bluuebunny/crossref_metadata_2025 huggingface dataset:
Preclinical models of treatment-resistant depression: challenges and perspectives
Authors: Kolasa Magdalena , Faron-Górecka Agata
Published: October 2023

Treatment-resistant depression (TRD) is a subgroup of major depressive disorder in which the use of classical antidepressant treatments fails to achieve satisfactory treatment results. Although there are various definitions and grading models for TRD, common criteria for assessing TRD have still not been established. However, a common feature of any TRD model is the lack of response to at least two attempts at antidepressant pharmacotherapy. The causes of TRD are not known; nevertheless, it is estimated that even 60% of TRD patients are so-called pseudo-TRD patients, in which multiple biological factors, e.g., gender, age, and hormonal disturbances are concomitant with depression and involved in antidepressant drug resistance. Whereas the phenomenon of TRD is a complex disorder difficult to diagnose and successfully treat, the search for new treatment strategies is a significant challenge of modern pharmacology. It seems that despite the complexity of the TRD phenomenon, some useful animal models of TRD meet the construct, the face, and the predictive validity criteria. Based on the literature and our own experiences, we will discuss the utility of animals exposed to the stress paradigm (chronic mild stress, CMS), and the Wistar Kyoto rat strain representing an endogenous model of TRD. In this review, we will focus on reviewing research on existing and novel therapies for TRD, including ketamine, deep brain stimulation (DBS), and psychedelic drugs in the context of preclinical studies in representative animal models of TRD.
Schweizer–Sklar Power Aggregation Operators Based on Complex Interval-Valued Intuitionistic Fuzzy Information for Multi-attribute Decision-Making
Authors: Kalsoom Umme , Ullah Kifayat , Akram Maria , Pamucar Dragan , Senapati Tapan , Naeem Muhammad , Pilla Francesco , Moslem Sarbast
Published: October 2023

This manuscript proposes the concept of Schweizer–Sklar operational laws under the consideration of the complex interval-valued intuitionistic fuzzy (CIVIF) set theory, where the Schweizer–Sklar norms are the essential and valuable modification of many norms, such as algebraic, Hamacher, and Lukasiewicz norms. Moreover, keeping the dominancy of the presented laws, we derive the concept of CIVIF Schweizer–Sklar power averaging (CIVIFSSPA), CIVIF Schweizer–Sklar power ordered averaging (CIVIFSSPOA), CIVIF Schweizer–Sklar power geometric (CIVIFSSPG), and CIVIF Schweizer–Sklar power ordered geometric (CIVIFSSPOG) operators, which are the combination of the three different structures for evaluating three different problems. Further, some reliable and feasible properties and results for derived work are also invented. Additionally, we also illustrate an application, called multi-attribute decision-making (MADM) scenario for evaluating some real-world problems with the help of discovered operators for showing the reliability and stability of the evaluated operators. Finally, we compare our mentioned operators with various prevailing operators for enhancing the worth and stability of the evaluated approaches.
Impact of transition to a hybrid model of biochemistry course-based undergraduate research experience during the COVID-19 pandemic on student science self-efficacy and conceptual knowledge
Authors: Zhang Jing , Kim Heejeong , Zhang Limei
Published: October 2023

The COVID-19 outbreak has had a significant impact on higher education worldwide. In-person courses had to be quickly transited to online, including lab courses embedded with Course-based Undergraduate Research Experiences (CUREs). In response to this challenge, we successfully converted a fully in-person biochemistry lab that integrated with a 6-week modular CURE (mCURE) into a hybrid CURE (hCURE) in Fall 2020, with support from the Malate dehydrogenase CUREs Community. The hCURE was structured to have in-person labs and online activities arranged on an alternating weekly basis, so that only half of the regular class size of students attended the hands-on labs at any given time to maintain proper social distancing. To evaluate the efficacy of the hCURE, student science self-efficacy and conceptual understanding of protein structure–function relationships were measured using pre-course and post-course surveys and tests, respectively. Our data showed a significant increase in student science self-efficacy and conceptual knowledge test scores. Furthermore, we compared the pre-lab quiz scores that assessed various biochemical concepts and skills across three different semesters, Fall 2019 with a fully in-person mCURE before the pandemic, Fall 2020 with the hCURE implemented during the pandemic, and Fall 2021 when the lab returned to the fully in-person mCURE following the pandemic. A significant decline in quiz scores from Fall 2019 to Fall 2020, and an even further decline from Fall 2019 to Fall 2021 were observed, suggesting that apart from the impact of course modality, the pandemic may have exerted a lasting adverse effect on student learning.
The Circular Bioeconomy
Authors: Morone Piergiuseppe , D'Amato Dalia , Befort Nicolas , Yilan Gülşah
Published: October 2023

Interest in issues surrounding sustainable production-consumption systems and alternatives to fossil fuels is booming. The circular bioeconomy is currently mainstreamed in policy-making, industry and academia as an important part of the solution to the climate crisis and towards the creation of more sustainable economies. Based on the University-level teaching and research experience of the four authors in Italy, Finland, and France, this textbook fills an important gap in the literature by providing an in-depth and unique guide to the circular bioeconomy. The chapters critically discuss the potential contribution of a circular bioeconomy to fostering societal and organizational transformations towards sustainability globally. This timely book joins a suite of important new titles on sustainability, environmental and ecological economics.
Building the Bridge From Pediatric to Adult Neurological Care
Authors: Sawicka Katherine M. , Vogt Lindsey M. , Andrade Danielle M. , Katzberg Hans D. , Miller Steven P. , Moharir Mahendranath , Tang-Wai David F. , Lagman-Bartolome Ana Marissa
Published: October 2023

