bluuebunny/crossref_metadata_2025 huggingface dataset:
History matters: societal acceptance of deep-sea mining and incipient conflicts in Papua New Guinea
Authors: van Putten E.I. , Aswani S. , Boonstra W.J. , De la Cruz-Modino R. , Das J. , Glaser M. , Heck N. , Narayan S. , Paytan A. , Selim S. , Vave R.
Published: July 2023

New marine industries that develop and grow in response to the changing demand for their products have the potential to exert pressure on fragile marine environments. These emerging industries can benefit local communities but equally can have negative environmental and socio-cultural impacts. The development of new and emerging industries, like deep seabed mining (DSM), requires the acceptance and involvement of local communities. Yet, the history of marine exploitation is imbued with conflicts between industries and local communities. This paper presents a DSM case study in Papua New Guinea (PNG) to stimulate debate around the potential for conflict in the pursuit of resource extraction from the deep sea and the social and environmental harm that these extractions can cause. We do so by first presenting a timeline of local and extra-local events and enabling conditions that form the development background for the DSM Solwara 1 project in PNG. We then undertake a media narrative analysis to consider the contribution of aspects of social acceptability to this highly complex and multi-scale conflict. We find that the lack of (or a decrease in) social acceptability contributed to the conflict situation and ultimately the demise of the Solwara 1 project. Extra-locally, the initial development was positively framed around solutions for decarbonisation using new technology. Over time, actions by international NGOs, financial issues related to foreign companies, and asymmetry in the power balance between the Pacific Island nation and global businesses played a role in growing negative perceptions of acceptability. Historical experiences with prior environmental mining disasters, together with sea tenure governance challenges, and a lack of community and stakeholder acceptance also contributed to the demise of the project. Untangling and debating these complex interactions provides context and reasons for the tension between the lack of societal acceptance at a local scale and the perceived need for DSM products in the global North for innovative technologies and decarbonising societies. Better understanding these interactions and tensions can help emerging industries navigate a future blue economy.
Cheminformatics identification of modulators of key carbohydrate-metabolizing enzymes from C. cujete for type-2 diabetes mellitus intervention
Authors: Balogun Fatai Oladunni , Singh Karishma , Rampadarath Athika , Akoonjee Ayesha , Naidoo Kayleen , Sabiu Saheed
Published: July 2023

Purpose

The therapeutic use of oral hypoglycaemic agents in the management of type-2 diabetes mellitus (T2DM) is without adverse effects; thus, calls for alternative and novel candidates from natural products in medicinal plants.

Method

The study explored molecular docking and molecular dynamics (MD) simulation approaches to identify key antidiabetic metabolites from Crescentia cujete.

Results

Molecular docking results identified four and/or five best compounds against each target enzyme (alpha-glucosidase, dipeptidyl peptidase-IV, aldose reductase, and protein tyrosine phosphatase-1B (PTP-1B)) implicated in diabetes. The resulting complexes (except against PTP-1B) had higher docking scores above respective standards (acarbose, Diprotin A, ranirestat). The MD simulation results revealed compounds such as benzoic acid (-48.414 kcal/mol) and phytol (-45.112 kcal/mol) as well as chlorogenic acid (-42.978 kcal/mol) and naringenin (-31.292 kcal/mol) had higher binding affinities than the standards [acarbose (-28.248 kcal/mol), ranirestat (-21.042 kcal/mol)] against alpha-glucosidase and aldose reductase, respectively while Diprotin A (-45.112 kcal/mol) and ursolic acid (-18.740 kcal/mol) presented superior binding affinities than the compounds [luteolin (-41.957 kcal/mol and naringenin (-16.518 kcal/mol)] against DPP-IV and PTP-1B respectively.

Conclusion

While isoflavone (alpha-glucosidase), xylocaine (DPP-IV), luteolin (aldose reductase,) and chlorogenic acid (PTP-1B) were affirmed as the best inhibitors of respective enzyme targets, luteolin, and chlorogenic acid may be suggested and proposed as probable candidates against T2DM and related retinopathy complication based on their structural stability, compactness and affinity for three (DPP-IV, aldose reductase, and PTP-1B) of the four targets investigated. Further studies are warranted in vitro and in vivo on the antihyperglycaemic effects of these drug candidates.
A Systematic Review to Move Australian Disability Employment Forward for Autistic People
Authors: Hayward Susan M. , Flower Rebecca L.
Published: July 2023

The current Disability Employment Service (DES) model serving autistic job seekers in Australia will end in the year 2023. The Australian Government is exploring new options for a replacement model. Aiding these efforts a systematic review of the literature examined the evidence base of effective assisted employment supports for autistic people in Australia. Using PRISMA guidelines, of 1839 search results, eight papers met inclusion criteria concerning: (a) autistic individuals, (b) assisted employment in Australia, (c) enablers to employment gain or retention, and (d) original evidence. All effective activities require providers to understand autism and the needs of autistic adults. We suggest the first steps in enhancing DES include educating providers and their staff in autism and hiring autistic employment consultants.
Production of Inorganic Hollow Cores Using Sacrificial Ice Cores
Authors: Locke Christopher , Polzin Hartmut , Bissels Joshua , Günther Daniel
Published: July 2023

