bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenine Base Editing in vivo with a Single Adeno-Associated Virus Vector
Authors: Zhang Han , Bamidele Nathan , Liu Pengpeng , Ojelabi Ogooluwa , Gao Xin D. , Rodriguez Tomás , Cheng Haoyang , Xie Jun , Gao Guangping , Wolfe Scot A. , Xue Wen , Sontheimer Erik J. 
Published: December 2021

AbstractBase editors (BEs) have opened new avenues for the treatment of genetic diseases. However, advances in delivery approaches are needed to enable disease targeting of a broad range of tissues and cell types. Adeno-associated virus (AAV) vectors remain one of the most promising delivery vehicles for gene therapies. Currently, most BE/guide combinations and their promoters exceed the packaging limit (~5 kb) of AAVs. Dual-AAV delivery strategies often require high viral doses that impose safety concerns. In this study, we engineered an adenine base editor using a compact Cas9 from Neisseria meningitidis (Nme2Cas9). Compared to the well-characterized Streptococcus pyogenes Cas9-containing ABEs, Nme2-ABE possesses a distinct PAM (N4CC) and editing window, exhibits fewer off-target effects, and can efficiently install therapeutically relevant mutations in both human and mouse genomes. Importantly, we show that in vivo delivery of Nme2-ABE and its guide RNA by a single-AAV vector can efficiently edit mouse genomic loci and revert the disease mutation and phenotype in an adult mouse model of tyrosinemia. We anticipate that Nme2-ABE, by virtue of its compact size and broad targeting range, will enable a range of therapeutic applications with improved safety and efficacy due in part to packaging in a single-vector system.
Bacteria-derived peptidoglycan triggers an NF-κB dependent response in Drosophila gustatory neurons
Authors: Masuzzo Ambra , Manière Gérard , Grosjean Yaël , Kurz Léopold , Royet Julien 
Published: December 2021

AbstractProbing the external world is essential for eukaryotes to distinguish beneficial from pathogenic microorganisms. If it is clear that this task falls to the immune cells, recent work shows that neurons can also detect microbes, although the molecules and mechanisms involved are less characterized. In Drosophila, detection of bacteria-derived peptidoglycan by pattern recognition receptor (PRR) of the PGRP family expressed in immune cells, triggers NF-κB/IMD dependent signaling. We show here that one PGRP protein, called PGRP-LB, is expressed in some proboscis’s bitter taste neurons. In vivo calcium imaging reveals that the PGRP/IMD pathway is cell-autonomously required in these neurons to transduce the PGN signal. We finally show that NF-κB/IMD pathway activation in bitter neurons influences fly behavior. This demonstrates that flies use the same bacterial elicitor and signaling module to sense bacterial presence via the peripheral nervous system and trigger an anti-bacterial response in immune-competent cells.
Topological damping in an ultrafast giant cell
Authors: Chang Ray , Prakash Manu 
Published: December 2021

