bluuebunny/crossref_metadata_2025 huggingface dataset:
Basal Forebrain Cholinergic Innervation Induces Depression-Like Behaviors Through Ventral Subiculum Hyperactivation
Authors: Yu Nana , Song Huina , Chu Guangpin , Zhan Xu , Liu Bo , Mu Yangling , Wang Jian-Zhi , Lu Yisheng
Published: November 2022

Malfunction of the ventral subiculum (vSub), the main subregion controlling the output connections from the hippocampus, is associated with major depressive disorder (MDD). Although the vSub receives cholinergic innervation from the medial septum and diagonal band of Broca (MSDB), whether and how the MSDB-to-vSub cholinergic circuit is involved in MDD is elusive. Here, we found that chronic unpredictable mild stress (CUMS) induced depression-like behaviors with hyperactivation of vSub neurons, measured by c-fos staining and whole-cell patch-clamp recording. By retrograde and anterograde tracing, we confirmed the dense MSDB cholinergic innervation of the vSub. In addition, transient restraint stress in CUMS increased the level of ACh in the vSub. Furthermore, chemogenetic stimulation of this MSDB-vSub innervation in ChAT-Cre mice induced hyperactivation of vSub pyramidal neurons along with depression-like behaviors; and local infusion of atropine, a muscarinic receptor antagonist, into the vSub attenuated the depression-like behaviors induced by chemogenetic stimulation of this pathway and CUMS. Together, these findings suggest that activating the MSDB-vSub cholinergic pathway induces hyperactivation of vSub pyramidal neurons and depression-like behaviors, revealing a novel circuit underlying vSub pyramidal neuronal hyperactivation and its associated depression.
The Evolution of Blue Carbon Science
Authors: Duarte de Paula Costa Micheli , Macreadie Peter I.
Published: November 2022

‘Blue carbon’ was coined over a decade ago to describe the contribution of mangroves, seagrasses, and tidal marshes to carbon drawdown in coasts and oceans, concomitantly attracting attention of policy-makers and resource managers to their potential as a natural climate solution. Here, we explore the emergence and evolution of this relatively new research field through bibliometrics approaches to investigate patterns and trends in scientific publications through time. Our aim was to understand the evolution of blue carbon science, from where we came from and where we are now. We analysed 1,729 papers from 5,763 authors. Overall, the carbon-sink capacity of these ecosystems has been recognised long before the term ‘blue carbon’ was coined; with an annual percentage growth rate of 20% y− 1. Research attention was highest for mangroves (~ 38% of publications), followed by saltmarshes (~ 22%), and seagrasses (~ 18%); while ~ 16% of the studies included two or more blue carbon ecosystems and 5% of the studies focused on other ecosystems. The citation burst analysis showed that, in the 1990s, the hot topic (i.e., fast-growing topic) was related to the overall flux and dynamics of carbon, with a recent transition to the role of coastal vegetation to climate change mitigation from 2009. The term ‘blue carbon’ became a hot topic in 2017, with the strongest citation burst between 2017 and 2020. This bibliometric study draws the patterns and trends of blue carbon science and indicate that this field is evolving through time to focus more on the blue carbon role as nature climate solutions.
Advanced shifted first-kind Chebyshev collocation approach for solving the nonlinear time-fractional partial integro-differential equation with a weakly singular kernel
Authors: Atta A. G. , Youssri Y. H.
Published: November 2022

This research apparatuses an approximate spectral method for the nonlinear time-fractional partial integro-differential equation with a weakly singular kernel (TFPIDE). The main idea of this approach is to set up a new Hilbert space that satisfies the initial and boundary conditions. The new spectral collocation approach is applied to obtain precise numerical approximation using new basis functions based on shifted first-kind Chebyshev polynomials (SCP1K). Furthermore, we support our study by a careful error analysis of the suggested shifted first-kind Chebyshev expansion. The results show that the new approach is very accurate and effective.
The Puzzle of Architecture and Bureaucracy
Authors: Agarez Ricardo Costa , Floré Fredie , Devos Rika
Published: November 2022

Architecture and bureaucracy: indissociable and irreconcilable? The two spheres are often seen in opposition — the latter curtailing the former’s creative power — yet might they not also overlap, partake and occasionally coincide in their processes? Dismissing the role of bureaucracy in architecture as extraneous or detrimental seems to hinder our capacity, as thinkers and producers of architecture, to work through this relationship and explore ways of dealing with a pervasive tool of contemporary societal organisation; whereas understanding the fraught relationship might help us bridge the gap that, in many contexts, separates architecture and the communities it exists to serve. This special collection explores how architecture and bureaucracy have negotiated their stances in the twentieth century. In particular, it aims to shed light on instances where knowledge of architecture was an element in, and a product of, the machinery of bureaucracy. Beyond the notion of bureaucracy in architecture as a site of imposition and control — and the vivid sentiments of frustration and deception it prompts — lies a terrain where less contrasted, more fine-grained actions and exchanges occur. The ways in which these two spheres relate are diverse and merit scholarly attention, as the articles that follow demonstrate.
Development Visions in Ghana: From Design Schools and Building Research to Tema New Town
Authors: Jackson Iain
Published: November 2022

