bluuebunny/crossref_metadata_2025_split huggingface dataset:
The RNA binding protein Nab2 genetically interacts with multiple RNA exosome cofactors to regulate target RNAs
Authors: Kinney Christy E. , Mills-Lujan Katherine , Fasken Milo B. , Corbett Anita H. 
Published: February 2022

AbstractRNA binding proteins play important roles in the processing and precise regulation of RNAs. Highlighting the biological importance of RNA binding proteins is the increasing number of human diseases that result from mutations in genes that encode these proteins. We recently discovered that mutations in theZC3H14gene, which encodes an evolutionarily conserved polyadenosine RNA-binding protein, cause intellectual disability. Studies of the budding yeast orthologue of ZC3H14, Nuclear Poly(A) Binding protein 2 (Nab2), have provided insight into the functions of this protein. TheNAB2gene is essential inS. cerevisiae, and conditionalnab2mutants cause defects in a number of steps in RNA processing. To explore the critical functions of the Nab2/ZC3H14 protein family, we performed a high-copy suppressor screen onnab2mutant cells. This screen identified genes encoding two core subunits of the RNA exosome, as well as Nrd1 and Ski7, nuclear and cytoplasmic cofactors of the RNA exosome, respectively. Nrd1 is an RNA binding protein that is part of the Nrd1-Nab3-Sen1 (NNS) complex, which plays an important role in transcription termination of non-coding RNAs. Ski7 is a GTP-binding protein that mediates interaction between the RNA exosome and the Ski complex, which targets RNA transcripts to the exosome for processing and degradation in the cytoplasm. To explore the functional interactions between the RNA exosome and Nab2, we employed RNA-seq analysis to identify the transcripts most impacted by overexpression of these exosome cofactors innab2mutant cells. This analysis revealed that many transcripts show small changes in steady-state levels, consistent with a global role of Nab2 in modulating transcript stability. This study uncovers functional interactions between the RNA exosome and Nab2 in both the nucleus and the cytoplasm.
Sinking the way: a dual role for CCR7 in collective leukocyte migration
Authors: Alanko Jonna , Ucar Mehmet Can , Canigova Nikola , Stopp Julian , Schwarz Jan , Merrin Jack , Hannezo Edouard , Sixt Michael 
Published: February 2022

AbstractImmune responses crucially rely on the rapid and coordinated locomotion of leukocytes. While it is well established that single-cell migration is often guided by gradients of chemokines and other chemoattractants, it remains poorly understood how such gradients are generated, maintained and modulated. Combining experiment and theory on leukocyte chemotaxis guided by the G protein-coupled receptor (GPCR) CCR7, we demonstrate that in addition to its role as the sensory receptor that steers migration, CCR7 also acts as a generator and modulator of chemotactic gradients. Upon exposure to the CCR7 ligand CCL19, dendritic cells (DCs) effectively internalize the receptor and ligand as part of the canonical GPCR-desensitization response. We show that CCR7 internalization also acts as an effective sink for the chemoattractant, thereby dynamically shaping the spatio-temporal distribution of the chemokine. This mechanism drives complex collective migration patterns, enabling DCs to create or sharpen chemotactic gradients. We further show that these self-generated gradients can sustain the long-range guidance of DCs, adapt collective migration patterns to the size and geometry of the environment, as well as provide a guidance cue for other co-migrating cells. Such dual role of CCR7 as a GPCR that both senses and consumes its ligand can thus provide a novel mode of cellular self-organization.
Inactivation of B. cereus Spores in Whole Milk and Almond Milk by Novel Serpentine Path Coiled Tube UV-C System
Authors: Pendyala Brahmaiah , Patras Ankit , Gopisetty Vybhav Vipul Sudhir , Vashisht Pranav , Ravi Ramasamy 
Published: February 2022

