bluuebunny/crossref_metadata_2025_split huggingface dataset:
SSBP1 is a novel prognostic marker and promotes disease progression via p38MAPK signaling pathway in multiple myeloma
Authors: Xiao Pingping , Wang Jizhen , Li Tingting , Yang Apeng , Qiu Dongbiao , Chen Junmin , Zeng Zhiyong 
Published: January 2024

AbstractMultiple myeloma (MM) remains an incurable disease. Identification of meaningful co‐expressed gene clusters or representative biomarkers of MM may help to identify new pathological mechanisms and promote the development of new therapies. Here, we performed weighted sgene co‐expression network analysis and a series of bioinformatics analysis to identify single stranded DNA binding protein 1 (SSBP1) as novel hub gene associated with MM development and prognosis. In vitro, CRISPR/cas9 mediated knockdown of SSBP1 can significantly inhibit the proliferation of MM cells through inducing apoptosis and cell cycle arrest in G0/G1 phase. We also found that decreased SSBP1 expression significantly increased mitochondrial reactive oxygen species (mtROS) generation and the level of phosphorylated p38MAPK. Furthermore, it was further verified that disruption of SSBP1 expression could inhibit the tumor growth via p38MAPK pathway in a human myeloma xenograft model. In summary, our study is the first to demonstrate that SSBP1 promotes MM development by regulating the p38MAPK pathway.
Gerstmann‐Sträussler‐Scheinker Disease Presenting as Late‐Onset Slowly Progressive Spinocerebellar Ataxia, and Comparative Case Series with Neuropathology
Authors: Stephen Christopher D. , de Gusmao Claudio Melo , Srinivasan Sharan R. , Olsen Abby , Freua Fernando , Kok Fernando , Montes Garcia Barbosa Renata , Chen Jin Yun (Helen) , Appleby Brian S. , Prior Thomas , Frosch Matthew P. , Schmahmann Jeremy D. 
Published: January 2024

AbstractBackgroundGenetic prion diseases, including Gerstmann‐Sträussler‐Scheinker disease (GSS), are extremely rare, fatal neurodegenerative disorders, often associated with progressive ataxia and cognitive/neuropsychiatric symptoms. GSS typically presents as a rapidly progressive cerebellar ataxia, associated with cognitive decline. Late‐onset cases are rare.ObjectiveTo compare a novel GSS phenotype with six other cases and present pathological findings from a single case.MethodsCase series of seven GSS patients, one proceeding to autopsy.ResultsCase 1 developed slowly progressive gait difficulties at age 71, mimicking a spinocerebellar ataxia, with a family history of balance problems in old age. Genome sequencing revealed a heterozygous c.392G > A (p.G131E) pathogenic variant and a c.395A > G resulting in p.129 M/V polymorphism in the PRNP gene. Probability analyses considering family history, phenotype, and a similar previously reported point mutation (p.G131V) suggest p.G131E as a new pathogenic variant. Clinical features and imaging of this case are compared with those six additional cases harboring p.P102L mutations. Autopsy findings of a case are described and were consistent with the prion pathology of GSS.ConclusionsWe describe a patient with GSS with a novel p.G131E mutation in the PRNP gene, presenting with a late‐onset, slowly progressive phenotype, mimicking a spinocerebellar ataxia, and six additional cases with the typical P102L mutation.
Corruption in Turkey and earthquakes: Policies for tackling corruption in the construction sector
Authors: Cifuentes‐Faura Javier 
Published: January 2024

AbstractThe earthquake in Turkey has resulted in thousands of fatalities and injuries and is considered one of the worst natural disasters in recent history. The disaster has also brought to light another major issue in Turkey, namely, corruption. Failure to comply with building regulations and successive government amnesties for unlicensed construction contributed to the high death toll. This paper aims to draw attention to the ongoing issue of corruption and the potential life‐saving benefits of ethical practices in business and government. Finally, relevant useful policies targeting corruption in real estate have been proposed.
Mental and Substance Use Disorders Prevalence Study: Background and Methods
Authors: Guyer Heidi , Ringeisen Heather , Dever Jill , Liao Dan , Peytchev Andy , Carr Christine , Geiger Paul , Stambaugh Leyla , Smith Tim , Dixon Lisa , Olfson Mark , First Michael , Stroup Scott , Chwastiak Lydia , Monroe‐Devita Maria , Swanson Jeff , Swartz Marvin , Kessler Ronald C. , Gibbons Robert , Bareis Natalie , Sinclair Hancq Elizabeth , Clarke Thomas , Edlund Mark ,   the MDPS Consortium
Published: January 2024