This article investigates a series of development strategies pursued in Ghana from the mid-1940s under British colonial rule to the early independence period of the 1960s, seeking to understand how the pace and location of development affected the wider built fabric and especially housing production. While two contrasting visions emerge — of rural extractive agriculture versus industrial urban manufacturing — the impact of these endeavours was most strongly felt in the accompanying housing developments. Attempts to create a new artisan school capable of manufacturing building materials, and a laboratory tasked with developing new local building materials, sought to preserve a mainly rural-based population and lifestyle while reducing costs and making dwellings more durable. However, with advancing industrialisation and rapidly expanding urban centres, efforts to accommodate this change with revised urban boundaries and new construction standards failed adequately to address the housing issues and revealed fundamental problems in the governance of newly urbanising and suburban settlements. Could the solution be to ’start again’, to build a new town without the difficulties of the past? This was the approach of the elected nationalist government that commissioned the new town of Tema, east of the capital Accra. As one of the grand projects of the then prime minister, Kwame Nkrumah, Tema has been the focus of much scholarly attention, but a new source has recently come to light that changes understanding of the project. The notebooks kept by Michael Hirst, one of those charged with its design and realisation, show how Tema became an unwitting design school with its own series of trials and tests performed by a team of newly qualified architects. It was not only a political new beginning, but also an experimental attempt to create a new urban environment built on the promise of an industrialised future.
Between Bureaucratic Tradition and Professional Discourse: Turkey and the Case of SİSAG, 1969–77
Authors: İmamoğlu Bilge
Published: November 2022

The history of twentieth-century architecture in Turkey can be presented as a conflict between a powerful state bureaucracy and an independent architectural community: the former producing most of the buildings and infrastructure but with little verbalisation; the latter producing most of the discourse but building relatively little. This article examines a case that challenges this dichotomy. It focuses on the architectural department of SİSAG (1969–77), a company associated with Hacettepe University in Ankara, and the organisational, institutional and occupational modes and practices that it employed. The article explores both the architectural production of SİSAG and its role as the setting for the first white-collar strike in Turkey, and it unearths the intellectual and institutional discourse on the organisation of architectural production that surfaced with this confrontation. The article shows how, in the relationship between bureaucratic tradition and professional discourse, SİSAG took an ‘in-between’ position, its architects seeking to replace conflict with cooperation, and to reconcile ideas of public service, public interest and social engagement on the one hand with disciplinary knowledge, planning and design and independent research on the other.
A growth-fragmentation model connected to the ricocheted stable process
Authors: Watson Alexander R.
Published: November 2022

Growth-fragmentation processes describe the evolution of systems in which cells grow slowly and fragment suddenly. Despite originating as a way to describe biological phenomena, they have recently been found to describe the lengths of certain curves in statistical physics models. In this note, we describe a new growth-fragmentation process connected to random planar maps with faces of large degree, having as a key ingredient the ricocheted stable process recently discovered by Budd. The process has applications to the excursions of planar Brownian motion and Liouville quantum gravity.
MIDDLE HOLOCENE GLACIER ACTIVITY IN THE RUSSIAN ALTAI: EVIDENCE FROM RADIOCARBON AND PALEOTREE DATA IN THE AKKOL VALLEY
Authors: Nepop R K , Agatova A R , Nazarov A N , Myglan V S , Moska P
Published: November 2022

The available paleosol and paleowood data from the head of the Akkol trough valley, South Chuya range, indicates a climatically driven glacier dynamic in the Russian Altai. Radiocarbon dating of paleosols and paleotree fragments help determine the beginning of the Neoglacial in this high mountain region in the middle of the Holocene. New data limit the advance of the Sofiysky glacier at that time by the front of the Historical moraine. Less so than during the Historical stage (2.3–1.7 cal kBP), glacial activity 5–4 cal kBP is also supported by rapid reforestation. The Akkem moraine in trough valleys of the Russian Altai accumulated prior to the Holocene. The limitations and difficulties of radiocarbon dating of paleosols should be considered when interpreting the dating results.
Calycosin attenuatesAngiostrongylus cantonensis-induced parasitic meningitis through modulation of HO-1 and NF-κB activation
Authors: Lu Cheng-You , Chen Ke-Min , Kuo Wei-Wen , Lai Shih-Chan , Ho Tsung-Jung , Lai Po-Tang , Huang Chih-Yang , Wang Tso-Fu
Published: November 2022

Angiostrongylus cantonensiscauses a form of parasitic meningitis in humans. Albendazole (ABZ) kills nematode larvae in the brain. However, dead larvae can trigger a severe inflammatory response, resulting in brain damage. Accumulating evidence suggests that calycosin represents a potential anti-inflammatory therapeutic candidate. In this study, we investigated the combined effects of ABZ and calycosin in angiostrongyliasis caused byA. cantonensisin BALB/c mice. Inflammatory mediators (such as phospho-nuclear factor-κB, cyclooxygenase-2, matrix metalloproteinase-9, tumour necrosis factor-αand interleukin-1β) are associated with the development of meningitis and immune inflammatory reactions. We found thatA. cantonensissignificantly induces inflammatory mediator production and increases the blood–brain barrier (BBB) permeability. However, co-administration of both ABZ and calycosin markedly suppressed meningitis and inflammatory mediator production and decreased the BBB permeability compared to treatment with a single drug. Furthermore, calycosin and ABZ plus calycosin treatment facilitated production of the antioxidant haem oxygenase-1 (HO-1). Moreover, co-therapy with ABZ and calycosin failed to mitigate angiostrongyliasis in the presence of tin-protoporphyrin IX, an HO-1-specific inhibitor. This finding suggests that the beneficial effects of ABZ plus calycosin treatment on the regulation of inflammation are mediated by the modulation of HO-1 activation. The present results provide new insights into the treatment of human angiostrongyliasis using co-therapy with ABZ and calycosin.
Chinese university students’ translanguaging hybrids on WeChat
Authors: Qi Fang , Li Junlong
Published: November 2022