The production of hollow cores using 3D sand printing is state-of-the-art. Hollow cores are advantageous in decoring, gas permeability and material consumption. The methodology for producing hollow cores, as in 3D sand printing, is not transferable to core shooting. However, using sacrificial ice cores (SaIC) as a tool to produce hollow cores in a core shooting process enable complex hollow structures, as in 3D sand printing. Recently there has been an effort towards more environmentally friendly production. In this regard, water glass binders are in the focus of the metal casting industry and research institutions. This work presents a new method for producing water glass-bonded hollow cores using SaIC in a core shooting process. The manufacturing principle is detailed using a bending test bar and a near-series prototype core. The bending strength of the hollow bending test bars reaches up to 300 N/cm2. Due to the hollow structure, the decoring behaviour is significantly improved compared to solid cores.
Bayesian learning models to measure the relative impact of ESG factors on credit ratings
Authors: Agosto Arianna , Cerchiello Paola , Giudici Paolo
Published: July 2023

Artificial intelligence methods, based on machine learning models, are rapidly changing financial services, and credit lending in particular, complementing traditional bank lending with platform lending. While financial technologies improve user experience and possibly lower costs, they may increase risks and, in particular, the model risks that derive from inaccurate credit rating assessments. In this paper, we will show how to reduce such model risks, using a S.A.F.E. statistical learning model, which improves: Sustainability, taking environmental, social and governance factors into account; Accuracy, building a model which maximises predictive accuracy; Fairness, merging ESG scores from different data providers, improving their representativeness; Explainability, clarifying the relative contribution of each ESG score to predictive accuracy.
Effect of Probe Lifting Height in Jumping Mode AFM for Living Cell Imaging
Authors: Cheng Can , Wang Xingyue , Dong Jianjun , Wang Zuobin
Published: July 2023

Atomic force microscopy (AFM) is one of the effective methods for imaging the morphological and physical properties of living cells in a near-physiological environment. However, several problems caused by the adhesion of living cells and extension of the cell membranes seriously affect the image quality during living cell imaging, hindering the study of living cells. In this work, jumping mode AFM imaging was used to image living cells at varied probe lifting heights to meet image quality requirements, and image quality related to the probe lifting height is discussed in detail. The jumping mode was divided into three parts based on the varying heights of the lifted probe, namely near-contact mode, half-jumping mode, and full-jumping mode, and the causes of their imaging drawbacks were analyzed. At an appropriate lifting height, the probe can be completely free from the influence of cell adhesion and self-excited oscillation, thus avoiding the occurrence of “trail” phenomena and invalid points in the imaging of living cells and improving the image quality. Additionally, this work provides a new approach to calculating the lateral force through the adhesion of trace and retrace scanning at a low height, which is important for studying the extension characteristics of the cell membrane.
Quantum computing for a profusion of postman problem variants
Authors: Pion Joel E. , Negre Christian F. A. , Mniszewski Susan M.
Published: July 2023

In this paper we study the viability of solving the Chinese Postman Problem, a graph routing optimization problem, and many of its variants on a quantum annealing device. Routing problem variants considered include graph type, directionally varying weights, number of parties involved in routing, among others. We put emphasis on the explanation of how to convert such problems into quadratic unconstrained binary optimization (QUBO) problems. QUBO is one of two equivalent natural paradigms for quantum annealing devices, the other being the Ising Model. We also expand upon a previously discovered algorithm for solving the Chinese Postman Problem on a closed undirected graph to decrease the number of constraints and variables used in the problem. Optimal annealing parameter settings and constraint weight values are discussed based on results from implementation on the D-Wave 2000Q and Advantage. Results from classical, purely quantum, and hybrid algorithms are compared.
Der Kompromiss in Geschichte und Gegenwart. Politische und historische Perspektiven
Authors: de Boer Jan-Hendryk , Westphal Manon
Published: July 2023

Der Kompromiss ist eine Technik, mit der Konflikte über Zugeständnisse an konfligierende Sichtweisen und Positionen reguliert werden. Dass er in unterschiedlichen historischen wie gegenwärtigen gesellschaftlichen Kontexten ermöglicht, mit Konflikten umzugehen, macht ihn zu einem relevanten Gegenstand politikwissenschaftlicher wie geschichtswissenschaftlicher Forschung. Dieser Rezensionsaufsatz diskutiert aktuelle Literatur zum Thema aus beiden Disziplinen und fokussiert vier Themen: die Rolle von Kompromissen in Demokratien und Nicht-Demokratien, schlechte und gute Kompromisse, die historische Variabilität von Kompromissen sowie Voraussetzungen von Kompromissen.
Environmental enrichment for reptiles in European zoos: Current status and perspectives
Authors: Bartolomé Alicia , Carazo Pau , Font Enrique
Published: July 2023

Zoos and aquaria are paying increasing attention to environmental enrichment, which has proven an effective tool for the improvement of animal welfare. However, several ongoing issues have hampered progress in environmental enrichment research. Foremost among these is the taxonomic bias, which hinders our understanding of the value of enrichment for neglected groups, such as reptiles. In this study, we evaluated the status of environmental enrichment for reptiles in European zoos using a survey approach. A total of 121 zoos (32% response rate) completed our main survey, focusing on the use of different enrichment types for reptiles. We found significant differences in the use and/or type of enrichment between reptile groups. Tortoises (family Testudinidae) and monitor lizards (genusVaranus) were the most enriched taxa while venomous snakes were the least. The enrichment types most used across taxa were structural/habitat design and dietary. A second, more detailed, questionnaire followed, where participants were questioned about specific enrichment techniques. A total of 42 enrichment methods were reported, with two being represented across all taxa: increasing structural/thermal complexity and enrichment objects. Finally, we present information from participating zoos on enrichment goals, assessment methods, sources of information for enrichment ideas, and whether enrichment for reptiles is considered essential and/or implemented routinely. Results suggest that, although usage is widespread across European zoos, our understanding of enrichment for reptiles needs to be re-evaluated, since many of the techniques reported tread a fine line between basic husbandry and actual enrichment.
From Gender Equity to Gendered Assignments? Women and Cabinet Committees in Canada and the United Kingdom
Authors: Siklodi Nora , Ie Kenny William , Allen Nicholas
Published: July 2023

