bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pair of transporters controls mitochondrial Zn2+ levels to maintain mitochondrial homeostasis
Authors: Ma Tengfei , Zhao Liyuan , Zhang Jie , Tang Ruofeng , Wang Xin , Liu Nan , Zhang Qian , Wang Fengyang , Li Meijiao , Shan Qian , Yang Yang , Yin Qiuyuan , Yang Limei , Gan Qiwen , Yang Chonglin 
Published: July 2021

AbstractZn2+ is required for the activity of many mitochondrial proteins, which regulate mitochondrial dynamics, apoptosis and mitophagy. However, it is not understood how the proper mitochondrial Zn2+ level is achieved to maintain mitochondrial homeostasis. Using Caenorhabditis elegans, we reveal here that a pair of mitochondrion-localized transporters controls the mitochondrial level of Zn2+. We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn2+ exporter. Loss of SLC-30A9 leads to mitochondrial Zn2+ accumulation, which damages mitochondria, impairs animal development and shortens the life span. We further identify SLC-25A25/SCaMC-2 as an important regulator of mitochondrial Zn2+ import. Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn2+ accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9. Moreover, we reveal that the endoplasmic reticulum contains the Zn2+ pool from which mitochondrial Zn2+ is imported. These findings establish the molecular basis for controlling the correct mitochondrial Zn2+ levels for normal mitochondrial structure and functions.SummaryZn2+ is a trace ion essential for the function of many mitochondrial proteins. It is not known how mitochondrial Zn2+ levels are regulated. Ma at al. identify transporters that mediate mitochondrial Zn2+ export and import to maintain mitochondrial homeostasis.
Systematic analysis of the R2R3-MYB family of transcription factors in Camellia sinensis: evidence for species-specific catechin biosynthesis regulation
Authors: Li Jingyi , Liu Shaoqun , Chen Peifen , Cai Jiarong , Tang Song , Yang Wei , Cao Fanrong , Zheng Peng , Sun Binmei 
Published: July 2021

AbstractThe R2R3-MYB transcription factor family regulates metabolism of phenylpropanoids in various plant lineages. Species-expanded or specific MYB transcription factors may regulate species-specific metabolite biosynthesis including phenylpropanoid-derived bioactive products. C. sinensis produces an abundance of specialized metabolites, which makes it an excellent model for digging into the genetic regulation of plant-specific metabolite biosynthesis. The most abundant health-promoting metabolites in tea are galloylated catechins, and the most bioactive of the galloylated catechins, epigallocatechin gallate (EGCG), is exclusively found in C. sinensis. However, the transcriptional regulation of galloylated catechin biosynthesis remains elusive. This study mined the R2R3-MYB transcription factors associated with galloylated catechin biosynthesis in C. sinensis. A total of 118 R2R3-MYB proteins, classified into 38 subgroups, were identified. R2R3-MYB subgroups specific to or expanded in C. sinensis were hypothesized to be essential to evolutionary diversification of tea-specific metabolites. Notably, nine of these R2R3-MYB genes were expressed preferentially in apical buds and young leaves, exactly where galloylated catechins accumulate. Three putative R2R3-MYB genes displayed strong correlation with key galloylated catechin biosynthesis genes, suggesting a role in regulating biosynthesis of epicatechin gallate (ECG) and EGCG. Overall, this study paves the way to reveal the transcriptional regulation of galloylated catechins in C. sinensis.
The RNA m6A binding protein YTHDF2 promotes the B cell to plasma cell transition
Authors: Turner David J. , Saveliev Alexander , Salerno Fiamma , Matheson Louise S. , Screen Michael , Lawson Hannah , Wotherspoon David , Kranc Kamil R. , Turner Martin 
Published: July 2021