AbstractA novel continuous thin-film (1.59 mm) serpentine path coiled tube (SPCT) UV system operating at 254 nm wavelength was designed and compared with flow field distribution of whole milk with helical path coiled tube (HPCT) UV system using computational fluid dynamics. The results revealed efficient velocity magnitude distribution at serpentine bend geometric locations of the SPCT UV system. Further in this study, we evaluated B. cereus Spores inactivation in whole milk (WM) and almond milk (AM) using the developed SPCT UV system. Experimental data showed that > 4 log reduction of spores was achieved after six and ten passes of WM and AM at a flow rate of 70 and 162 mL/min, respectively. The biodosimetry method was used to verify the delivered reduction equivalent fluence (REF) and reported as 33 ± 0.73 and 36.5 ± 1.9 mJ/cm2. We noticed no significant effect on lipid oxidation and volatiles profile (p > 0.05) up to delivered REF of 60 mJ/cm2. This study demonstrated that high levels of inactivation of B. cereus spores could be feasible with minimal impact on product quality by UV-C processing of dairy and non-dairy opaque scattering fluids.
Blockage of Lamin-A/C loss diminishes the pro-inflammatory macrophage response
Authors: Mehl Johanna L. , Earle Ashley , Lammerding Jan , Mhlanga Musa , Vogel Viola , Jain Nikhil 
Published: February 2022

AbstractMutations and defects in nuclear lamins can cause major pathologies in affected tissues. Recent studies have also established potential links between lamins, inflammation, and inflammatory diseases but the underlying molecular mechanisms are unknown. We now report that pro-inflammatory activation of macrophages reduces levels of Lamin-A/C to augment pro-inflammatory gene expression and cytokine secretion. We show that activation of bone-marrow derived macrophages (BMDMs) degrades Lamin-A/C, as preceded by its phosphorylation, which is mediated by Caspase-6 and CDK1, respectively. Inhibiting Lamin-A/C phosphorylation and degradation severely inhibits pro-inflammatory gene expression and cytokine secretion. Using LPS-activated Lamin-A/C Knock Out BMDMs, we confirmed that the activation of the IFN-β-STAT pathway is amplified due to Lamin-A/C reduction, which ultimately augments the pro-inflammatory response. As Lamin-A/C is a previously unappreciated regulator of the pro-inflammatory macrophage response, our findings could provide novel opportunities to treat inflammatory diseases. In first proof-of-concept studies we show that macrophage pro-inflammation, as induced by Lipopolysaccharide or pathogenic E. coli, could be reduced by inhibiting Lamin-A/C phosphorylation and degradation. The inhibition of macrophage pro-inflammation could also be achieved by inhibiting members of the Lamin-A/C regulated IFN-β-STAT pathway, i.e., phospho-STAT1 and phospho-STAT3. This newly found mechanism to suppress the pro-inflammatory response of macrophages will provoke a re-thinking of how inflammation can be addressed therapeutically.
Estrogen suppresses DMRT1 expression during ovarian development in the chicken
Authors: Zhao Debiao , Liu Long , Nandi Sunil , Ioannidis Jason , Yang Xiurong , Gong Daoqing , McGrew Mike J. , Clinton Michael 
Published: February 2022

AbstractPrimary sex determination is the choice between two different developmental fates, a testis or an ovary. This selection is thought to require the action of a master regulator gene that triggers expression of a gene cascade in the bipotential gonad precursor in one sex. The selection of a particular developmental pathway is also thought to suppress the alternative developmental pathway.In birds, where the male is the homogametic sex (ZZ) and females the heterogametic sex (ZW), the Z-linked transcription factor DMRT1 is considered the master regulator and has been shown to be essential for testis development, and to also inhibit the ovarian pathway. Here, we characterise in detail, DMRT1 transcription and protein levels during gonadal development in the chick. Our analysis suggests that DMRT1 protein levels are equivalent in male and female gonads during the bipotential phase of development, and that DMRT1 protein levels are reduced in the developing ovary during the differentiation phase. The reduction in DMRT1 protein levels in the somatic cells of the female medulla, coincides with the induction of aromatase expression and the initiation of estrogen synthesis. Analysis of sex-reversed gonads and mixed-sex chimeric gonads, suggests that the reduction in DMRT1 protein is due to inhibition of DMRT1 expression by estrogen.Our data suggests that estrogen signalling is involved in primary sex determination by regulation of DMRT1 protein expression.
Structural Basis of HIV-1 Maturation Inhibitor Binding and Activity
Authors: Sarkar Sucharita , Zadrozny Kaneil K. , Zadorozhnyi Roman , Russell Ryan W. , Quinn Caitlin M. , Kleinpeter Alex , Ablan Sherimay , Xu Chaoyi , Perilla Juan R. , Freed Eric O. , Ganser-Pornillos Barbie K. , Pornillos Owen , Gronenborn Angela M. , Polenova Tatyana 
Published: February 2022

