bluuebunny/crossref_metadata_2025_split huggingface dataset:
Entdeckung eines potenten PROTAC ermöglicht die gezielte Ausschaltung der Gerüstfunktionen von FKBP51
Authors: Geiger Thomas M. , Walz Michael , Meyners Christian , Kuehn Angela , Dreizler Johannes K. , Sugiarto Wisely O. , Maciel Edvaldo V. S. , Zheng Min , Lermyte Frederik , Hausch Felix 
Published: November 2023

AbstractDas FK506‐bindende Protein 51 (FKBP51) stellt ein vielversprechendes Wirkstoffziel zur Behandlung von verschiedenen Krankheiten dar, darunter Depression, chronischer Schmerz und Fettleibigkeit. Bisherige FKBP51‐gerichtete Wirkstoffe waren auf die Blockade der FK506‐Bindestelle beschränkt, wodurch Kernfunktionen von FKBP51 jedoch nicht beeinträchtigt werden. Hier präsentieren wir die Entwicklung des ersten FKBP51 Proteolysis Targeting Chimeras (PROTAC), der den Abbau von FKBP51 ermöglicht und damit auch die Gerüstfunktion von FKBP51 ausschalten kann. Die initiale Synthese von 220 FKBP‐gerichteten PROTACs ergab eine Vielzahl aktiver PROTACs für FKBP12, sechs für FKBP51 und keinen für FKBP52. Die Strukturanalyse eines binären FKBP12:PROTAC‐Komplexes offenbarte die molekulare Grundlage für negative Kooperativität. Die Linker‐Optimierung eines FKBP51 PROTACs der ersten Generation führte zur Entwicklung von SelDeg51 mit verbesserter zellulärer Aktivität, Selektivität und hoher Kooperativität. Die Struktur des ternären FKBP51:SelDeg51:VCB Komplexes zeigte, wie SelDeg51 durch Dimerisierung von FKBP51 und VHL Kooperativität herstellt, die dem Bindungsmodus von molekularen Klebern ähnelt. SelDeg51 baut FKBP51 auf effiziente Weise in Zellen ab und reaktiviert den GR‐Signalweg, was die erhöhte Wirksamkeit des Proteinabbaus im Vergleich zur klassischen FKBP51‐Besetzung demonstriert.
Fluorescent naphthalimide containing polyurethanes for the detection and removal of Hg2+/Hg+ and Fe3+ ions
Authors: Xie Meng , Yang Ke , Wang Yuye , Cheng Xinjian 
Published: November 2023

AbstractHeavy metal (HM) pollution is getting worse with the society progress. Identification and separation of HM ions are urgent issues in environmental protection and social development. In this work, 4‐bromo‐1,8‐naphthalic anhydride was first reacted with amino‐propylene glycol to synthesize naphthimide fluorophores bearing two hydroxyl groups. And then, –Br was substituents by 8‐mercaptoquinoline, 2‐mercaptoimidazole, and 4‐mercaptopyridine, respectively. Eventually, it was reacted with 1,5‐naphthalene diisocyanate (NDI) to synthesize fluorescent polyurethane (PU) films through the reaction between –OH and –NCO. It is found that the PU film not only has a specific identification ability to Hg2+/Hg+ and Fe3+ ions, but also can efficiently remove Hg2+/Hg+ and Fe3+ ions through adsorption. In addition, selective identification by fluorescence quenching was investigated. It is due to the photoinduced electron transfer mechanism (PET). Furthermore, the lowest detection limits for Fe3+, Hg2+, and Hg+ were 6.0 × 10−7 M, 4.7 × 10−7 M, and 9.7 × 10−7 M, respectively, which reflected the sensitivity of the probe and made it fluorescence probes. The three fluorescent small molecules were incorporated into PU, which not only retain their identification function, but also serve the purpose of adsorption and separation of HM ions.
#Anatomynotes: A temporal content analysis of anatomy education posts on Instagram
Authors: Hussain Ishrat , Dsouza Ciana , Yip Sharon Wing Lam , Flynn Matthew , Rashid Mohammed Ahmed 
Published: November 2023

