bluuebunny/crossref_metadata_2025 huggingface dataset:
Molekulare Kontrolle der Stabilität und Plastizität von Synapsen
Authors: Mushtaq Zeeshan , Pielage Jan
Published: October 2021

The precise regulation of synaptic connectivity is essential for the processing of information in the brain. Any aberrant loss of synaptic connectivity due to genetic mutations will disrupt information flow in the nervous system and may represent the underlying cause of psychiatric or neurodegenerative diseases. Therefore, identification of the molecular mechanisms controlling synaptic plasticity and maintenance is essential for our understanding of neuronal circuits in development and disease.
Pyrrolysyl-tRNA-Synthetase: Methanogenese und Gencode-Erweiterung
Authors: Koch Nikolaj Georg , Budisa Nediljko
Published: October 2021

Pyrrolysyl-tRNA synthetase (PylRS) is an enzyme of some methanogenic Archaea for the natural incorporation of pyrrolysine into proteins. The discovery of PylRS as a natural tool for genetic code expansion paved the way for site-specific incorporation of non-canonical amino acids (ncAAs) into proteins, with versatile side chains useful in biotechnology. Almost 20 years after the discovery, we describe the journey which led to three distinct classes of PylRSs with unique ncAA recognitions.
Vorsicht, Verwundung! Reizweiterleitung mit mechanosensitiven Proteinen
Authors: Wudick Michael M.
Published: October 2021

Being sessile, plants are exposed to adverse stresses, including wounding by insects. Albeit lacking experimental evidence, one hypothesis predicted involvement of hydro-electric signals in wound signaling. Now, we could show that the mechanosensitive anion channel MSL10 is necessary for wound-induced long-distance signaling in plants. By linking mechano-sensing, ion fluxes, membrane depolarization and electrical signal propagation, MSL10 might integrate hydraulic and electric wound signals.
Trepostome bryozoans buck the trend and ignore calcite-aragonite seas
Authors: Key Marcus M. , Wyse Jackson Patrick N. , Reid Catherine M.
Published: October 2021

Trepostome bryozoan skeletalisation did not passively respond to changes in seawater chemistry associated with calcite-aragonite seas. According to Stanley and others, trepostome bryozoans were passive hypercalcifiers. However, if this was the case, we would expect their degree of calcitic colony calcification to have decreased across the Calcite I Sea to the Aragonite II Sea at its transition in the Middle Mississippian. Data from the type species of all 184 trepostome genera from the Early Ordovician to the Late Triassic were utilised to calculate the Bryozoan Skeletal Index (BSI) as a proxy for the degree of calcification. BSI values and genus-level diversity did not decrease across the transition from the Calcite I Sea to the Aragonite II Sea. Nor were there any changes in the number of genus originations and extinctions. This suggests that trepostome bryozoans were not passive hypercalcifiers but active biomineralisers that controlled the mineralogy and robustness of their skeletons regardless of changes in seawater chemistry.
Development of the UKESM-TOPAZ Earth System Model (Version 1.0) and Preliminary Evaluation of its Biogeochemical Simulations
Authors: Lee Hyomee , Moon Byung-Kwon , Jung Hyun-Chae , Park Jong-Yeon , Shim Sungbo , La Nary , Kim Ah-Hyun , Yum Seong Soo , Ha Jong-Chul , Byun Young-Hwa , Sung Hyun Min , Lee Johan
Published: October 2021

Earth system models (ESMs) comprise various Earth system components and simulate the interactions between these components. ESMs can be used to understand climate feedbacks between physical, chemical, and biological processes and predict future climate. We developed a new ESM, UKESM-TOPAZ, by coupling the UK ESM (UKESM1) and the Tracers of Phytoplankton with Allometric Zooplankton (TOPAZ) biogeochemical module. We then compared the preliminary simulated biogeochemical variables, which were conducted over a period of 70 years, using observational and existing UKESM1 model data. Similar to UKESM1, the newly developed UKESM-TOPAZ closely simulated the relationship between the El Niño-Southern Oscillation and chlorophyll concentration anomalies during the boreal winter. However, there were differences in the chlorophyll distributions in the eastern equatorial Pacific between the two models, which were due to dissolved iron, as this value was higher in UKESM-TOPAZ than in UKESM1. In a mean field analysis, the distributions of the major marine biogeochemical variables in UKESM-TOPAZ (i.e., nitrate, silicate, dissolved oxygen, dissolved inorganic carbon, and alkalinity) were not significantly different from those of UKESM1, likely because the models share the same initial conditions. Our results indicate that TOPAZ has a simulation performance that does not lag behind UKESM1’s basic biogeochemical model (Model of Ecosystem Dynamics, nutrient Utilisation, Sequestration, and Acidification; MEDUSA). The UKESM-TOPAZ model can simulate the variability of the observed Niño 3.4 and 4 indices more closely than UKESM1. Thus, the UKESM-TOPAZ model can be used to deepen our understanding of the Earth system and to estimate ESM uncertainty.
Exploring the coupling relationship between hydrocarbon generation of continental shale and nanopore structure evolution—A case study of Shahejie formation in Bohai Bay Basin
Authors: Zheng Youwei , Fu Deliang , Qin Jianqiang , Liu Xianrong , Tian Bing , Sun Lina
Published: October 2021

