bluuebunny/crossref_metadata_2025 huggingface dataset:
Differentiation signals from glia are fine-tuned to set neuronal numbers during development
Authors: Prasad Anadika R , Lago-Baldaia Inês , Bostock Matthew P , Housseini Zaynab , Fernandes Vilaiwan M
Published: September 2022

Neural circuit formation and function require that diverse neurons are specified in appropriate numbers. Known strategies for controlling neuronal numbers involve regulating either cell proliferation or survival. We used the Drosophila visual system to probe how neuronal numbers are set. Photoreceptors from the eye-disc induce their target field, the lamina, such that for every unit eye there is a corresponding lamina unit (column). Although each column initially contains ~6 post-mitotic lamina precursors, only 5 differentiate into neurons, called L1-L5; the ‘extra’ precursor, which is invariantly positioned above the L5 neuron in each column, undergoes apoptosis. Here, we showed that a glial population called the outer chiasm giant glia (xgO), which resides below the lamina, secretes multiple ligands to induce L5 differentiation in response to epidermal growth factor (EGF) from photoreceptors. By forcing neuronal differentiation in the lamina, we uncovered that though fated to die, the ‘extra’ precursor is specified as an L5. Therefore, two precursors are specified as L5s but only one differentiates during normal development. We found that the row of precursors nearest to xgO differentiate into L5s and, in turn, antagonise differentiation signalling to prevent the ‘extra’ precursors from differentiating, resulting in their death. Thus, an intricate interplay of glial signals and feedback from differentiating neurons defines an invariant and stereotyped pattern of neuronal differentiation and programmed cell death to ensure that lamina columns each contain exactly one L5 neuron.
DNA passes through cohesin’s hinge as well as its Smc3–kleisin interface
Authors: Collier James E , Nasmyth Kim A
Published: September 2022

The ring model proposes that sister chromatid cohesion is mediated by co-entrapment of sister DNAs inside a single tripartite cohesin ring. The model explains how Scc1 cleavage triggers anaphase but has hitherto only been rigorously tested using small circular mini-chromosomes in yeast, where covalently circularizing the ring by crosslinking its three interfaces induces catenation of individual and sister DNAs. If the model applies to real chromatids, then the ring must have a DNA entry gate essential for mitosis. Whether this is situated at the Smc3/Scc1 or Smc1/Smc3 hinge interface is an open question. We have previously demonstrated DNA entrapment by cohesin in vitro (Collier et al., 2020). Here we show that cohesin in fact possesses two DNA gates, one at the Smc3/Scc1 interface and a second at the Smc1/3 hinge. Unlike the Smc3/Scc1 interface, passage of DNAs through SMC hinges depends on both Scc2 and Scc3, a pair of regulatory subunits necessary for entrapment in vivo. This property together with the lethality caused by locking this interface but not that between Smc3 and Scc1 in vivo suggests that passage of DNAs through the hinge is essential for building sister chromatid cohesion. Passage of DNAs through the Smc3/Scc1 interface is necessary for cohesin’s separase-independent release from chromosomes and may therefore largely serve as an exit gate.
REVIEW ON AYURVEDA DARSHANA: A PHILOSOPHICAL VIEW
Authors: Kumari Soumya , K Vidyalakshmi , DN Likhita
Published: September 2022

The word Darshana is derived from the root “Drishyate” or “Drish” means to see.“Drishyate Anena iti Darshana” means that which facilitates to visualisation the facts pertaining to the universe. “Sarve Darshanaha Jnanartha saadhanaha” All the Darshanas are the means or instruments of knowledge. They were born out of Upanishads. The Upanishads were commonly referred to as Vedas. One section of Darshana known as Asthika Darshana believed that the vedas are “Apourusheya”(not created by man or beyond the intellectual capacity of a common man).They believe in the existence of Atma(soul),Paramatma(supreme soul),Janana(birth),Marana(death),Moksha(salvation) and Ishwara(creator). Dukha Nivritti and Moksha Prapti is the purpose of all the Darshanas or philosophical preaches. Moksha is the ultimate aim of life i.e., after attaining Moksha, there is no further Sukha Dukha Bhava in that individual and the person attains blissfulness. Ayurveda, the science of life, also stresses upon “Purushartha Chathushtaya” where Moksha can be achieved through a Swastha Shareera, explaining the methods to attain Jeevan mukti (attainment of Moksha during one period of life span itself). Since the purpose of Ayurveda is also towards the achievement of Moksha either in this loka and the paraloka (Imam Cha Amum Cha) we can say that it is an independent Darshana.
RASAYANA YOGAS IN CHAKRADATTA: A REVIEW
Authors: S Deekshitha , Hussain Gazala , . Vijayalakshmi
Published: September 2022

Ayurveda is a comprehensive life science that incorporates all elements of human living. Rasayana is one of Ayurveda's clinical specialties. Rasayana is more than a medication therapy; it's a specialised procedure that includes rejuvenating recipes and a dietary regimen that promotes healthy attitudes. Chakradatta's principal goal was to represent it as a literature pertaining of Ayurvedic medicine for the benefit of mankind. The purpose of this study is to highlight Chakradatta's framework while also providing information on the various Rasayana yogas. A thorough analysis has been done to enumerate Rasayana yogas mentioned under the Rasayanaadhikara of Chakradatta. In total twenty-one formulations are said as Rasayana; in which five are of single drugs, a ghrita yoga, two tamra yogas and herbo- mineral combinations too. The formulations enlisted have Vatakapha samana and Tridoshahara characteristics. The primary objective of Chakradatta was to present it as a Traditional Ayurvedic treatise for the benefit of a healthy lifestyle. Chakradatta's guidelines for therapeutic principles pertaining to the condition are still helpful for Ayurvedic practitioners today.
A REVIEW ON AYURVEDA DARSHANA: A PHILOSOPHICAL VIEW
Authors: Kumari Soumya , K Vidyalakshmi , DN Likhita
Published: September 2022

