes in Phase IIa trials from preclinical mouse studies. In this study, we extended our platform to include PK-PD models that account for drug-drug interactions in combination regimens and bacterial regrowth in our bacterial dynamics model to predict cure at the end of treatment and relapse 6 months post-treatment. The Phase III STAND trial testing a new regimen comprised of pretomanid (Pa), moxifloxacin (M), and pyrazinamide (Z) (PaMZ) was suspended after a separate ongoing trial (NC-005) suggested that adding bedaquiline (B) to the PaMZ regimen would improve efficacy. To forecast if the addition of B would, indeed, benefit the PaMZ regimen, we applied an extended translational platform to both regimens. We predicted currently available short- and long-term clinical data well for drug combinations related to BPaMZ. We predicted the addition of B to PaMZ to shorten treatment duration by 2 months and to have similar bacteriological success to standard HRZE treatment (considering only treatment success but not withdrawal from side effects and other adverse events), both at the end of treatment for treatment efficacy and 6 months after treatment has ended in relapse prevention. Using BPaMZ as a case study, we have demonstrated our translational platform can predict Phase II and III outcomes prior to actual trials, allowing us to better prioritize the regimens most likely to succeed.
Phospholipid biosynthesis regulation for improving pigment production by
Monascus
in response to ammonium chloride stress
Authors: Jiang Xiaofei , Hong Xiya , Wang Zhulin , Liu Jun , Zhong Haiyan , Ren Jiali , Zhou Bo
Published: September 2024

In the actual industrial production process, the efficient biosynthesis and secretion of
Monascus
pigments (MPs) tend to take place under abiotic stresses, which often result in an imbalance of cell homeostasis. The present study aimed to thoroughly describe the changes in lipid profiles in
Monascus purpureus
by absolute quantitative lipidomics and tandem mass tag-based quantitative proteomics. The results showed that ammonium chloride stress (15 g/L) increased MP production while inhibiting ergosterol biosynthesis, leading to an imbalance in membrane lipid homeostasis in
Monascus
. In response to the imbalance of lipid homeostasis, the regulation mechanism of phospholipids in
Monascus
was implemented, including the inhibition of lysophospholipids production, maintenance of the ratio of PC/PE, and improvement of the biosynthesis of phosphatidylglycerol, phosphatidylserine, and cardiolipin with high saturated and long carbon chain fatty acids through the CDP-DG pathway rather than the Kennedy pathway. The inhibition of lysophospholipid biosynthesis was attributed to the upregulated expression of protein and its gene related to lysophospholipase NTE1, while maintenance of the PC/PE ratio was achieved by the upregulated expression of protein and its gene related to CTP: phosphoethanolamine cytidylyltransferase and phosphatidylethanolamine N-methyltransferase in the Kennedy pathway. These findings provide insights into the regulation mechanism of MP biosynthesis from new perspectives.

IMPORTANCE

Monascus
is important in food microbiology as it produces natural colorants known as
Monascus
pigments (MPs). The industrial production of MPs has been achieved by liquid fermentation, in which the nitrogen source (especially ammonium chloride) is a key nutritional parameter. Previous studies have investigated the regulatory mechanisms of substance and energy metabolism, as well as the cross-protective mechanisms in
Monascus
in response to ammonium chloride stress. Our research in this work demonstrated that ammonium chloride stress also caused an imbalance of membrane lipid homeostasis in
Monascus
due to the inhibition of ergosterol biosynthesis. We found that the regulation mechanism of phospholipids in
Monascus
was implemented, including inhibition of lysophospholipids production, maintenance of the ratio of PC/PE, and improvement of biosynthesis of phosphatidylglycerol, phosphatidylserine, and cardiolipin with high saturated and long carbon chain fatty acids through the CDP-DG pathway. These findings further refine the regulatory mechanisms of MP production and secretion.
Conserved linear motif within the immediate early protein ORF45 promotes its engagement with KSHV lytic cycle-promoting forkhead transcription factors, FOXK1 and FOXK2
Authors: Palmer Marley , Leo Alessandro , Atyeo Natalie , Tomacari Christiana , Nguyen Xuan , Papp Bernadett
Published: September 2024