The nano-scale pore structure of shale is closely related to the self-generated and self-accumulated shale oil and gas. The Bohai Bay Basin is a crucial oil-bearing basin in eastern China, and the Paleogene Shahejie Formation is the most important source rock section in this area. In order to study the internal relationship between hydrocarbon generation evolution and pore structure characteristics of source rocks, we conducted hydrocarbon generation simulation tests with a closed gold tube system, and heated up original rocks from Shahejie Formation in Laizhou Bay Sag, southern Bohai Bay Basin, from 290 °C to 440°C at different heating rates. Besides, we carried out low-temperature N2 adsorption experiments on sample residues, and measured their pore structure characteristic parameters. The results show that with the increase of simulated temperature, the specific surface area and pore volume of nano-pores below 10 nm (which are mainly organic pores) decrease first and then increase, while those of nano-pores above 10 nm increase all the way. The evolution trend of total specific surface area and pore volume is mainly controlled by pores below 10 nm which are mainly organic pores, especially micropores below 2 nm. There are two main factors affecting the development of inorganic pores: (1) Dissolution of organic acids produced by pyrolysis of organic matter in hydrocarbon-generation evolution; (2) Deformation of crystal structure of mineral components under the combined action of temperature and pressure. The experimental results at different heating rates demonstrate that rapid settlement under geological conditions is not conducive to the development of nano-pores, especially micro-pores composed of organic pores.
Inhibiting wax deposition using palm oil additives
Authors: Ragunathan Thevaruban , Wood Colin D. , Husin Hazlina
Published: October 2021

Among the flow assurance problems that the petroleum industry faces, the deposition of paraffin waxes on to the wall of the pipeline is the most challenging. The challenge arises when the crude oil temperature decreases below the wax appearance temperature which prompts wax crystallization in the crude oil. An efficient method in remedying paraffin wax deposition is the utilization of chemical inhibitors. However, currently used chemical inhibitors are costly and environmentally harmful if a spillage occurs. Therefore, the use of biodegradable or environmentally friendly inhibitors as potential chemical inhibitors is being studied by various researchers. This study investigated oleic acid, poly (ethylene-co-vinyl acetate) (EVA) and triethanolamine (TEA) as inhibitors that perform based on the van der Waals intermolecular interaction between the main wax component molecule eicosane C20H42 using molecular dynamics simulations Material Studio 8.0 software package. In order to analyse the desired structural property which is the radial distribution function (RDF), COMPASS force field was used. The RDF and g(r) function portrayed the functional atoms which aid in inhibiting the agglomeration and crystallization of the wax crystal formation. The presence of a carbonyl oxygen in oleic acid plays a vital role to inhibit the wax formation through the van der Waals interaction between active hydrogen atoms in eicosane molecule. Therefore, the chances of wax inhibition in eicosane are higher by introducing oleic acid as an inhibitor as compared to EVA and TEA. The results were then validated experimentally utilizing a cold finger technique under static condition.
Novel hybrid machine learning optimizer algorithms to prediction of fracture density by petrophysical data
Authors: Rajabi Meysam , Beheshtian Saeed , Davoodi Shadfar , Ghorbani Hamzeh , Mohamadian Nima , Radwan Ahmed E. , Alvar Mehdi Ahmadi
Published: October 2021

One of the challenges in reservoir management is determining the fracture density (FVDC) in reservoir rock. Given the high cost of coring operations and image logs, the ability to predict FVDC from various petrophysical input variables using a supervised learning basis calibrated to the standard well is extremely useful. In this study, a novel machine learning approach is developed to predict FVDC from 12-input variable well-log based on feature selection. To predict the FVDC, combination of two networks of multiple extreme learning machines (MELM) and multi-layer perceptron (MLP) hybrid algorithm with a combination of genetic algorithm (GA) and particle swarm optimizer (PSO) has been used. We use a novel MELM-PSO/GA combination that has never been used before, and the best comparison result between MELM-PSO-related models with performance test data is RMSE = 0.0047 1/m; R2 = 0.9931. According to the performance accuracy analysis, the models are MLP-PSO < MLP-GA < MELM-GA < MELM-PSO. This method can be used in other fields, but it must be recalibrated with at least one well. Furthermore, the developed method provides insights for the use of machine learning to reduce errors and avoid data overfitting in order to create the best possible prediction performance for FVDC prediction.
Case report. Geschokt door de wachttijd: ESWL bij blaasstenen
Authors: Zeelenberg Anna M. , Hendriks Nora , Schout Barbara M. A. , van der Spruit Joost A.
Published: October 2021

Samenvatting

De behandeling van eerste keuze voor vesicale stenen is de transurethrale cystolithotripsie (TUCL). Door de COVID-19-pandemie kampen ziekenhuizen echter met lange wachttijden voor – onder meer – deze operaties. Daarnaast komen sommige patiënten niet in aanmerking voor een operatie door hun comorbiditeit. In de jaren negentig van de vorige eeuw was extracorporele shockwave lithotripsie (ESWL) een veel gebruikte, veilige behandelmethode voor blaasstenen. Toen TUCL effectiever bleek, is ESWL voor blaasstenen echter in de vergetelheid geraakt. ESWL is poliklinisch uit te voeren, waardoor wachttijden korter zijn dan die voor operatieve ingrepen. Gedurende de COVID-19-pandemie hebben we enkele patiënten met blaasstenen behandeld met ESWL. We concluderen dat ESWL een geschikt alternatief is voor de TUCL bij geselecteerde patiënten, maar dat voor een effectieve behandeling meerdere ESWL-procedures nodig zijn.
Efficient photocatalytic hydrogen production over Ce/ZnO from aqueous methanol solution
Authors: Patil Ashokrao B. , Jadhav Balaso D. , Bhoir Poonam V.
Published: October 2021