AbstractObjectiveThe Mental and Substance Use Disorders Prevalence Study (MDPS) builds upon previous epidemiologic studies to provide estimates of prevalence and treatment rates of mental and substance use disorders among adults aged 18–65 in the U.S. The study background and methods are described.MethodThe MDPS employed novel techniques such as the inclusion of household, prison, homeless and state psychiatric hospital populations, a semi‐structured clinical interview administered by trained clinical interviewers to assess disorders, the assessment of both past year and lifetime schizophrenia spectrum disorder (SSD) using full Diagnostic and Statistical Manual 5 criteria, as well as other mental and substance use disorders, and video‐based interviewing. Population specific and combined sample weights were developed to estimate nationally representative prevalence and treatment rates.ResultsData collection was conducted between October 2020 and October 2022 resulting in 5679 clinical interviews. The statistical weighting and analytic plan are described. Weighted response rates and reasons for non‐response are provided for each study population.ConclusionsThe MDPS successfully developed and employed novel techniques to estimate the prevalence and treatment rates of mental and substance use disorders in both household and non‐household populations, including some of the most impairing disorders such as SSD.
A fully coupled regularized mortar‐type finite element approach for embedding one‐dimensional fibers into three‐dimensional fluid flow
Authors: Hagmeyer Nora , Mayr Matthias , Popp Alexander 
Published: January 2024

SummaryThe present article proposes a partitioned Dirichlet‐Neumann algorithm, that allows to address unique challenges arising from a novel mixed‐dimensional coupling of very slender fibers embedded in fluid flow using a regularized mortar‐type finite element discretization. The fibers are modeled via one‐dimensional (1D) partial differential equations based on geometrically exact nonlinear beam theory, while the flow is described by the three‐dimensional (3D) incompressible Navier‐Stokes equations. The arising truly mixed‐dimensional 1D‐3D coupling scheme constitutes a novel approximate model and numerical strategy, that naturally necessitates specifically tailored solution schemes to ensure an accurate and efficient computational treatment. In particular, we present a strongly coupled partitioned solution algorithm based on a Quasi‐Newton method for applications involving fibers with high slenderness ratios that usually present a challenge with regard to the well‐known added mass effect. The influence of all employed algorithmic and numerical parameters, namely the applied acceleration technique, the employed constraint regularization parameter as well as shape functions, on efficiency and results of the solution procedure is studied through appropriate examples. Finally, the convergence of the two‐way coupled mixed‐dimensional problem solution under uniform mesh refinement is demonstrated, a comparison to a 3D reference solution is performed, and the method's capabilities in capturing flow phenomena at large geometric scale separation is illustrated by the example of a submersed vegetation canopy.
Sustainability: We need to focus on overall system outcomes rather than simplistic targets
Authors: Fisher Len , Gross Thilo , Hillebrand Helmut , Sandberg Anders , Sayama Hiroki 
Published: January 2024

Abstract

Many of the global challenges that confront humanity are interlinked in a dynamic complex network, with multiple feedback loops, nonlinear interactions and interdependencies that make it difficult, if not impossible, to consider individual threats in isolation.

These challenges are mainly dealt with, however, by considering individual threats in isolation (at least in political terms). The mitigation of dual climate and biodiversity threats, for example, is linked to a univariate 1.5°C global warming boundary and a global area conservation target of 30% by 2030.

The situation has been somewhat improved by efforts to account for interactions through multidimensional target setting, adaptive and open management and market‐based decision pathways.

But the fundamental problem still remains—that complex systems such as those formed by the network of global threats have emergent properties that are more than the sum of their parts. We must learn how to deal with or live with these properties if we are to find effective ways to cope with the threats, individually and collectively.