In this brief communication, we discuss the current landscape and unmet needs of pediatric to adult transition care in neurology. Optimizing transition care is a priority for patients, families, and providers with growing discussion in neurology. We also introduce the activities of the University of Toronto Pediatric-Adult Transition Working Group – a collaborative interdivisional and inter-subspeciality group of faculty, advanced-practice providers, trainees, and patient-family advisors pursuing collaboration with patients, families, and universities from across Canada. We envision that these efforts will result in a national neurology transition strategy that will inform designation of health authority attention and funding.
Economic voting goes local: evidence from the Italian regions
Authors: Rombi Stefano , Valbruzzi Marco
Published: October 2023

This article investigates the pattern of economic voting at the regional level in Italy. It focuses on the elections held in 18 out of 20 Italian regions from 1995 to 2020. Retrospective voting is examined by using the theory of economic voting, measured at the subnational level. By providing some inferential models and controlling for the impact of phases of recession, this article tests the hypothesis whereby the incumbent regional government is rewarded (or punished) by voters in the event of a good (or poor) state of the regional economy. It mainly considers macroeconomic variables, focusing on the relationship between the unemployment rate (at both national and regional levels) and the electoral performance of the incumbent executive. The empirical analysis shows that, particularly during periods of ‘quiet politics’, economic voting also occurs at the local level and thus the regional unemployment rate affects regional rulers' electoral outcomes.
Prescribing nearly constant curvatures on balls
Authors: Battaglia Luca , Cruz-Blázquez Sergio , Pistoia Angela
Published: October 2023

In this paper, we address two boundary cases of the classical Kazdan–Warner problem. More precisely, we consider the problem of prescribing the Gaussian and boundary geodesic curvature on a disk of

$\mathbb {R}^2$

, and the scalar and mean curvature on a ball in higher dimensions, via a conformal change of the metric. We deal with the case of negative interior curvature and positive boundary curvature. Using a Ljapunov–Schmidt procedure, we obtain new existence results when the prescribed functions are close to constants.
The space of commuting elements in a Lie group and maps between classifying spaces
Authors: Kishimoto Daisuke , Takeda Masahiro , Tsutaya Mitsunobu
Published: October 2023

Let$\pi$be a discrete group, and let$G$be a compact-connected Lie group. Then, there is a map$\Theta \colon \mathrm {Hom}(\pi,G)_0\to \mathrm {map}_*(B\pi,BG)_0$between the null components of the spaces of homomorphisms and based maps, which sends a homomorphism to the induced map between classifying spaces. Atiyah and Bott studied this map for$\pi$a surface group, and showed that it is surjective in rational cohomology. In this paper, we prove that the map$\Theta$is surjective in rational cohomology for$\pi =\mathbb {Z}^m$and the classical group$G$except for$SO(2n)$, and that it is not surjective for$\pi =\mathbb {Z}^m$with$m\ge 3$and$G=SO(2n)$with$n\ge 4$. As an application, we consider the surjectivity of the map$\Theta$in rational cohomology for$\pi$a finitely generated nilpotent group. We also consider the dimension of the cokernel of the map$\Theta$in rational homotopy groups for$\pi =\mathbb {Z}^m$and the classical groups$G$except for$SO(2n)$.
Trends and long-term variation explaining nutritional determinants of child linear growth: analysis of Bangladesh Demographic and Health Surveys 1996–2018
Authors: Ahmed Khandaker Tanveer , Karimuzzaman Md , Afroz Sabrina , Hossain Md Moyazzem , Huq Syeda Shahanara , Abdulla Faruq , Rahman Azizur
Published: October 2023

Objective:

To examine the height-for-age z-score (HAZ) of 0–35 months’ children along with stunting prevalence to identify trends, changes and available nutrition-sensitive and specific determinants that could help explain the long-term variation in child linear growth using successive Bangladesh Demographic and Health Surveys (BDHS) data from 1996 to 2018.

Design:

The BDHS pooled data are used for determining the key outcome variables HAZ, stunting and severe stunting. Trends, kernel-weighted local polynomial smoothing illustrations, pooled multivariable linear probability model (LPM), ordinary least squares method (OLS) and regression decomposition were used.

Participants:

Mothers having 0–35 months’ children, the most critical age range for growth faltering.

Results:

The mean HAZ increased by 0·91(±1·53) with 0·041 annual average change, while the percentages of stunting (–26·63 ± 0·54) and severe stunting (–21·12 ± 0·48) showed a reduction with 1·21 and 0·96 average annual changes, respectively. The average HAZ improvement (0·42 ± 1·56) in urban areas was less than the rural areas (1·16 ± 1·44). Similar patterns followed for stunting and severe stunting. The prenatal doctor visits (3064·65 %), birth in a medical facility (1054·32 %), breastfeeding initiation (153·18 %) and asset index (144·73 %) demonstrated a huge change. The findings of OLS, LPM and regression decomposition identified asset index, birth order, paternal and maternal education, bottle-fed, prenatal doctor visit, birth in a medical facility, vaccination, maternal BMI and ever-breastfed as influencing factors to predict the long-term changes of stunting and severe stunting.