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that can cause several cancers, such as Kaposi sarcoma and primary effusion lymphoma (PEL). We and others have recently demonstrated that Forkhead box (FOX) transcription factors can be dysregulated by KSHV, and they can affect KSHV infection. Herein, we focus on dissecting the role of two FOXK subfamily members, FOXK1 and FOXK2, in the KSHV life cycle. FOXK proteins are key host regulators of cellular functions, yet their role in KSHV infection remains unknown. Here, we demonstrated that both FOXK proteins are essential for efficient KSHV lytic reactivation in PEL cells. FOXK1 and FOXK2 are unique as they are the only FOX proteins that contain a Forkhead-associated (FHA) domain. The FHA domain is a specialized protein binding domain that recognizes a short linear serine/threonine-rich (S/T) motif. Through an unbiased motif survey, we found that KSHV viral protein ORF45 and its gammaherpesvirus homologs contain a putative FHA-binding motif. ORF45 is an immediate early tegument protein, vital for lytic reactivation and virus production. We demonstrated that ORF45 uses its novel conserved motif to interact with the FHA domain containing FOXK factors in the nucleus of infected cells. A single-point mutation of the conserved threonine residue in the motif within ORF45 abolished the ORF45-FOXK1/2 interaction. Our data indicates that FOXK proteins interact with ORF45 homologs encoded by murine gammaherpesvirus 68 (MHV68) and Rhesus macaque rhadinovirus (RRV), and that the FHA domains of FOXK proteins are sufficient for their interactions, highlighting a conserved mechanism.

IMPORTANCE

The dysregulation of Forkhead transcription factors contributes to many different human diseases, including cancers, but their impact on herpesvirus lifecycle and pathogenesis is less understood. Our study uncovers a critical pro-lytic function of the FOXK subfamily and its requirement for KSHV lytic reactivation in PEL. We found that FOXK proteins bind to a key immediate early KSHV protein ORF45 using its novel short linear S/T motif. Notably, even though ORF45 homologs in gammaherpesviruses are highly diverse, we identified a similar S/T short linear motif in ORF45 homologs and also showed an evolutionary conserved interaction between FOXK proteins and ORF45 homologs of MHV68 and RRV. Our study provides a basis for future studies in animal models to evaluate the role of FOXK proteins and the impact of their interactions with ORF45 in gammaherpesvirus infection and pathogenesis. Targeting these interactions could allow a novel way to limit gammaherpesvirus infections.
Sodium-dependent phosphate transporter PiT1/SLC20A1 as the receptor for the endogenous retroviral envelope syncytin-B involved in mouse placenta formation
Authors: Mousseau Guillaume , Préault Noémie , Souquere Sylvie , Bireau Caroline , Cassonnet Patricia , Bacquin Agathe , Beck Laurent , Pierron Gérard , Jacob Yves , Dupressoir Anne , Heidmann Thierry
Published: September 2024

Syncytins
are envelope genes of retroviral origin that play a critical role in the formation of a syncytial structure at the fetomaternal interface
via
their fusogenic activity. The mouse placenta is unique among placental mammals since the fetomaternal interface comprises two syncytiotrophoblast layers (ST-I and ST-II) instead of one observed in all other hemochorial placentae. Each layer specifically expresses a distinct mouse syncytin, namely syncytin-A (SynA) for ST-I and syncytin-B (SynB) for ST-II, which have been shown to be essential to placentogenesis and embryonic development. The cellular receptor for SynA has been identified as the membrane protein LY6E and is not the receptor for SynB. Here, by combining a cell–cell fusion assay with the screening of a human ORFeome-derived expression library, we identified the transmembrane multipass sodium-dependent phosphate transporter 1 PiT1/SLC20A1 as the receptor for SynB. Transfection of cells with the cloned receptor, but not the closely related PiT2/SLC20A2, leads to their fusion with cells expressing SynB, with no cross-reactive fusion activity with SynA. The interaction between the two partners was further demonstrated by immunoprecipitation. PiT1/PiT2 chimera and truncation experiments identified the PiT1 N-terminus as the major determinant for SynB-mediated fusion. RT-qPCR analysis of PiT1 expression on a panel of mouse adult and fetal tissues revealed a concomitant increase of PiT1 and SynB specifically in the developing placenta. Finally, electron microscopy analysis of the placenta of PiT1 null embryo before they die (E11.5) disclosed default of ST-II formation with lack of syncytialization, as previously observed in cognate SynB null placenta, and consistent with the present identification of PiT1 as the SynB partner.

IMPORTANCE

Syncytins are envelope genes of endogenous retroviruses, coopted for a physiological function in placentation. They are fusogenic proteins that mediate cell–cell fusion by interacting with receptors present on the partner cells. Here, by devising an
in vitro
fusion assay that enables the screening of an ORFeome-derived expression library, we identified the long-sought receptor for syncytin-B (SynB), a mouse syncytin responsible for syncytiotrophoblast formation at the fetomaternal interface of the mouse placenta. This protein – PiT1/SLC20A1 – is a multipass transmembrane protein, also known as the receptor for a series of infectious retroviruses. Its profile of expression is consistent with a role in both ancestral endogenization of a SynB founder retrovirus and present-day mouse placenta formation, with evidence—in PiT1 knockout mice—of unfused cells at the level of the cognate placental syncytiotrophoblast layer.