Cellular systems are known to exhibit some of the fastest movements in biology - but little is known as to how single cells can dissipate this energy rapidly and adapt to such large accelerations without disrupting internal architecture. To address this, we investigateSpirostomum ambiguum- a giant cell (1-4 mm in length) well-known to exhibit ultrafast contractions (50% of body length) within 5 msec with a peak acceleration of 15g. Utilizing transmitted electron microscopy (TEM) and confocal imaging, we discover a novel association of rough endoplasmic reticulum (RER) and vacuoles throughout the cell - forming a contiguous fenestrated membrane architecture that topologically entangles these two organelles. A nearly uniform inter-organelle spacing of 60 nm is observed between RER and vacuoles, closely packing the entire cell. Inspired by the entangled organelle structure, we study the mechanical properties of entangled deformable particles using a vertex-based model, with all simulation parameters matching 10 dimensionless numbers to ensure dynamic similarity. We demonstrate how entangled deformable particles respond to external loads by an increased viscosity against squeezing and help preserve spatial relationships. Because this enhanced damping arises from the entanglement of two networks incurring a strain-induced jamming transition at subcritical volume fractions, which is demonstrated through the spatial correlation of velocity direction, we term this phenomenon “topological damping”. Our findings suggest a new mechanical role of RER-vacuolar meshwork as a metamaterial capable of damping an ultra-fast contraction event.Significance StatementLittle is known about how single-cell organisms with extreme motility can decelerate or dissipate energy, as they lack connective tissues. Our study discovered a novel entangled rough endoplasmic reticulum (RER)-vacuolar meshwork architecture inSpirostomum ambiguum, an ultrafast giant cell that can contract itself with 15gaccelerations. We demonstrate through an entangled deformable particle model that the entangled architecture increases the squeeze-flow viscosity of particle systems and helps dampen the motion, a phenomenon we called “topological damping”. For biologists, our study suggests the mechanical role of RER through topological constraints on nearby organelles. For physicists, we point out a new way to create a system with strain-induced jamming. For engineers, we present a novel architecture that can provide braking functions.
Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma
Authors: Rosenberg MI , Greenstein E , Buchkovich M , Mikl M , Peres A , Santoni-Rugiu E , Reshef D , Salovin A , Gibbs DL , Irwin MS , Naranjo A , Ulitsky I , de Alarcon PA , Weigman V , Yaari G , Panzer JA , Friedman N , Maris JM 
Published: December 2021

SummaryNeuroblastoma is a lethal childhood solid tumor of developing peripheral nerves. Two percent of children with neuroblastoma develop Opsoclonus Myoclonus Ataxia Syndrome (OMAS), a paraneoplastic disease characterized by cerebellar and brainstem-directed autoimmunity, but typically with outstanding cancer-related outcomes. We compared tumor transcriptomes and tumor infiltrating T- and B-cell repertoires from 38 OMAS subjects with neuroblastoma to 26 non- OMAS associated neuroblastomas. We found greater B- and T-cell infiltration in OMAS- associated tumors compared to controls, but unexpectedly showed that both were polyclonal expansions. Tertiary lymphoid structures (TLS) were enriched in OMAS-associated tumors. We identified significant enrichment of the MHC Class II allele HLA-DOB*01:01 in OMAS patients. OMAS severity scores were associated with the expression of several candidate autoimmune genes. We propose a model in which polyclonal autoreactive B lymphocytes act as antigen presenting cells and drive TLS formation, thereby crucially supporting both sustained polyclonal T-cell-mediated anti-tumor immunity and paraneoplastic OMAS neuropathology.
The contribution of business continuity management (BCM) to supply chain resilience: a qualitative study on the response to COVID-19 outbreak
Authors: Riglietti Gianluca , Piraina Mariachiara , Trucco Paolo 
Published: December 2021

PurposeThis paper investigates the relationships between the core elements of a BCM system and SCRES constituents, i.e. visibility, agility, flexibility, velocity and collaboration. An explorative multiple case studies methodology was adopted, consisting of organizations in the retail, manufacturing and humanitarian sectors that had to withstand the impact of the first wave of the COVID-19 pandemic (January to June 2020).Design/methodology/approachThe paper adopts an interpretative approach to understand organizational behavior through observations. The source of data comes from in-depth interviews as well as the scrutiny of available official documents for triangulation. The unit of analysis is the organizations internal supply chain with a specific focus on their BCM system and SCM arrangements.FindingsThis paper shows how core BCM practices have a direct impact on supply chain resilience constituents. Specifically practices such as establishing a crisis management committee and risk assessments boost constituents such as agility and flexibility. This advances the theoretical discussion on supply chain resilience, while providing practical examples for organizations to build a response to pandemic incidents.Originality/valueThis paper validates the contribution of business continuity management to supply chain resilience, a concept that has mainly been linked to practices such as risk management. In this regard, this paper enriches the discussion. Secondly, the analysis explains how specific BCM practices worked during the first wave of the pandemic and how they were implemented, providing a clear path for supply chain resilience.
A 3-Ф grid connected wind system with a technique of DC link control using fewer sensors with fuzzy controller
Authors: Naveen Kilari D. , Sekhar A. Hema , Reddy N. Sudhakar , Dharani N.P. 
Published: December 2021