The word Darshana is derived from the root “Drishyate” or “Drish” means to see.“Drishyate Anena iti Darshana” means that which facilitates to visualisation the facts pertaining to the universe. “Sarve Darshanaha Jnanartha saadhanaha” All the Darshanas are the means or instruments of knowledge. They were born out of Upanishads. The Upanishads were commonly referred to as Vedas. One section of Darshana known as Asthika Darshana believed that the vedas are “Apourusheya”(not created by man or beyond the intellectual capacity of a common man).They believe in the existence of Atma(soul),Paramatma(supreme soul),Janana(birth),Marana(death),Moksha(salvation) and Ishwara(creator). Dukha Nivritti and Moksha Prapti is the purpose of all the Darshanas or philosophical preaches. Moksha is the ultimate aim of life i.e., after attaining Moksha, there is no further Sukha Dukha Bhava in that individual and the person attains blissfulness. Ayurveda, the science of life, also stresses upon “Purushartha Chathushtaya” where Moksha can be achieved through a Swastha Shareera, explaining the methods to attain Jeevan mukti (attainment of Moksha during one period of life span itself). Since the purpose of Ayurveda is also towards the achievement of Moksha either in this loka and the paraloka (Imam Cha Amum Cha) we can say that it is an independent Darshana.
Assessing Rice Farmers’ Coping Strategies to Labour Scarcity in Guma Local Government Area of Benue State, Nigeria
Authors: Pinga Esther Seember , Fatty Lamin K. M. , Gomez David
Published: September 2022

This study assessed the coping strategies of small holder rice farmers in the face of agricultural labour challenges in Guma local government area of Benue state, Nigeria. Literature was reviewed to ascertain the results of other scholars across the globe on the various strategies that farmers have used to cope with the challenge of labour scarcity in agriculture. This study adopted a survey research design with a population of 5125 small holder rice farmers, out of whom 371 respondents were determined using Taro Yamane’s formula. These respondents were sampled using a multi-stage sampling strategy (simple and purposive random sampling techniques). Pre-tested and well structured questionnaires were used for data collection. Data collected was analyzed using Statistical Package for Social Sciences (SPSS 26.0); frequencies and percentages derived were presented in tables and a bar chart. Study findings indicated that the farmers adopt coping strategies such as the intense use of family labour; increased use of chemicals; preference for other crops (such as cassava, sweet potatoes and vegetables); importation of labour from other regions; marrying more wives and leasing out fadama (swampy and fertile) land. The study concluded that, the coping strategies adopted are not viable and sustainable in the 21st century; and thus recommended that the task of overcoming agricultural labour scarcity must not be left in the hands of the rural farmers alone; all stakeholders must be actively involved in finding sustainable coping strategies which must include mechanization of farms.
Reflections on the Design of Junior High School Science Homework Pointing to the Core Literacy under the Background of "Double Reduction"
Authors: Zhou Hancai , Xu Wenjie , Zhang Yaobo , Wang Zijun , Li Jiahui , Zhang Yiping
Published: September 2022

Science homework is an important part of junior high school science teaching and learning, playing an important role in the whole subject curriculum teaching system. How to design homework scientifically, reasonably and effectively according to the teaching contents and learning conditions is the key exploration of junior high school science teaching under the background of “double reduction”. Based on the understanding of the core literacy of science and the analysis of the current status of science homework in junior high schools, we combined with the teaching practice of science homework design, and considered the improvement path for the design of junior high school science homework that points to the core literacy under the "double reduction" policy. Teachers can proceed with the following four aspects to improve the quality of homework design: designing conceptual homework from science concepts to consolidate basic knowledge; designing improving homework from science thinking to enhance the quality of assignments; designing practice-based homework from inquiry and practice to enrich the form of assignments; designing value-oriented homework from attitude and responsibility to bring out the value of educating people, so as to truly help students achieve "quality improvement, efficiency increase, and burden reduction" in learning, and cultivate students' core literacy.
A Review on Pyrolysis for Sustainable Biomass Conversion
Authors: Jawale Laleet , Rupnar A. K.
Published: September 2022

The use of bio-energy is rapidly increasing which is become a crucial significant way to replace fossil fuel. The depletion of fossil fuels is responsible for initiating the utilization of the sustainable energy which has been available surrounding human beings. The employment of such sustainable energy can be possible from waste procreated by living creatures and that is feasible because of thermal decomposition processes, which comprise the gasification, combustion, and pyrolysis process for the production of biochar. The present study portrayed the very promising thermal decomposition process that is the pyrolysis process. The two main pyrolysis processes explained where basic feedstock is biomass invested. This feedstock may have diverse versions as natural live or dead plants, wastage of animals, organic waste, etc. All these feedstocks are responsible for the emission of some amount of carbon which relates to the different modes of operation used in the pyrolysis biomass conversion process. The bioproduct varies due to the effect of various operating conditions such as temperature, heating rate, feedstock, reactors configuration, and reaction time. Demand for bioproducts rising in daily life Due to this circumstance Sustainability of products become prominent while exploited in the proper application such as soil amendment, soil fertility, climate change mitigation, and waste management. This review demonstrates the pyrolysis process to convert simple biomass to sustainable biochar, bio-oil, and syngas with the variation of the amount of product depending on different pyrolysis processes.
Role of Root Traits and Root Phenotyping in Drought Tolerance
Authors: Dutta Chumki , Sarma Ramendra Nath
Published: September 2022