This article explores women's access to ministerial power in an important but understudied arena of executive politics: cabinet committees. Specifically, we analyse the gendered patterns in the distribution of cabinet committee assignments in two ‘typical’ Westminster cases, Canada and the United Kingdom, and under two prime ministers, Justin Trudeau (2015–2021) and David Cameron (2010–2016), who both made explicit gender-equity pledges. Informed by previous research into gendered allocation of ministerial portfolios, we investigate the overall extent of women's committee assignments, the gendered dimensions of these assignments and the status of assignments, namely the ‘prestige’ of committee remits, whether committees were chaired by the prime minister and the allocation of chairing responsibilities across committees. In both cases, overall assignment broadly matched shares of women ministers at the cabinet level, but less so during the Conservative–Liberal Democrat coalition in the UK (2010–2015). Women's shares of committee assignments were likely to be lower on ‘masculine’ and ‘high-prestige’ committees compared to ‘neutral’, ‘feminine’ and ‘low-prestige’ committees, but commitment to gender equity is more evident in the Canadian case. While our aim is exploratory and descriptive, we offer several explanations for these patterns, including the supply of women ministers, departmentalism, party branding and the low public profile of cabinet committees.
Simulated mechanical control of Nitellopsis obtusa under mesocosm conditions
Authors: Haram Alyssa M. , Wersal Ryan M.
Published: July 2023

Management efforts to control starry stonewort [Nitellopsis obtusa (Desvaux in Loiseleur) J. Groves] have been limited to stressing the thalli and have not been able to directly target the reproductive bulbils. Smaller-scale efforts such as the use of hand pulling can be employed, but hand pulling is not realistic for larger infestations. This research was conducted to test the effects of clipping stress on N. obtusa to provide a baseline for the effect of stress on the production of bulbils and the regrowth of thalli. Mesocosms were set up under greenhouse conditions to test the effects on N. obtusa of simulated mechanical harvesting once, twice, and four times per growing season. Different seasonal timing and frequency of clipping treatments will remove different amounts of thalli biomass. The four-clipping treatment always reduced thalli biomass in this study at both 16 and 52 wk after treatment (WAT) compared with the nontreated reference, but there was no difference among clipping treatments at 52 WAT. At 16 WAT, one clipping reduced bulbil density by 44% (Trial 1) to 50% (Trial 2), two clippings reduced bulbil density by 28% (Trial 2) to 52% (Trial 1), and four clippings reduced bulbil density by 22% (Trial 2) to 88% (Trial 1). At 52 WAT, bulbil densities were 69% and 93% lower than those of the nontreated reference Trials 2 and 1, respectively. Results from this study indicate that clipping may be effective for N. obtusa control and could impact bulbil production.
A New Dawn for Gay Rights in Botswana: A Commentary on the Decision of the High Court and Court of Appeal in the Motshidiemang Cases
Authors: Lekgowe Gosego Rockfall
Published: July 2023

In 2003, the Botswanan Court of Appeal decided inKanane v The Statethat discrimination on the basis of sexual orientation was not proscribed by the Botswanan Constitution because no evidence had been adduced showing that the society of Botswana was ready for gay individuals. After sixteen years, things changed: in 2019, inLetsweletse Motshidiemang and LEGABIBO (as amicus) v The Attorney General, the High Court held that the law criminalizing anal intercourse violated the fundamental rights of gay people. In 2021, the Court of Appeal upheld the High Court decision. This commentary briefly examines these three decisions. It argues thatKananegave too much weight to public opinion to the detriment of constitutional interpretation. Through a robust approach to generous interpretation of fundamental rights, the Motshidiemang decisions partly remedied the flaw inKanane. However, judicial clarification is still required on some aspects of the decision.
A HOME IN ROME: VILLA MILLS AND THE PALATINE HILL
Authors: Zerbi Tommaso
Published: July 2023

Prior to the acts of demolition pursued in theventennioto recover and celebrate the heirlooms of antiquity as the simulacra of a fascist restoration of the Roman Empire, a Gothic Revival villa stood atop the Palatine Hill. A transhistorical palimpsest, this edifice incorporated a portion of the imperial palace that was erected for Domitian after his accession to power (AD 81). Through the disclosure of groundbreaking archival documentation, this article reveals that the Gothic Revival mansion, commonly known as ‘Villa Mills’, can be renamed ‘Villa Smith’. It was Robert Smith (1787–1873), a lieutenant-colonel of the East India Company, who embarked on the medievalist makeover rather than the previous owner, a fellow Englishman named Charles Andrew Mills (1770–1846). In spite of an exceptional location in the imperial heart of the Eternal City, knowledge of the nineteenth-century history of the site is very limited and tends to be derived from hearsay and hypothesis, rather than primary information. Drawing on broad textual and iconographical sources, this article aims to fill this gap by reflecting closely upon the relationships in pre-unification Rome between architecture and political and cultural intent, between Italy and Britain, and between modernity and antiquity. After a reconstruction of British presence above theDomus Augustanaand an investigation of the person behind the neo-Gothic reworking, the study offers a critical reconsideration of Villa Mills and the character of (Charles Andrew) Mills.
Seismic Scattering and Absorption Properties of Mars Estimated Through Coda Analysis on a Long‐Period Surface Wave of S1222a Marsquake
Authors: Onodera Keisuke , Maeda Takuto , Nishida Kiwamu , Kawamura Taichi , Margerin Ludovic , Menina Sabrina , Lognonné Philippe , Banerdt William Bruce
Published: July 2023