Ce/ZnO crystallites along with bare ZnO were prepared by solution free mechanochemical method and characterized with powder XRD, SEM, EDX, XPS, UV–Visible and Photoluminescence (PL) spectra. The visible light photocatalytic performance of these materials was investigated for H2 evolution with the aqueous 10vol% methanol solution under one sun conditions using solar simulator. X-ray diffraction data suggests the hexagonal wurtzite structure for Ce/ZnO crystallites and the incorporation of Ce4+ ion in ZnO is supported by the shifting of XRD peaks to lower Bragg angles that indicate lattice expansion. With the increase of Ce content in ZnO, the crystallite size of Ce/ZnO decreases and the specific surface area increases. UV–Visible spectra propose the decrease in optical band gap of Ce incorporated ZnO with the increase of Ce content up to 3 mol. %. The XPS analysis supports the incorporation of Ce4+ in Ce/ZnO. The PL spectra propose that, with the insertion of Ce ions into ZnO, intensity of UV emission band decreases that reflects the low recombination rate of photogenerated charge carriers, which is responsible for higher photocatalytic H2 production. The extent of hydrogen production is affected by calcination temperature of Ce/ZnO. 2 mol. % Ce incorporated ZnO calcined at 600 °C produces43 μmolh−1 g−1 of hydrogen.
Extended-release calcifediol in stage 3–4 chronic kidney disease: a new therapy for the treatment of secondary hyperparathyroidism associated with hypovitaminosis D
Authors: Cozzolino Mario , Minghetti Paola , Navarra Pierluigi
Published: October 2021

A high percentage of patients with chronic kidney disease have hypovitaminosis D, which is a driver of secondary hyperparathyroidism and an important factor in chronic kidney disease-mineral and bone disorder. Vitamin D deficiency (serum total 25-OH vitamin D levels < 30 ng/mL) occurs early in the course of chronic kidney disease and treatment guidelines recommend early intervention to restore 25-OH vitamin D levels as a first step to prevent/delay the onset/progression of secondary hyperparathyroidism. The vitamin D forms administered to replace 25-OH vitamin D include cholecalciferol, ergocalciferol, and immediate- or extended-release formulations of calcifediol. Most patients with intermediate-stage chronic kidney disease will develop secondary hyperparathyroidism before dialysis is required. Control of parathyroid hormone levels becomes a major focus of therapy in these patients. This article focuses on the position of extended-release calcifediol in the treatment of patients with stage 3–4 chronic kidney disease and secondary hyperparathyroidism with hypovitaminosis D. Several characteristics of extended-release calcifediol support its use in the intermediate stages of chronic kidney disease. The pharmacokinetics of extended-release calcifediol make it effective for replenishing 25-OH vitamin D levels, with minimal impact on vitamin D catabolism from fibroblast-growth factor-23 and CYP24A1 upregulation. Extended-release calcifediol increases circulating 25-OH vitamin D levels in a dose-dependent manner and lowers parathyroid hormone levels by a clinically relevant extent, comparable to what can be achieved by administering active vitamin D analogues, though with a lower risk of hypercalcaemia and hyperphosphataemia. Active vitamin D analogues are reserved for patients undergoing dialysis or pre-dialysis patients with severe progressive secondary hyperparathyroidism.

Graphic abstract
Hyperledger blockchain enabled secure medical record management with deep learning-based diagnosis model
Authors: Sammeta Naresh , Parthiban Latha
Published: October 2021

In recent times, advanced developments in healthcare sector result in the generation of massive amounts of electronic health records (EHRs). EHR system enables the data owner to control his/her data and share it with designated people. The vast volume of data in the healthcare system makes it difficult for data to ensure security and diagnostic processes. To resolve these issues, this paper develops a new hyperledger blockchain enabled secure medical data management with deep learning (DL)-based diagnosis (HBESDM-DLD) model. The presented model involves distinct stages of operations such as encryption, optimal key generation, hyperledger blockchain-based secure data management, and diagnosis. The presented model allows the user to control access to data, permit the hospital authorities to read/write data, and alert emergency contacts. For encryption, SIMON block cipher technique is applied. At the same time, to improve the efficiency of the SIMON technique, a group teaching optimization algorithm (GTOA) is applied for the optimal key generation of the SIMON technique. Moreover, the sharing of medical data takes place using multi-channel hyperledger blockchain that utilizes a blockchain for storing patient visit data and for the medical institutions to record links for the EHRs saved in external databases. Once the data are decrypted at the receiving end, finally, variational autoencoder (VAE)-based diagnostic model is applied to detect the existence of the diseases. The performance validation of the HBESDM-DLD model takes place on benchmark medical dataset and the results are inspected under various performance measures. The experimental results proves that the HBESDM-DLD methodology is superior to state-of-the-art methods.
The differences between the horizontal membership function used in multidimensional fuzzy arithmetic and the inverse membership function used in gradual arithmetic
Authors: Piegat Andrzej , Pluciński Marcin
Published: October 2021