The popularity of the online social media in China promotes a dynamic digital drive for both global and glocalised communications, facilitating the emergence of more connected intercultural language practices unimaginable in the past. Social media also creates a vast community where pervasive translanguaging practices take place daily. Translanguaging hybrids coined by Chinese university students on WeChat are exactly a case in point. WeChat is a free platform launched in 2011 by Tencent. Well established in China and the world over, Tencent provides multimodal instant messaging services. Open to world cultures, these students show ingenuity in translanguaging linguistic play in their daily text messages; meanwhile, their creative coinage of translanguaging hybrids influences the entire WeChat community. Written language in the WeChat community, often amounting to a new form of speech, deserves serious scholarly inquiry.
ADAPTATION FOR NONPARAMETRIC ESTIMATORS OF LOCALLY STATIONARY PROCESSES
Authors: Dahlhaus Rainer , Richter Stefan
Published: November 2022

Two adaptive bandwidth selection methods for minimizing the mean squared error of nonparametric estimators in locally stationary processes are proposed. We investigate a cross-validation approach and a method based on contrast minimization and derive asymptotic properties of both methods. The results are applicable for different statistics under a general setting of local stationarity including nonlinear processes. At the same time, we deepen the general framework for local stationarity based on stationary approximations. For example, a general Bernstein inequality is derived for such processes. The properties of the bandwidth selection methods are also investigated in several simulation studies.
A forgotten cirripedological gem: a new species of whale barnacle of the genus Cetopirus from the Pleistocene of the United States West Coast
Authors: COLLARETA Alberto , BOSSELAERS Mark , HOLROYD Patricia A. , DINEEN Ashley
Published: November 2022

A small lot of fossil whale barnacles from the Upper Pleistocene of California and the Middle Pleistocene (Chibanian) of Oregon (United States West Coast), described in a 1972 unpublished MA thesis, are formally described and illustrated herein. In that thesis, a new genus and species name were proposed; however, according to the International Code of Zoological Nomenclature, they have no taxonomic standing and are thus unavailable. Based on our reappraisal, two specimens in this lot belong to a new, extinct species that can be assigned to the purportedly extant genus Cetopirus. Cetopirus polysyrinx sp. nov. differs from congeners in that its secondary T-shaped flanges are multitubiferous internally, that is, they are perforated by a high number of irregularly-sized and irregularly-spaced tubules that result in a spongy aspect in transverse section. Whether or not this peculiar condition had any adaptive significance is difficult to determine. Considering that Cetopirus is currently known as an obligate epibiont of right whales (including the North Pacific form Eubalaena japonica (Lacépède 1818)), the host of C. polysyrinx sp. nov. was E. japonica or some other species of Eubalaena. The Plio-Pleistocene deposits of the Pacific coast of North America have yielded a rather idiosyncratic fossil whale barnacle fauna, inclusive of the genera Cetolepas, Cryptolepas and now Cetopirus, which seemingly contrasts with all other coeval assemblages worldwide, the latter being in turn dominated by Coronula spp.
Protecting disabled people during armed conflict in North Kivu: Challenges and perspectives
Authors: Ngila Kikuni Ibrahim , Munenge Mudage Florent
Published: November 2022

This study analyses the situation of persons with disabilities caught up in armed conflict in the Democratic Republic of the Congo, in particular in North Kivu Province. The study goes beyond the few statistics available – which show the vulnerability of persons with disabilities during humanitarian crises – to identify the obstacles to taking persons with disabilities into account in humanitarian action in North Kivu. As a result, the study provides practical recommendations to overcome these obstacles, fill in the gaps in humanitarian action and improve the situation of persons with disabilities by ensuring efficient and effective protection in times of armed conflict.
Malathion exposure during juvenile and peripubertal periods downregulate androgen receptor and 17-ß-HSD testicular gene expression and compromised sperm quality in rats
Authors: Erthal Rafaela Pires , Siervo Gláucia Eloisa Munhoz de Lion , Frigoli Giovanna Fachetti , Zaninelli Tiago Henrique , Verri Waldiceu Aparecido , Fernandes Glaura Scantamburlo Alves
Published: November 2022