PurposeThis paper aims to provide a permanent magnet synchronous generator (PMSG) wind turbine, which feeds electric power (AC) to the power grid. The converter, located on the machine side, is used to produce the full amount of wind power. Research on wind energy conversion system (WECS) is carried out in this study using a direct wind turbine in MATLAB with constant and variable speeds.Design/methodology/approachThis paper is about WECS using PMSG and is connected to a grid of two serial converters with common DC connections.FindingsThis paper aims to provide the value of DC connection voltage at its base, regardless of the wind speed alterations, the inverter's output ac voltage can be kept constant.Originality/valueThis paper aims to provide a Hill Climb Search maximum power point tracking (MPPT) algorithm is an effective control system for extracting maximum energy, also called voltage control, pitch control, phase-locked loop (PLL) controls, from a wind turbine. Using the Fuzzy controller, the grid side converter is controlled.
Gender stereotypes change outcomes: a systematic literature review
Authors: Priyashantha K.G. , De Alwis A. Chamaru , Welmilla Indumathi 
Published: December 2021

PurposeEven though researchers have discussed gender stereotype change, only a few studies have specifically projected outcomes or consequences. Hence, the main purpose of this study is to examine the impact of gender stereotype change concerning the different outcomes.Design/methodology/approachIn achieving the purpose, the authors searched and reviewed current empirical knowledge on the outcomes of gender stereotype change in the Scopus and EBSCOhost databases from 1970 to 2020. The entire process was conducted through a systematic literature review methodology. The article selection criteria were executed using the PRISMA article selection flowchart steps, and 15 articles were included for the review.FindingsThe findings reveal that the outcomes from gender stereotype change research can be categorized mainly under the themes of “family and children,” “marriage” and “equality and women's employment.”Research limitations/implicationsThe co-occurrence network visualization map reveals gaps in the existing literature. There may be more possible outcomes relating to the current realities, and more cross-cultural research is needed.Practical implicationsThese outcomes provide some implications for policymakers.Originality/valueEven though researchers have discussed gender stereotype change on its various outcomes or consequences, research is less. Hence, this study provides a synthesis of consequences and addresses the gaps in the area.
Constraints and strategies for municipal Sukuk issuance in Indonesia
Authors: Mawardi Imron , Widiastuti Tika , Al Mustofa Muhammad Ubaidillah 
Published: December 2021

Purpose
This study aims to examine the constraints in the issuance of municipal Sukuk in Indonesia and proposed potential solutions and strategies to support its implementation.

Design/methodology/approach
This study used the analytic network process (ANP) method with four groups of relevant respondents that comprised representatives from the local government, universities (academicians), experts (practitioners) and regulators.

Findings
Four elements support municipal Sukuk issuance: issuer (regional government or municipality), investor, market and infrastructure. The element with the highest score was the lack of commitment from the regional government in issuing municipal sukuk due to leadership change that occurs every five years. Thus, specific regulations that strengthen and regulate municipal Sukuk issuance and the support from the central government are the priority solutions and strategies that should be undertaken to encourage regional governments in issuing municipal Sukuk.

Practical implications
The establishment of specific regulations by the central government that support and strengthen municipal Sukuk issuance is necessary to promote successful implementation. Supports from the central government include tax incentives, accessible licensing processes and bureaucracy aids.