Here, we argue that recent progresses in complex systems research and related fields have enhanced our ability to analyse and model such entwined systems to the extent that it offers the promise of a new approach to sustainability. We discuss how this may be achieved, both in theory and in practice, and how human cultural factors play an important but neglected role that could prove vital to achieving success.

Read the free Plain Language Summary for this article on the Journal blog.
Distinct specificities of the HEMK2 protein methyltransferase in methylation of glutamine and lysine residues
Authors: Weirich Sara , Ulu Gizem T. , Chandrasekaran Thyagarajan T. , Kehl Jana , Schmid Jasmin , Dorscht Franziska , Kublanovsky Margarita , Levy Dan , Jeltsch Albert 
Published: January 2024

AbstractThe HEMK2 protein methyltransferase has been described as glutamine methyltransferase catalyzing ERF1‐Q185me1 and lysine methyltransferase catalyzing H4K12me1. Methylation of two distinct target residues is unique for this class of enzymes. To understand the specific catalytic adaptations of HEMK2 allowing it to master this chemically challenging task, we conducted a detailed investigation of the substrate sequence specificities of HEMK2 for Q‐ and K‐methylation. Our data show that HEMK2 prefers methylation of Q over K at peptide and protein level. Moreover, the ERF1 sequence is strongly preferred as substrate over the H4K12 sequence. With peptide SPOT array methylation experiments, we show that Q‐methylation preferentially occurs in a G‐Q‐X3‐R context, while K‐methylation prefers S/T at the first position of the motif. Based on this, we identified novel HEMK2 K‐methylation peptide substrates with sequences taken from human proteins which are methylated with high activity. Since H4K12 methylation by HEMK2 was very low, other protein lysine methyltransferases were examined for their ability to methylate the H4K12 site. We show that SETD6 has a high H4K12me1 methylation activity (about 1000‐times stronger than HEMK2) and this enzyme is mainly responsible for H4K12me1 in DU145 prostate cancer cells.
Improving enzyme functional annotation by integrating in vitro and in silico approaches: The example of histidinol phosphate phosphatases
Authors: Kinateder Thomas , Mayer Carina , Nazet Julian , Sterner Reinhard 
Published: January 2024

AbstractAdvances in sequencing technologies have led to a rapid growth of public protein sequence databases, whereby the fraction of proteins with experimentally verified function continuously decreases. This problem is currently addressed by automated functional annotations with computational tools, which however lack the accuracy of experimental approaches and are susceptible to error propagation. Here, we present an approach that combines the efficiency of functional annotation by in silico methods with the rigor of enzyme characterization in vitro. First, a thorough experimental analysis of a representative enzyme of a group of homologues is performed which includes a focused alanine scan of the active site to determine a fingerprint of function‐determining residues. In a second step, this fingerprint is used in combination with a sequence similarity network to identify putative isofunctional enzymes among the homologues. Using this approach in a proof‐of‐principle study, homologues of the histidinol phosphate phosphatase (HolPase) from Pseudomonas aeruginosa, many of which were annotated as phosphoserine phosphatases, were predicted to be HolPases. This functional annotation of the homologues was verified by in vitro testing of several representatives and an analysis of the occurrence of annotated HolPases in the corresponding phylogenetic groups. Moreover, the application of the same approach to the homologues of the HolPase from the archaeon Nitrosopumilus maritimus, which is not related to the HolPase from P. aeruginosa and was newly discovered in the course of this work, led to the annotation of the putative HolPase from various archaeal species.
Identification of the pyridoxal 5′‐phosphate allosteric site in human pyridox(am)ine 5′‐phosphate oxidase
Authors: Barile Anna , Graziani Claudio , Antonelli Lorenzo , Parroni Alessia , Fiorillo Annarita , di Salvo Martino Luigi , Ilari Andrea , Giorgi Alessandra , Rosignoli Serena , Paiardini Alessandro , Contestabile Roberto , Tramonti Angela 
Published: January 2024

