bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shifting KRAS hotspot mutations inhibition paradigm in colorectal cancer
Authors: Brás Ana Rita , Lopes Ana , Mendes Nuno , Costa Paulo J. , Ferreira Anabela , Granja Sara , Silva Ana Paula , Tortosa Francisco , Baltazar Fátima , Gärtner Fátima , Sousa Maria João , Valente Andreia , Preto Ana 
Published: August 2023

AbstractKRAS hotspot mutations are difficult to target, highlighting the need of developing new specific target drugs for cancers driven by these mutations, like colorectal cancer (CRC). Here, we discover a new ruthenium compound, PMC79, that inhibits specifically mutated KRAS and the downstream signaling ERK and AKT proteins both “in vitro” and “in vivo”. We demonstrated that PMC79 inhibits KRAS mutated kinase activity and is selective for KRAS mutations not affecting the KRAS wild-type protein. KRAS inhibition is not dependent on actin polymerization or on proteasome. Molecular docking analysis suggests that this effect might result from protein dynamics associated with the mutations. We demonstrated that low doses of PMC79 potentiate 5-fluorouracil anticancer effect. “In vivo” PMC79 “proof of concept” showed that it reduces tumor growth in the CAM-xenograft model and induces necrosis of the tumor in the xenograft mice model. PMC79 is a promising new “magic bullet” for CRCs harboring mutated KRAS.
Molecular basis for proofreading by the unique exonuclease domain of Family-D DNA polymerases
Authors: Betancurt-Anzola Leonardo , Martinez-Carranza Markel , Delarue Marc , Zatopek Kelly M. , Gardner Andrew F. , Sauguet Ludovic 
Published: August 2023

AbstractReplicative DNA polymerases duplicate entire genomes at high fidelity. This feature is shared among the three domains of life and is facilitated by their dual polymerase and exonuclease activities. Family D replicative DNA polymerases (PolD), found exclusively in Archaea, contain an unusual RNA polymerase-like catalytic core, and a unique Mre11-like proofreading active site. Here, we present cryo-EM structures of PolD trapped in a proofreading mode, revealing an unanticipated correction mechanism that extends the repertoire of protein domains known to be involved in DNA proofreading. Based on our experimental structures, mutants of PolD were designed and their contribution to mismatch bypass and exonuclease kinetics was determined. This study sheds light on the convergent evolution of structurally distinct families of DNA polymerases, and the domain acquisition and exchange mechanism that occurred during the evolution of the replisome in the three domains of life.
Cell-type-specific plasticity shapes neocortical dynamics for motor learning
Authors: Majumder Shouvik , Hirokawa Koichi , Yang Zidan , Paletzki Ronald , Gerfen Charles R. , Fontolan Lorenzo , Romani Sandro , Jain Anant , Yasuda Ryohei , Inagaki Hidehiko K. 
Published: August 2023

AbstractNeocortical spiking dynamics control aspects of behavior, yet how these dynamics emerge during motor learning remains elusive. Activity-dependent synaptic plasticity is likely a key mechanism, as it reconfigures network architectures that govern neural dynamics. Here, we examined how the mouse premotor cortex acquires its well-characterized neural dynamics that control movement timing, specifically lick timing. To probe the role of synaptic plasticity, we have genetically manipulated proteins essential for major forms of synaptic plasticity, Ca2+/calmodulin-dependent protein kinase II (CaMKII) and Cofilin, in a region and cell-type-specific manner. Transient inactivation of CaMKII in the premotor cortex blocked learning of new lick timing without affecting the execution of learned action or ongoing spiking activity. Furthermore, among the major glutamatergic neurons in the premotor cortex, CaMKII and Cofilin activity in pyramidal tract (PT) neurons, but not intratelencephalic (IT) neurons, is necessary for learning. High-density electrophysiology in the premotor cortex uncovered that neural dynamics anticipating licks are progressively shaped during learning, which explains the change in lick timing. Such reconfiguration in behaviorally relevant dynamics is impeded by CaMKII manipulation in PT neurons. Altogether, the activity of plasticity-related proteins in PT neurons plays a central role in sculpting neocortical dynamics to learn new behavior.
PII signal transduction superfamily acts as a valve plug to control bicarbonate and ammonia homeostasis among different bacterial phyla
Authors: Haffner Michael , Hou Wen-Tao , Mantovani Oliver , Walke Peter R. , Hauf Ksenia , Borisova Marina , Hagemann Martin , Zhou Cong-Zhao , Forchhammer Karl , Selim Khaled A. 
Published: August 2023