Conclusion:

The nutrition-sensitive and specific factors identified through regression decomposition describing long-term variation in child linear growth should be focused further to attain the sustainable development goals.
The Fairey Gyrodyne
Authors: Bennett J A J
Published: October 2023

Ladies and Gentlemen,

I am sure you will agree that it is quite unnecessary for me to introduce DR BENNETT formally He has previously lectured before the Helicopter Association, to say nothing of numerous lectures to learned Societies both at home and abroad I also feel quite certain that most of you are familiar with his background in the rotary wing field of aviation

On behalf of all Association Members and their guests, I should like to thank the Directors of the Fairey Aviation Company for their kindness and hospitality to us today, and also thank those members of the Fairey Company Helicopter Division whose work has made this visit possible

Finally, on behalf of the Association, may I congratulate the Fairey Aviation Company again, together with all those responsible, for the excellent show in their recent successful attempt to raise the Helicopter world speed record Personally, I feel that given the right conditions they are quite capable of increasing this record still further
Rotor Stations—Some Architectural and Engineering Aspects
Authors: Colquhoun R S
Published: October 2023

Previous papers have dealt with the operational and planning criteria for Rotor Stations The architectural and engineering aspects will derive directly from the site selected in accordance with these requirements Such sites can be classified into the categories of ground level, roof-top, bridge platform and flexible pontoon sites These will be examined in detail, together with some estimates of the clear spans and floor areas of the buildings required to serve the stations

Ground level sites have much to commend them from the engineering point of view For relatively low rates of operation, the landing area may be turf, provided that the subgrade is well drained For aircraft movements of the order of 10 to 15 per hour, however, a paved surface will be required The buildings necessary will comprise the terminal building and control tower, fuel store, and open air parking facilities for aircraft passengers’ and staff cars, and in some cases hangars and workshops From the layout aspect, it would be desirable to keep all buildings to one side of the landing area, though the car parking area need not be so located
The Manufacture of Wooden Helicopter Blades
Authors: Morris N B
Published: October 2023

Our Company has been making wooden helicopter blades of different types since 1937 I want to tell you something of their materials and manufacture and would welcome questions in the course of my talk

Fig 1 shows a cross-section of the big Cierva blade as used on the W 11 This is monocoque construction Notice the centre of gravity of the blade and the incidence of the tip superimposed on that at its widest section

The main spar is built up at one-inch thick blocks of compressed wood laminated of 1/32 inch Canadian birch veneers bonded with resin film and pressed to about 2,000 lbs per square inch at 300°F The density is about 1 2

As a matter of interest, by laminated wood we mean that the grain in all the laminations runs parallel, whereas in plywood the grain of adjoining laminations is at right angles
High‐Density Integrated GNSS and Hydrologic Monitoring Network for Short‐Scale Hydrogeodesy in High Mountain Watersheds
Authors: White Alissa M. , Lajoie Lia J. , Knappe Ellen , Martens Hilary R. , Swarr Matthew J. , Khatiwada Ashlesha , Oliver Brett , Perry Mason , Clayton Noah , Bendick Rebecca , Borsa Adrian A. , Argus Donald F. , Gardner W. Payton
Published: October 2023

We installed a purpose‐built network of co‐located Global Navigation Satellite System (GNSS) stations and meteorological instrumentation to investigate water storage in a high‐mountain watershed along the Idaho‐Montana border. Twelve GNSS stations are distributed across the Selway‐Lochsa watersheds at approximately 30–40 km spacing, filling a critical observational gap between localized point measurements and regional geodetic and satellite data sets. The unique coupling of geodetic and hydrologic observations in this network enables direct comparison between co‐located GNSS measurements of the elastic response of the solid Earth and local changes in measured water storage. This network is specifically designed to address questions of hydrologic storage and movement at the mountain watershed scale. Here, we describe technical details of the network and its deployment; introduce new hydrologic, meteorologic, and geodetic data sets recorded by the network; process and analyze the source data (e.g., time series of daily three‐dimensional GNSS site positions, removal of non‐hydrologic signals); and characterize basic empirical relationships between water storage, water movement, and GNSS‐inferred surface displacement. The network shows preliminary evidence for spatial differences in displacement resulting from a range of snow loads across elevations, but longer and more complete data records are needed to support these initial findings. We also provide examples of additional scientific applications of this network, including estimations of snow depth and snow water equivalent from GNSS multipath reflectometry. Finally, we consider the challenges, limitations, and opportunities of deploying GNSS and weather stations at high elevations with heavy snowpack and offer ideas for technical improvements.
Biodegradable Sensors Could Explore the Seas More Sustainably
Authors: Aubry Lisa
Published: October 2023

Researchers are developing environmentally friendly instruments to monitor the oceans.
Ash Deposition Triggers Phytoplankton Blooms at Nishinoshima Volcano, Japan
Authors: Kelly Liam J. , Fauria Kristen E. , Mittal Tushar , El Kassar Jan , Bennartz Ralf , Nicholson David , Subramaniam Ajit , Gupta Ashok Kumar
Published: October 2023