Malathion is an insecticide that is used to control arboviruses and agricultural pests. Adolescents that are exposed to this insecticide are the most vulnerable as they are in the critical period of postnatal sexual development. This study aimed to evaluate whether malathion damage can affect sperm function and its respective mechanisms when adolescents are exposed during postnatal sexual development. Twenty-four male Wistar rats (PND 25) were divided into three experimental groups and treated daily for 40 d: control group (saline 0.9%), 10 mg/kg (M10 group), or 50 mg/kg (M50 group) of malathion. At PND 65, the rats were anesthetized and euthanized. Testicles were collected for the evaluation of gene expression. Sperm cells from the epididymis were used for evaluation of the oxidative profile or spermatic function. Data showed that a lower dose of malathion downregulated the gene expression of androgen receptors and testosterone converter enzyme 17-β-HSD in the testis. The acrosomal integrity of sperm cells was compromised in the M50 group, but not the M10 group. The mitochondrial activity was not impaired by exposure. Finally, although no alterations in malondialdehyde and glutathione levels were observed, malathion, at both doses, increased antioxidant enzyme catalase activity and, at a higher dose, superoxide dismutase activity. The present study showed that low doses of malathion considered to be inoffensive are capable of impairing sperm quality and function through the downregulation of testicular genic expression of AR enzyme 17-β-HSD and can damage the spermatic antioxidant profile during critical periods of development.
Understanding the importance of the early-life period for adult health: a systematic review
Authors: Hildreth Jillian R. , Vickers Mark H. , Buklijas Tatjana , Bay Jacquie L.
Published: November 2022

Evidence clearly indicates that the nutritional and non-nutritional environment and level of physical activity during the early-life period from preconception through infancy has a lifelong impact on the child’s health. However this message must be communicated effectively to parents and other stakeholders such as grandparents, health professionals, policymakers and the wider community in order for positive change to occur. This systematic review explores how both awareness and understanding of the long-term effects of the early-life environment have been measured in various populations and whether any patterns are evident. Ten articles were retrieved via a search of Embase, Medline and Scopus databases for peer-reviewed studies designed to assess participants’ knowledge of the links between early-life exposures and adult health. Eligible articles spanned a wide range of countries, population groups and research methods. Three common themes were identified using thematic analysis: 1. a tendency for researchers to conflate participant understanding of the issue (the WHY) with a knowledge of key phrases and nutrition guidelines (the WHAT); 2. bias in both researchers and participants towards short-term thinking due to difficulty conceptualising long-term risk; and 3. challenges in comprehending the complexity of the evidence resulting in oversimplification and the overemphasis of maternal factors. Taken together these findings underscore the importance of a multi-level, whole-of-society approach to communicating the evidence, with the goal of influencing policy decisions as well as building a foundation of community support for parents and prospective parents to create a healthy early-life environment for the long-term wellbeing of all.
Documentation of Peripheral Auditory Function in Studies of the	Auditory P300 Response
Authors: van der Merwe Janushca , Biagio-de Jager Leigh , Mahomed-Asmail Faheema , Hall James W.
Published: November 2022

Abstract: A critical review was conducted to examine whether the peripheral hearing status of participants with neurological and psychological disorders was documented in published clinical studies of the auditory P300 response. Literature searches were conducted with three databases: PubMed, PsycINFO, and Scopus. Studies of participants with seven neurological or psychological disorders were included in the study. Each disorder was coupled with the main search phrase in separate searches on each database. Of the total 102 papers which met the inclusion criteria, the majority (64%) did not describe the peripheral hearing sensitivity of participants. In this review with studies that included participants at risk for hearing impairment, particularly age-related hearing loss, only a single publication adequately described formal hearing evaluation. Peripheral hearing status is rarely defined in studies of the P300 response. The inclusion of participants with a hearing loss likely affects the validity of findings for these studies. We recommend formal hearing assessment prior to inclusion of participants in studies of the auditory P300 response. The findings of this study may increase the awareness among researchers outside the field of audiology of the effects of peripheral hearing loss on the auditory P300.
“When the Wild Roses Bloom”: Indigenous Knowledge and Environmental Change in Northwestern North America
Authors: Turner Nancy J. , Reid Andrea J.
Published: November 2022

Indigenous Peoples in Northwestern North America have always worked with predictable cycles of day and night, tides, moon phases, seasons, and species growth and reproduction, including such phenological indicators as the blooming of flowers and the songs of birds. Negotiating variability has been constant in people's lives. Long‐term monitoring and detailed knowledge of other lifeforms and landscapes of people's home territories have assisted in responding and adapting to change. Aspects of cultural knowledge and practice that have helped Indigenous Peoples navigate nature's cycles at different scales of time and space include kin ties and social relationships, experiential learning, language, storytelling and timing of ceremonies such as “First Foods” celebrations. Working with ecological processes, Indigenous Peoples have been able to maintain optimal conditions for preferred species, reducing variability and uncertainty through taking care of productive habitats, leaving ecosystems intact, and allowing other species to change in their own cycles. Since the onset of colonization, however, Indigenous Peoples' lifeways have been changed drastically, culminating with the current impacts of global climate change and biodiversity loss. This paper, based on contributions of numerous Indigenous Knowledge holders from across Northwestern North America, outlines some of the key ways in which Indigenous Peoples have embraced predictability and change in their environments and lifeways, and addresses the particular threat of climate change: its recognition, ways of adapting to it, and, ultimately, how it might be reversed through developing more careful, respectful relationships with and responsibilities for the other‐than‐human world.
Episodic Plate Tectonics on Europa: Evidence for Widespread Patches of Mobile‐Lid Behavior in the Antijovian Hemisphere
Authors: Collins Geoffrey C. , Patterson G. Wesley , Detelich Charlene E. , Prockter Louise M. , Kattenhorn Simon A. , Cooper Catherine M. , Rhoden Alyssa R. , Cutler Benjamin B. , Oldrid Samantha R. , Perkins Reid P. , Rezza Craig A.
Published: November 2022