In the last few years, the number of applications of the multidimensional fuzzy arithmetic (MFA) and the multidimensional interval arithmetic is expanding. Authors of new papers about applications of MFA are often faced with comments from other researchers, especially the gradual arithmetic (GA) proponents, that the horizontal membership function (HMF) used in MFA is the same as the inverse membership function (InvMF) used in GA, and that MFA itself adds nothing new to the fuzzy arithmetic. This view leads to unfair evaluations of scientific papers about MFA applications submitted to scientific journals and to unnecessary disagreements between MFA and GA proponents. The purpose of this paper is to carefully analyze the two types of functions (HMF and InvMF) and to demonstrate their important differences. The basic and decisive difference is the dimensionality of both functions, which is illustrated by examples. It should also be added that HMF has proven its usefulness in solving difficult problems such as: systems of fuzzy equations or fuzzy differential equations, which is confirmed by numerous publications. The paper enable the reader to have a deeper understanding of the multidimensional fuzzy arithmetic.
Delirium screening with 4AT in patients aged 65 years and older admitted to the Emergency Department with suspected sepsis: a prospective cohort study
Authors: Myrstad Marius , Kuwelker Kanika , Haakonsen Sigurd , Valebjørg Therese , Langeland Nina , Kittang Bård Reiakvam , Hagberg Guri , Neerland Bjørn Erik , Bakken Marit Stordal
Published: October 2021

Purpose

We aimed to study the use of The 4 ‘A’s test (4AT), a rapid delirium screening tool, performed upon Emergency Department (ED) admission, and to characterize older patients admitted to the ED with and without sepsis in terms of delirium features.

Methods

In this prospective cohort study, we included patients aged ≥ 65 years, admitted to the ED with suspected sepsis. ED nurses and doctors performed delirium screening with 4AT within two hours after ED admission, and registered the time spent on the screening in each case. Sepsis and delirium during the hospital stay were diagnosed retrospectively, according to recommended diagnosis criteria.

Results

Out of the 196 patients included (mean age 81 years, 60% men), 100 patients fulfilled the sepsis diagnosis criteria. The mean 4AT screening time was 2.5 Minutes. In total, 114 patients (58%) had a 4AT score ≥ 1, indicating cognitive impairment, upon ED admission. Sepsis patients more often had a 4AT score ≥ 4, indicating delirium, than patients without sepsis (40% vs. 26%, p < 0.05). Out of the 100 patients with sepsis, 68 (68%) had delirium during the hospital stay, as compared to 34 out of 96 patients (35%) without sepsis (p < 0.05).

Conclusion

Delirium screening upon ED admission, using 4AT, was feasible among patients aged ≥ 65 years admitted with suspected sepsis. Two out of three patients had at least one feature of delirium upon admission. The prevalence of delirium during the hospital stay was high, particularly in patients with sepsis.

Graphic abstract
CrMnFeCoNi high entropy alloys with carbon and nitrogen: mechanical properties, wear and corrosion resistance
Authors: Chmielak L. , Mujica Roncery L. , Niederhofer P. , Weber S. , Theisen W.
Published: October 2021

The use of interstitial elements has been a key factor for the development of different kinds of steels. However, this aspect has been little explored in the field of high entropy alloys (HEAs). In this investigation, the effect of carbon and nitrogen in a near-equiatomic CrMnFeCoNi HEA is studied, analyzing their impact on the microstructure, and mechanical properties from 77K to 673K, as well as wear, and corrosion resistance. Carbon and nitrogen are part of the FCC solid solution and contribute to the formation of precipitates. An increase in the yield and ultimate tensile strength accompanied with a decrease in the ductility are the main effects of C and N. The impact toughness of the interstitial-free material is higher than that of C and C+N alloyed systems. Compared to CrNi and CrMn austenitic steels, the wear resistance of the alloys at room temperature is rather low. The surface corrosion resistance of HEAs is comparable to austenitic steels; nevertheless HEAs are more susceptible to pitting in chloride containing solutions.
The impact of the consumer’s decision on the life cycle assessment of organic pasta
Authors: Gnielka Anna Elisabeth , Menzel Christof
Published: October 2021

Every consumer’s decision has an impact on the environment, and even basic food products such as pasta have an impact due to their high consumption rates. Factors that can be influenced by the consumer include the preparation (cooking), last mile and packaging phases. The last mile has not been considered in most studies but contributes considerably to the environmental impact of pasta. The three phases and their environmental impact on the life cycle of pasta are analyzed in this cradle-to-grave life cycle assessment. The focus of the study lies on the impact categories climate change, agricultural land occupation, fossil depletion, water depletion, freshwater eutrophication and freshwater ecotoxicity. Inventory data were taken from other studies, were collected in cooperation with a zero-packaging organic grocery store in Germany or were gained in test series. Our results show that the preparation of pasta has the greatest environmental impact (over 40% in the impact categories climate change and fossil depletion and over 50% in the impact category freshwater eutrophication), followed by the last mile (over 20% in the impact categories climate change and fossil depletion) and lastly the packaging (nearly 9% in the impact categories freshwater eutrophication and freshwater ecotoxicity). Based on our study´s results, we provide some recommendations for minimizing the environmental impacts of pasta.
Production of oxalic acid from sawdust using coal fly ash as a catalyst
Authors: Kuipa O. , Kasungasunge G. , Kuipa P. K.
Published: October 2021