Volcanoes that deposit eruptive products into the ocean can trigger phytoplankton blooms near the deposition area. Phytoplankton blooms impact the global carbon cycle, but the specific conditions and mechanisms that facilitate volcanically triggered blooms are not well understood, especially in low nutrient ocean regions. We use satellite remote sensing to analyze the chlorophyll response to an 8‐month period of explosive and effusive activity from Nishinoshima volcano, Japan. Nishinoshima is an ocean island volcano in a low nutrient low chlorophyll region of the Northern Pacific Ocean. From June to August 2020, during explosive activity, satellite‐derived chlorophyll‐a was detectable with amplitudes significantly above the long‐term climatological value. After the explosive activity ceased in mid‐August 2020, these areas of heightened chlorophyll concentration decreased as well. In addition, we used aerial observations and satellite imagery to demonstrate a spatial correlation between blooms and ash plume direction. Using a sun‐induced chlorophyll‐a fluorescence satellite product, we confirmed that the observed chlorophyll blooms are phytoplankton blooms. Based on an understanding of the nutrients needed to supply blooms, we hypothesize that blooms of nitrogen‐fixing phytoplankton led to a 1010–1012 g drawdown of carbon. Thus, the bloom could have significantly mediated the output of carbon from the explosive phase of the eruption but is a small fraction of anthropogenic CO2 stored in the ocean or the global biological pump. Overall, we provide a case study of fertilization of a nutrient‐poor ocean with volcanic ash and demonstrate a scenario where multi‐month scale deposition triggers continuous phytoplankton blooms across 1,000s of km2.
A Deep Learning Approach Based on Physical Constraints for Predicting Soil Moisture in Unsaturated Zones
Authors: Wang Yi , Wang Wenke , Ma Zhitong , Zhao Ming , Li Wanxin , Hou Xinyue , Li Jie , Ye Fei , Ma Wenjing
Published: October 2023

Water transport in the unsaturated zone is an important part of the hydrological cycle and is the link between the atmosphere‒soil‐groundwater for material and energy transport. The accurate prediction of soil moisture (SM) is essential for the rational exploitation of water resources. Data‐driven deep learning methods are widely used in many fields; however, the lack of physical mechanisms limits their application in hydrological fields, especially for SM prediction in unsaturated zones. To solve this problem, this study proposes a new deep learning method that introduces the water balance principle, Richard's equation, and SM boundary conditions as constraints to construct the new loss function that guides the training process of deep learning, called physics‐informed deep learning (PIDL). In tests consisting of a large number of data sets acquired from in situ observation sites in the field, PIDL exhibits higher accuracy than ordinary deep learning (long short‐term memory) and physical models, with 51.03% and 53.46% reduction in root mean square error of SM prediction, respectively. PIDL performance significantly improved in predicting scenarios that are difficult for ordinary deep learning to handle, such as sparse data sets, extreme values, and mutated values. In addition, PIDL maintains high accuracy over a longer prediction period. The addition of physical mechanisms allows deep learning to mine patterns not only from the data itself but also from a priori physical theoretical knowledge for guidance, and this hybrid modeling approach can also be generalized to prediction problems in other hydrological domains.
Predation-resistant Pseudomonas bacteria engage in symbiont-like behavior with the social amoeba Dictyostelium discoideum
Authors: Steele Margaret I , Peiser Jessica M , Shreenidhi P M , Strassmann Joan E , Queller David C
Published: October 2023

The soil amoeba Dictyostelium discoideum acts as both a predator and potential host for diverse bacteria. We tested fifteen Pseudomonas strains that were isolated from transiently infected wild D. discoideum for ability to escape predation and infect D. discoideum fruiting bodies. Three predation-resistant strains frequently caused extracellular infections of fruiting bodies but were not found within spores. Furthermore, infection by one of these species induces secondary infections and suppresses predation of otherwise edible bacteria. Another strain can persist inside of amoebae after being phagocytosed but is rarely taken up. We sequenced isolate genomes and discovered that predation-resistant isolates are not monophyletic. Many Pseudomonas isolates encode secretion systems and toxins known to improve resistance to phagocytosis in other species, as well as diverse secondary metabolite biosynthetic gene clusters that may contribute to predation resistance. However, the distribution of these genes alone cannot explain why some strains are edible and others are not. Each lineage may employ a unique mechanism for resistance.
Dental students' attitudes on cardiopulmonary resuscitation training via virtual reality: an exploratory study
Authors: Bjelovucic Ruza , Bak Jesper , Wolff Jan , Taneja Pankaj
Published: October 2023

Purpose Resuscitation guidelines have advocated the use of virtual learning as a form of pre-course e-learning. Virtual reality (VR) has been identified to provide a method of constructive learning with instant feedback. There are increasing publications of VR use in cardiopulmonary resuscitation (CPR) training; however, there is a dearth from the dental profession. Therefore, the aim of this exploratory study was to investigate dental students' opinions in CPR training using VR.

Methods In total, 120 dental students undertook both conventional (manikin) and VR CPR training in a cross-over design. The VR scenario was in a hospital setting. Following, students completed a questionnaire evaluating their experiences.

Results The majority of students (n = 88) reported that this was the first time that they had utilised VR. The experience of using VR in CPR training was rated as very good. Most students felt that the inclusion of VR in CPR training created a better learning experience and had a high learning potential. However, the hospital setting was not entirely relevant.

Conclusion Dental students recommended that VR CPR training should be used as an adjunct to conventional training in dental education, but the VR scenario would benefit being a virtual dental environment.
Implications of maternal-fetal health on perinatal stem cell banking
Authors: Zhu Dandan , Barabadi Mehri , McDonald Courtney , Kusuma Gina , Inocencio Ishmael Miguel , Lim Rebecca
Published: October 2023

Cell based therapies are being assessed for their therapeutic potential across a variety of diseases. Gestational tissues are attractive sources for cell therapy. The large number of births worldwide ensures sufficient access to gestational tissues, however, limited information has been reported around the impact of birth trends, delivery methods and pregnancy conditions on perinatal stem cell banking. This review describes the current state of banking of gestational tissues and their derived perinatal stem cells, discusses why the changes in birth trends and delivery methods could affect gestational tissue banking practices, and further explores how common pregnancy complications can potentially influence perinatal stem cell banking.
Cascading events during the 1650 tsunamigenic eruption of Kolumbo volcano
Authors: Karstens Jens , Crutchley Gareth J. , Hansteen Thor H. , Preine Jonas , Carey Steven , Elger Judith , Kühn Michel , Nomikou Paraskevi , Schmid Florian , Dalla Valle Giacomo , Kelfoun Karim , Berndt Christian
Published: October 2023