Originality/value
This study extended the literature by examining problems, solutions and strategies for municipal Sukuk issuance in terms of four aspects: the issuer (municipal government), investors, markets and infrastructure. The multiple aspect analyses provided a broader understanding of the lack of municipal Sukuk issuance in Indonesia.
Tensile and shear strength for a self-drilling screw and transition of failure-modes and shear-strengths for self-drilling screwed connections at elevated-temperatures
Authors: Ozaki Fuminobu , Liu Ying , Ye Kai 
Published: December 2021

PurposeThe purpose of this study is to clarify both tensile and shear strength for self-drilling screws, which are manufactured from high-strength, martensitic-stainless and austenitic stainless-steel bars, and the load-bearing capacity of single overlapped screwed connections using steel sheets and self-drilling screws at elevated temperatures.Design/methodology/approachTensile/shear loading tests for the self-drilling screw were conducted to obtain basic information on the tensile and shear strengths at elevated temperatures and examine the relationships between both. Shear loading tests for the screwed connections at elevated temperatures were conducted to examine the shear strength and transition of failure modes depending on the test temperature.FindingsThe tensile and shear strengths as well as the reduction factors at the elevated temperature for each steel grade of the self-drilling screw were quantified. Furthermore, either screw shear or sheet bearing failure mode depending on the test temperature was observed for the screwed connection.Originality/valueThe transition of the failure modes for the screwed connection could be explained using the calculation formulae for the shear strengths at elevated temperatures, which were proposed in this study.
Understanding the Dynamics of UK Covid‐19 SME Financing
Authors: Calabrese Raffaella , Cowling Marc , Liu Weixi 
Published: December 2021

AbstractThe scale of the UK government's response to the Covid‐19 crisis after the first lockdown in March 2020 was unprecedented. For the business sector, two financing schemes were particularly relevant: the Coronavirus Business Interruption Loan Scheme (CBILS) and the Bounce Back Loan Scheme (BBLS). Both were designed to support the capitalization of businesses through this difficult trading period. In this paper, we use data covering the first two quarters of the Covid‐19 crisis to explore the dynamics of small and medium‐sized enterprise (SME) financing and in particular the role of government support schemes. Our findings show that 92.1% of all debt funds provided in this period were backed by the UK government, which compares to less than 5% under normal circumstances. We find that the demand, supply and government share of SME lending increased from Covid‐19 quarter 1 (April–June 2020) to quarter 2 (July–September 2020), that micro and small businesses had the highest demand for loans, and that better‐performing firms were more likely to receive loans. Further, in a world where more loan requests than ever were granted, the government share of this pool of loans had a different risk profile than the small pool of non‐government‐backed loans.
A multitechnique approach for discrimination and identification of lipsticks for forensic purposes
Authors: Gładysz Marta , Król Małgorzata , Karoly Agnes , Szalai Rita , Kościelniak Paweł 
Published: December 2021

AbstractCosmetics are becoming more and more popular; consequently, the chance of finding them as microtraces at a crime scene increases. They are easily transferable and can provide a link between a suspect and a victim. For this reason, identifying and comparative analysis of red lipstick – the most popular and used – is required.The aim of this study was to apply a multitechnique methodology for the comparative forensic analysis of the red lipsticks traces of a very similar hue. For this purpose, four methods of different physicochemical basics – two nondestructive spectroscopic and two destructive separation techniques – were used. The possibilities and advantages of attenuated total reflection infrared spectroscopy (ATR‐FTIR), confocal Raman microscopy (CRM), capillary electrophoresis (MEKC) and gas chromatography‐mass spectrometry (GC‐MS) have been combined. Specially prepared lipstick traces in various forms (imprints, smears) on different surfaces (absorbent and nonabsorbent) were analyzed to confirm the usefulness of the proposed methods. The premise is that if two methods yield a consistent result, the investigation is terminated at this stage.All investigated traces were properly identified. First, the ATR‐FTIR method as a nondestructive technique is recommended. Sometimes, due to strong interferences from the substrates, the newly proposed method with the use of confocal Raman microscopy may be an alternative. The next recommendation is the MEKC method. Only in case of the absence of unambiguous conclusions, it is proposed to use the GC‐MS method. This methodology has the potential to be applied in the comparative analysis of red lipsticks for forensic purposes.
Evolution of holometaboly revealed by developmental transformation of internal thoracic structures in a green lacewing Chrysopa pallens (Neuroptera: Chrysopidae)
Authors: Zhao Chenjing , Wang Mengqing , Gao Caixia , Li Min , Zhang Kuiyan , Yang Ding , Liu Xingyue 
Published: December 2021