The production of oxalic acid from sawdust using a mixture of strong nitric acid and concentrated sulphuric acid with coal fly ash as a catalyst has been explored. Operating parameters affecting the reaction were determined to be temperature, mesh size and amount of fly ash catalyst, time and the$${\text{HNO}}_{3} :{\text{H}}_{2} {\text{SO}}_{4}$$HNO3:H2SO4ratio. A maximum oxalic acid yield of 84% was obtained using a mixture of 60%$${\text{HNO}}_{3} {\text{ and }}40 \%{\text{ H}}_{2} {\text{SO}}_{4}$$HNO3and40%H2SO4at 70 °C and a reaction time of 150 minutes. Coal fly ash with particle size of 50–100 μm proved to be a suitable and efficient catalyst, and the optimum quantity of catalyst employed was 5g of fly ash for every 100g of sawdust.
Projekt abgebrochen, Folgeband nicht erschienen. Unvollendete Werke in der Wissenschaftsgeschichte der Geschichtswissenschaft
Authors: Weber Wolfgang E. J.
Published: October 2021

Die Konkurrenz zwischen Wissenschaftstheorie (Historik) und Wissenschaftsgeschichte der Geschichtswissenschaft scheint heute zugunsten der Wissenschaftsgeschichte entschieden. Dort herrscht allerdings zumindest in Deutschland noch der individualbiografische Ansatz vor. Wie innovativ dennoch auch dieser Zugriff sein kann, belegt die einschlägige jüngste Monografie von Heinz Duchhardt. Sie befasst sich mit den inneren und äußeren Ursachen nicht zustande gekommener oder abgebrochener Geschichtswerke und dem psychisch-ethischen Umgang der verantwortlichen Historiker mit ihrem „Versagen“. Das Review Essay stellt diese Perspektive kritisch in den übergreifenden wissenschaftshistorischen Kontext und macht weiterführende Forschungsvorschläge.
Increase of 5-HT levels is induced both in mouse brain and HEK-293 cells following their exposure to a non-viral tryptophan hydroxylase construct
Authors: Tesoro-Cruz Emiliano , Manuel-Apolinar Leticia , Oviedo Norma , Orozco-Suárez Sandra , Crespo Ramírez Minerva , Bekker-Méndez Vilma Carolina , Aguirre-García M. Magdalena , Rojas-Osornio Sandra Angélica , Paredes-Cervantes Vladimir , Pérez de la Mora Miguel
Published: October 2021

Tryptophan hydroxylase type 2 (Tph2) is the rate-limiting enzyme for serotonin (5-HT) biosynthesis in the brain. Dysfunctional Tph2 alters 5-HT biosynthesis, leading to a deficiency of 5-HT, which could have repercussions on human behavior. In the last decade, several studies have associated polymorphisms of the TPH2 gene with suicidal behavior. Additionally, a 5-HT deficiency has been implicated in various psychiatric pathologies, including alcoholism, impulsive behavior, anxiety, and depression. Therefore, the TPH2 gene could be an ideal target for analyzing the effects of a 5-HT deficiency on brain function. The aim of this study was to use the construct pIRES-hrGFP-1a-Tph2-FLAG to treat CD1-male mice and to transfect HEK-293-cells and then to evaluate whether this treatment increases 5-HT production. 5-HT levels were enhanced 48 h post-transfection, in HEK-293 cells. Three days after the ocular administration of pIRES-hrGFP-1a-Tph2-FLAG to mice, putative 5-HT production was significantly higher than in the control in both hypothalamus and amygdala, but not in the brainstem. Further research will be needed on the possible application of this treatment for psychiatric diseases involving a Tph2 dysfunction or serotonin deficiency.
Mechanisms of neuroplasticity linking early adversity to depression: developmental considerations
Authors: Ho Tiffany C. , King Lucy S.
Published: October 2021

Early exposure to psychosocial adversity is among the most potent predictors of depression. Because depression commonly emerges prior to adulthood, we must consider the fundamental principles of developmental neuroscience when examining how experiences of childhood adversity, including abuse and neglect, can lead to depression. Considering that both the environment and the brain are highly dynamic across the period spanning gestation through adolescence, the purpose of this review is to discuss and integrate stress-based models of depression that center developmental processes. We offer a general framework for understanding how psychosocial adversity in early life disrupts or calibrates the biobehavioral systems implicated in depression. Specifically, we propose that the sources and nature of the environmental input shaping the brain, and the mechanisms of neuroplasticity involved, change across development. We contend that the effects of adversity largely depend on the developmental stage of the organism. First, we summarize leading neurobiological models that focus on the effects of adversity on risk for mental disorders, including depression. In particular, we highlight models ofallostatic load, acceleration maturation, dimensions of adversity, and sensitive or critical periods. Second, we expound on and review evidence for the formulation that distinct mechanisms of neuroplasticity are implicated depending on the timing of adverse experiences, and that inherent within certain windows of development are constraints on the sources and nature of these experiences. Finally, we consider other important facets of adverse experiences (e.g., environmental unpredictability, perceptions of one’s experiences) before discussing promising research directions for the future of the field.
ECT-induced cognitive side effects are associated with hippocampal enlargement
Authors: Argyelan Miklos , Lencz Todd , Kang Simran , Ali Sana , Masi Paul J. , Moyett Emily , Joanlanne Andrea , Watson Philip , Sanghani Sohag , Petrides Georgios , Malhotra Anil K.
Published: October 2021