A nearly pole‐to‐pole survey near 140°E longitude on Europa revealed many areas that exhibit past lateral surface motions, and these areas were examined to determine whether the motions can be described by systems of rigid plates moving across Europa's surface. Three areas showing plate‐like behavior were examined in detail to determine the sequence of events that deformed the surface. All three areas were reconstructed to reveal the original pre‐plate motion surfaces by performing multi‐stage rotations of plates in spherical coordinates. Several motions observed along single plate boundaries were also noted in previous works, but this work links together isolated observations of lateral offsets into integrated systems of moving plates. Not all of the surveyed surface could be described by systems of rigid plates. There is evidence that the plate motions did not all happen at the same time, and that they are not happening today. We conclude that plate tectonic‐like behavior on Europa occurs episodically, in limited regions, with less than 100 km of lateral motion accommodated along any particular boundary before plate motions cease. Europa may represent a world perched on the theoretical boundary between stagnant and mobile lid convective behavior, or it may represent an additional example of the wide variations in possible planetary convective regimes. Differences in observed strike‐slip sense and plate rotation directions between the northern and southern hemispheres raise the question of whether tidal forces may influence plate motions.
Gastrointestinal cancer occurs as extramuscular manifestation in FSHD1 patients
Authors: Kurashige Takashi , Morino Hiroyuki , Ueno Hiroki , Murao Tomomi , Watanabe Tomoaki , Hinoi Takao , Nishino Ichizo , Torii Tsuyoshi , Maruyama Hirofumi
Published: November 2022

Facioscapulohumeral dystrophy type1 (FSHD1) patients with a shortened D4Z4 repeat containing the DUX4 gene have a broad spectrum of clinical manifestations. In addition, high expression of DUX4 protein with an aberrant C terminus is frequently identified in B cell acute lymphoblastic leukemia. We investigated clinical manifestations in 31 FSHD1 patients and 30 non-affected individuals. Gastrointestinal cancers (gastric and colorectal cancers) increased after the age of 40 years and were more frequently observed in FSHD1 patients (n = 10) than in non-affected individuals (n = 2, p = 0.0217), though the incidence of cancers occurring in non-gastrointestinal tissues of FSHD1 patients was the same as that of non-affected individuals (p > 0.999). These comorbidities of FSHD1 patients were not associated with D4Z4 repeat number. Our results suggest that gastrointestinal cancers are among the extramuscular manifestations of adult FSHD1 patients, and do not depend on D4Z4 repeat number.
Epigenetic regulation of aging: implications for interventions of aging and diseases
Authors: Wang Kang , Liu Huicong , Hu Qinchao , Wang Lingna , Liu Jiaqing , Zheng Zikai , Zhang Weiqi , Ren Jie , Zhu Fangfang , Liu Guang-Hui
Published: November 2022

Aging is accompanied by the decline of organismal functions and a series of prominent hallmarks, including genetic and epigenetic alterations. These aging-associated epigenetic changes include DNA methylation, histone modification, chromatin remodeling, non-coding RNA (ncRNA) regulation, and RNA modification, all of which participate in the regulation of the aging process, and hence contribute to aging-related diseases. Therefore, understanding the epigenetic mechanisms in aging will provide new avenues to develop strategies to delay aging. Indeed, aging interventions based on manipulating epigenetic mechanisms have led to the alleviation of aging or the extension of the lifespan in animal models. Small molecule-based therapies and reprogramming strategies that enable epigenetic rejuvenation have been developed for ameliorating or reversing aging-related conditions. In addition, adopting health-promoting activities, such as caloric restriction, exercise, and calibrating circadian rhythm, has been demonstrated to delay aging. Furthermore, various clinical trials for aging intervention are ongoing, providing more evidence of the safety and efficacy of these therapies. Here, we review recent work on the epigenetic regulation of aging and outline the advances in intervention strategies for aging and age-associated diseases. A better understanding of the critical roles of epigenetics in the aging process will lead to more clinical advances in the prevention of human aging and therapy of aging-related diseases.
The interplay of dopamine metabolism abnormalities and mitochondrial defects in the pathogenesis of schizophrenia
Authors: Xu Haiyun , Yang Fan
Published: November 2022

Dopamine (DA) is a major monoamine neurotransmitter in the brain and has essential roles in higher functions of the brain. Malfunctions of dopaminergic signaling have been implicated in various mental disorders such as addiction, attention deficit/hyperactivity disorder, Huntington’s disease, Parkinson’s disease (PD), and schizophrenia. The pathogenesis of PD and schizophrenia involves the interplay of mitochondrial defect and DA metabolism abnormalities. This article focuses on this issue in schizophrenia. It started with the introduction of metabolism, behavioral action, and physiology of DA, followed by reviewing evidence for malfunctions of dopaminergic signaling in patients with schizophrenia. Then it provided an overview of multiple facets of mitochondrial physiology before summarizing mitochondrial defects reported in clinical studies with schizophrenia patients. Finally, it discussed the interplay between DA metabolism abnormalities and mitochondrial defects and outlined some clinical studies showing effects of combination therapy of antipsychotics and antioxidants in treating patients with schizophrenia. The update and integration of these lines of information may advance our understanding of the etiology, pathogenesis, phenomenology, and treatment of schizophrenia.
Stepwise molecular mechanisms responsible for chemoresistance in bladder cancer cells
Authors: Mun Jeong-Yeon , Baek Seung-Woo , Jeong Mi-So , Jang In-Hwan , Lee Se-Ra , You Jae-Young , Kim Jeong-Ah , Yang Gi-Eun , Choi Yung-Hyun , Kim Tae-Nam , Chu In-Sun , Leem Sun-Hee
Published: November 2022