The spatial distribution of all root parts in a particular growth environment is collectively referred to as root system architecture (RSA). Root length, cortical cell file number, number of roots and cell size help in determining water uptake ability among various root types as an adaptation strategy under dry conditions. Using a combination of root phenotyping techniques that include laboratory, greenhouse, and field evaluations, root characteristics can be identified and selected. Roots play a significant role in the plant's capacity to recover from drought stress. Root attributes are influenced by environmental factors, are difficult to measure in the field, and are regulated by polygenes. Different root properties, including root number, root length, root angle, and root surface area, have quantitative trait loci that have been found. Crop yield and the efficiency with which nutrients and water are used could both be improved genetically by improving the root system architecture in drought-prone areas. Different alleles may be introduced into elite cultivars to create desired root phenotypes through molecular breeding in order to ensure crop productivity in a harsh environment.
Medicinal and Biological Importance of Pumpkin Seeds and Its Impact on Weight
Authors: Shaikh Yasmin , Shaikh Kashif Rasheed , Tunio Ali Gul , Shaikh Habibullah , Dahri Ghulam Mustafa , Irfan Rao
Published: September 2022

Aim: To evaluate the pharmacological effects of pumpkin seeds in correlation to weight gain in rabbits.

Methodology: After observing as standard inclusion and exclusion criteria, thirty healthy adult rabbits recommended in study. Calculated amount 250 mg and 500 mg of powder of pumpkin seeds given. 1stanalysis denoted as day zero. Afterward more analysis were taken twice monthly for sixty days. The blood specimens passed immediately to the DR Lab by the side at the PUMHS Nawabshah. CBC analyzed using an automatic hemoglobin analyzer. Data were statistically evaluated in groups as mean by t-test and by SPSS version 21.0. A P value of 0.05 for all comparisons counted significant.

Results: While comparing study groups with control, the mean Haemoglobin, RBCs and Platelets value at day zero were established as non-significant statistically. TLC and Weight means were significant statistically. A rising boost observed on further readings taken in all Hematological parameters. When compared with control, all the interpretation was highly significance statistically except weight which remains non-significant statistically.

Conclusion: Pumpkin seeds can be replaced by ordinary method as a best plant food supply for improving hematological markers. It bears no any side effect of weight gain or patients non- cooperation like with medical therapy because of its high cost or side effects.
Tax Overbooking Of Msme Individuals On The Impact Of The Harmonization Of Tax Regulation Socialization
Authors: Triyono Dedy , Kusumawardhani Adhityawati
Published: September 2022

The COVID-19 pandemic situation made the Government enact Law No. 7 of 2021 about Harmonization of Tax Regulations (Law 7/2021) which aimed to improve the budget and increase taxes. The purpose of this study was to identify the tax overbooking practices of Micro, Small and Medium Enterprises (MSME) owned by individuals in light of the Law 7/2021 socialization. The methodology used is qualitative. Respondents are East Java-based individuals who own MSMEs. The imposition of income tax rates in Law 7/2021 is that individual taxpayers and individual taxpayers who owned MSMEs whose income is approximately Rp. 500 million a year, are exempt from paying final income tax of 0.5% in accordance with the rates in government regulation No. 23 of 2018. In reality, individual taxpayers who owned MSMEs and had already paid taxes in accordance with the rates specified in government regulation no. 23 of 2018 in January and February 2022 may make a tax overbook of the tax already paid if the annual turnover exceeds Rp 500 million in the month in which the calculated turnover exceeds Rp 500 million. This is because the Directorate General of Taxes' socialization efforts during the Covid 19 pandemic received little attention from taxpayers who owned MSMEs.
Racial and Ethnic Equity in Neuromuscular Care—Time for Our Action to Live Up to Potential
Authors: Porter Neil C. , Morgenstern Lewis B.
Published: September 2022

This Viewpoint discusses the need to improve the quality of care in neuromuscular disease for all individuals, no matter their race and ethnicity.
Housing Instability and Homelessness—An Undertreated Pediatric Chronic Condition
Authors: Gabbay Jonathan M. , Stewart Amanda M. , Wu Ann Chen
Published: September 2022

This Viewpoint discusses housing instability and homelessness among children as well as the significance of the Housing First model, with particular focus on children in families.
Why do we share aggressive online content? Testing a short cycle model
Authors: Santos Isabella L. S. , Pimentel Carlos Eduardo , Mariano Tailson E. , Dias Ericarla Verônica Almeida
Published: September 2022