Volcanic eruptions can trigger tsunamis, which may cause significant damage to coastal communities and infrastructure. Tsunami generation during volcanic eruptions is complex and often due to a combination of processes. The 1650 eruption of the Kolumbo submarine volcano triggered a tsunami causing major destruction on surrounding islands in the Aegean Sea. However, the source mechanisms behind the tsunami have been disputed due to difficulties in sampling and imaging submarine volcanoes. Here we show, based on three-dimensional seismic data, that ~1.2 km³ of Kolumbo’s northwestern flank moved 500–1000 m downslope along a basal detachment surface. This movement is consistent with depressurization of the magma feeding system, causing a catastrophic explosion. Numerical tsunami simulations indicate that only the combination of flank movement followed by an explosive eruption can explain historical eyewitness accounts. This cascading sequence of natural hazards suggests that assessing submarine flank movements is critical for early warning of volcanogenic tsunamis.
Boosting lithium ion conductivity of antiperovskite solid electrolyte by potassium ions substitution for cation clusters
Authors: Gao Lei , Zhang Xinyu , Zhu Jinlong , Han Songbai , Zhang Hao , Wang Liping , Zhao Ruo , Gao Song , Li Shuai , Wang Yonggang , Huang Dubin , Zhao Yusheng , Zou Ruqiang
Published: October 2023

Solid-state electrolytes with high ionic conductivities are crucial for the development of all-solid-state lithium batteries, and there is a strong correlation between the ionic conductivities and underlying lattice structures of solid-state electrolytes. Here, we report a lattice manipulation method of replacing [Li2OH]+ clusters with potassium ions in antiperovskite solid-state electrolyte (Li2OH)0.99K0.01Cl, which leads to a remarkable increase in ionic conductivity (4.5 × 10‒3 mS cm‒1, 25 °C). Mechanistic analysis indicates that the lattice manipulation method leads to the stabilization of the cubic phase and lattice contraction for the antiperovskite, and causes significant changes in Li-ion transport trajectories and migration barriers. Also, the Li||LiFePO4 all-solid-state battery (excess Li and loading of 1.78 mg cm‒2 for LiFePO4) employing (Li2OH)0.99K0.01Cl electrolyte delivers a specific capacity of 116.4 mAh g‒1 at the 150th cycle with a capacity retention of 96.1% at 80 mA g‒1 and 120 °C, which indicates potential application prospects of antiperovskite electrolyte in all-solid-state lithium batteries.
Mechanism of substrate hydrolysis by the human nucleotide pool sanitiser DNPH1
Authors: Rzechorzek Neil J. , Kunzelmann Simone , Purkiss Andrew G. , Silva Dos Santos Mariana , MacRae James I. , Taylor Ian A. , Fugger Kasper , West Stephen C.
Published: October 2023

Poly(ADP-ribose) polymerase (PARP) inhibitors are used in the clinic to treat BRCA-deficient breast, ovarian and prostate cancers. As their efficacy is potentiated by loss of the nucleotide salvage factor DNPH1 there is considerable interest in the development of highly specific small molecule DNPH1 inhibitors. Here, we present X-ray crystal structures of dimeric DNPH1 bound to its substrate hydroxymethyl deoxyuridine monophosphate (hmdUMP). Direct interaction with the hydroxymethyl group is important for substrate positioning, while conserved residues surrounding the base facilitate target discrimination. Glycosidic bond cleavage is driven by a conserved catalytic triad and proceeds via a two-step mechanism involving formation and subsequent disruption of a covalent glycosyl-enzyme intermediate. Mutation of a previously uncharacterised yet conserved glutamate traps the intermediate in the active site, demonstrating its role in the hydrolytic step. These observations define the enzyme’s catalytic site and mechanism of hydrolysis, and provide important insights for inhibitor discovery.
Wildfire precursors show complementary predictability in different timescales
Authors: Qu Yuquan , Miralles Diego G. , Veraverbeke Sander , Vereecken Harry , Montzka Carsten
Published: October 2023

In most of the world, conditions conducive to wildfires are becoming more prevalent. Net carbon emissions from wildfires contribute to a positive climate feedback that needs to be monitored, quantified, and predicted. Here we use a causal inference approach to evaluate the influence of top-down weather and bottom-up fuel precursors on wildfires. The top-down dominance on wildfires is more widespread than bottom-up dominance, accounting for 73.3% and 26.7% of regions, respectively. The top-down precursors dominate in the tropical rainforests, mid-latitudes, and eastern Siberian boreal forests. The bottom-up precursors dominate in North American and European boreal forests, and African and Australian savannahs. Our study identifies areas where wildfires are governed by fuel conditions and hence where fuel management practices may be more effective. Moreover, our study also highlights that top-down and bottom-up precursors show complementary wildfire predictability across timescales. Seasonal or interannual predictions are feasible in regions where bottom-up precursors dominate.
PH13 improves soybean shade traits and enhances yield for high-density planting at high latitudes
Authors: Qin Chao , Li Ying-hui , Li Delin , Zhang Xueru , Kong Lingping , Zhou Yonggang , Lyu Xiangguang , Ji Ronghuan , Wei Xiuzhi , Cheng Qican , Jia Zhiwei , Li Xiaojiao , Wang Qiang , Wang Yueqiang , Huang Wen , Yang Chunyan , Liu Like , Wang Xing , Xing Guangnan , Hu Guoyu , Shan Zhihui , Wang Ruizhen , Li Haiyan , Li Hongyu , Zhao Tao , Liu Jun , Lu Yuping , Hu Xiping , Kong Fanjiang , Qiu Li-juan , Liu Bin
Published: October 2023