ABSTRACTHIV-1 maturation inhibitors (MIs) interfere with the final step in the viral lifecycle by disrupting the ordered proteolytic processing of the viral Gag polyprotein into its individual domains. Bevirimat (BVM) and its analogs interfere with the final catalytic cleavage of spacer peptide 1 (SP1) from the capsid protein (CA) C-terminal domain (CACTD), by binding to and stabilizing the CACTD-SP1 region. MIs are under development as alternative drugs to augment current antiretroviral therapies. Although promising, their mechanism of action and associated virus resistance pathways remain poorly understood at the molecular, biochemical, and structural levels. Here, we report atomic-resolution magic angle spinning (MAS) NMR structures of microcrystalline assemblies of CACTD-SP1 complexed with BVM and/or the assembly cofactor inositol hexakisphosphate (IP6). BVM and IP6 can bind simultaneously to SP1, with BVM positioned in the center of its 6-helix bundle in a unique conformation. Importantly, the NMR-observed structural effects of BVM on IP6 binding suggest that the inhibitor stabilizes the 6-helix bundle in multiple ways. In addition, BVM-resistant SP1-A1V and SP1-V7A variants exhibit distinct conformational and binding characteristics. Taken together, our results reveal a novel allosteric mechanism by which BVM disrupts maturation and provide a structural explanation for BVM resistance as well as important guidance for the design of new MIs.
Social dominance and reproduction result in increased integration of oxidative state in males of an African cichlid fish
Authors: Fialkowski Robert J. , Border Shana E. , Bolitho Isobel , Dijkstra Peter D. 
Published: February 2022

AbstractOxidative stress is a potential cost of social dominance and reproduction, which could mediate life history trade-offs between current and future reproductive fitness. However, the evidence for an oxidative cost of social dominance and reproduction is mixed, in part because organisms have efficient protective mechanisms that can counteract oxidative insults. Further, previous studies have shown that different aspects of oxidative balance, including oxidative damage and antioxidant function, varies dramatically between tissue types, yet few studies have investigated oxidative cost in terms of interconnectedness and coordination within the system. Here, we tested whether dominant and subordinate males of the cichlid Astatotilapa burtoni differ in integration of different components of oxidative stress. We assessed 7 markers of oxidative stress, which included both oxidative damage and antioxidant function in various tissue types (total of 14 measurements). Across all oxidative stress measurements, we found more co-regulated clusters in dominant males, suggesting that components of oxidative state are more functionally integrated in dominant males than they are in subordinate males. We discuss how a high degree of functional integration reflects increased robustness or efficiency of the system (e.g. increased effectiveness of antioxidant machinery in reducing oxidative damage), but we also highlight potential costs (e.g. activation of cytoprotective mechanisms may have unwanted pleiotropic effects). Overall, our results suggest that quantifying the extent of functional integration across different components of oxidative stress could reveal insights into the oxidative cost of important life history events.
6-Phosphogluconate dehydrogenase and its crystal structures
Authors: Hanau Stefania , Helliwell John R. 
Published: February 2022