The present study aimed to observe the impacts of aggressive online content exposure and personality on aggressive content sharing, considering the mediating role of positive and negative affects. A total of 302 Brazilians, equally divided into two groups, participated in a social network simulation, being exposed to aggressive (experimental group) or neutral (control group) posts and choosing what they would like to share on this site (among aggressive or nonaggressive material). A factorial MANOVA showed a significant difference for positive and negative affects and aggressive content sharing (Wilks' Λ = 0.936; F[3, 298] = 6.812; p = .001; η2 = 0.064). Through structural equation modeling, an explanatory model was also tested, in which this behavior was directly predicted by aggressive online content exposure and suffered indirect effects from openness, conscientiousness, and extroversion, mediated by positive affects (goodness‐of‐fit index = 0.997, comparative fit‐index = 0.998, Tucker‐Lewis index = 0.996, SRMR = 0.028, root‐mean‐square error of approximation = 0.035, CI = 0.003−0.054). It is possible to conclude that the objectives are met, highlighting the contribution to understanding aggressive online behavior through the proximal processes described in the general aggression model.
Countering conspiracy theory beliefs: Understanding the conjunction fallacy and considering disconfirming evidence
Authors: Stall Lindsay M. , Petrocelli John V.
Published: September 2022

Research suggests that a number of cognitive processes—including pattern perception, intentionality bias, proportionality bias, and confirmation bias—may underlie belief in a conspiracy theory. However, there are reasons to believe that conspiracy theory beliefs also depend in part on a failure to understand the probability of actual events allegedly supporting those conspiracy theories as well as a failure to entertain disconfirming evidence that may contradict those beliefs. Study 1 examines the relationships between general beliefs in conspiracy theories, belief in a novel conspiracy theory, conjunctive error propensity, and the propensity to consider disconfirming evidence. Study 2 investigates the roles of confronting both the propensity to make conjunctive errors and the failure to consider disconfirming evidence in changing conspiracy theory beliefs as well as attitudes associated with those beliefs. The results of both studies suggest that corrections to one's propensity to make conjunctive errors and mindful consideration of disconfirming evidence may serve as viable methods of self‐persuasion pertaining to conspiracy theory beliefs.
The Hydrophobicity of AIE Dye Facilitates DNA Condensation for Carrier‐Free Gene Therapy
Authors: Chen Zhe , Wei Zixiang , Xiao Fan , Chao Zhicong , Lu Jingxiong , Wang Zhiming , Tian Leilei
Published: September 2022

A nanomaterial with a high payload of nucleic acid drugs and low cytotoxicity is desirable for gene therapy. Herein, a new DNA assembly method triggered by hydrophobic interaction and strengthened by Mg2+ electrostatic interaction for carrier‐free gene transfection is reported. It is discovered that a hydrophobic aggregation‐induced emission dye with a low molecular weight that is modified to an oligonucleotide will greatly change the condensation properties of DNA. The conditions and the possible mechanism of such an aggregation process are carefully investigated. Further, it is revealed that the resultant aggregate is suitable for gene delivery, as in which the oligonucleotides are protected from degradation, and the intracellular permeability is enhanced. For the delivery of Bcl‐2 antisense oligonucleotide, such a system exhibits a high gene transfection efficiency both in vitro and in vivo. Accordingly, an interesting observation is reported in this study that an aggregation‐induced emission dye with a molecular weight much lower than the nucleic acid drugs can cause oligonucleotide aggregation and facilitate gene transfection. Such a delivery system provides a practical and inspiring example for the development of gene therapy in the future.
High‐Quality Cs3Cu2I5 Single‐Crystal is a Fast‐Decaying Scintillator
Authors: Yao Qian , Li Jiaming , Li Xuesong , Zheng Xiaoxin , Wang Zungang , Tao Xutang
Published: September 2022

Copper(I) halide perovskite Cs3Cu2I5 has recently attracted tremendous interest and has been considered an exceptionally promising scintillator due to its high quantum yield. However, its slow scintillation decay time, previously considered an intrinsic property, is a significant drawback preventing its practical application and commercialization. But in this work, it is found that the high‐quality Cs3Cu2I5 single‐crystal grown by the designed aqueous solution method surprisingly exhibits a fast scintillation decay time of 39 ns (82%), quite different from previous reports. This subversive change may be due to the high crystal quality with denser 0D structure and low trap density (6.41 × 108 cm–3), changing the excited‐state structural deformation and accelerating the recombination of electrons and holes while directly reducing the prolongation of decay time caused by inherent defects. Moreover, the single‐crystal with a rocking curve FWHM value of only 50.4˝ has a high optical transmittance (85%), a very high absolute photoluminescence quantum yield (PLQY, 97.76%), superior environmental stability, and excellent light‐yield and energy resolution under different γ‐ray sources (241Am, 60Co, 22Na, 137Cs, 152Eu). These extraordinary properties pave the way for the subsequent development of practical applications.
Optically Active Chalcogen Vacancies in Monolayer Semiconductors
Authors: Zhang Zhepeng , Liang Haidong , Loh Leyi , Chen Yifeng , Chen Yuan , Watanabe Kenji , Taniguchi Takashi , Quek Su Ying , Bosman Michel , Bettiol Andrew A. , Eda Goki
Published: September 2022

Defect engineering of atomically thin semiconducting crystals is an attractive route to developing single‐photon sources and valleytronic devices. For these applications, defects with well‐defined optical characteristics need to be generated in a precisely controlled manner. However, defect‐induced optical features are often complicated by the presence of multiple defect species, hindering the identification of their structural origin. Here, we report systematic generation of optically active atomic defects in monolayer MoS2, WS2, MoSe2, and WSe2 via proton‐beam irradiation. Defect‐induced emissions are found to occur ≈100 to 200 meV below the neutral exciton peak, showing typical characteristics of localized excitons such as saturation at high‐excitation rates and long lifetime. Using scanning transmission electron microscopy, it is shown that freshly created chalcogen vacancies are responsible for the localized exciton emission. Density functional theory and ab initio GW plus Bethe‐Salpeter‐equation calculations reveal that the observed emission can be attributed to transitions involving defect levels of chalcogen vacancy and the valence band edge state.
Overcharge‐Induced Phase Heterogeneity and Resultant Twin‐Like Layer Deformation in Lithium Cobalt Oxide Cathode for Lithium‐Ion Batteries
Authors: Oh Juhyun , Lee Seung‐Yong , Kim Hwangsun , Ryu Jinseok , Gil Byeongjun , Lee Jongki , Kim Miyoung
Published: September 2022