On 4 May 2022, the seismometer on Mars observed the largest marsquake (S1222a) during its operation. One of the most specific features of S1222a is the long event duration lasting more than 8 hr, in addition to the clear appearance of body and surface waves. As demonstrated on Earth, by modeling a long‐lasting and scattered surface wave with the radiative transfer theory under the isotropic scattering condition, we estimated the scattering and intrinsic quality factors of Mars (Qs and Qi). This study especially focused on the frequency range between 0.05–0.09 Hz, where Qs and Qi have not been constrained yet. Our results revealed that Qi = 1,000–1,500 and Qs = 30–500. By summarizing the Martian Qi and Qs estimated so far and by comparing them with those of other celestial bodies, we found that, overall, the Martian scattering and absorption properties showed Earth‐like values.
Future Change Projections of Extreme Floods at Catchment Scale and Hydrodynamic Response of Its Downstream Lake Based on Catchment‐Waterbody Relationship Simulation
Authors: Hua Ruixiang , Zhang Yongyong , Zhang Shiyan , Zhao Tongtiegang , Tang Qiuhong , Zhang Yongqiang , Feng Aiping
Published: July 2023

Extreme riverine floods and hydrodynamic response of downstream lakes are the main focus of catchment flood control, especially under climate change. In this study, future changes in the extreme floods and their hydrodynamic responses are projected by driving the external coupling of the hydrological and hydrodynamic models using the precipitation and temperature outputs of the general circulation models (GCMs) in seven emission scenarios, and the impact of climate change is evaluated. The Baiyangdian Lake and its controlled catchment are selected as our study area. Results show that: (a) both the daily runoff and the lake water levels are well simulated, (b) compared with the baseline scenario, extreme riverine floods are projected to increase evidently throughout the catchment with mean rates of 33.2%, 14.1% and 10.9% in the RCP2.6, 4.5 and 8.5 scenarios, respectively because of increasing precipitation; consequently, the total lake inflow also increases by 13.5%–150.9%, most of which are from Zhulong, Xiaoyi, Tanghe, and Fuhe Rivers, and (c) the water level of the Baiyangdian Lake increases temporally during the flood seasons in all the scenarios, and the increase in water level is 0.27–1.29 m greater than that in the baseline scenario; consequently, the water depth in 55.8% and 73.4% of lake area increases over 1.0 m in the future short‐term and long‐term scenarios, respectively; the inundation area also increases by 23.4%–26.7% in the future scenarios, except in the long‐term RCP4.5 scenario. The northeastern and south‐central regions of Baiyangdian, which are near Xiong'an New Area, have a relatively high inundation risk.
Influence of Stratosphere Polar Vortex Variability on the Mesosphere, Thermosphere, and Ionosphere
Authors: Pedatella N. M.
Published: July 2023

The Whole Atmosphere Community Climate Model with thermosphere‐ionosphere eXtension (WACCM‐X) is used to investigate the influence of stratosphere polar vortex variability on the mesosphere, thermosphere, and ionosphere during Northern Hemisphere winter. Based on 40 simulated Northern Hemisphere winters, the mesosphere and lower thermosphere (MLT) residual circulation is found to depend on whether the stratosphere polar vortex is strong or weak. In particular, during weak stratosphere polar vortex time periods, the MLT circulation anomalies are characterized by clockwise and anti‐clockwise flow in the Northern and Southern Hemispheres, respectively. Opposite, though weaker, anomalies are found to occur during time periods when the stratosphere polar vortex is strong. The MLT circulation anomalies influence the composition of the lower thermosphere, leading to ±5% changes in the thermosphere column integrated atomic oxygen to molecular nitrogen ratio (ΣO/N2). Large differences between strong and weak stratosphere polar vortex events are also found to occur in the semidiurnal migrating tide (SW2) in the MLT, which leads to ±15%–20% differences in the SW2 component of the ionosphere total electron content (TEC) at low latitudes. The WACCM‐X simulation results indicate that variability in the stratosphere polar vortex can explain ∼30% and ∼18% of the quiet time variability in thermosphere ΣO/N2 and the SW2 component of TEC during Northern Hemisphere winter, respectively.
Scale‐Dependent Influence of Permafrost on Riverbank Erosion Rates
Authors: Rowland Joel C. , Schwenk Jonathan P. , Shelef Eitan , Muss Jordan , Ahrens Daniel , Stauffer Sophie , Pilliouras Anastasia , Crosby Benjamin , Chadwick Austin , Douglas Madison M. , Kemeny Preston C. , Lamb Michael P. , Li Gen K. , Vulis Lawrence
Published: July 2023