AbstractTo identify roles of RNA binding proteins (RBPs) in the differentiation of B cells to antibody-secreting plasma cells we performed a CRISPR/Cas9 knockout screen of 1213 mouse RBPs for their ability to affect proliferation and/or survival, and the emergence of differentiated CD138+ cells in vitro. We identified RBPs that promoted the appearance of CD138+ cells including CSDE1 and STRAP, as well as RBPs that inhibited CD138+ cell appearance such as EIF3 subunits EIF3K and EIF3L. Furthermore, we identified RBPs that share the property of recruiting the CCR4-NOT complex to their target transcripts have the potential to mediate opposing outcomes on B cell differentiation. One such RBP, the m6A binding protein YTHDF2 promotes the appearance of CD138+ cells in vitro. In chimeric mouse models YTHDF2-deficient B cells formed germinal centers in a cell-autonomous manner, however plasma cells failed to accumulate.
Characterization of brown-black pigment isolated from soil bacteria,Beijerinckia fluminensis
Authors: Joshi Mahesh H. , Patil Ashwini A. , Adivarekar Ravindra V. 
Published: July 2021

AbstractMelanin is a ubiquitous pigment found in most organisms, it is a dark-brown or black pigment formed by the oxidation of phenolic compounds. They are negatively charged amorphous compounds having quinone groups. In this study; melanin-producing microorganism was isolated from soil obtained from iron ore mine. The soil was enriched in modified Ashby’s glucose broth for 15 days at 30°C further to which it was isolated on modified Ashby’s agar at 30°C for seven days; the colonies showing pigmentation were selected for further study. Conditions were optimized for maximal production of melanin pigment. The effect of carbon, nitrogen, tyrosine, and metal salts on pigment production was studied. Alkaline conditions were used to extract the pigment from cells, further characterized by UV-VIS spectroscopy for λ-max. FTIR was done to identify the native functional groups, and XRD was performed to determine the melanin’s structure. TGA analysis was done to check its thermal stability. SEM was carried out to check the size and shape of the melanin pigment. The melanin pigment was also analyzed for UV protectant property which was studied by exposure of both melanized and non-melanized cells to UV light at 254nm.
VAL1 as an assembly platform co-ordinating co-transcriptional repression and chromatin regulation at Arabidopsis FLC
Authors: Mikulski Pawel , Wolff Philip , Lu Tiancong , Zhu Danling , Dean Caroline 
Published: July 2021

AbstractPolycomb (PcG) silencing is crucial for development across eukaryotes, but how PcG targets are regulated is still incompletely understood. The slow timescale of cold-induced PcG silencing at Arabidopsis thaliana FLOWERING LOCUS C (FLC) makes it an excellent system to dissect this mechanism. Binding of the DNA binding protein VAL1 to an FLC intronic RY motif within the PcG nucleation region is an early step in the silencing process. VAL1 interacts with APOPTOSIS AND SPLICING ASSOCIATED PROTEIN (ASAP) complex and POLYCOMB REPRESSIVE COMPLEX 1 (PRC1). Here, we show that ASAP and PRC1 function as co-repressors that quantitatively regulate FLC transcription. Upon the shift to cold PRC1-mediated H2Aub accumulates only at the nucleation region, is transiently maintained after transfer back to warm, but unlike the PRC2-delivered H3K27me3 does not spread across the locus. H2K27me3 thus provides long-term epigenetic silencing, whereas H2Aub is a transient repression signal. Overall, our work highlights how a DNA sequence-specific binding protein can act as an assembly platform co-ordinating the co-transcriptional repression and chromatin regulation necessary for Polycomb silencing.
Toxoplasma gondii subverts the host ESCRT machinery for parasite uptake of host cytosolic proteins
Authors: Rivera-Cuevas Yolanda , Mayoral Joshua , Di Cristina Manlio , Lawrence Anna-Lisa E. , Olafsson Einar B. , Thornhill Dishari , Waldman Benjamin S. , Ono Akira , Sexton Jonathan , Lourido Sebastian , Weiss Louis M. , Carruthers Vern B. 
Published: July 2021