Electroconvulsive therapy (ECT) is of the most effective treatments available for treatment-resistant depression, yet it is underutilized in part due to its reputation of causing cognitive side effects in a significant number of patients. Despite intensive neuroimaging research on ECT in the past two decades, the underlying neurobiological correlates of cognitive side effects remain elusive. Because the primary ECT-related cognitive deficit is memory impairment, it has been suggested that the hippocampus may play a crucial role. In the current study, we investigated 29 subjects with longitudinal MRI and detailed neuropsychological testing in two independent cohorts (N = 15/14) to test if volume changes were associated with cognitive side effects. The two cohorts underwent somewhat different ECT study protocols reflected in electrode placements and the number of treatments. We used longitudinal freesurfer algorithms (6.0) to obtain a bias-free estimate of volume changes in the hippocampus and tested its relationship with neurocognitive score changes. As an exploratory analysis and to evaluate how specific the effects were to the hippocampus, we also calculated this relationship in 41 other areas. In addition, we also analyzed cognitive data from a group of healthy volunteers (N = 29) to assess practice effects. Our results supported the hypothesis that hippocampus enlargement was associated with worse cognitive outcomes, and this result was generalizable across two independent cohorts with different diagnoses, different electrode placements, and a different number of ECT sessions. We found, in both cohorts, that treatment robustly increased the volume size of the hippocampus (Cohort 1: t = 5.07, Cohort 2: t = 4.82; p < 0.001), and the volume increase correlated with the neurocognitive T-score change. (Cohort 1: r = −0.68, p = 0.005; Cohort 2: r = −0.58; p = 0.04). Overall, our research indicates that novel treatment methods serving to avoid hippocampal volume increase may result in a better side effect profile.
Dysregulated APOBEC3G causes DNA damage and promotes genomic instability in multiple myeloma
Authors: Talluri Srikanth , Samur Mehmet K. , Buon Leutz , Kumar Subodh , Potluri Lakshmi B. , Shi Jialan , Prabhala Rao H. , Shammas Masood A. , Munshi Nikhil C.
Published: October 2021

Multiple myeloma (MM) is a heterogeneous disease characterized by significant genomic instability. Recently, a causal role for the AID/APOBEC deaminases in inducing somatic mutations in myeloma has been reported. We have identified APOBEC/AID as a prominent mutational signature at diagnosis with further increase at relapse in MM. In this study, we identified upregulation of several members of APOBEC3 family (A3A, A3B, A3C, and A3G) with A3G, as one of the most expressed APOBECs. We investigated the role of APOBEC3G in MM and observed that A3G expression and APOBEC deaminase activity is elevated in myeloma cell lines and patient samples. Loss-of and gain-of function studies demonstrated that APOBEC3G significantly contributes to increase in DNA damage (abasic sites and DNA breaks) in MM cells. Evaluation of the impact on genome stability, using SNP arrays and whole genome sequencing, indicated that elevated APOBEC3G contributes to ongoing acquisition of both the copy number and mutational changes in MM cells over time. Elevated APOBEC3G also contributed to increased homologous recombination activity, a mechanism that can utilize increased DNA breaks to mediate genomic rearrangements in cancer cells. These data identify APOBEC3G as a novel gene impacting genomic evolution and underlying mechanisms in MM.
Myosin 1f-mediated activation of microglia contributes to the photoreceptor degeneration in a mouse model of retinal detachment
Authors: Wang Yimin , Zhao Xiaohuan , Gao Min , Wan Xiaoling , Guo Yinong , Qu Yingying , Chen Yuhong , Li Tong , Liu Haiyun , Jiang Mei , Wang Feng , Sun Xiaodong
Published: October 2021

Photoreceptor death and neurodegeneration is the leading cause of irreversible vision loss. The inflammatory response of microglia plays an important role in the process of neurodegeneration. In this study, we chose retinal detachment as the model of photoreceptor degeneration. We found Myosin 1f was upregulated after retinal detachment, and it was specifically expressed in microglia. Deficiency of myosin 1f protected against photoreceptor apoptosis by inhibiting microglia activation. The elimination of microglia can abolish the protective effect of myosin 1f deficiency. After stimulation by LPS, microglia with myosin 1f deficiency showed downregulation of the MAPK and AKT pathways. Our results demonstrated that myosin 1f plays a crucial role in microglia-induced neuroinflammation after retinal injury and photoreceptor degeneration by regulating two classic inflammatory pathways and thereby decreasing the expression of inflammatory cytokines. Knockout of myosin 1f reduces the intensity of the immune response and prevents cell death of photoreceptor, suggesting that myosin 1f can be inhibited to prevent a decline in visual acuity after retinal detachment.
AMPK agonist alleviate renal tubulointerstitial fibrosis via activating mitophagy in high fat and streptozotocin induced diabetic mice
Authors: Han Ya-chun , Tang Shi-qi , Liu Yu-ting , Li Ai-mei , Zhan Ming , Yang Ming , Song Na , Zhang Wei , Wu Xue-qin , Peng Can-hui , Zhang Hao , Yang Shikun
Published: October 2021