Whether permafrost systematically alters the rate of riverbank erosion is a fundamental geomorphic question with significant importance to infrastructure, water quality, and biogeochemistry of high‐latitude watersheds. For over four decades, this question has remained unanswered due to a lack of data. Using remotely sensed imagery, we addressed this knowledge gap by quantifying riverbank erosion rates across the Arctic and subarctic. To compare these rates to non‐permafrost rivers, we assembled a global data set of published riverbank erosion rates. We found that erosion rates in rivers influenced by permafrost are on average nine times lower than non‐permafrost systems; erosion rate differences increase up to 40 times for the largest rivers. To test alternative hypotheses for the observed erosion rate difference, we examined differences in total water yield and erosional efficiency between these rivers and non‐permafrost rivers. Neither of these factors nor differences in river sediment loads provided compelling alternative explanations, leading us to conclude that permafrost limits riverbank erosion rates. This conclusion was supported by field investigations of rates and patterns of erosion along three rivers flowing through discontinuous permafrost in Alaska. Our results show that permafrost limits maximum bank erosion rates on rivers with stream powers greater than 900 Wm−1. On smaller rivers, however, hydrology rather than thaw rate may be the dominant control on bank erosion. Our findings suggest that Arctic warming and hydrological changes should increase bank erosion rates on large rivers but may reduce rates on rivers with drainage areas less than a few thousand km2.
Decorin: a potential therapeutic candidate for ligamentum flavum hypertrophy by antagonizing TGF-β1
Authors: Wang Shanxi , Qu Yunkun , Fang Xuan , Ding Qing , Zhao Hongqi , Yu Xiaojun , Xu Tao , Lu Rui , Jing Shaoze , Liu Chaoxu , Wu Hua , Liu Yang
Published: July 2023

Ligamentum flavum hypertrophy (LFH) is the main physiological and pathological mechanism of lumbar spinal canal stenosis (LSCS). The specific mechanism for LFH has not been completely clarified. In this study, bioinformatic analysis, human ligamentum flavum (LF) tissues collection and analysis, and in vitro and in vivo experiments were conducted to explore the effect of decorin (DCN) on LFH pathogenesis. Here, we found that TGF-β1, collagen I, collagen III, α-SMA and fibronectin were significantly upregulated in hypertrophic LF samples. The DCN protein expression in hypertrophic LF samples was higher than that in non-LFH samples, but the difference was not significant. DCN inhibited the expression of TGF-β1-induced fibrosis-associated proteins in human LF cells, including collagen I, collagen III, α-SMA, and fibronectin. ELISAs showed that TGF-β1 can upregulate PINP and PIIINP in the cell supernatant, and this effect was inhibited after DCN administration. Mechanistic studies revealed that DCN suppressed TGF-β1-induced fibrosis by blocking the TGF-β1/SMAD3 signaling pathway. In addition, DCN ameliorated mechanical stress-induced LFH in vivo. In summary, our findings indicated that DCN ameliorated mechanical stress-induced LFH by antagonizing the TGF-β1/SMAD3 signaling pathway in vitro and in vivo. These findings imply that DCN is a potential therapeutic candidate for ligamentum flavum hypertrophy.
PHF6 maintains acute myeloid leukemia via regulating NF-κB signaling pathway
Authors: Hou Shuaibing , Wang Xiaomin , Guo Tengxiao , Lan Yanjie , Yuan Shengnan , Yang Shuang , Zhao Fei , Fang Aizhong , Liu Na , Yang Wanzhu , Chu Yajing , Jiang Erlie , Cheng Tao , Sun Xiaojian , Yuan Weiping
Published: July 2023

Acute myeloid leukemia (AML) is a major hematopoietic malignancy characterized by the accumulation of immature and abnormally differentiated myeloid cells in bone marrow. Here with in vivo and in vitro models, we demonstrate that the Plant homeodomain finger gene 6 (PHF6) plays an important role in apoptosis and proliferation in myeloid leukemia. Phf6 deficiency could delay the progression of RUNX1-ETO9a and MLL-AF9-induced AML in mice. PHF6 depletion inhibited the NF-κB signaling pathways by disrupting the PHF6-p50 complex and partially inhibiting the nuclear translocation of p50 to suppress the expression of BCL2. Treating PHF6 over-expressed myeloid leukemia cells with NF-κB inhibitor (BAY11-7082) significantly increased their apoptosis and decreased their proliferation. Taken together, in contrast to PHF6 as a tumor suppressor in T-ALL as reported, we found that PHF6 also plays a pro-oncogenic role in myeloid leukemia, and thus potentially to be a therapeutic target for treating myeloid leukemia patients.
Seasonal effect—an overlooked factor in neuroimaging research
Authors: Zhang Rui , Shokri-Kojori Ehsan , Volkow Nora D.
Published: July 2023

In neuroimaging research, seasonal effects are often neglected or controlled as confounding factors. However, seasonal fluctuations in mood and behavior have been observed in both psychiatric disorders and healthy participants. There are vast opportunities for neuroimaging studies to understand seasonal variations in brain function. In this study, we used two longitudinal single-subject datasets with weekly measures over more than a year to investigate seasonal effects on intrinsic brain networks. We found that the sensorimotor network displayed a strong seasonal pattern. The sensorimotor network is not only relevant for integrating sensory inputs and coordinating movement, but it also affects emotion regulation and executive function. Therefore, the observed seasonality effects in the sensorimotor network could contribute to seasonal variations in mood and behavior. Genetic analyses revealed seasonal modulation of biological processes and pathways relevant to immune function, RNA metabolism, centrosome separation, and mitochondrial translation that have a significant impact on human physiology and pathology. In addition, we revealed critical factors such as head motion, caffeine use, and scan time that could interfere with seasonal effects and need to be considered in future studies.
LncRNA miR663AHG represses the development of colon cancer in a miR663a-dependent manner
Authors: Yuan Hongfan , Ren Qianwen , Du Yantao , Ma Yuwan , Gu Liankun , Zhou Jing , Tian Wei , Deng Dajun
Published: July 2023