Overcharging is expected to be one of the solutions to overcome the current energy density limitation of lithium‐ion battery cathodes, which will support the rapid growth of the battery market. However, high‐voltage charging often poses a major safety threat including fatal incendiary incidents, limiting further application. Numerous researches are dedicated to the disadvantages of the overcharging process; nonetheless, the urgent demand for addressing failure mechanisms is still unfulfilled. Herein, it is revealed that overcharging induces phase heterogeneity into layered and cobalt oxide phases, and consequent “twin‐like deformation” in lithium cobalt oxide. The interplay between the uncommon cobalt(III) oxide and the deformation is investigated by revealing the atomistic formation mechanism. Most importantly, abnormal cracking is discovered in the vicinity of the cobalt oxide where structural instability induces substantial contraction. In addition, surface degradation is widely observed in the crack boundary inside the particle. As unintentional overcharging can occur due to local imbalance in state‐of‐charge in severe operating conditions such as fast charging, the issues on overcharging should be emphasized to large extent and this study provides fundamental knowledge of overcharge by elucidating the crack development mechanism of layered cathodes, which is expected to broaden the horizon into high voltage operation.
Surface and Defect Engineering Coupling of Halide Double Perovskite Cs2NaBiCl6 for Efficient CO2 Photoreduction
Authors: Pi Jiacheng , Jia Xiaofang , Long Zhangwen , Yang Shuai , Wu Hao , Zhou Dacheng , Wang Qi , Zheng Huibin , Yang Yong , Zhang Junying , Qiu Jianbei
Published: September 2022

Non‐toxic halide double perovskite materials have many advantages of lead halide perovskite. Whereas, they usually exhibit poor stability and very low intrinsic photocatalytic CO2 reduction activity due to the insufficient separation of photogenerated charges and the lack of active sites. In this work, stable chlorine‐deficient 3D hierarchical Cs2NaBiCl6 porous microspheres assembled by highly crystalline nanoflakes were prepared by a simple grinding method. An unprecedented CO yield of 30.22 µmol g−1 h−1 was achieved in the gas‐solid photocatalytic reduction of CO2 without sacrificial agents, which is the highest value among lead‐free halide perovskite photocatalysts. Experimental results and density‐functional theory calculations show that the chlorine vacancy plays the triple role of suppressing photogenerated electron‐holes recombination, enhancing CO2 adsorption, and significantly reducing the free energy barrier for the key intermediate COOH* generation. In comparison with the pristine Cs2NaBiCl6, coupling of surface and defect engineering of the hierarchical sample brings 12.34 times enhancement of CO2 photoreduction activity. This work proposes a simple method to synthesize a chlorine‐vacancy rich 3D hierarchical lead‐free halide perovskite and offers a new design idea to substantially enhance the photocatalytic activity, opening a door for the prospective contribution of these materials to carbon neutralization.
Influence of antidepressant treatment on SLC6A4 methylation in Korean patients with major depression
Authors: Moon Young Kyung , Kim Hyeseung , Kim Seonwoo , Lim Shinn‐Won , Kim Doh Kwan
Published: September 2022

Genetic variation of the serotonin transporter gene (SLC6A4) has been suggested as potential mediator for antidepressant response in patients with depression. This study aimed to determine whether DNA methylation in SLC6A4 changes after antidepressant treatment and whether it affects treatment response in patients with depression. Overall, 221 Korean patients with depression completed 6 weeks of selective serotonin reuptake inhibitor (SSRI) monotherapy. DNA was extracted from venous blood pre‐ and post‐treatment, and DNA methylation was analyzed using polymerase chain reaction. We used Wilcoxon's signed‐rank test to verify the difference in methylation after treatment. Treatment response was assessed using the 17‐item Hamilton Depression Rating Scale, and mRNA levels were quantified.

After adjusting for relevant covariates, DNA methylation was significantly altered in specific CpG sites in SLC6A4 (p < .001 in CpG3, CpG4, and CpG5) following 6 weeks of treatment. Methylation change's magnitude (ΔDNA methylation) after drug treatment was not associated with treatment response or mRNA level change. SSRI antidepressants can influence SLC6A4 methylation in patients with depression. However, ΔDNA methylation at CpG3, CpG4, and CpG5 in SLC6A4 was not associated with treatment response. Future studies should investigate the integrative effect of other genetic variants and CpG methylation on gene transcription and antidepressant treatment response.
Chimpanzee pant‐hoots encode individual information more reliably than group differences
Authors: Desai Nisarg P. , Fedurek Pawel , Slocombe Katie E. , Wilson Michael L.
Published: September 2022