Shading in combination with extended photoperiods can cause exaggerated stem elongation (ESE) in soybean, leading to lodging and reduced yields when planted at high-density in high-latitude regions. However, the genetic basis of plant height in adaptation to these regions remains unclear. Here, through a genome-wide association study, we identify a plant height regulating gene on chromosome 13 (PH13) encoding a WD40 protein with three main haplotypes in natural populations. We find that an insertion of a Ty1/Copia-like retrotransposon in the haplotype 3 leads to a truncated PH13H3 with reduced interaction with GmCOP1s, resulting in accumulation of STF1/2, and reduced plant height. In addition, PH13H3 allele has been strongly selected for genetic improvement at high latitudes. Deletion of both PH13 and its paralogue PHP can prevent shade-induced ESE and allow high-density planting. This study provides insights into the mechanism of shade-resistance and offers potential solutions for breeding high-yielding soybean cultivar for high-latitude regions.
Transcriptional dissection of symptomatic profiles across the brain of men and women with depression
Authors: Mansouri Samaneh , Pessoni André M. , Marroquín-Rivera Arturo , Parise Eric M. , Tamminga Carol A. , Turecki Gustavo , Nestler Eric J. , Chen Ting-Huei , Labonté Benoit
Published: October 2023

Major depressive disorder (MDD) is one of the most important causes of disability worldwide. While recent work provides insights into the molecular alterations in the brain of patients with MDD, whether these molecular signatures can be associated with the expression of specific symptom domains remains unclear. Here, we identified sex-specific gene modules associated with the expression of MDD, combining differential gene expression and co-expression network analyses in six cortical and subcortical brain regions. Our results show varying levels of network homology between males and females across brain regions, although the associations between these structures and the expression of MDD remain highly sex specific. We refined these associations to several symptom domains and identified transcriptional signatures associated with distinct functional pathways, including GABAergic and glutamatergic neurotransmission, metabolic processes and intracellular signal transduction, across brain regions associated with distinct symptomatic profiles in a sex-specific fashion. In most cases, these associations were specific to males or to females with MDD, although a subset of gene modules associated with common symptomatic features in both sexes were also identified. Together, our findings suggest that the expression of distinct MDD symptom domains associates with sex-specific transcriptional structures across brain regions.
Mitochondrial matrix RTN4IP1/OPA10 is an oxidoreductase for coenzyme Q synthesis
Authors: Park Isaac , Kim Kwang-eun , Kim Jeesoo , Kim Ae-Kyeong , Bae Subin , Jung Minkyo , Choi Jinhyuk , Mishra Pratyush Kumar , Kim Taek-Min , Kwak Chulhwan , Kang Myeong-Gyun , Yoo Chang-Mo , Mun Ji Young , Liu Kwang-Hyeon , Lee Kyu-Sun , Kim Jong-Seo , Suh Jae Myoung , Rhee Hyun-Woo
Published: October 2023

Targeting proximity-labeling enzymes to specific cellular locations is a viable strategy for profiling subcellular proteomes. Here, we generated transgenic mice (MAX-Tg) expressing a mitochondrial matrix-targeted ascorbate peroxidase. Comparative analysis of matrix proteomes from the muscle tissues showed differential enrichment of mitochondrial proteins. We found that reticulon 4-interacting protein 1 (RTN4IP1), also known as optic atrophy-10, is enriched in the mitochondrial matrix of muscle tissues and is an NADPH oxidoreductase. Interactome analysis and in vitro enzymatic assays revealed an essential role for RTN4IP1 in coenzyme Q (CoQ) biosynthesis by regulating the O-methylation activity of COQ3. Rtn4ip1-knockout myoblasts had markedly decreased CoQ9 levels and impaired cellular respiration. Furthermore, muscle-specific knockdown of dRtn4ip1 in flies resulted in impaired muscle function, which was reversed by dietary supplementation with soluble CoQ. Collectively, these results demonstrate that RTN4IP1 is a mitochondrial NAD(P)H oxidoreductase essential for supporting mitochondrial respiration activity in the muscle tissue.
Evidence for a role of Anopheles stephensi in the spread of drug- and diagnosis-resistant malaria in Africa
Authors: Emiru Tadele , Getachew Dejene , Murphy Maxwell , Sedda Luigi , Ejigu Legesse Alamerie , Bulto Mikiyas Gebremichael , Byrne Isabel , Demisse Mulugeta , Abdo Melat , Chali Wakweya , Elliott Aaron , Vickers Eric Neubauer , Aranda-Díaz Andrés , Alemayehu Lina , Behaksera Sinknesh W. , Jebessa Gutema , Dinka Hunduma , Tsegaye Tizita , Teka Hiwot , Chibsa Sheleme , Mumba Peter , Girma Samuel , Hwang Jimee , Yoshimizu Melissa , Sutcliffe Alice , Taffese Hiwot Solomon , Bayissa Gudissa Aseffa , Zohdy Sarah , Tongren Jon Eric , Drakeley Chris , Greenhouse Bryan , Bousema Teun , Tadesse Fitsum G.
Published: October 2023