The MIR663AHG gene encodes both miR663AHG and miR663a. While miR663a contributes to the defense of host cells against inflammation and inhibits colon cancer development, the biological function of lncRNA miR663AHG has not been previously reported. In this study, the subcellular localization of lncRNA miR663AHG was determined by RNA-FISH. miR663AHG and miR663a were measured by qRT-PCR. The effects of miR663AHG on the growth and metastasis of colon cancer cells were investigated in vitro and in vivo. CRISPR/Cas9, RNA pulldown, and other biological assays were used to explore the underlying mechanism of miR663AHG. We found that miR663AHG was mainly distributed in the nucleus of Caco2 and HCT116 cells and the cytoplasm of SW480 cells. The expression level of miR663AHG was positively correlated with the level of miR663a (r = 0.179, P = 0.015) and significantly downregulated in colon cancer tissues relative to paired normal tissues from 119 patients (P < 0.008). Colon cancers with low miR663AHG expression were associated with advanced pTNM stage (P = 0.021), lymph metastasis (P = 0.041), and shorter overall survival (hazard ratio = 2.026; P = 0.021). Experimentally, miR663AHG inhibited colon cancer cell proliferation, migration, and invasion. The growth of xenografts from RKO cells overexpressing miR663AHG was slower than that of xenografts from vector control cells in BALB/c nude mice (P = 0.007). Interestingly, either RNA-interfering or resveratrol-inducing expression changes of miR663AHG or miR663a can trigger negative feedback regulation of transcription of the MIR663AHG gene. Mechanistically, miR663AHG could bind to miR663a and its precursor pre-miR663a, and prevent the degradation of miR663a target mRNAs. Disruption of the negative feedback by knockout of the MIR663AHG promoter, exon-1, and pri-miR663A-coding sequence entirely blocked these effects of miR663AHG, which was restored in cells transfected with miR663a expression vector in rescue experiment. In conclusion, miR663AHG functions as a tumor suppressor that inhibits the development of colon cancer through its cis-binding to miR663a/pre-miR663a. The cross talk between miR663AHG and miR663a expression may play dominant roles in maintaining the functions of miR663AHG in colon cancer development.
Lesion area progression in eyes with neovascular age-related macular degeneration treated using a proactive or a reactive regimen
Authors: Cozzi Mariano , Monteduro Davide , Esposito Raffaele Antonio , Spooner Kimberly L. , Fraser-Bell Samantha , Staurenghi Giovanni , Romano Francesco , Airaldi Matteo , Chang Andrew A. , Invernizzi Alessandro
Published: July 2023

Background

To compare the change in lesion area over 4 years of follow-up in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a proactive or a reactive regimen in routine clinical practice.

Methods

This was a multicentre, retrospective comparative study. Totally, 202 treatment-naïve nAMD eyes (183 patients) received anti-VEGF therapy according to a proactive (n = 105) or reactive (n = 97) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4 years and had baseline fluorescein angiography and annual optical coherence tomography (OCT) imaging. Two masked graders independently delineated the lesion’s margins from serial OCT images and growth rates were calculated.

Results

At baseline, the mean [SD] lesion area was 7.24 [5.6] mm2 in the proactive group and 6.33 [4.8] mm2 in the reactive group respectively (p = 0.22). After four years of treatment, the mean [SD] lesion area in the proactive group was 5.16 [4.5] mm2 showing a significant reduction compared to the baseline (p < 0.001). By contrast, the mean [SD] lesion area kept expanding in the reactive group during the follow-up and was 9.24 [6.0] mm2 at four years (p < 0.001). The lesion area at 4 years was significantly influenced by treatment regimen, baseline lesion area, and proportion of visits with active lesions.

Conclusions

Eyes treated using a reactive strategy had an increased lesion area and worse visual outcomes at 4 years. By contrast, the proactive regimen was associated with fewer recurrences of active disease, shrinkage of the lesion area, and better vision at four years.
Causal associations between cardiorespiratory fitness and type 2 diabetes
Authors: Cai Lina , Gonzales Tomas , Wheeler Eleanor , Kerrison Nicola D. , Day Felix R. , Langenberg Claudia , Perry John R. B. , Brage Soren , Wareham Nicholas J.
Published: July 2023

Higher cardiorespiratory fitness is associated with lower risk of type 2 diabetes. However, the causality of this relationship and the biological mechanisms that underlie it are unclear. Here, we examine genetic determinants of cardiorespiratory fitness in 450k European-ancestry individuals in UK Biobank, by leveraging the genetic overlap between fitness measured by an exercise test and resting heart rate. We identified 160 fitness-associated loci which we validated in an independent cohort, the Fenland study. Gene-based analyses prioritised candidate genes, such as CACNA1C, SCN10A, MYH11 and MYH6, that are enriched in biological processes related to cardiac muscle development and muscle contractility. In a Mendelian Randomisation framework, we demonstrate that higher genetically predicted fitness is causally associated with lower risk of type 2 diabetes independent of adiposity. Integration with proteomic data identified N-terminal pro B-type natriuretic peptide, hepatocyte growth factor-like protein and sex hormone-binding globulin as potential mediators of this relationship. Collectively, our findings provide insights into the biological mechanisms underpinning cardiorespiratory fitness and highlight the importance of improving fitness for diabetes prevention.
A rapid cell-free expression and screening platform for antibody discovery
Authors: Hunt Andrew C. , Vögeli Bastian , Hassan Ahmed O. , Guerrero Laura , Kightlinger Weston , Yoesep Danielle J. , Krüger Antje , DeWinter Madison , Diamond Michael S. , Karim Ashty S. , Jewett Michael C.
Published: July 2023