AbstractLife on Earth relies on carbon and nitrogen assimilation by RubisCO and GS-GOGAT enzymes, respectively, whose activities depend on a constant supply of inorganic carbon (Ci) and nitrogen (N). Members of the PII signal transduction superfamily are among the most ancient and widespread cell signaling proteins in nature. One of their most highly conserved functions is controlling Ci- and N-transporters, a feature found in different phyla of the Archaea and in both Gram-positive and Gram-negative bacteria. Recently, we identified the PII-like protein SbtB as Ci-sensing module, mainly controlling the HCO3-transporter SbtA in cyanobacteria. Similar to canonical PII proteins, SbtB is able to bind the adenine nucleotides ATP and ADP. Unlike those, it also binds AMP and preferentially binds the second messenger cAMP and c-di-AMP. The functional significance of the binding of different adenyl-nucleotides to SbtB has remained elusive, particularly in the context of the interaction of SbtB with SbtA. By a combination of structural, biochemical and physiological analysis, we revealed that by binding to SbtA, SbtB acts as unidirectional valve, preventing the reverse transport of intracellular enriched bicarbonate. This mechanistic principle holds true for the PII protein fromBacillusacting on the ammonium transporter AmtB, suggesting an evolutionary conserved role for PII superfamily proteins in controlling unidirectional flow of different transporters.
Mode of carbon and energy metabolism shifts lipid composition in the thermoacidophileAcidianus
Authors: Rhim Jeemin H. , Zhou Alice , Amenabar Maximiliano J. , Elling Felix J. , Weber Yuki , Pearson Ann , Boyd Eric S. , Leavitt William D. 
Published: August 2023

AbstractThe degree of cyclization, or ring index (RI), in archaeal glycerol dibiphytanyl glycerol tetraether (GDGT) lipids was long thought to reflect homeoviscous adaptation to temperature. However, more recent experiments show that other factors (e.g., pH, growth phase, and energy flux) can also affect membrane composition. The main objective of this study was to investigate the effect of carbon and energy metabolism on membrane cyclization. To do so we cultivatedAcidianussp. DS80, a metabolically flexible and thermoacidophilic archaeon, on different electron donor, acceptor and carbon source combinations (S0/Fe3+/CO2, H2/Fe3+/CO2, H2/S0/CO2, or H2/S0/glucose). We show that differences in energy and carbon metabolism can result in over a full unit of change in RI in the thermoacidophileAcidianussp. DS80. The patterns in RI correlated with the normalized electron transfer rate between electron donor and acceptor and did not always align with thermodynamic predictions of energy yield. In light of this, we discuss other factors that may affect the kinetics of cellular energy metabolism: electron transfer chain (ETC) efficiency, location of ETC reaction components (cytoplasmicvs. extracellular), and the physical state of electron donors and acceptors (gasvs. solid). Furthermore, assimilation of a more reduced form of carbon during heterotrophy appears to decrease the demand for reducing equivalents during lipid biosynthesis, resulting in lower RI. Together, these results point to the fundamental role of the cellular energy state in dictating GDGT cyclization, with those cells experiencing greater energy limitation synthesizing more cyclized GDGTs.ImportanceSome archaea make unique membrane-spanning lipids with different numbers of five or six membered rings in the core structure that modulate membrane fluidity and permeability. Changes in membrane core lipid composition reflect fundamental adaptation strategies of archaea in response to stress, but multiple environmental and physiological factors may affect the needs for membrane fluidity and permeability. In this study, we tested howAcidianussp. DS80 changed its core lipid composition when grown with different electron donor/acceptor pairs. We show that changes in energy and carbon metabolisms significantly affected the relative abundance of rings in the core lipids of DS80. These observations highlight the need to better constrain metabolic parameters, in addition to environmental factors, that may influence changes in membrane physiology in Archaea. Such consideration would be particularly important for studying archaeal lipids from habitats that experience frequent environmental fluctuations and/or where metabolically diverse archaea thrive.
Prokaryotic microbial diversity analysis and metabolic function prediction of salt lakes on the Qinghai-Tibet Plateau
Authors: Zhang Man , Li Yongzhen , Zhu Derui , Xing Jiangwa , Long Qifu , Shen Guoping 
Published: August 2023