Chemotherapy resistance is an obstacle to cancer therapy and is considered a major cause of recurrence. Thus, understanding the mechanisms of chemoresistance is critical to improving the prognosis of patients. Here, we have established a stepwise gemcitabine-resistant T24 bladder cancer cell line to understand the molecular mechanisms of chemoresistance within cancer cells. The characteristics of the stepwise chemoresistance cell line were divided into 4 phases (parental, early, intermediate, and late phases). These four phase cells showed increasingly aggressive phenotypes in vitro and in vivo experiments with increasing phases and revealed the molecular properties of the biological process from parent cells to phased gemcitabine-resistant cell line (GRC). Taken together, through the analysis of gene expression profile data, we have characterized gene set of each phase indicating the response to anticancer drug treatment. Specifically, we identified a multigene signature (23 genes including GATA3, APOBEC3G, NT5E, MYC, STC1, FOXD1, SMAD9) and developed a chemoresistance score consisting of that could predict eventual responsiveness to gemcitabine treatment. Our data will contribute to predicting chemoresistance and improving the prognosis of bladder cancer patients.
Discerning asthma endotypes through comorbidity mapping
Authors: Jia Gengjie , Zhong Xue , Im Hae Kyung , Schoettler Nathan , Pividori Milton , Hogarth D. Kyle , Sperling Anne I. , White Steven R. , Naureckas Edward T. , Lyttle Christopher S. , Terao Chikashi , Kamatani Yoichiro , Akiyama Masato , Matsuda Koichi , Kubo Michiaki , Cox Nancy J. , Ober Carole , Rzhetsky Andrey , Solway Julian
Published: November 2022

Asthma is a heterogeneous, complex syndrome, and identifying asthma endotypes has been challenging. We hypothesize that distinct endotypes of asthma arise in disparate genetic variation and life-time environmental exposure backgrounds, and that disease comorbidity patterns serve as a surrogate for such genetic and exposure variations. Here, we computationally discover 22 distinct comorbid disease patterns among individuals with asthma (asthma comorbidity subgroups) using diagnosis records for >151 M US residents, and re-identify 11 of the 22 subgroups in the much smaller UK Biobank. GWASs to discern asthma risk loci for individuals within each subgroup and in all subgroups combined reveal 109 independent risk loci, of which 52 are replicated in multi-ancestry meta-analysis across different ethnicity subsamples in UK Biobank, US BioVU, and BioBank Japan. Fourteen loci confer asthma risk in multiple subgroups and in all subgroups combined. Importantly, another six loci confer asthma risk in only one subgroup. The strength of association between asthma and each of 44 health-related phenotypes also varies dramatically across subgroups. This work reveals subpopulations of asthma patients distinguished by comorbidity patterns, asthma risk loci, gene expression, and health-related phenotypes, and so reveals different asthma endotypes.
Tunable critical Casimir forces counteract Casimir–Lifshitz attraction
Authors: Schmidt Falko , Callegari Agnese , Daddi-Moussa-Ider Abdallah , Munkhbat Battulga , Verre Ruggero , Shegai Timur , Käll Mikael , Löwen Hartmut , Gambassi Andrea , Volpe Giovanni
Published: November 2022

In developing micro- and nanodevices, stiction between their parts, that is, static friction preventing surfaces in contact from moving, is a well-known problem. It is caused by the finite-temperature analogue of the quantum electrodynamical Casimir–Lifshitz forces, which are normally attractive. Repulsive Casimir–Lifshitz forces have been realized experimentally, but their reliance on specialized materials severely limits their applicability and prevents their dynamic control. Here we demonstrate that repulsive critical Casimir forces, which emerge in a critical binary liquid mixture upon approaching the critical temperature, can be used to counteract stiction due to Casimir–Lifshitz forces and actively control microscopic and nanoscopic objects with nanometre precision. Our experiment is conducted on a microscopic gold flake suspended above a flat gold-coated substrate immersed in a critical binary liquid mixture. This may stimulate the development of micro- and nanodevices by preventing stiction as well as by providing active control and precise tunability of the forces acting between their constituent parts.
Computational simulation and target prediction studies of solubility optimization of decitabine through supercritical solvent
Authors: Alshahrani Saad M. , Almutairy Bjad K. , Alfadhel Munerah M. , Belal Amany , Abourehab Mohammed A. S. , Saqr Ahmed Al. , Alshetaili Abdullah S. , Venkatesan Kumar , Alsubaiyel Amal M. , Pishnamazi Mahboubeh
Published: November 2022