AbstractSocial media platforms such as Instagram are becoming increasingly popular sources for students to access anatomy educational resources. This review used content analysis to examine posts under the hashtag #anatomynotes and is the first to map the characteristics of anatomy education posts on Instagram and determine any temporal changes. Sample posts were gathered from April 2019 and April 2021 and categorized according to the technical format, purpose and author credentials. Engagement was recorded in the form of likes and comments. Overall, posts depicting illustrations remained the most popular format within both time periods. Three‐dimensional models saw an increase in popularity with a 62.5% rise. Students remained the most common author type throughout and increased further in 2021 by 25%. Clinician authors and posts focusing on clinical education also increased in 2021 by 17.9% and 227%, respectively. Humor‐based posts saw the greatest increase among the post purposes, with 1000% more recorded in 2021. Engagement overall saw a decline with notably significant reductions in average likes per post among all text‐based posts (−72%, p < 0.0001), all illustrative posts (−51%, p = 0.0013), and a decline in the presence of comments among all text‐based posts (−65.1%, p = 0.0158). These findings highlight that Instagram is a popular platform for facilitating near‐peer teaching while increasingly providing a space where students and clinicians can interact. Additionally, it highlights the benefits of the platform for visually focused learners. However, future research should seek to determine whether Instagram can facilitate deeper learning and have an impact on academic and clinical performance.
Toward a modeling, optimization, and predictive control framework for fed‐batch metabolic cybergenetics
Authors: Espinel‐Ríos Sebastián , Morabito Bruno , Pohlodek Johannes , Bettenbrock Katja , Klamt Steffen , Findeisen Rolf 
Published: November 2023

AbstractBiotechnology offers many opportunities for the sustainable manufacturing of valuable products. The toolbox to optimize bioprocesses includes extracellular process elements such as the bioreactor design and mode of operation, medium formulation, culture conditions, feeding rates, and so on. However, these elements are frequently insufficient for achieving optimal process performance or precise product composition. One can use metabolic and genetic engineering methods for optimization at the intracellular level. Nevertheless, those are often of static nature, failing when applied to dynamic processes or if disturbances occur. Furthermore, many bioprocesses are optimized empirically and implemented with little‐to‐no feedback control to counteract disturbances. The concept of cybergenetics has opened new possibilities to optimize bioprocesses by enabling online modulation of the gene expression of metabolism‐relevant proteins via external inputs (e.g., light intensity in optogenetics). Here, we fuse cybergenetics with model‐based optimization and predictive control for optimizing dynamic bioprocesses. To do so, we propose to use dynamic constraint‐based models that integrate the dynamics of metabolic reactions, resource allocation, and inducible gene expression. We formulate a model‐based optimal control problem to find the optimal process inputs. Furthermore, we propose using model predictive control to address uncertainties via online feedback. We focus on fed‐batch processes, where the substrate feeding rate is an additional optimization variable. As a simulation example, we show the optogenetic control of the ATPase enzyme complex for dynamic modulation of enforced ATP wasting to adjust product yield and productivity.
Stylized facts of performance measures for sustaining the farmer producer companies in India
Authors: Chintamani Bhupesh Gopal , Yadav Hema , Kumari Sneha 
Published: November 2023

AbstractFarmer producer companies (FPCs) have widely transformed the livelihoods of the people and mainly squeezed the income and living standard conditions in the rural sectors, specifically a primary sector engaged majorly with village economies. This article diagnoses the collective cooperative concept and formation of FPCs in the country since their establishment in the year 2008–2021. We utilized secondary data from the Ministry of Corporate Affairs (MCA) and the outcome of the study discusses the state and zone‐wise performance of FPCs in the country. The result found that only a few zones are performing in the FPCs businesses which makes it sustainable. The study further adds the sustainable measures for performance of the FPCs.
Global evidence on the association between environmental, social, and governance disclosures and future earnings risk
Authors: Arif Muhammad , Gan Christopher , Bataineh Hussein Ahmed 
Published: November 2023

AbstractMotivated by growing stakeholder demands for environmental, social and governance (ESG) disclosures and enhanced information transparency, this study investigates the relationship between ESG disclosures and future earnings risk in a globally diverse sample of firms. Using fixed‐effects panel regression models and endogeneity controls, we show that ESG disclosures exhibit a substantial negative impact on earnings risk. The sub‐dimensions, except governance, of ESG disclosures also reveal a negative impact on earnings risk. Notably, the social dimension's impact is economically more pronounced than the other ESG disclosure dimensions, indicating that social issues carry more value in reducing the uncertainty surrounding the future earnings risk of a firm. Besides, higher ESG reporting firms benefit more from reducing future earnings risk than low‐reporting firms. Our findings suggest that enhancing information transparency can help alleviate the agency problem arising from information asymmetry between corporate managers and shareholders. Moreover, higher disclosure in various ESG dimensions can address stakeholders' concerns regarding firm's social and environmental impacts.
New and Ultra‐Rapid Approach for Electrosynthesis of Highly Efficient Catalysts of Poly(para‐phenylenediamine) Supported Copper Oxide for Ethanol Oxidation in Alkaline Medium
Authors: El Attar Anas , Bouljoihel Badr , Ezzahi Amine , El Rhazi Mama 
Published: November 2023