ABSTRACTThe Dong Taijinar Salt Lake (DT) and Xi Taijinar Salt Lake (XT) have been widely studied as mineral-rich areas. However, little is known about the composition and distribution of the microbial communities in these two lakes. In this study, metagenomics sequencing was used to analyze the diversity and potential functions of the microbial communities in DT and XT. According to our report, the salinity of DT (332.18–358.30 g/L) was 10 times higher than that of XT (20.09–36.83 g/L). Interestingly, the dominant domain in DT was Archaea (96.16%), while that in XT was Bacteria (93.09%). The distribution ofBacteriain the DT revealed 33 phyla and 1717 genera. The dominant genus in DT wasMarinobacillus, which was positively correlated with total phosphorus content. There were four main phyla and 153 genera identified in theArchaeaof DT. The most abundantArchaeagenera in DT wereNatronomonas(24.61%) andHalorubrum(23.69%), which were mainly positively correlated with the Na+, Ca2+, and Cl−contents. Similarly, there were 33 phyla and 1906 genera ofBacteriain XT, andLoktanellawas the dominant genus. The archaeal taxonomy in XT mainly included four phyla and 149 genera.ProteobacteriaandEuryarchaeotawere the most abundant bacterial and archaeal phyla in the two salt lakes. Analysis of the halophilic mechanisms of the microorganisms identified in these two salt lakes revealed that theBacteriain XT preferred to synthesize compatible solutes, whereas theArchaeain DT preferred a “salt-in” adaptation strategy in salt-stressed environments.IMPORTANCEThe Qinghai-Tibet Plateau is the origin of many lakes and mountains in China. Among them, the Dong Taijinar and Xi Taijinar salt lakes are important biological resources with unknown microbial community compositions and functional potentials. The results of this study revealed significant differences in the distribution ofBacteriaandArchaeabetween the two salt lakes. Salinity mainly drives lower biodiversity and restricted bacterial growth and metabolism in the high-salinity and near-saturated Dong Taijinar Salt Lake. This study not only identifies the key microorganisms in two penetrating salt lakes, but also provides insights into the mechanisms of salinity tolerance and the unknown ecological functions of microorganisms in extreme environments.
Impaired extinction of cocaine seeking in HIV-infected mice is accompanied by peripheral and central immune dysregulation
Authors: Buck Lauren A , Xie Qiaowei , Willis Michelle , Side Christine M , Giacometti Laura L , Gaskill Peter J , Park Kyewon , Shaheen Farida , Guo Lili , Gorantla Santhi , Barker Jacqueline M 
Published: August 2023

AbstractSubstance use disorders (SUDs) are highly comorbid with HIV infection, necessitating an understanding of the interactive effects of drug exposure and HIV. The relationship between progressive HIV infection and cocaine use disorder is likely bidirectional, with cocaine use having direct effects on immune function while HIV infection can alter addiction-related behavior. To better characterized the neurobehavioral and immune consequences of HIV infection and cocaine exposure, this study utilized a humanized mouse model to investigate the outcomes of progressive HIV infection on cocaine-related behaviors in a cocaine conditioned place preference (CPP) model, and the interactive effects of cocaine and HIV infection on peripheral and central nervous system inflammation. HIV infection did not impact the formation of a cocaine CPP, but did result in resistance to extinction of the CPP. No effects of HIV on yohimbine-primed reinstatement or cocaine seeking under conflict were observed. These behavioral alterations were accompanied by immune changes in HIV infected mice, including increased prefrontal cortex astrocyte immunoreactivity and brain-region specific effects on microglia number and reactivity. Peripheral immune system changes were observed in both mouse and human markers. Among other targets, this included HIV-induced reductions in mouse IL-1α and G-CSF and human TNFα and cocaine-induced alterations in human TNFα and mouse GM-CSF such that cocaine exposure increases both cytokines only in the absence of HIV infection. Together these data provide new insights into the unique neurobehavioral processes underlying HIV infection and cocaine use disorders, and further how they interact to effect immune responses.
Grocery retailer's brand performances from brand personalities and marketing offerings
Authors: Duh Helen Inseng , Pwaka Oliver 
Published: August 2023