AbstractToxoplasma gondii is a master manipulator capable of effectively siphoning the resources from the host cell for its intracellular subsistence. However, the molecular underpinnings of how the parasite gains resources from its host remain largely unknown. Residing within a non-fusogenic parasitophorous vacuole, the parasite must acquire resources across the limiting membrane of its replicative niche, which is decorated with parasite proteins including those secreted from dense granules. We discovered a role for the Endosomal Sorting Complex Required for Transport (ESCRT) machinery in host cytosolic protein uptake by T. gondii by disrupting host ESCRT function. We identified the transmembrane dense granule protein TgGRA14, which contains motifs homologous to the late domain motifs of HIV-1 Gag, as a candidate for the recruitment of the host ESCRT machinery to the PV membrane. Using an HIV virus-like particle (VLP) release assay, we found that the motif-containing portion of TgGRA14 is sufficient to substitute for HIV Gag late domain to mediate ESCRT-dependent VLP budding. We also show that TgGRA14 is proximal to and interacts with host ESCRT components and other dense granule proteins during infection. Furthermore, analysis of GRA14-deficient parasites revealed a marked reduction in ingestion of a host cytosolic protein compared to WT parasites. Thus, we propose a model in which T. gondii recruits the host ESCRT machinery to the PV where it can interact with TgGRA14 for the internalization of host cytosolic proteins across the PVM. These findings provide new insight into how T. gondii accesses contents of the host cytosol by exploiting a key pathway for vesicular budding and membrane scission.Author summaryIntracellular pathogens exploit their host to gain the resources necessary to sustain infection; however, precisely how the intracellular parasite Toxoplasma gondii acquires essential nutrients from its host remains poorly understood. Previous work showed that T. gondii is capable of internalizing host derived cytosolic proteins and delivering them to its lysosome-like compartment for degradation. However, the mechanism by which the material is trafficked across the membrane delimiting the replicative vacuole in which the parasite resides remained unclear. Here, we report a role for the parasite effector protein TgGRA14 in the recruitment of the host ESCRT machinery for the uptake of host cytosolic proteins. Important human pathogens have developed strategies for exploiting the host ESCRT machinery for intracellular subsistence. Our study sheds lights on the strategy used by a eukaryotic pathogen in subverting the host ESCRT machinery for the internalization of resources from its host cells.
Efficient inhibition of HIV using CRISPR/Cas13d nuclease system
Authors: Nguyen Hoang , Wilson Hannah , Jayakumar Sahana , Kulkarni Viraj , Kulkarni Smita 
Published: July 2021

AbstractRecently discovered Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas13 proteins are programmable RNA-guided ribonucleases that target single-stranded RNA (ssRNA). CRISPR/Cas13 mediated RNA targeting has emerged as a powerful tool for detecting and eliminating RNA viruses. Here, we demonstrate the effectiveness of CRISPR/Cas13d to inhibit HIV-1 replication. We designed guide RNAs (gRNAs) targeting highly conserved regions of HIV-1. RfxCas13d (CasRx) in combination with HIV-specific gRNAs efficiently inhibited HIV-1 replication in cell line models. Furthermore, simultaneous targeting of four distinct sites in the HIV-1 transcript resulted in robust inhibition of HIV-1 replication. We also show the effective HIV-1 inhibition in primary CD4+T-cells and suppression of HIV-1 reactivated from latently infected cells using the CRISPR/Cas13d system. Our study demonstrates the utility of the CRISPR/Cas13d nuclease system to target acute and latent HIV infection and provides an alternative treatment modality against HIV.
Developmental stage-specific spontaneous activity contributes to callosal axon projections
Authors: Tezuka Yuta , Hagihara Kenta M. , Ohki Kenichi , Hirano Tomoo , Tagawa Yoshiaki 
Published: July 2021