Computational analysis of drug solubility was carried out using machine learning approach. The solubility of Decitabine as model drug in supercritical CO2 was studied as function of pressure and temperature to assess the feasibility of that for production of nanomedicine to enhance the solubility. The data was collected for solubility optimization of Decitabine at the temperature 308–338 K, and pressure 120–400 bar used as the inputs to the machine learning models. A dataset of 32 data points and two inputs (P and T) have been applied to optimize the solubility. The only output is Y = solubility, which is Decitabine mole fraction solubility in the solvent. The developed models are three models including Kernel Ridge Regression (KRR), Decision tree Regression (DTR), and Gaussian process (GPR), which are used for the first time as a novel model. These models are optimized using their hyper-parameters tuning and then assessed using standard metrics, which shows R2-score, KRR, DTR, and GPR equal to 0.806, 0.891, and 0.998. Also, the MAE metric shows 1.08E−04, 7.40E−05, and 9.73E−06 error rates in the same order. The other metric is MAPE, in which the KRR error rate is 4.64E−01, DTR shows an error rate equal to 1.63E−01, and GPR as the best mode illustrates 5.06E−02. Finally, analysis using the best model (GPR) reveals that increasing both inputs results in an increase in the solubility of Decitabine. The optimal values are (P = 400, T = 3.38E + 02, Y = 1.07E−03).
Comparative and pangenomic analysis of the genus Streptomyces
Authors: Otani Hiroshi , Udwary Daniel W. , Mouncey Nigel J.
Published: November 2022

Streptomycetes are highly metabolically gifted bacteria with the abilities to produce bioproducts that have profound economic and societal importance. These bioproducts are produced by metabolic pathways including those for the biosynthesis of secondary metabolites and catabolism of plant biomass constituents. Advancements in genome sequencing technologies have revealed a wealth of untapped metabolic potential from Streptomyces genomes. Here, we report the largest Streptomyces pangenome generated by using 205 complete genomes. Metabolic potentials of the pangenome and individual genomes were analyzed, revealing degrees of conservation of individual metabolic pathways and strains potentially suitable for metabolic engineering. Of them, Streptomyces bingchenggensis was identified as a potent degrader of plant biomass. Polyketide, non-ribosomal peptide, and gamma-butyrolactone biosynthetic enzymes are primarily strain specific while ectoine and some terpene biosynthetic pathways are highly conserved. A large number of transcription factors associated with secondary metabolism are strain-specific while those controlling basic biological processes are highly conserved. Although the majority of genes involved in morphological development are highly conserved, there are strain-specific varieties which may contribute to fine tuning the timing of cellular differentiation. Overall, these results provide insights into the metabolic potential, regulation and physiology of streptomycetes, which will facilitate further exploitation of these important bacteria.
Transplacental transfer of total immunoglobulin G and antibodies to Plasmodium falciparum antigens between the 24th week of gestation and term
Authors: Kayatani Alexander K. K. , Leke Rose G. F. , Leke Robert I. J. , Fogako Josephine , Taylor Diane Wallace
Published: November 2022

Full-term newborns have antibody (Ab) repertoires and levels similar to their mothers to help protect them from environmental pathogens. Unfortunately, preterm babies, especially those born < 34 weeks, have reduced levels of protective antibodies. In Africa, antibodies to Plasmodium falciparum are important in protection from malaria. This study investigated the transfer of total IgG and antibodies to 9 P. falciparum antigens and tetanus toxoid between 24 weeks and term. Paired maternal and cord samples from 166 preterm (24–37 weeks) and 154 term deliveries were used. Transfer efficiency was expressed as the ratio of Ab levels in cord to maternal plasma (CMR). At 24–25 weeks, CMR ranged from 0.31 to 0.94 for the different antigens; the rate of transfer was similar for all antigens between 24 and 40 weeks; resulting in median CMR of 0.49–0.95 at term. Babies of mothers with hypergammaglobulinemia and normal IgG levels had similar amounts of IgG, supporting data that saturation of the neonatal Fc-receptor occurs at ~ 16 mg IgG/ml. Thus, babies born prior to 34–35 weeks in Africa are likely to have reduced Ab levels to some, but not all antigens. Since IgG transfer is Fc-mediated, why differences exist in CMR among the antigens warrants further investigation.
Medication non-adherence and therapeutic inertia independently contribute to poor disease control for cardiometabolic diseases
Authors: Yan Xiaowei , Mudiganti Satish , Husby Hannah , Hudnut Andrew , Gbotoe Madina , Jones J. B.
Published: November 2022

Poorly controlled cardiometabolic biometric health gap measures [e.g.,uncontrolled blood pressure (BP), HbA1c, and low-density lipoprotein cholesterol (LDL-C)] are mediated by medication adherence and clinician-level therapeutic inertia (TI). The study of comparing relative contribution of these two factors to disease control is lacking. We conducted a retrospective cohort study using 7 years of longitudinal electronic health records (EHR) from primary care cardiometabolic patients who were 35 years or older. Cox-regression modeling was applied to estimate how baseline proportion of days covered (PDC) and TI were associated with cardiometabolic related health gap closure. 92,766 patients were included in the analysis, among which 89.9%, 85.8%, and 73.3% closed a BP, HbA1c, or LDL-C gap, respectively, with median days to gap closure ranging from 223 to 408 days. Patients who did not retrieve a medication were the least likely to achieve biometric control, particularly for LDL-C (HR = 0.58, 95% CI: 0.55–0.60). TI or uncertainty of TI was associated with a high risk of health gap persistence, particularly for LDL-C (HR ranges 0.46–0.48). Both poor medication adherence and TI are independently associated with persistent health gaps, and TI has a much higher impact on disease control compared to medication adherence, implying disease management strategies should prioritize reducing TI.
Modeling a semi-optimal deceleration of a rigid body rotational motion in a resisting medium
Authors: El-Sabaa F. M. , Amer T. S. , Sallam A. A. , Abady I. M.
Published: November 2022