6-Phosphogluconate dehydrogenase (6PGDH; EC 1.1.1.44) catalyses the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate in the context of the oxidative part of the pentose phosphate pathway. Depending on the species, it can be a homodimer or a homotetramer. Oligomerization plays a functional role not only because the active site is at the interface between subunits but also due to the interlocking tail-modulating activity, similar to that of isocitrate dehydrogenase and malic enzyme, which catalyse a similar type of reaction. Since the pioneering crystal structure of sheep liver 6PGDH, which allowed motifs common to the β-hydroxyacid dehydrogenase superfamily to be recognized, several other 6PGDH crystal structures have been solved, including those of ternary complexes. These showed that more than one conformation exists, as had been suggested for many years from enzyme studies in solution. It is inferred that an asymmetrical conformation with a rearrangement of one of the two subunits underlies the homotropic cooperativity. There has been particular interest in the presence or absence of sulfate during crystallization. This might be related to the fact that this ion, which is a competitive inhibitor that binds in the active site, can induce the same 6PGDH configuration as in the complexes with physiological ligands. Mutagenesis, inhibitors, kinetic and binding studies, post-translational modifications and research on the enzyme in cancer cells have been complementary to the crystallographic studies. Computational modelling and new structural studies will probably help to refine the understanding of the functioning of this enzyme, which represents a promising therapeutic target in immunity, cancer and infective diseases. 6PGDH also has applied-science potential as a biosensor or a biobattery. To this end, the enzyme has been efficiently immobilized on specific polymers and nanoparticles. This review spans the 6PGDH literature and all of the 6PGDH crystal structure data files held by the Protein Data Bank.
How can NGO accountability practices be improved with technologies such as blockchain and triple-entry accounting?
Authors: Kuruppu Sanjaya Chinthana , Dissanayake Dinithi , de Villiers Charl 
Published: February 2022

PurposeThe purpose of this paper is to explore how blockchain and triple-entry accounting technologies may improve non-governmental organisation (NGO) accountability by amplifying the social and economic outcomes of aid. It also provides a critique of these technologies from an accountability perspective.Design/methodology/approachAn in-depth case study of a large NGO, relying on semi-structured interviews, document analysis and non-participant observation, provides an understanding of current issues in existing NGO accountability and reporting systems. A novel case-conceptual critical analysis is then used to explore how blockchain and triple-entry accounting systems may potentially address some of the challenges identified with NGO accountability.FindingsAn empirical case study outlines the current processes which discharge accountability to a range of stakeholders, emphasising how “upward” accountability is privileged over other forms. This provides a foundation to illustrate how new technology can improve upward accountability to donors by enabling more efficient, accurate and auditable record-keeping and reporting, creating space for an NGO to focus on horizontal accountability to partner organisations and downward accountability to beneficiaries. Greater accountability exposes NGOs to diverse views from partner organisations and beneficiaries, potentially enhancing opportunities for learning and growth, i.e. greater impact. However, blockchain and triple-entry accounting can also create “over-accounting” and further entrench the power of upward stakeholders, such as donors, if not implemented carefully.Research limitations/implicationsA novel case-conceptual critical analysis furnishes new insights into how existing NGO accountability systems can be improved with technology. Despite the growing excitement about the possibilities of blockchain and triple-entry accounting systems, this paper offers a critical reflection on the limitations of these technologies and suggests avenues for future research.Practical implicationsExamples of how blockchain and triple-entry accounting systems can be integrated into NGO systems are presented. This research also raises the importance of creating a strong nexus between humans and technology, which ensures that “socialising” forms of accountability that empower vulnerable stakeholders, are embedded into international aid.Originality/valueThis research provides insight into present challenges with NGO accountability, using empirical evidence, furnishing potential solutions using novel blockchain and triple-entry accounting systems. Greater accountability to partner organisations and beneficiaries is important, as it potentially enables NGOs to learn how to be more impactful. Therefore, this paper introduces rich, contextually embedded perspectives on how NGO managers can exploit such technologies to enhance accountability and impact.
Benchmarking the banking sector of Bangladesh: a comprehensive analysis of performance and efficiency
Authors: Yesmine Tamanna , Hossain Md. Emran , Khan Md. Akhtaruzzaman , Mitra Sandip , Saha Sourav Mohan , Amin Md. Ruhul 
Published: February 2022