Anopheles stephensi, an Asian malaria vector, continues to expand across Africa. The vector is now firmly established in urban settings in the Horn of Africa. Its presence in areas where malaria resurged suggested a possible role in causing malaria outbreaks. Here, using a prospective case–control design, we investigated the role of An. stephensi in transmission following a malaria outbreak in Dire Dawa, Ethiopia in April–July 2022. Screening contacts of patients with malaria and febrile controls revealed spatial clustering of Plasmodium falciparum infections around patients with malaria in strong association with the presence of An. stephensi in the household vicinity. Plasmodium sporozoites were detected in these mosquitoes. This outbreak involved clonal propagation of parasites with molecular signatures of artemisinin and diagnostic resistance. To our knowledge, this study provides the strongest evidence so far for a role of An. stephensi in driving an urban malaria outbreak in Africa, highlighting the major public health threat posed by this fast-spreading mosquito.
A global long-term daily reanalysis of reference evapotranspiration for drought and food-security monitoring
Authors: Hobbins Mike , Jansma Timen , Sarmiento Daniel P. , McNally Amy , Magadzire Tamuka , Jayanthi Harikishan , Turner Will , Hoell Andrew , Husak Greg , Senay Gabriel , Boiko Olena , Budde Michael , Mogane Pamella , Dewes Candida F.
Published: October 2023

NOAA has developed a global reference evapotranspiration (ET0) reanalysis using the UN Food and Agriculture Organization formulation (FAO-56) of the Penman-Monteith equation forced by MERRA phase 2 (MERRA2) meteorological and radiative drivers. The NOAA ET0 reanalysis is provided daily from January 1, 1980 to the near-present at a resolution of 0.5° latitude × 0.625° longitude. The reanalysis is verified against station data across southern Africa, a region presenting both significant challenges regarding hydroclimatic variability and observational quantity and quality and significant potential benefits to food-insecure populations. These data are generated from observations from the Southern African Science Service Centre for Climate Change and Adaptive Land Management (SASSCAL) network. We further verified globally against spatially distributed ET0 derived from two reanalyses–the Global Data Assimilation System (GDAS) and Princeton Global Forcing (PGF)–and these verifications produced similar results, yet demonstrated wide regional and seasonal differences. We also present cases that verify the operational applicability of the reanalysis in long-established drought, famine, crop- and pastoral-stress metrics, and in predictability assessments of drought forecasts.
Association between HbA1c and hearing loss: a tertiary care center-based study
Authors: Lee Hyun Jin , Yoo Sung Goo , Lee Sun Jung , Han Jae Sang , Choi In Young , Park Kyoung Ho
Published: October 2023

The purpose of this study was to investigate the correlation between glycated hemoglobin (HbA1c) levels and hearing loss (HL) using data from a tertiary hospital. Our hypothesis regarding the relationship between HL and HbA1c levels was that elevated HbA1c levels are associated with an increased risk of HL. We retrospectively reviewed the medical charts of patients diagnosed with sensorineural HL or diabetes between 2006 and 2021 at the Catholic Medical Center (CMC). Data were collected from the CMC’s Clinical Data Warehouse. Participants were selected from patients who were prescribed pure-tone audiometry and an HbA1c blood test. The survey was completed for 5287 participants. The better ear pure-tone audiometry (PTA) for air conduction thresholds at 500, 1000, 2000, and 4000 Hz was calculated. Sensorineural HL was defined as a better ear PTA of 25 dB or higher. We used the HbA1c level as a diagnostic criterion for diabetes. The following criteria were used to define the HbA1c level: normal, HbA1c level below 5.6%; prediabetes, level between 5.6 and 6.4%; and diabetes, level of 6.5% or more. Among 5287 participants, 1129 were categorized as normal, 2119 as prediabetic, and 2039 as diabetic. The diabetic group was significantly older (p < 0.05). The PTA also significantly deteriorated in the diabetes group (p < 0.05). We analyzed the effects of age, sex, and HbA1c level on frequency-specific hearing using multiple regression. The hearing thresholds at all frequencies deteriorated significantly with increasing age and HbA1c level (p < 0.05). A case–control study was also performed to facilitate a comprehensive comparison between distinct groups. The participants were categorized into two groups: a case (PTA > 25 dB) and control group (PTA ≤ 25 dB), based on their PTA threshold of four frequencies. After adjusting for age and sex, we found no significant odds ratio (OR) of HL between the prediabetes group and the normal group. Notably, the OR of HL was significantly higher in the diabetes group with each PTA threshold and frequency. The 6.3% HbA1c level cutoff value was determined by analyzing the receiver operating characteristic curve for predicting hearing impairment > 25 dB. Diabetes was associated with hearing loss in all frequency ranges, particularly at high frequencies. Screening for HL is strongly recommended for patients with elevated HbA1c levels.
Scribble deficiency mediates colon inflammation by inhibiting autophagy-dependent oxidative stress elimination
Authors: Sun Xia , Lu Liying , Wang Kai , Song Lele , Jiao Jiazheng , Wu Yanjun , Wang Xinyu , Song Yanan , Zhan Lixing
Published: October 2023