AbstractHerein, a new and simple strategy based on electrochemical cascade reactions was used to prepare copper/poly(para‐phenylenediamine). The catalysts were prepared by a facile one‐pot synthesis via an electrochemical method in a solution containing monomer and copper in a suitable concentration using potentiostatic or galvanostatic mode. Using galvanostatic mode leads to the formation of nanodendritic shape of copper hydroxide‐copper oxide in contrast with potentiostatic mode which leads to a spherical form. The response toward ethanol oxidation was greatly affected by the morphology of the obtained nanocomposite. Indeed, the current density obtained when using potentiostatic mode is about 26.55 mA cm−2 at 1.05 V vs Ag/AgCl. This performance is about 2.4 times higher than of the electrocatalyst prepared by galvanostatic mode (11.09 mA cm−2 at 0.85 V). The durability and long‐term stability of the obtained electrocatalysts were investigated using chronoamperometry and cyclic voltammetry. The decrease in current density is about 19 % and 49 % for electrocatalysts prepared by galvanostatic and potentiostatic mode respectively, after 700 scans. Finally, ex–situ FTIR spectroscopy was conducted in order to understand the reaction mechanism of ethanol oxidation in alkaline medium. It demonstrates that Cu(OH)2−Cu2O@PpPD can perform the complete oxidation of ethanol molecules, leading to the formation of CO2 molecule as the final product. This study highlighted a new simple and facile approach for synthesizing electrocatalysts based on Cu(OH)2−Cu2O@PpPD for alcohol oxidation applications.
Sequence Information Transfer in Oligoarylacetylenes
Authors: Strom Kyle R. , Szostak Jack W. 
Published: November 2023

AbstractThe ability of genetic biopolymers to store and transfer information provides the mechanism for the evolution of function from a population of sequences. Synthetic polymers with the ability to transmit information are exceedingly rare. This work demonstrates template‐directed information transfer in oligoarylacetylene trimers that use reversible covalent bonds to form base pairing interactions. Information was encoded as a sequence of aniline and benzaldehyde subunits linked together by a diethynylbenzene backbone. Trimers formed sequence‐specific, imine‐linked monomer‐template complexes, which could be oligomerized using palladium mediated Sonogashira coupling to generate daughter trimers with complementary sequences.
Studying the Effect of Oxidation on the Thermolysis of (NH4)2WS4 with In‐ and Ex‐Situ Electron Microscopy
Authors: Rowe Casey F. , Allen John T. , Threlkeld Holli L. , Formo Eric V. 
Published: November 2023

AbstractThermolysis is a common technique in materials synthesis; however, oxidation of precursors used in these processes destroys the ability to generate end‐products with the desired composition and structure. Herein, the effects of oxidation on the thermolysis of (NH4)2WS4, a common precursor in the production of WS2 films, are studied utilizing electron microscopy. Specifically, in situ bright field, dark field, and secondary electron images were collected during heating of the aforementioned oxidized precursor from RT to 800 °C in 100 °C steps within a low kV scanning transmission electron microscope. These imaging results detail how the precursor transforms from its largely nondescript room temperature morphology to one having well formed 2D, 1D, and 0D nanostructures. Subsequent ex situ atomic level imaging shows that the 2D and 1D nanomaterials are composed of δ‐WO3 which has grown along its c‐axis, whereas the 0D nanoparticles are made solely of α‐W. Through the combination of both in and ex situ images, we have gained valuable insights into the structural and chemical changes that occur owing to the additional oxygen in the system, as well as the role that precursor density plays on the formation of these as formed nanomaterials.
Association of plasma biomarkers with cognitive function in persons with dementia and cognitively healthy in the Democratic Republic of Congo
Authors: Ikanga Jean , Patel Saranya Sundaram , Roberts Blaine R. , Schwinne Megan , Hickle Sabrina , Verberk Inge M. W. , Epenge Emmanuel , Gikelekele Guy , Tshengele Nathan , Kavugho Immaculee , Mampunza Samuel , Yarasheski Kevin E. , Teunissen Charlotte E. , Stringer Anthony , Levey Allan , Alonso Alvaro 
Published: November 2023