AbstractThe developing neocortex exhibits spontaneous network activity with various synchrony levels, which has been implicated in the formation of cortical circuits. We previously reported that the development of callosal axon projections, one of the major long-range axonal projections in the brain, is activity dependent. However, what sort of and when activity is indispensable are not known. Here, using a genetic method to manipulate network activity in a stage-specific manner, we demonstrated that network activity contributes to callosal axon projections in the mouse visual cortex during a “critical period”: restoring neuronal activity during that period resumed the projections, whereas restoration after the period failed. Furthermore, in vivo Ca2+ imaging revealed that the projections could be established even without fully restoring highly synchronous activity. Overall, our findings suggest that the spontaneous network activity is selectively required during a critical developmental time window for the formation of long-range axonal projections in the cortex. (150)
TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling
Authors: Sivakumar Sushama , Qi Shutao , Cheng Ningyan , Sathe Adwait A. , Kanchwala Mohammed , Kumar Ashwani , Evers Bret M. , Xing Chao , Yu Hongtao 
Published: July 2021

SUMMARYAneuploidy, defective differentiation, and inactivation of the tumor suppressor TP53 all occur frequently during tumorigenesis. Here, we probe the potential links among these cancer traits by inactivating TP53 in human embryonic stem cells (hESCs). TP53−/− hESCs exhibit increased proliferation rates, mitotic errors, and low-grade structural aneuploidy; produce poorly differentiated immature teratomas in mice; and fail to differentiate into neural progenitor cells (NPC) in vitro. Genome-wide CRISPR screen reveals requirements of ciliogenesis and sonic hedgehog (Shh) pathways for hESC differentiation into NPCs. TP53 deletion causes abnormal ciliogenesis in neural rosettes. In addition to restraining cell proliferation through CDKN1A, TP53 activates the transcription of BBS9, which encodes a ciliogenesis regulator required for proper Shh signaling and NPC formation. This developmentally regulated transcriptional program of TP53 promotes ciliogenesis, restrains Shh signaling, and commits hESCs to neural lineages.
The dimensional linkage between public service motivation and innovative behavior in public sector institutions; the mediating role of psychological empowerment
Authors: Rafique Muhammad Asim , Hou Yumei , Chudhery Muhammad Adnan Zahid , Gull Nida , Ahmed Syed Jameel 
Published: July 2021

PurposeInnovations are imperative for organizational growth and sustainability. This study focuses on the employees' innovative behavior, a source of organizational innovations, which has received substantial attention from the researchers. Based on the psychological empowerment theory, the study exposes the effect of the various dimensions of public service motivation (PSM) on employees' innovative behavior (IB) in public sector institutions especially in the context of developing countries such as Pakistan. Moreover, the study also investigates the mediating role of psychological empowerment (PSE) between the dimensions of PSM and IB.Design/methodology/approachThis study used the cross-sectional research design. By using random sampling, the adapted survey questionnaires were used to collect data from 346 faculty members of public sector universities located in provincial capitals of Pakistan. A partial least square–structural equation modeling (PLS-SEM) tool was used to assess the proposed hypotheses through SMART-PLS software.FindingsResults revealed that attraction to policymaking (APM), compassion (COM), self-sacrifice (SS) have a significant impact on employees' PSE and their innovative behavior, while the relationship of commitment to the public interest (CPI) with PSE and IB was found insignificant. Moreover, PSE partially mediated the relationship between PSM dimensions and employees' IB.Originality/valueThere was a scarcity of research on IB especially in public sector institutions such as academia. This study theoretically contributed to the literature by providing a refined picture in assessing the proposed relationship of the constructs. This is also one of the original studies that examine the relationship between the dimensions of PSM and IB.
Higher education student engagement in times of pandemic: the role of e-learning system usability and teacher behavior
Authors: Dahleez Khalid Abed , El-Saleh Ayman A. , Al Alawi Abrar Mohammed , Abdelmuniem Abdelfattah Fadi 
Published: July 2021