Antibody discovery is bottlenecked by the individual expression and evaluation of antigen-specific hits. Here, we address this bottleneck by developing a workflow combining cell-free DNA template generation, cell-free protein synthesis, and binding measurements of antibody fragments in a process that takes hours rather than weeks. We apply this workflow to evaluate 135 previously published antibodies targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including all 8 antibodies previously granted emergency use authorization for coronavirus disease 2019 (COVID-19), and demonstrate identification of the most potent antibodies. We also evaluate 119 anti-SARS-CoV-2 antibodies from a mouse immunized with the SARS-CoV-2 spike protein and identify neutralizing antibody candidates, including the antibody SC2-3, which binds the SARS-CoV-2 spike protein of all tested variants of concern. We expect that our cell-free workflow will accelerate the discovery and characterization of antibodies for future pandemics and for research, diagnostic, and therapeutic applications more broadly.
Jamming and unusual charge density fluctuations of strange metals
Authors: Thornton Stephen J. , Liarte Danilo B. , Abbamonte Peter , Sethna James P. , Chowdhury Debanjan
Published: July 2023

The strange metallic regime across a number of high-temperature superconducting materials presents numerous challenges to the classic theory of Fermi liquid metals. Recent measurements of the dynamical charge response of strange metals, including optimally doped cuprates, have revealed a broad, featureless continuum of excitations, extending over much of the Brillouin zone. The collective density oscillations of this strange metal decay into the continuum in a manner that is at odds with the expectations of Fermi liquid theory. Inspired by these observations, we investigate the phenomenology of bosonic collective modes and the particle-hole excitations in a class of strange metals by making an analogy to the phonons of classical lattices falling apart across an unconventional jamming-like transition associated with the onset of rigidity. By making comparisons to the experimentally measured dynamical response functions, we reproduce many of the qualitative features using the above framework. We conjecture that the dynamics of electronic charge density over an intermediate range of energy scales in a class of strongly correlated metals can be at the brink of a jamming-like transition.
Understanding the unique S-scheme charge migration in triazine/heptazine crystalline carbon nitride homojunction
Authors: Li Fang , Yue Xiaoyang , Liao Yulong , Qiao Liang , Lv Kangle , Xiang Quanjun
Published: July 2023

Understanding charge transfer dynamics and carrier separation pathway is challenging due to the lack of appropriate characterization strategies. In this work, a crystalline triazine/heptazine carbon nitride homojunction is selected as a model system to demonstrate the interfacial electron-transfer mechanism. Surface bimetallic cocatalysts are used as sensitive probes during in situ photoemission for tracing the S-scheme transfer of interfacial photogenerated electrons from triazine phase to the heptazine phase. Variation of the sample surface potential under light on/off confirms dynamic S-scheme charge transfer. Further theoretical calculations demonstrate an interesting reversal of interfacial electron-transfer path under light/dark conditions, which also supports the experimental evidence of S-scheme transport. Benefiting from the unique merit of S-scheme electron transfer, homojunction shows significantly enhanced activity for CO2 photoreduction. Our work thus provides a strategy to probe dynamic electron transfer mechanisms and to design delicate material structures towards efficient CO2 photoreduction.
Loss of the batten disease protein CLN3 leads to mis-trafficking of M6PR and defective autophagic-lysosomal reformation
Authors: Calcagni’ Alessia , Staiano Leopoldo , Zampelli Nicolina , Minopoli Nadia , Herz Niculin J. , Di Tullio Giuseppe , Huynh Tuong , Monfregola Jlenia , Esposito Alessandra , Cirillo Carmine , Bajic Aleksandar , Zahabiyon Mahla , Curnock Rachel , Polishchuk Elena , Parkitny Luke , Medina Diego Luis , Pastore Nunzia , Cullen Peter J. , Parenti Giancarlo , De Matteis Maria Antonietta , Grumati Paolo , Ballabio Andrea
Published: July 2023

Batten disease, one of the most devastating types of neurodegenerative lysosomal storage disorders, is caused by mutations in CLN3. Here, we show that CLN3 is a vesicular trafficking hub connecting the Golgi and lysosome compartments. Proteomic analysis reveals that CLN3 interacts with several endo-lysosomal trafficking proteins, including the cation-independent mannose 6 phosphate receptor (CI-M6PR), which coordinates the targeting of lysosomal enzymes to lysosomes. CLN3 depletion results in mis-trafficking of CI-M6PR, mis-sorting of lysosomal enzymes, and defective autophagic lysosomal reformation. Conversely, CLN3 overexpression promotes the formation of multiple lysosomal tubules, which are autophagy and CI-M6PR-dependent, generating newly formed proto-lysosomes. Together, our findings reveal that CLN3 functions as a link between the M6P-dependent trafficking of lysosomal enzymes and lysosomal reformation pathway, explaining the global impairment of lysosomal function in Batten disease.
Dynamics of lattice disorder in perovskite materials, polarization nanoclusters and ferroelectric domain wall structures
Authors: Očenášek Jan , Minár Ján , Alcalá Jorge
Published: July 2023