Vocal learning, the ability to modify the acoustic structure of vocalizations based on social experience, is a fundamental feature of speech in humans (Homo sapiens). While vocal learning is common in taxa such as songbirds and whales, the vocal learning capacities of nonhuman primates appear more limited. Intriguingly, evidence for vocal learning has been reported in chimpanzees (Pan troglodytes), for example, in the form of regional variation (“dialects”) in the “pant‐hoot” calls. This suggests that some capacity for vocal learning may be an ancient feature of the Pan‐Homo clade. Nonetheless, reported differences have been subtle, with intercommunity variation representing only a small portion of the total acoustic variation. To gain further insights into the extent of regional variation in chimpanzee vocalizations, we performed an analysis of pant‐hoots from chimpanzees in the neighboring Kasekela and Mitumba communities at Gombe National Park, Tanzania, and the geographically distant Kanyawara community at Kibale National Park, Uganda. We did not find any statistically significant differences between the neighboring communities at Gombe or among geographically distant communities. Furthermore, we found differences among individuals in all communities. Hence, the variation in chimpanzee pant‐hoots reflected individual differences, rather than group differences. Thus, we did not find evidence of dialects in this population, suggesting that extensive vocal learning emerged only after the lineages of Homo and Pan diverged.
Phase 1 Evaluation of Elezanumab (Anti–Repulsive Guidance Molecule A Monoclonal Antibody) in Healthy and Multiple Sclerosis Participants
Authors: Kalluri Hari V. , Rosebraugh Matthew R. , Misko Thomas P. , Ziemann Adam , Liu Wei , Cree Bruce A. C.
Published: September 2022

Objective

This study was undertaken to describe the safety, tolerability, pharmacokinetics, and immunogenicity of elezanumab (ABT‐555), a fully human monoclonal antibody (mAb) directed against repulsive guidance molecule A (RGMa), in healthy and multiple sclerosis (MS) study participants.

Methods

The single‐center, first‐in‐human, single ascending dose (SAD) study evaluated elezanumab (50–1,600mg intravenous [IV] and 150mg subcutaneous) in 47 healthy men and women. The multicenter multiple ascending dose (MAD; NCT02601885) study evaluated elezanumab (150mg, 600mg, and 1,800mg) in 20 adult men and women with MS, receiving either maintenance or no immunomodulatory treatment.

Results

No pattern of study drug‐related adverse events was identified for either the SAD or MAD elezanumab regimens. Across both studies, the Tmax occurred within 4 hours of elezanumab IV infusion, and the harmonic mean of t1/2 ranged between 18.6 and 67.7 days. Following multiple dosing, elezanumab Cmax, area under the curve, and Ctrough increased dose‐proportionally and resulted in dose‐dependent increases in elezanumab cerebrospinal fluid (CSF) concentrations. Elezanumab CSF penetration was 0.1% to 0.4% across both studies, with CSF levels of free RGMa decreased by >40%. Changes in CSF interleukin‐10 (IL‐10) and free RGMa demonstrated dose/exposure‐dependence.

Interpretation

The elezanumab pharmacokinetic profile supports monthly, or bimonthly, administration of up to 1,800mg with the option of a loading dose of 3,600mg. Elezanumab partitioning into CSF is within the range expected for mAbs. Reduced CSF levels of free RGMa demonstrate central nervous system target binding of elezanumab with an apparent maximal effect at 1,800mg IV. Exposure‐associated increases in CSF IL‐10, an anti‐inflammatory cytokine with neuroprotective/neurorestorative properties, support potential pathway modulation in MS participants. ANN NEUROL 2023;93:285–296
New Insights into Physical Aging‐Induced Structure Evolution in Carbon Molecular Sieve Membranes
Authors: Liu Zhongyun , Qiu Wulin , Koros William J.
Published: September 2022

Carbon molecular sieve (CMS) membranes offer the best available combination of scalable economical processability with excellent separation performance. Physical aging of CMS membranes causes pore structure changes over time that affect CMS membrane performance. To provide fundamental insights into the structure evolution in CMS membranes during physical aging, a combined dual‐mode sorption and transport model is used in this study to characterize the diffusion coefficients of gas molecules in fresh and 7‐day vacuum aged CMS membranes. The results show physical aging of CMS membrane is primarily “diffusion related” and such aging behavior simultaneously causes ultramicropore changes in the continuous phase and Langmuir phase of CMS membrane. The new insights offered in this study suggest strategies to control the physical aging of CMS membranes and even use it as a valuable tool to tune the separation performance of CMS membranes for demanding gas separations.
The Continuum Between Hexagonal Planar and Trigonal Planar Geometries**
Authors: Garçon Martí , Phanopoulos Andreas , Sackman George A. , Richardson Christopher , White Andrew J. P. , Cooper Richard I. , Edwards Alison J. , Crimmin Mark R.
Published: September 2022

New heterometallic hydride complexes that involve the addition of {Mg−H} and {Zn−H} bonds to group 10 transition metals (Pd, Pt) are reported. The side‐on coordination of a single {Mg−H} to Pd forms a well‐defined σ‐complex. In contrast, addition of three {Mg−H} or {Zn−H} bonds to Pd or Pt results in the formation of planar complexes with subtly different geometries. We compare their structures through experiment (X‐ray diffraction, neutron diffraction, multinuclear NMR), computational methods (DFT, QTAIM, NCIPlot), and theoretical analysis (MO diagram, Walsh diagram). These species can be described as snapshots along a continuum of bonding between ideal trigonal planar and hexagonal planar geometries.
Electroacupuncture modulates gut microbiota in mice: A potential target in postoperative cognitive dysfunction
Authors: Zhu Binbin , Zhou Yanling , Zhou Weijian , Chen Chunqu , Wang Jianhua , Xu Shujun , Wang Qinwen
Published: September 2022