PurposeDespite competition and supply-chain disruptions during Covid-19 pandemic (2019–2021), one grocery retailer consistently thrived and was ranked top. The sources of the sustained performances needed examination. Guided by self-congruity theory and integrating three models, the authors examined how much the retailer's brand performances (brand loyalty, equity, preference and repurchase intentions) were emanating from brand personalities and marketing offerings. The mediating roles of brand loyalty and equity were tested.Design/methodology/approachCross-sectional data was collected from 480 frequent customers using an online questionnaire posted on the researchers' social media pages. Factor analysis was conducted to identify the dimension that best describes the grocery retailer. Partial least square–structural equation modelling (PLS-SEM) was used to test a conceptual model.FindingsFactor analysis results show that brand sincerity (28.582% variance-explained; M = 4.1) was top (factor 1), followed by excitement (20.336% variance-explained; M = 3.9) and then trustworthiness (18.854% variance-explained; M = 3.87). PLS-SEM results revealed that two brand personalities (brand excitement and trustworthiness) and marketing offerings (price, place, product, promotion) impacted loyalty found to be a strong driver of brand equity. Repurchase intention and brand preference were influenced by brand equity. Brand loyalty mediated most of the relationships between brand personality dimensions, marketing offerings and brand equity. Brand equity also significantly mediated the relationships between brand loyalty, preference and repurchase intentions. The integrated model produced high explanatory powers with brand equity (67.8%), brand preference (71.7%), brand loyalty (63.2%) and repurchase intentions (54.2%).Originality/valueThe study extends a brand personality-loyalty model through integrating two other models that provided marketing offerings and brand equity outcomes. It demonstrates that a stream of profitable customers' responses awaits a retailer who holds both brand and customer mindsets by building admired brand personalities while providing desired marketing offerings.
The effect of NPLs management in the PIIGS banking efficiency: an approach using non-parametric partial order-m frontiers
Authors: Chalampalakis Emmanouil G. , Dokas Ioannis , Spyromitros Eleftherios 
Published: August 2023

PurposeThis study focuses on the banking systems evaluation in Portugal, Italy, Ireland, Greece and Spain (known as the PIIGS) during the financial and post-financial crisis period from 2009 to 2018.Design/methodology/approachA conditional robust nonparametric frontier analysis (order-m estimators) is used to measure banking efficiency combined with variables highlighting the effects of Non-Performing Loans. Next, a truncated regression is used to examine if institutional, macroeconomic, and financial variables affect bank performance differently. Unlike earlier studies, we use the Corruption Perception Index (CPI) as an institutional variable that affects banking sector efficiency.FindingsThis research shows that the PIIGS crisis affects each bank/country differently due to their various efficiency levels. Most of the study variables — CPI, government debt to GDP ratio, inflation, bank size — significantly affect banking efficiency measures.Originality/valueThe contribution of this article to the relevant banking literature is two-fold. First, it analyses the efficiency of the PIIGS banking system from 2009 to 2018, focusing on NPLs. Second, this is the first empirical study to use probabilistic frontier analysis (order-m estimators) to evaluate PIIGS banking systems.
Are the traditional socio-economic causes of poverty still pertinent nowadays? Evidence from Romania within the European Union context
Authors: Ulman Simona-Roxana , Dobay Krisztina Melinda 
Published: August 2023

PurposeFirstly, the authors aimed at offering a general perspective on poverty, highlighting important directions of thinking from the theoretical development, including poverty's main causes (like education, health, social protection, economic growth, employment and good governance). Secondly, it was investigated the problem of poverty in Romania after its accession to the European Union (EU), aiming to show (1) Romania's position among the EU member states, nearby (2) the direct and indirect effects of the selected factors particularly in this country.Design/methodology/approachBased on data from Eurostat and Global Competitiveness Index (GCI), descriptive and path analyses were performed for the period between 2007 and 2020.FindingsThe main results emphasized (1) the critical position of Romania among the EU member states in 2020 and the progress recorded since 2007, nearby (2) the direct and indirect effects of the selected factors on poverty in this country. The study highlighted the limited chances for the full participation of the poor people of Romania in the progress of the entire society, especially in terms of education and economic growth.Originality/valueThe major contribution of this study is that it assumes to investigate a profound and persistent societal phenomenon in Romania that is not sufficiently analyzed, discussed and understood. Consequently, this study attained its main objective of showing that the main traditional socio-economic causes of poverty are still pertinent in the actual Romanian society.
Climate change risk perception and pro-environmental behavior: the moderating role of environmental values and psychological contract breach
Authors: Latif Badar , Gaskin James , Gunarathne Nuwan , Sroufe Robert , Sharif Arshian , Hanan Abdul 
Published: August 2023