PurposeThe economic development of Bangladesh is heavily reliant on the banking industry, yet it faces numerous hurdles, including liquidity issues, capital shortages, non-performing loans, inefficiencies and so on. Therefore, this study investigated the performance and efficiency of scheduled banks (state-owned, private commercial, foreign commercial and specialized banks) operating in Bangladesh.Design/methodology/approachThe research was conducted using secondary data from annual reports of banks. The CAMELS rating system and Data Envelopment Analysis (DEA) methods were employed to measure the performance and efficiency of banks, respectively.FindingsIn the overall bank rankings, results revealed that foreign commercial Standard Chartered Bank and state-owned Sonali Bank Limited came in first and last position, respectively. Among the four categories of banks, foreign commercial banks were the best performer, while state-owned banks were the worst. Only two banks, i.e. Citibank NA and HSBC Bank, were scale efficient while the remaining banks were inefficient. In terms of performance and efficiency, state-owned and specialized banks were deemed wanting.Practical implicationsThis study proposes recommendations to the policymakers that could lead to more effective tactics for improving the banking industry's performance and efficiency.Originality/valueAs far as the authors are concerned, this study presents empirical evidence on the performance and efficiency of different types of banks and explores comparisons among them, which has never been done to this extent in the country before.
Bajaj Auto (a) – catering to the African market
Authors: Gupta Nitin 
Published: February 2022

Learning outcomes
After working through the case and assignment questions, students will be able to: understand how product markets in a given global region are to be analysed and assessed; assess various dimensions of consumer behaviour that would impact the strategies of a firm under consideration; identify how a firm can create its brand image and value proposition in a given international market; and evaluate and categorize various threat dimensions that a firm would experience in an international market.

Case overview/Synopsis
Bajaj Auto (BA) was India’s largest two-wheeler exporter, with ongoing exports to more than 75 countries worldwide. Besides being in other regions of the world, BA’s foray into the African market had been very successful, and it was growing from strength to strength in this market. BA’s motorcycles, three-wheeler rickshaws and small commercial vehicles had been successfully plying the roads of many countries in Africa such as Egypt, Nigeria and Kenya.
Rakesh Sharma (Sharma), the Executive Director of BA, knew very well that Africa was a high-risk-high-gain market for BA. Intense competition from Indian and international two-wheeler and three-wheeler manufacturers, global supply chain and logistics issues, various economic and legal challenges, and the threat of losing African consumer patronage were the challenging issues that Sharma was facing in this market. Would Sharma be able to effectively assess the market environment and consumer behaviour prevalent in the African countries? Would he be able to recognize BA’s brand and value-propositions and identify the international marketing challenges threatening BA’s smooth ride in this market?

Complexity academic level
The case can be taught in advanced undergraduate, MBA or executive-level programs.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 5: International Business.
The impact of ecotourism on local rural households' livelihood around Wolong Nature Reserve
Authors: Shi Huiyun , Zhang Lu , Song Boyao , He Chao 
Published: February 2022

PurposeThe development of tourism around Wolong Nature Reserve changes the local communities' ways of life. This study discusses how ecotourism affects the households' use of their capitals, the livelihood strategies as well as illustrates the impact on the habitats in the reserve through Department for International Development’s (DFID) Sustainable Livelihood Framework (SLF) with data collected during fieldwork.Design/methodology/approachThe study focuses on (1) Calculating Livelihood Capital Index. (2) The effects of livelihood capitals on livelihood strategy were calculated by multinomial logistic regression.FindingsThe study has yielded the following results: (1) In general, tourism promotes people's livelihood capitals. The growth in different types of households under tourism settings is ranked as full-time tourism operators > part-time tourism operators > traditional living households. (2) Tourism development mainly shifts livelihood strategies in two ways. Firstly, travel operating replaces some traditional practices that make livings; secondly, increased needs for potherbs and herbs from tourists let households enter into the hills to pick the plants more actively, which intensifies the destruction of giant panda's habitats. (3) Nine types of livelihood capitals indicators, namely farmland quality, distance between house and roads, number of laborers, average housing area, average income per person, whether family members being village cadres, and ever having received skills training shape livelihood strategies in different levels.Originality/valueThree discussions are drawn from the study: (1) Enhancing the exploit for tourism resources to form a diversified competition. (2) Introducing herb growing to fulfill tourists' needs and improve people's livelihood in the meantime. (3) Optimizing the tourism surveillance and management system and improving the rules and regulations.