The detailed mechanism of inflammation in postoperative cognitive dysfunction (POCD) is unclear. This study aimed to determine whether electroacupuncture (EA) ameliorates POCD by modulating gut microbial dysbiosis. Compared to the control group, mice in the EA group were treated at the acupoints Zusanli (ST36), Quchi (L111), Baihui (GV20), and Dazhui (GV14) 1 week before appendectomy. Novel object recognition and the Morris water maze tests were used to assess learning and spatial reference memory deficits, whereas hippocampus samples and stool samples were collected for central inflammatory tests and 16S‐rRNA sequencing of intestinal flora, respectively. In amyloid precursor protein/presenilin 1 (APP/PS1) mice, EA enhanced spatial memory and learning deficits. The fecal microbial community was altered in APP/PS1 mice in the absence of EA following surgery. Among them, Coprococcus and Bacteroidetes were more abundant in the EA groups than in the control groups; however, Actinobacteriota, Helicobacteraceae, and Escherichia/shigella constitute the minor bacterial colonization in the EA groups. Furthermore, we found a significant negative correlation between Firmicutes and escape latency (Pearson correlation coefficient − 0.551, p < 0.01) and positive correlation between Proteobacteria and escape latency (Pearson correlation coefficient 0.462, p < 0.05). Electron microscopy revealed signs of blood–brain barrier (BBB) impairments and immunofluorescence images showed glial cells activated in the hippocampus of APP/PS mice without EA, and serum diamine oxidase levels were increased in these mice; whereas EA treatment significantly relieved the above pathological changes. Our findings implied that EA decreases hippocampal inflammation of APP/PS1 by upregulating benificial  gut microbiota, reducing BBB and intestinal barrier dysfunction, thus alleviates postoperative cognitive dysfunction. This may provide a novel target in POCD management.
Accelerated Discovery of Ternary Gold Alloy Materials with Low Resistivity via an Interpretable Machine Learning Strategy
Authors: Wang Xiangdong , Lu Tian , Zhou Wenyan , Ji Xiaobo , Lu Wencong , Yang Jiong
Published: September 2022

New ternary gold alloys with low resistivities (ρ) were screened out via an interpretable machine learning strategy by using the support vector regression (SVR) model integrated with SHAP analysis. The correlation coefficient (R) and the root mean square error (RMSE) of test set were 0.876 and 0.302, respectively, indicating the strong generalization ability of the model. The average ρ of top 10 candidates was 1.22×10−7 Ω m, which was 41% lower than the known minimum of 2.08×10−7 Ω m. The outputs of SVR model were analyzed with the critical SHAP values including first ionization energy of C‐site (584 kJ ⋅ mol−1), electronegativity of C‐site (1.72) and the second ionization energy of B‐site (1135 kJ ⋅ mol−1), respectively. Moreover, an online web server was developed to share the model at http://materials‐data‐mining.com/onlineservers/wxdaualloy.
Multiple subtypes of coxsackievirus group B can cause congenital heart disease
Authors: Sharma Vipul , Goessling Lisa S. , Brar Anoop K. , Eghtesady Pirooz
Published: September 2022

Background

Different serotypes of coxsackievirus B (CVB), which is the most common cause of viral myocarditis, target cardiomyocytes through Coxsackie and Adenovirus Receptor and Decay‐Accelerating Factor. Both receptors are expressed in the fetal heart. We hypothesized that infection with different serotypes of CVB during early pregnancy plays a role in pathogenesis of congenital heart defect (CHD).

Methods

In this study, we use a murine model to infect with CVB1, CVB4, and combination of CVB3 + CVB4 during a critical period in gestation. We examined offspring of pregnant mice for fetal death and heart defects following viral infection.

Result

Fetuses from uninfected control dams showed normal heart development, while maternal CVB infection precipitates CHD: majorly ventricular septal defects (VSD) and non‐compaction of ventricular myocardium (NC), with some infrequent cases of double outlet right ventricle, left ventricle wall rupture, right ventricle hypertrophy, and thickened/dysplastic semilunar valves. Infection of pregnant dams with CVB1 leads to 44% VSD and 41.2% NC cases, while with CVB4 leads to 31.7% VSD and 13.3% NC cases. Co‐infection with CVB3 + CVB4 increases fetal pathology to 51.3% VSD and 41% NC cases. Infection can also result in fetal death, with higher incidences with CVB3 + CVB4 with 46.2% cases, compared to 33.3% by CVB1 and 21.7% by CVB4. Male fetuses were more susceptible to all phenotypes.