Purpose
Debates regarding climate change risk perception (CCRP), particularly its scale and impact on social and environmental sustainability, have continued for decades. CCRP is experiencing a renaissance with an increased focus on environmentally relevant behaviors to mitigate the effects of climate change. However, CCRP lacks investigation from the employee perspective. Supported by the social exchange and value–belief–norm theories, this study aims to address the impact of employees’ CCRP on their proenvironmental behavior (PEB) via the moderating roles of environmental values and psychological contract breach.

Design/methodology/approach
The nonprobability convenience sampling technique was used to collect survey data from a sample of 299 employees across 138 manufacturing firms in Pakistan.

Findings
The results show that employees’ CCRP positively impacts their PEB and that this relationship is moderated by their environmental values and psychological contract breach. Specifically, environmental values strengthen the CCRP–PEB relationship, while psychological contract breach weakens it.

Practical implications
The findings of the study emphasize useful guidance for managers and practitioners as a future avenue to restructure the climate change framework by emphasizing the conditions (i.e. environmental values and psychological contract breach). In doing so, the study is beneficial for managers and practitioners in helping to increase employees’ PEB through the development of climate change action plans.

Originality/value
To the best of the authors’ knowledge, this study is one of the first investigations into CCRP–employees’ PEB nexus in the developing country context. The study incorporates social exchange and value–belief–norm theory, which serve as the CCRP’s theoretical underpinnings. The findings advance the new knowledge about a firm’s social responsibility to achieve the sustainable development goals outlined in the UN’s 2030 Agenda.
Failure
Authors: Decker Scott H. 
Published: August 2023

AbstractThe Vollmer Award: The award honoring August Vollmer was first made in 1959. It is meant to recognize outstanding contributions to justice as well as scholarship and professional activity. I am honored to be the 2022 awardee because so many of the previous winners are individuals whose careers and work I have great respect for.Focus of My Remarks: This essay focuses on many failures in criminal justice policy and research. Costly though they may be, failures have the potential to teach us a good deal and we ignore them at our own peril.
Description of a new genus and species of Euptychiina (Lepidoptera: Nymphalidae) from the Brazilian Amazon rainforest
Authors: Barbosa Eduardo P. , Siewert Ricardo R. , Marín Mario A. , Machado Patrícia A. , Oliveira Isabela F. , Filho José A. C. , Freitas André V. L. 
Published: August 2023

AbstractA new monotypic genus in the ‘Archeuptychia clade’ Xikrin Barbosa, Freitas, Siewert & Marín gen. nov. (Nymphalidae: Satyrinae: Euptychiina) is described to accommodate a new species, Xikrin ueharapradoi Freitas & Barbosa gen. et sp. nov., in the highly diverse Satyrinae subtribe Euptychiina, based mainly on molecular data. To date, this species is known only from the region of Carajás, in the eastern Amazon rainforest. The phylogenetic relationship and taxonomy of this new taxon are discussed.
Dolichostylus gen. nov., a new Amazonian genus of portanine leafhoppers (Hemiptera: Cicadellidae) with two new species
Authors: Prando Jádila Santos , Gonçalves Clayton Corrêa , Dietrich Christopher H. , Takiya Daniela Maeda 
Published: August 2023

AbstractDolichostylus gen. nov., a new genus of Portanini, is described, and illustrated, based on two new species: Dolichostylus amazonicus gen. et sp. nov. from Brazil and Ecuador and Dolichostylus zahniseri gen. et sp. nov. from Ecuador. The new genus differs from other portanine genera in having the crown short and rounded, forewing without m‐cu2 vein, connective H‐shaped, style very long and slender, aedeagus with pair of elongate caudoventral processes, female sternite VII longer than wide and first valvula of ovipositor without a distinctly expanded area.