AbstractIntroductionThis study investigates whether plasma biomarkers (Aβ42/40 and p‐tau 181), APS, as well as apolipoprotein E (APOE) proteotype predict cognitive deficits in elderly adults from the Democratic Republic of Congo.MethodsForty‐four with possible AD (pAD) and 41 healthy control (HC) subjects were screened using CSID and AQ, underwent cognitive assessment with the African Neuropsychology Battery (ANB), and provided blood samples for plasma Aβ42, Aβ40, Aβ42/40, and APOE proteotype. Linear and logistic regression were used to evaluate the associations of plasma biomarkers with ANB tests and the ability of biomarkers to predict cognitive status.ResultsPatients with pAD had significantly lower plasma Aβ42/40 levels, higher APS, and higher prevalence of APOE E4 allele compared to HC. Groups did not differ in levels of Aβ40, Aβ42, or P‐tau 181. Results showed that Aβ42/40 ratio and APS were significantly associated with African Naming Test (ANT), African List Memory Test (ALMT), and African Visuospatial Memory Test (AVMT) scores, while the presence of APOE E4 allele was associated with ANT, ALMT, AVMT, and APT scores. P‐tau 181 did not show any significant associations while adjusting for age, education, and gender. APS showed the highest area under the curve (AUC) value (AUC = 0.78, 95% confidence interval [CI]: 0.68–0.88) followed by Aβ42/40 (AUC = 0.75, 95% CI: 0.66–0.86) and APOE E4 (AUC = 0.69 (CI 0.57–0.81) in discriminating pAD from HC.DiscussionThese results demonstrate associations between select plasma biomarker of AD pathology (Aβ42/40), APS, and APOE E4 allele) and ANB test scores and the ability of these biomarkers to differentiate pAD from cognitively normal SSA individuals, consistent with findings reported in other settings.
Heat‐shock protein A12A attenuates oxygen‐glucose deprivation/reoxygenation‐induced human brain microvascular endothelial cell dysfunction via PGC‐1α/SIRT3 pathway
Authors: Li Jun , Shen Shouyin , Shen Haiyan 
Published: November 2023

AbstractIschemic stroke is a life‐threatening brain disease with the leading cause of disability and mortality worldwide. Heat‐shock protein A12A (HSPA12A) is recognized as a neuroprotective target for treating ischemic stroke; however, its regulatory mechanism has been not fully elucidated yet. Human brain microvascular endothelial cells (hBMECs) were induced by oxygen‐glucose deprivation/reoxygenation (OGD/R) to mimic ischemic stroke. Gain‐ and loss‐of‐function experiments were conducted to explore the regulation of HSAPA12 and PGC‐1α. Cell viability, apoptosis, and permeability were assessed by CCK‐8, TUNEL, and transendothelial electrical resistance (TEER) assays, respectively. The expression of HSPA12A and corresponding proteins was measured by western blot. Cell immunofluorescence was adopted to evaluate ZO‐1 expression. THP‐1 cells were applied to adhere hBMECs in vitro to simulate leukocyte adhesion in the brain. HSPA12A was downregulated in OGD/R‐treated hBMECs. HSPA12A overexpression significantly suppressed OGD/R‐induced cell viability loss and apoptosis in hBMECs. Meanwhile, HSPA12A overexpression attenuated blood–brain barrier (BBB) integrity in OGD/R‐induced hBMECs, evidenced by the restored TEER value and the upregulated ZO‐1, occludin, and claudin‐5. HSPA12A also restricted OGD/R‐induced attachment of THP‐1 cells to hBMECs, accompanied with downregulating ICAM‐1 and VCAM‐1. Additionally, OGD/R‐caused downregulation of PGC‐1α/SIRT3 in hBMECs was partly restored by HSPA12A overexpression. Furthermore, the above effects of HSPA12A on OGD/R‐induced hBMECs injury were partly reversed by PGC‐1α knockdown. HSPA12A plays a protective role against OGD/R‐induced hBMECs injury by upregulating PGC‐1α, providing a potential neuroprotective role of HSPA12A in ischemic stroke.
Drivers of legacy soil organic matter decomposition after fire in boreal forests
Authors: Izbicki Brian , Walker Xanthe J. , Baltzer Jennifer L. , Day Nicola J. , Ebert Christopher , Johnstone Jill F. , Pegoraro Elaine , Schuur Edward A. G. , Turetsky Merritt R. , Mack Michelle C. 
Published: November 2023