AbstractAdequate levels of pyridoxal 5′‐phosphate (PLP), the catalytically active form of vitamin B6, and its proper distribution in the body are essential for human health. The PLP recycling pathway plays a crucial role in these processes and its defects cause severe neurological diseases. The enzyme pyridox(am)ine 5′‐phosphate oxidase (PNPO), whose catalytic action yields PLP, is one of the key players in this pathway. Mutations in the gene encoding PNPO are responsible for a severe form of neonatal epilepsy. Recently, PNPO has also been described as a potential target for chemotherapeutic agents. Our laboratory has highlighted the crucial role of PNPO in the regulation of PLP levels in the cell, which occurs via a feedback inhibition mechanism of the enzyme, exerted by binding of PLP at an allosteric site. Through docking analyses and site‐directed mutagenesis experiments, here we identified the allosteric PLP binding site of human PNPO. This site is located in the same protein region as the allosteric site we previously identified in the Escherichia coli enzyme homologue. However, the identity and arrangement of the amino acid residues involved in PLP binding are completely different and resemble those of the active site of PLP‐dependent enzymes. The identification of the PLP allosteric site of human PNPO paves the way for the rational design of enzyme inhibitors as potential anti‐cancer compounds.
AlphaFold2‐guided description ofCoBaHMA, a novel family of bacterial domains within the heavy‐metal‐associated superfamily
Authors: Gaschignard Geoffroy , Millet Maxime , Bruley Apolline , Benzerara Karim , Dezi Manuela , Skouri‐Panet Feriel , Duprat Elodie , Callebaut Isabelle 
Published: January 2024

AbstractThree‐dimensional (3D) structure information, now available at the proteome scale, may facilitate the detection of remote evolutionary relationships in protein superfamilies. Here, we illustrate this with the identification of a novel family of protein domains related to the ferredoxin‐like superfold, by combining (i) transitive sequence similarity searches, (ii) clustering approaches, and (iii) the use of AlphaFold2 3D structure models. Domains of this family were initially identified in relation with the intracellular biomineralization of calcium carbonates by Cyanobacteria. They are part of the large heavy‐metal‐associated (HMA) superfamily, departing from the latter by specific sequence and structural features. In particular, most of them share conserved basic amino acids (hence their name CoBaHMA forConservedBasic residuesHMA), forming a positively charged surface, which is likely to interact with anionic partners. CoBaHMA domains are found in diverse modular organizations in bacteria, existing in the form of monodomain proteins or as part of larger proteins, some of which are membrane proteins involved in transport or lipid metabolism. This suggests that the CoBaHMA domains may exert a regulatory function, involving interactions with anionic lipids. This hypothesis might have a particular resonance in the context of the compartmentalization observed for cyanobacterial intracellular calcium carbonates.
Thin‐section‐ and matrix‐free mass spectrometry imaging: Reproducible sample transfer using novel platinum‐coated porous plate formed of glass beads
Authors: Ikeda Takamasa , Kotani Masahiro 
Published: January 2024

RationaleMatrix‐assisted laser desorption/ionization mass spectrometry imaging (MALDI‐MSI) typically requires sample preparation such as sectioning and spraying of the matrix. Sample transfer using a Pt‐coated porous plate formed of glass beads simplifies preparation and enables reproducible MSI measurements.MethodsThe surface of a sintered‐glass‐bead porous plate was coated with Pt on one side of the plate. Polymer additives and the cross‐section of a strawberry were chosen as the sample and transferred to the Pt‐coated surface of the plate. This process was completely thin‐section‐ and matrix‐free. The prepared plates were analyzed using a commercial MALDI time‐of‐flight instrument.ResultsSeveral constituents of the polymer additives (Irgafos 168 and Irganox 1010) and strawberry metabolites (hexose, citric acid, and sucrose) were detected without organic matrices. These ion images were obtained with a special distribution of the retained constituents. Duplicate prepared plates using the same strawberry cross‐section reproduced the ion images.ConclusionsA sample transfer process using a Pt‐coated porous plate formed of glass beads was demonstrated as an alternative preparation method for MSI. This process has the potential to simplify MSI preparation and achieve easily reproducible MSI measurements.
Ion‐Exchange Enabled Dual‐Functional Swarms with Reconfigurability and Magnetic Controllability
Authors: Chen Ling , Feng Kai , Zhang Xinle , Gong Jiang , Qu Jinping , Niu Ran 
Published: January 2024