Scribble is a master scaffold protein in apical-basal polarity. Current knowledge about the biological function of Scribble in colonic epithelial plasticity/regeneration during intestinal inflammation is limited. Here, we showed that the level of Scribble is decreased in inflammatory bowel disease (IBD) patients and mice with DSS-induced colitis. ScribΔIEC mice develops severe acute colitis with disrupted epithelial barrier integrity and impaired crypt stem cell’s function. Mechanistically, Scribble suppressed the process of autophagy by modulating the stability of caspase-dependent degradation of Atg16L1 by directly interacting with Atg16L1 in a LRR domain-dependent manner in IECs and led to an accumulation of ROS both in intestinal stem cells and epithelial cells. In addition, further study indicates that dietary sphingomyelin alleviates DSS-induced colitis by increase the expression of Scribble, which suggests that Scribble may be the critical marker of IBD. Our study shows that Scribble deficiency is associated with the dysregulated autophagy and impaired maintenance of colonic stemness, and it may be a target for diagnosis and treatment of IBD.
Associations of corticosteroid therapy and tonsillectomy with kidney survival in a multicenter prospective study for IgA nephropathy
Authors: Kawamura Tetsuya , Hirano Keita , Koike Kentaro , Nishikawa Masako , Shimizu Akira , Joh Kensuke , Katafuchi Ritsuko , Hashiguchi Akinori , Matsuzaki Keiichi , Maruyama Shoichi , Tsuboi Nobuo , Narita Ichiei , Yano Yuichiro , Yokoo Takashi , Suzuki Yusuke
Published: October 2023

Efficacy of systemic corticosteroid therapy (CS) for long-term kidney survival in patients with IgA nephropathy (IgAN) is controversial. Therefore, prospective studies evaluating targeted therapies to lymphatic tissues in mucosal immune system responsible for production of nephritogenic IgA have been desired worldwide. Here, we aimed to evaluate the associations of CS and combination therapy of CS and tonsillectomy (CS + Tx) with kidney survival, using database from a nationwide multicenter prospective cohort study on IgAN. Primary outcome was a 50% increase in serum creatinine from baseline or dialysis induction. The analysis included 941 patients (CS/CS + Tx/non-CS 239/364/338), 85 (9.0%) of whom reached outcomes during median follow-up of 5.5 (interquartile range 2.0–8.0) years. On overlap weighting analysis with balanced baseline characteristics, CS and CS + Tx were associated with lower risk of kidney events when compared with non-CS (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.29–0.88 and HR 0.20, 95%CI 0.09–0.44, respectively). Notably, when compared with the CS, CS + Tx was associated with a lower risk of kidney events (HR 0.40, 95%CI 0.18–0.91). Present study demonstrated, keeping with favorable association of systemic CS with kidney survival, concurrent tonsillectomy as one of targeted interventions to lymphatic tissues may provide additional improvement to kidney survival in patients with IgAN.
Mucosal expression of PI3, ANXA1, and VDR discriminates Crohn’s disease from ulcerative colitis
Authors: James Jaslin Pallikkunnath , Nielsen Boye Schnack , Christensen Ib Jarle , Langholz Ebbe , Malham Mikkel , Poulsen Tim Svenstrup , Holmstrøm Kim , Riis Lene Buhl , Høgdall Estrid
Published: October 2023

Differential diagnosis of inflammatory bowel disease (IBD) to Crohn’s disease (CD) or ulcerative colitis (UC) is crucial for treatment decision making. With the aim of generating a clinically applicable molecular-based tool to classify IBD patients, we assessed whole transcriptome analysis on endoscopy samples. A total of 408 patient samples were included covering both internal and external samples cohorts. Whole transcriptome analysis was performed on an internal cohort of FFPE IBD samples (CD,n = 16 and UC,n = 17). The 100 most significantly differentially expressed genes (DEG) were tested in two external cohorts. Ten of the DEG were further processed by functional enrichment analysis from which seven were found to show consistent significant performance in discriminating CD from UC:PI3, ANXA1, VDR, MTCL1, SH3PXD2A-AS1, CLCF1, and CD180. Differential expression ofPI3,ANXA1, andVDRwas reproduced by RT-qPCR, which was performed on an independent sample cohort of 97 patient samples (CD,n = 44 and UC,n = 53). Gene expression levels of the three-gene profile, resulted in an area under the curve of 0.84 (P = 0.02) in discriminating CD from UC, and therefore appear as an attractive molecular-based diagnostic tool for clinicians to distinguish CD from UC.
Starvation induces changes in abundance and small RNA cargo of extracellular vesicles released from Plasmodium falciparum infected red blood cells
Authors: Vetter Leonie , Bajalan Amanj , Ahamed Mohammad Tanvir , Scasso Caterina , Shafeeq Sulman , Andersson Björn , Ribacke Ulf
Published: October 2023

The lethal malaria parasite Plasmodium falciparum needs to constantly respond and adapt to changes within the human host in order to survive and transmit. One such change is composed of nutritional limitation, which is augmented with increased parasite loads and intimately linked to severe disease development. Extracellular vesicles released from infected red blood cells have been proposed as important mediators of disease pathogenesis and intercellular communication but whether important for the parasite response to nutritional availability is unknown. Therefore, we investigated the abundance and small RNA cargo of extracellular vesicles released upon short-term nutritional starvation of P. falciparum in vitro cultures. We show that primarily ring-stage parasite cultures respond to glucose and amino acid deprivation with an increased release of extracellular vesicles. Small RNA sequencing of these extracellular vesicles further revealed human miRNAs and parasitic tRNA fragments as the main constituent biotypes. Short-term starvations led to alterations in the transcriptomic profile, most notably in terms of the over-represented biotypes. These data suggest a potential role for extracellular vesicles released from P. falciparum infected red blood cells in the response to nutritional perturbations, their potential as prognostic biomarkers and point towards an evolutionary conserved role among protozoan parasites.