Renal tubulointerstitial fibrosis was a crucial pathological feature of diabetic nephropathy (DN), and renal tubular injury might associate with abnormal mitophagy. In this study, we investigated the effects and molecular mechanisms of AMPK agonist metformin on mitophagy and cellular injury in renal tubular cell under diabetic condition. The high fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice model and HK-2 cells were used in this study. Metformin was administered in the drinking water (200 mg/kg/d) for 24 weeks. Renal tubulointerstitial lesions, oxidative stress and some indicators of mitophagy (e.g., LC3II, Pink1, and Parkin) were examined both in renal tissue and HK-2 cells. Additionally, compound C (an AMPK inhibitor) and Pink1 siRNA were applied to explore the molecular regulation mechanism of metformin on mitophagy. We found that the expression of p-AMPK, Pink1, Parkin, LC3II, and Atg5 in renal tissue of diabetic mice was decreased obviously. Metformin reduced the levels of serum creatinine, urine protein, and attenuated renal oxidative injury and fibrosis in HFD/STZ induced diabetic mice. In addition, Metformin reversed mitophagy dysfunction and the over-expression of NLRP3. In vitro pretreatment of HK-2 cells with AMPK inhibitor compound C or Pink1 siRNA negated the beneficial effects of metformin. Furthermore, we noted that metformin activated p-AMPK and promoted the translocation of Pink1 from the cytoplasm to mitochondria, then promoted the occurrence of mitophagy in HK-2 cells under HG/HFA ambience. Our results suggested for the first time that AMPK agonist metformin ameliorated renal oxidative stress and tubulointerstitial fibrosis in HFD/STZ-induced diabetic mice via activating mitophagy through a p-AMPK-Pink1-Parkin pathway.
TDAG51 induces renal interstitial fibrosis through modulation of TGF-β receptor 1 in chronic kidney disease
Authors: Carlisle Rachel E. , Mohammed-Ali Zahraa , Lu Chao , Yousof Tamana , Tat Victor , Nademi Samera , MacDonald Melissa E. , Austin Richard C. , Dickhout Jeffrey G.
Published: October 2021

Chronic kidney disease (CKD) is characterized by the gradual loss of renal function and is a major public health concern. Risk factors for CKD include hypertension and proteinuria, both of which are associated with endoplasmic reticulum (ER) stress. ER stress-induced TDAG51 protein expression is increased at an early time point in mice with CKD. Based on these findings, wild-type and TDAG51 knock-out (TDKO) mice were used in an angiotensin II/deoxycorticosterone acetate/salt model of CKD. Both wild-type and TDKO mice developed hypertension, increased proteinuria and albuminuria, glomerular injury, and tubular damage. However, TDKO mice were protected from apoptosis and renal interstitial fibrosis. Human proximal tubular cells were used to demonstrate that TDAG51 expression induces apoptosis through a CHOP-dependent mechanism. Further, a mouse model of intrinsic acute kidney injury demonstrated that CHOP is required for ER stress-mediated apoptosis. Renal fibroblasts were used to demonstrate that TGF-β induces collagen production through an IRE1-dependent mechanism; cells treated with a TGF-β receptor 1 inhibitor prevented XBP1 splicing, a downstream consequence of IRE1 activation. Interestingly, TDKO mice express significantly less TGF-β receptor 1, thus, preventing TGF-β-mediated XBP1 splicing. In conclusion, TDAG51 induces apoptosis in the kidney through a CHOP-dependent mechanism, while contributing to renal interstitial fibrosis through a TGF-β-IRE1-XBP1 pathway.
Requirement of transcription factor NME2 for the maintenance of the stemness of gastric cancer stem-like cells
Authors: Qi Yaxin , Wei Jun , Zhang Xiaobo
Published: October 2021

Cancer stem cells (CSCs), which can self-renew and produce heterogeneous cancer cells, are the key factors during tumorigenesis. Transcription factors take essential effects on CSCs. However, the role of transcription factors in regulating the stemness of gastric cancer stem-like cells has not been well explored. In this investigation, it was found that transcription factor NME2 (NME/NM23 nucleoside diphosphate kinase 2) was upregulated in gastric cancer stem-like cells that sorted from the solid tumors of patients with gastric cancer and gastric cancer cell lines. NME2 could preserve the stemness of gastric cancer stem-like cells via suppressing their apoptosis. In vitro and in vivo data revealed that NME2 was crucial for maintaining the stemness of gastric cancer stem cells by enhancing the expression of anti-apoptosis genes. Consequently, our data contributed a new perspective to the relationship between transcription factor and the stemness maintenance of gastric cancer stem cells.
Silk fibroin directs the formation of monetite nanocrystals and their assembly into hierarchical composites
Authors: Huang Ying , Xie Hao , Fang Weijian , Zou Zhaoyong , Fu Zhengyi
Published: October 2021

A gel-like silk film is used as the substrate to regulate the formation of monetite with hierarchical structure. The silk film not only changed the crystallization pathway, but also significantly modified the morphology of the crystals.
Estrogen receptors and the aging brain
Authors: Maioli Silvia , Leander Karin , Nilsson Per , Nalvarte Ivan
Published: October 2021

The female sex hormone estrogen has been ascribed potent neuroprotective properties. It signals by binding and activating estrogen receptors that, depending on receptor subtype and upstream or downstream effectors, can mediate gene transcription and rapid non-genomic actions. In this way, estrogen receptors in the brain participate in modulating neural differentiation, proliferation, neuroinflammation, cholesterol metabolism, synaptic plasticity, and behavior. Circulating sex hormones decrease in the course of aging, more rapidly at menopause in women, and slower in men. This review will discuss what this drop entails in terms of modulating neuroprotection and resilience in the aging brain downstream of spatiotemporal estrogen receptor alpha (ERα) and beta (ERβ) signaling, as well as in terms of the sex differences observed in Alzheimer’s disease (AD) and Parkinson’s disease (PD). In addition, controversies related to ER expression in the brain will be discussed. Understanding the spatiotemporal signaling of sex hormones in the brain can lead to more personalized prevention strategies or therapies combating neurodegenerative diseases.
Membrane lipid raft homeostasis is directly linked to neurodegeneration
Authors: Moll Tobias , Marshall Jack N.G. , Soni Nikita , Zhang Sai , Cooper-Knock Johnathan , Shaw Pamela J.
Published: October 2021