This paper studies the shortest time of slowing rotation of a free dynamically asymmetric rigid body (RB), analogous to Euler’s case. This body is influenced by a rotatory moment of a tiny control torque with closer coefficients but not equal, a gyrostatic moment (GM) due to the presence of three rotors, and in the presence of a modest slowing viscous friction torque. Therefore, this problem can be regarded as a semi-optimal one. The controlling optimal decelerating law for the rotation of the body is constructed. The trajectories that are quasi-stationary are examined. The obtained new results are displayed to identify the positive impact of the GM. The dimensionless form of the regulating system of motion is obtained. The functions of kinetic energy and angular momentum besides the square module are drawn for various values of the GM’s projections on the body’s principal axes of inertia. The effect of control torques on the body's motion is investigated in a case of small perturbation, and the achieved results are compared with the unperturbed one. For the case of a lack of GM, the comparison between our results and those of the prior ones reveals a high degree of consistency, in which the deviations between them are examined. As a result, these outcomes generalized those that were acquired in previous studies. The significance of this research stems from its practical applications, particularly in the applications of gyroscopic theory to maintain the stability and determine the orientation of aircraft and undersea vehicles.
Biosynthesis of gamma-aminobutyric acid by Lactiplantibacillus plantarum K16 as an alternative to revalue agri-food by-products
Authors: Diez-Gutiérrez Lucía , Vicente Leire San , Sáenz Jessica , Esquivel Argitxu , Barron Luis Javier R. , Chávarri María
Published: November 2022

Probiotic metabolites, known as postbiotics, have received attention due to their wide variety of promoting health effects. One of the most exciting postbiotic is gamma-aminobutyric acid (GABA), widely produced by lactic acid bacteria, due to its benefits in health. In addition, the performance of the biosynthesis of GABA by Lactiplantibacillus plantarum could be modulated through the modification of fermentation parameters. Due to their high nutritional value, agri-food by-products could be considered a useful fermentation source for microorganisms. Therefore, these by-products were proposed as fermentation substrates to produce GABA in this study. Previously, several experiments in Man Rogosa Sharpe (MRS) broth were performed to identify the most critical parameters to produce GABA using the strain Lactiplantibacillus plantarum K16. The percentage of inoculum, the initial pH, and the concentration of nutrients, such as monosodium glutamate or glucose, significantly affected the biosynthetic pathway of GABA. The highest GABA yield was obtained with 500 mM of monosodium glutamate and 25 g/L of glucose, and an initial pH of 5.5 and 1.2% inoculum. Furthermore, these investigated parameters were used to evaluate the possibility of using tomato, green pepper, apple, or orange by-products to get GABA-enriched fermented media, which is an excellent way to revalorise them.
A multi-marker integrative analysis reveals benefits and risks of bariatric surgery
Authors: Palleschi Simonetta , Guglielmi Valeria , Nisticò Lorenza , Ferreri Carla , Tabolacci Claudio , Facchiano Francesco , Iorio Egidio , Giuliani Alessandro , Brescianini Sonia , Medda Emanuela , Fagnani Corrado , Rossi Barbara , Minoprio Anna , Chirico Mattea , Pisanu Maria Elena , Di Nolfo Federica , Fortini Paola , Simonelli Valeria , Baccarini Sara , Laterza Serena , Morretti Tiziana , Dell’Orso Ambra , Manganello Federico , Gentileschi Paolo , Sbraccia Paolo , Dogliotti Eugenia
Published: November 2022

Bariatric surgery (BS) is an effective intervention for severe obesity and associated comorbidities. Although several studies have addressed the clinical and metabolic effects of BS, an integrative analysis of the complex body response to surgery is still lacking. We conducted a longitudinal data study with 36 patients with severe obesity who were tested before, 6 and 12 months after restrictive BS for more than one hundred blood biomarkers, including clinical, oxidative stress and metabolic markers, peptide mediators and red blood cell membrane lipids. By using a synthetic data-driven modeling based on principal component and correlation analyses, we provided evidence that, besides the early, well-known glucose metabolism- and weight loss-associated beneficial effects of BS, a tardive, weight-independent increase of the hepatic cholesterol metabolism occurs that is associated with potentially detrimental inflammatory and metabolic effects. Canonical correlation analysis indicated that oxidative stress is the most predictive feature of the BS-induced changes of both glucose and lipids metabolism. Our results show the power of multi-level correlation analysis to uncover the network of biological pathways affected by BS. This approach highlighted potential health risks of restrictive BS that are disregarded with the current practice to use weight loss as surrogate of BS success.