Conclusion

Our report shows that prenatal CVB infections can lead to pathogenesis of certain heart defects in mouse model, particularly exacerbated with co‐infections. This data confirms a link between prenatal CVB infection and CHD development and highlights it is not unique to just one serotype of CVB.
Antihyperlipidemic Activity of Glycoconjugated Phthalimides in Mice Submitted to a Model of Dyslipidemia and Insulin Resistance
Authors: da Silva Júnior José Guedes , de Araújo Hallysson Douglas Andrade , da Rocha Ismael Gomes , da Silva Neto Jacinto Costa , Oliveira Ronaldo Nascimento , de Oliveira Assis Shalom Pôrto , de Menezes Lima Vera Lúcia
Published: September 2022

Alterations in lipid and lipoprotein metabolism are factors that trigger several negative metabolic complications. Hyperlipidemia is the starting point for the development of comorbidities of the cardiovascular system, such as atherosclerosis. The search for compounds that reduce high levels of total cholesterol and triglycerides has been widely reported in several publications in the literature. Phthalimide derivatives have been extensively researched with various biological actions. In this study we evaluated the antihyperlipidemic ability of three phthalimide derivatives (FGT‐2, FGT‐3 and FGT‐4) on a model of obesity and insulin resistance in mice. The animals were submitted to a hyperlipid diet for 60 days. On the thirtieth day they were treated with phthalimides (20 mg/kg). The positive control group was treated with Simvastatin (20 mg/kg) and the negative control received only the carboxymethylcellulose vehicle. Biochemical and histological analyzes of all groups were analyzed. The animals treated with phthalimidic derivatives had a reduction in total cholesterol, low density and very low density lipoproteins (LDL‐c and VLDL‐c), triglycerides and fasting glycemia when compared to the negative control group. The treated animals also showed good results when analyzing the atherogenic indexes Castelli i and II and the ratio Triglycerides/HDL‐c. In the oral glucose tolerance test and in the insulin tolerance test, animals treated with phthalimides were more sensitive to the action of the hormone regulating carbohydrate uptake. In the evaluation of the transaminases (AST/ALT), the animals of the group treated with phthalimides presented a lower elevation than the other groups of the experiment, the same observed with the uric acid evaluation. Histological analyzes were performed on liver, kidney, heart and pancreas samples. The groups treated with the compounds FGT‐2 and FGT3 presented discrete alterations in the liver and kidney. FGT‐4 did not present histological alterations for both tissues and the three phthalimide derivatives did not cause alterations in the other organs. These results suggest that the phthalimides tested can act as antihyperlipidemic agents and have a pleiotropic action, by acting also reducing glycemia in insulin resistance model mimicking diabetes mellitus type 2. These compounds may appear as a new approach in the treatment of obesity and complications, which are multifaceted.
Application Areas of Ionic Hydraulic Fluids
Authors: Lovrec Darko , Kalb Roland , Tič Vito
Published: September 2022

Ionic liquids, as high‐tech technical fluids, have been in practical application in various fields of technology for several years. The search for ionic liquids suitable for use within hydraulic systems, as another new very important field of technology, has taken more than a decade. The development included the identification of material properties important for usage as a hydraulic fluid, an extensive preselection process and laboratory testing of suitable ionic liquids, as well as long‐term testing using real hydraulic components under real operating conditions. Based on the findings, potential areas of industrial application of ionic liquids as hydraulic fluids are presented, which arise from their extraordinary physicochemical properties.
Chemoselective Coupling of π‐Systems to Access Metallated 1,4‐ or 1,5‐Skipped Dienes in Multicomponent Reactions
Authors: Pradhan Tapas R. , Kyoon Park Jin
Published: September 2022

Integrating distinct unsaturated C−C systems while simultaneously installing metallic groups has been significantly challenging to execute in a multicomponent reaction. Therefore, designing a suitable mechanistic pathway that provides the required reactivity and selectivity for target C−C bonds with metallic reagents to ensure successful coupling is the key to success. Copper‐catalyzed borylallylation and silylallylation have emerged as the most efficient strategies for assembling borylated/silylated skipped (1,4 or 1,5) dienes by catalytically combining an organocopper intermediate with allyl electrophiles. However, reactions involving interelemental reagents (e. g., [Si]−[B]) to accomplish intermolecular atom‐economic couplings have not been studied thoroughly. Therefore, to aid the development of new transformations in this research area, this article attempts to include all precedents, including recent studies by the authors. The present Concept article may be helpful for researchers working in this area as it provides a basic conceptual framework.
Enrollment of adolescent and young adult patients newly diagnosed with cancer in NCI CTEP‐sponsored clinical trials before and after launch of the NCI National Clinical Trials Network
Authors: Sankaran Hari , Finnigan Shanda R. , McShane Lisa M. , Best Ana F. , Seibel Nita L.
Published: September 2022

Background

Participation of adolescents and young adults (AYAs) in oncology clinical trials is important to ensure adequate opportunities for AYA patients to contribute to, and benefit from, advances in cancer treatment.

Methods

Accrual data for National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP) cooperative group‐led treatment trials were examined to assess enrollment of newly diagnosed AYA patients (15–39 years) during the period 2004–2019, with particular interest in comparing enrollment before launch of the NCI National Clinical Trials Network (NCTN) to after. All phase 2, 2/3, and 3 trials activated during the period between January 1, 2004, and December 31, 2019, were identified (n = 1568) and reduced to a set of 304 that met predetermined criteria to focus on cooperative group‐led trials that involved therapy for newly diagnosed cancer and had age eligibility overlapping the AYA range. The proportion of AYA patients relative to total accrual, along with 95% bootstrapped CI was calculated for patients enrolled pre‐NCTN and post‐NCTN.

Results

AYA accrual comprised 9.5% (95% CI, 7.6–11.8) pre‐NCTN compared with 14.0% (95% CI, 9.9–18.3) post‐NCTN. The mean difference in proportions post‐NCTN compared with pre‐NCTN was 4.4% (0.7%–8.3%).

Conclusions

These results indicate an increase in AYA participation in trials conducted within the NCTN relative to the pre‐NCTN period. This suggests an awareness and utilization of NCTN trials for AYAs with cancer.