Age-associated neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD) are an unmet health need, with significant economic and societal implications, and an ever-increasing prevalence. Membrane lipid rafts (MLRs) are specialised plasma membrane microdomains that provide a platform for intracellular trafficking and signal transduction, particularly within neurons. Dysregulation of MLRs leads to disruption of neurotrophic signalling and excessive apoptosis which mirrors the final common pathway for neuronal death in ALS, PD and AD. Sphingomyelinase (SMase) and phospholipase (PL) enzymes process components of MLRs and therefore play central roles in MLR homeostasis and in neurotrophic signalling. We review the literature linking SMase and PL enzymes to ALS, AD and PD with particular attention to attractive therapeutic targets, where functional manipulation has been successful in preclinical studies. We propose that dysfunction of these enzymes is upstream in the pathogenesis of neurodegenerative diseases and to support this we provide new evidence that ALS risk genes are enriched with genes involved in ceramide metabolism (P=0.019, OR = 2.54, Fisher exact test). Ceramide is a product of SMase action upon sphingomyelin within MLRs, and it also has a role as a second messenger in intracellular signalling pathways important for neuronal survival. Genetic risk is necessarily upstream in a late age of onset disease such as ALS. We propose that manipulation of MLR structure and function should be a focus of future translational research seeking to ameliorate neurodegenerative disorders.
The high-throughput production of membrane proteins
Authors: Birch James , Quigley Andrew
Published: October 2021

Membrane proteins, found at the junctions between the outside world and the inner workings of the cell, play important roles in human disease and are used as biosensors. More than half of all therapeutics directly affect membrane protein function while nanopores enable DNA sequencing. The structural and functional characterisation of membrane proteins is therefore crucial. However, low levels of naturally abundant protein and the hydrophobic nature of membrane proteins makes production difficult. To maximise success, high-throughput strategies were developed that rely upon simple screens to identify successful constructs and rapidly exclude those unlikely to work. Parameters that affect production such as expression host, membrane protein origin, expression vector, fusion-tags, encapsulation reagent and solvent composition are screened in parallel. In this way, constructs with divergent requirements can be produced for a variety of structural applications. As structural techniques advance, sample requirements will change. Single-particle cryo-electron microscopy requires less protein than crystallography and as cryo-electron tomography and time-resolved serial crystallography are developed new sample production requirements will evolve. Here we discuss different methods used for the high-throughput production of membrane proteins for structural biology.
Modified Halbach design for torque profile improvement in a permanent magnet synchronous motor dedicated to an electric city bus
Authors: Nobahari Amin , Vahedi Abolfazl
Published: October 2021

In this work, a permanent magnet synchronous motor is designed for an electric city bus. The unit winding factor is considered for torque capability enhancement and completely open slots are adopted for low‐cost rectangular wire winding implementation. Accordingly, extremely large pulsating torques that are predictable should be mitigated through the rotor design possibilities. In this regard, a modified Halbach pole configuration, named axially segmented Halbach, that is capable of producing considerably smooth torque as well as retaining the large mean torque is proposed. First, an optimised conventional Halbach array is calculated as the initial design. Then, following a detailed introduction to the new design concept, the modified Halbach pole parameters are obtained through the proposed 2D model‐based optimisation algorithm. A rotor step skewing scheme is also evaluated to make the final comparisons, which are carried out via 3D FE models. The results demonstrate the admirable performance of the proposed Halbach configuration as an effective solution for torque profile improvement.
A multi‐objective optimization for planning of networked microgrid using a game theory for peer‐to‐peer energy trading scheme
Authors: Ali Liaqat , Muyeen S. M. , Bizhani Hamed , Ghosh Arindam
Published: October 2021

In this paper, a multi‐objective optimization technique is proposed for the planning of a networked microgrid based on peer‐to‐grid (P2G) and peer‐to‐peer (P2P) energy trading schemes. Two different criteria's including annual profit and energy index of reliability are taken into consideration to form a multi‐objective function. The networked microgrid consists of three individual microgrids containing their own combinations of generation resources, batteries and residential loads. All microgrids are connected together and also to the main grid to meet the energy exchange requirements of P2P energy trading. A cooperative game theory technique based on a particle swarm optimization algorithm is used to model the networked microgrid, and to find the suitable sizes of the players that simultaneously maximize the payoff values of both objective functions. Besides, a comparative analysis is carried out for both P2G and P2P energy trading schemes. The results show that the outcomes are maximum when both criteria are considered in the optimization and P2P energy trading is carried out. The sensitivity analysis is performed on the selected parameters and verified the right change 0.003% and 4.5% in discount rate and electricity prices, respectively.
Asymmetric Aldol Reaction of Alkenyl Esters with α-Keto Esters Catalyzed by Chiral Tin Alkoxides
Authors: Yanagisawa Akira , Uchiyama Chika , Takagi Kotaro
Published: October 2021

A catalytic enantioselective aldol reaction of alkenyl esters with α-keto esters was achieved by using an (R)-BINOL-derived chiral tin dibromide possessing 4-t-butylphenyl groups at the 3- and 3′-positions as a chiral precatalyst in the presence of sodium methoxide and methanol. Optically active aldol products possessing a chiral tertiary carbon were diastereoselectively obtained with up to 92% ee and moderate to high yields, not only from cyclic alkenyl esters, but also from acyclic ones under the influence of the chiral tin methoxide generated in situ.