The nexus between classic ferroelectricity and the structure of perovskite materials hinges on the concept of lattice disorder. Although the ordered perovskites display short-range displacements of the central cations around their equilibrium points, the lattice disorder dynamically unfolds to generate a myriad of distorted rhombohedral lattices characterized by the hopping of the central cations across <111> directions. It is discovered that the lattice disorder correlates with the emergence of minimum configuration energy <100> pathways for the central cations, resulting in spatially modulated ultrafast polarization nanocluster arrangements that are stabilized by the electric charge defects in the material. Through high-resolution phonon dispersion analyses encompassing molecular dynamics (MD) and density functional theory (DFT) simulations, we provide unequivocal evidence linking the hopping of central cations to the development of diffuse soft phonon modes observed throughout the phase transitions of the perovskite. Through massive MD simulations, we unveil the impact of lattice disorder on the structures of domain walls at finite-temperature vis-à-vis collective activation and deactivation of <100> pathways. Furthermore, our simulations demonstrate the development of hierarchical morphotropic phase boundary (MPB) nanostructures under the combined influence of externally applied pressure and stress relaxation, characterized by sudden emergence of zig-zagged monoclinic arrangements that involve dual <111> shifts of the central cations. These findings have implications for tailoring MPBs in thin-film structures and for the light-induced mobilization of DWs. Avenues are finally uncovered to the exploration of lattice disorder through gradual shear strain application.
Global volcanic rock classification of Holocene volcanoes
Authors: Oggier Frédérique , Widiwijayanti Christina , Costa Fidel
Published: July 2023

This data descriptor assigns the major and minor rock names from worldwide Holocene volcanoes of the Global Volcanism Program (GVP) using the Total Alkali-Silica diagram (TAS) for the chemical classification of volcanic rocks using the Geochemistry of Rocks of the Oceans and Continents (GEOROC) database. The precompiled files of the GEOROC database provide the chemical composition of volcanic rock samples, from which we computed major and minor rocks for global Holocene volcanoes reported in GVP. The combined dataset associates each volcano with the relative abundance of each volcanic sample type (whole rock, glass, melt inclusion) and provides the five major (more than 10% abundance) and minor rock names. In total, over 138,000 GEOROC volcanic rock samples were considered, for ~1000 Holocene volcanoes. The resulting major rock compositions are in general consistent with those given in GVP. The dataset provides a global panorama of rock composition for Holocene volcanoes.
Inventory of landslides triggered by an extreme rainfall event in Marche-Umbria, Italy, on 15 September 2022
Authors: Santangelo M. , Althuwaynee O. , Alvioli M. , Ardizzone F. , Bianchi C. , Bornaetxea T. , Brunetti M. T. , Bucci F. , Cardinali M. , Donnini M. , Esposito G. , Gariano S. L. , Grita S. , Marchesini I. , Melillo M. , Peruccacci S. , Salvati P. , Yazdani M. , Fiorucci F.
Published: July 2023

Systematic and timely documentation of triggered (i.e. event) landslides is fundamental to build extensive datasets worldwide that may help define and/or validate trends in response to climate change. More in general, preparation of landslide inventories is a crucial activity since it provides the basic data for any subsequent analysis. In this work we present an event landslide inventory map (E-LIM) that was prepared through a systematic reconnaissance field survey in about 1 month after an extreme rainfall event hit an area of about 5000 km2 in the Marche-Umbria regions (central Italy). The inventory reports evidence of 1687 triggered landslides in an area of ~550 km2. All slope failures were classified according to type of movement and involved material, and documented with field pictures, wherever possible. The database of the inventory described in this paper as well as the collection of selected field pictures associated with each feature is publicly available at figshare.
Brain imaging signatures of neuropathic facial pain derived by artificial intelligence
Authors: Latypov Timur H. , So Matthew C. , Hung Peter Shih-Ping , Tsai Pascale , Walker Matthew R. , Tohyama Sarasa , Tawfik Marina , Rudzicz Frank , Hodaie Mojgan
Published: July 2023

Advances in neuroimaging have permitted the non-invasive examination of the human brain in pain. However, a persisting challenge is in the objective differentiation of neuropathic facial pain subtypes, as diagnosis is based on patients’ symptom descriptions. We use artificial intelligence (AI) models with neuroimaging data to distinguish subtypes of neuropathic facial pain and differentiate them from healthy controls. We conducted a retrospective analysis of diffusion tensor and T1-weighted imaging data using random forest and logistic regression AI models on 371 adults with trigeminal pain (265 classical trigeminal neuralgia (CTN), 106 trigeminal neuropathic pain (TNP)) and 108 healthy controls (HC). These models distinguished CTN from HC with up to 95% accuracy, and TNP from HC with up to 91% accuracy. Both classifiers identified gray and white matter-based predictive metrics (gray matter thickness, surface area, and volume; white matter diffusivity metrics) that significantly differed across groups. Classification of TNP and CTN did not show significant accuracy (51%) but highlighted two structures that differed between pain groups—the insula and orbitofrontal cortex. Our work demonstrates that AI models with brain imaging data alone can differentiate neuropathic facial pain subtypes from healthy data and identify regional structural indicates of pain.