AbstractIn nature, many organisms are capable of self‐organizing into collective groups through local communications to perform complex tasks that individuals cannot complete. To date, the reported artificial microswarms either rely on toxic chemical reactions for communication or lack the hierarchical controllability and functionality, which is unfavorable for practical applications. To this end, this exploits the ion‐exchange reaction enabled hierarchical swarm composed of cationic ion exchange resin and magnetic microspheres of internal information exchange. The swarm is reconfigurable under magnetic fields, generating ordered structures of controllable mobilities and even reversed hierarchy, able to navigate in confined and complex environments. Moreover, the swarm shows interesting communications among each other, such as merging, splitting, and member exchange, forming multi‐leader groups, living crystals, and complex vortices. Furthermore, the swarm functions as a dual‐functional microreactor, which can load, transport, and release drugs in a pH‐enhanced manner, as well as effectively degrade antibiotics via light‐enhanced Fenton‐like reaction in polluted water. The organized structure of the swarm greatly improves the drug loading/transport efficiency and the local concentration of catalysts for fast pollutant removal. This design lays the foundation for the design of dual‐functional micro/nanorobots for intelligent drug delivery and advanced environmental remediation.
Multi‐Functional Regulation on Buried Interface for Achieving Efficient Triple‐Cation Perovskite Solar Cells
Authors: Ding Yang , Feng Xiangxiang , Feng Erming , Chang Jianhui , Li Hengyue , Long Caoyu , Gao Yuanji , Lu Siyuan , Yang Junliang 
Published: January 2024

AbstractMixed‐cation perovskite solar cells (PSCs) have attracted much attention because of the advantages of suitable bandgap and stability. It is still a challenge to rationally design and modify the perovskite/tin oxide (SnO2) heterogeneous interface for achieving highly efficient and stable PSCs. Herein, a strategy of one‐stone‐for‐three‐birds is proposed to achieve multi‐functional interface regulation via introducing N‐Chlorosuccinimide (NCS) into the solution of SnO2: i) C═O functional group in NCS can induces strong binding affinity to uncoordinated defects (oxygen vacancies, free lead ions, etc) at the buried interface and passivate them; ii) incomplete in situ hydrolysis reactions can occur spontaneously and adjust the pH value of the SnO2 solution to achieve a more matchable energy level; iii) effectively releasing the residual stress of the underlying perovskite. As a result, a champion power conversion efficiency (PCE) of 24.74% is achieved with a device structure of ITO/SnO2/Perovskite/Spiro‐OMeTAD/Ag, which is one of the highest values for cesium‐formamidinium‐methylammonium (CsFAMA) triple cation PSCs. Furthermore, the device without encapsulation can sustain 94.6% of its initial PCE after the storage at room temperature and relative humidity (RH) of 20% for 40 days. The research provides a versatile way to manipulate buried interface for achieving efficient and stable PSCs.
IGZO/WO3−x‐Heterostructured Artificial Optoelectronic Synaptic Devices Mimicking Image Segmentation and Motion Capture
Authors: Wu Tong , Gao Song , Li Yang 
Published: January 2024

AbstractCurrently, artificial neural networks (ANNs) based on memristors are limited to recognizing static images of objects when simulating human visual system, preventing them from performing high‐dimensional information perception, and achieving more complex biomimetic functions is subject to certain limitations. In this work, indium gallium zinc oxide (IGZO)/tungsten oxide (WO3−x)‐heterostructured artificial optoelectronic synaptic devices mimicking image segmentation and motion capture exhibiting high‐performance optoelectronic synaptic responses are proposed and demonstrated. Upon electrical and optical stimulations, the device shows a variety of fundamental and advanced electrical and optical synaptic plasticity. Most importantly, outstanding and repeatable linear synaptic weight changes are attained by the developed memristor. By taking advantage of the notable linear synaptic weight changes, ANNs have been constructed and successfully utilized to demonstrate two applications in the field of computer vision, including image segmentation and object tracking. The accuracy attained by the memristor‐based ANNs is similar to that of the computer algorithms, while its power has been significantly reduced by 105orders of magnitude. With successful emulations of the human brain reactions when observing objects, the demonstrated memristor and related ANNs can be effectively utilized in constructing artificial optoelectronic synaptic devices and show promising potential in emulating human visual perception.