PurposeThis research examined the factors affecting several types of student engagement, namely agentic, behavioral, emotional and cognitive engagement. Specifically, it examined the effect of e-learning system usability on student engagement and explored teacher behavior's possible intervening impact on this relationship.Design/methodology/approachData were collected from 418 students studying at different specializations at Omani private academic institutions. This study employed a quantitative methodology and utilized the Smart-PLS for data analyses.FindingsThe findings showed that e-learning system usability influenced significantly and positively agentic, behavioral and cognitive engagement. However, the link between e-learning system usability and emotional engagement was not significant. Moreover, teacher behavior mediated the relationship between e-learning system usability and the four types of engagement.Originality/valueThis study improves one’s understanding of how the interaction of e-learning system usability and teacher behavior affects several aspects of student engagement. It also helps higher education administrators and policymakers by exploring the influential effects of e-learning systems usability and teacher behavior on facilitating students' engagement.
Determinants of environmental degradation in Saudi Arabia: exploring the unexplored
Authors: Tahir Muhammad , Hayat Arshad , Burki Umar 
Published: July 2021

Purpose
Environmental degradation is recognized as a serious problem globally, and hence, Saudi Arabia is no exception. This paper aims to focus on the economy of Saudi Arabia to identify the determinants of environmental degradation.

Design/methodology/approach
Time series data spanning from 1971 to 2014 is used and analyzed using the recently developed autoregressive distributed lag modeling approach.

Findings
The obtained results reflected that natural resources, per person income and urbanization, have impacted environmental degradation both positively and significantly in the long run. Similarly, an insignificant negative relationship is established between trade openness and environmental degradation. Moreover, energy consumption has positively but insignificantly affected environmental degradation. In the short run, only per capita income has positively influenced environmental degradation while the rest of the variables have lost either significance levels or their direction of relationship has reversed.

Originality/value
As this is a pioneering study on the economy of Saudi Arabia, therefore, the authors assume that policymakers will find the findings of the current study very useful while formulating and implementing policies to control environmental degradation.
Lesson study as a research approach: a case study
Authors: Jansen Susanne , Knippels Marie-Christine P.J. , van Joolingen Wouter R. 
Published: July 2021

PurposeThe purpose of this paper is to explore the merits of lesson study (LS) as a research approach for research in (science) education. A lesson was developed to introduce students to model-based reasoning: a higher order thinking skill that is seen as one of the major reasoning strategies in science.Design/methodology/approachParticipants of the LS team were three secondary school teachers and two educational researchers. Additionally, one participant fulfilled both roles. Both qualitative and quantitative data were used to investigate the effect of the developed lesson on students and to formulate focal points for using the LS as a research approach.FindingsThe developed lesson successfully familiarized students with model-based reasoning. Three main focal points were formulated for using LS as a research approach: (1) make sure that the teachers support the research question that the researchers bring into the LS cycle, (2) take into account that the lesson is supposed to answer a research question that might cause extra stress for the teachers in an LS team and (3) state the role of both researchers and teachers in an LS team clearly at the beginning of the LS cycle.Originality/valueThis study aims to investigate whether LS can be used as a research approach by the educational research community.
Data-driven performance management of business units using process mining and DEA: case study of an Iranian chain store
Authors: Maddah Negin , Roghanian Emad 
Published: July 2021

PurposeThe underlying purpose of this paper is to propose a comprehensive framework evaluating the performance of business units of an organization with a process perspective, identifying the most influential performance indicators, enabling managers to make more informed decisions based on data recording every day in their operational information systems.Design/methodology/approachFor proposing the conceptual framework of performance evaluation a synchronized analysis of selected process' data, obtained from an integrated information system of an Iranian chain store, was performed.FindingsThe superiority of the proposed framework results is demonstrated in comparison to applying the process mining solely; principal component analysis was identified as an efficient link between process mining and data envelopment analysis. Also, based on the final data analytics, the units' throughput times and the variety of brands and suppliers had the most impact on their performances.Research limitations/implicationsThe data of abundant business units and performance indicators, which would have allowed adding data prediction and other data analytics techniques for more insight, was not able to be accessed.Practical implicationsOrganizations' managers can use the framework to evaluate their business units' current status and then prioritize their resources based on the most influential performance indicators for overall improvement.Originality/valueThe study contributes to the research on performance management and process mining by presenting a comprehensive framework with two levels of data analytics. It stresses discovering what is happening in business units, and how to prioritize their improvement opportunities learning the significant correlations between performance indicators and units' performance.