AbstractBoreal forests harbor as much carbon (C) as the atmosphere and significant amounts of organic nitrogen (N), the nutrient most likely to limit plant productivity in high‐latitude ecosystems. In the boreal biome, the primary disturbance is wildfire, which consumes plant biomass and soil material, emits greenhouse gasses, and influences long‐term C and N cycling. Climate warming and drying is increasing wildfire severity and frequency and is combusting more soil organic matter (SOM). Combustion of surface SOM exposes deeper older layers of accumulated soil material that previously escaped combustion during past fires, here termed legacy SOM. Postfire SOM decomposition and nutrient availability are determined by these layers, but the drivers of legacy SOM decomposition are unknown. We collected soils from plots after the largest fire year on record in the Northwest Territories, Canada, in 2014. We used radiocarbon dating to measure Δ14C (soil age index), soil extractions to quantify N pools and microbial biomass, and a 90‐day laboratory incubation to measure the potential rate of element mineralization and understand patterns and drivers of legacy SOM C decomposition and N availability. We discovered that bulk soil C age predicted C decomposition, where cumulatively, older soil (approximately −450.0‰) produced 230% less C during the incubation than younger soil (~0.0‰). Soil age also predicted C turnover times, with old soil turnover 10 times slower than young soil. We found respired C was younger than bulk soil C, indicating most C enters and leaves relatively quickly, while the older portion remains a stable C sink. Soil age and other indices were unrelated to N availability, but microbial biomass influenced N availability, with more microbial biomass immobilizing soil N pools. Our results stress the importance of legacy SOM as a stable C sink and highlight that soil age drives the pace and magnitude of soil C contributions to the atmosphere between wildfires.
A 5‐year‐old boy with super‐refractory status epilepticus and RANBP2 variant warranting life‐saving hemispherotomy
Authors: Straka Barbora , Koblížek Miroslav , Splítková Barbora , Valkovičová Radka , Krsková Lenka , Kalinová Markéta , Vlčková Markéta , Zámečník Josef , Laššuthová Petra , Sedláčková Lucie , Staněk David , Maulisová Alice , Tichý Michal , Kynčl Martin , Kršek Pavel 
Published: November 2023

AbstractFocal cortical dysplasia (FCD) represents the most common cause of drug‐resistant epilepsy in adult and pediatric surgical series. However, genetic factors contributing to severe phenotypes of FCD remain unknown. We present a patient with an exceptionally rapid development of drug‐resistant epilepsy evolving in super‐refractory status epilepticus. We performed multiple clinical (serial EEG, MRI), biochemical (metabolic and immunological screening), genetic (WES from blood‐ and brain‐derived DNA), and histopathological investigations. The patient presented 1 month after an uncomplicated varicella infection. MRI was negative, as well as other biochemical and immunological examinations. Whole‐exome sequencing of blood‐derived DNA detected a heterozygous paternally inherited variant NM_006267.4(RANBP2):c.5233A>G p.(Ile1745Val) (Chr2[GRCh37]:g.109382228A>G), a gene associated with a susceptibility to infection‐induced acute necrotizing encephalopathy. No combination of anti‐seizure medication led to a sustained seizure freedom and the patient warranted induction of propofol anesthesia with high‐dose intravenous midazolam and continuous respiratory support that however failed to abort seizure activity. Brain biopsy revealed FCD type IIa; this finding led to the indication of an emergency right‐sided hemispherotomy that rendered the patient temporarily seizure‐free. Postsurgically, he remains on antiseizure medication and experiences rare nondisabling seizures. This report highlights a uniquely severe clinical course of FCD putatively modified by the RANBP2 variant.Plain Language SummaryWe report a case summary of a patient who came to our attention for epilepsy that could not be controlled with medication. His clinical course progressed rapidly to life‐threatening status epilepticus with other unusual neurological findings. Therefore, we decided to surgically remove a piece of brain tissue in order to clarify the diagnosis that showed features of a structural brain abnormality associated with severe epilepsy, the focal cortical dysplasia. Later, a genetic variant in a gene associated with another condition, was found, and we hypothesize that this genetic variant could have contributed to this severe clinical course of our patient.