AbstractDespite extensive studies on the morphology of holometabolous insects and their larvae, the morphological transformations of internal structures during metamorphosis have been rarely documented. Here, we used micro‐computed tomography to investigate the developmental transformations of thoracic structures in the green lacewing Chrysopa pallens (Rambur, 1838) (Neuroptera: Chrysopidae), with emphasis on the development of the digestive, tracheal, and thoracic skeleto‐muscular system. All the adult organs were modified during the prepupal or early pupal stage. The histolysis and remodeling began with the skeletal elements, followed by changes in the digestive system before it concluded with modifications of the musculature. Similar to the tracheal system's development, the digestive system did not disappear completely throughout metamorphosis but underwent a dramatic morphological change, which included the midgut significantly decreasing in size during the pupal stage. Our results provide important evidence for understanding the evolutionary pattern of developmental transformations in different major lineages of Holometabola.
Monitoring COVID‐19 through SARS‐CoV‐2 quantification in wastewater: progress, challenges and prospects
Authors: Alhama José , Maestre Juan P. , Martín M. Ángeles , Michán Carmen 
Published: December 2021

SummaryWastewater‐Based Epidemiology (WBE) is widely used to monitor the progression of the current SARS‐CoV‐2 pandemic at local levels. In this review, we address the different approaches to the steps needed for this surveillance: sampling wastewaters (WWs), concentrating the virus from the samples and quantifying them by qPCR, focusing on the main limitations of the methodologies used. Factors that can influence SARS‐CoV‐2 monitoring in WWs include: (i) physical parameters as temperature that can hamper the detection in warm seasons and tropical regions, (ii) sampling methodologies and timetables, being composite samples and Moore swabs the less variable and more sensitive approaches, (iii) virus concentration methodologies that need to be feasible and practicable in simpler laboratories and (iv) detection methodologies that should tend to use faster and cost‐effective procedures. The efficiency of WW treatments and the use of WWs for SARS‐CoV‐2 variants detection are also addressed. Furthermore, we discuss the need for the development of common standardized protocols, although these must be versatile enough to comprise variations among target communities. WBE screening of risk populations will allow for the prediction of future outbreaks, thus alerting authorities to implement early action measurements.
Regulatory role of cathepsin L in induction of nuclear laminopathy in Alzheimer’s disease
Authors: Islam Md Imamul , Nagakannan Pandian , Shcholok Tetiana , Contu Fabio , Mai Sabine , Albensi Benedict C , Del Bigio Marc R. , Wang Jun‐Feng , Sharoar Md Golam , Yan Riqiang , Park Il‐Seon , Eftekharpour Eftekhar 
Published: December 2021

AbstractExperimental and clinical therapies in the field of Alzheimer's disease (AD) have focused on elimination of extracellular amyloid beta aggregates or prevention of cytoplasmic neuronal fibrillary tangles formation, yet these approaches have been generally ineffective. Interruption of nuclear lamina integrity, or laminopathy, is a newly identified concept in AD pathophysiology. Unraveling the molecular players in the induction of nuclear lamina damage may lead to identification of new therapies. Here, using 3xTg and APP/PS1 mouse models of AD, and in vitro model of amyloid beta42 (Aβ42) toxicity in primary neuronal cultures and SH‐SY5Y neuroblastoma cells, we have uncovered a key role for cathepsin L in the induction of nuclear lamina damage. The applicability of our findings to AD pathophysiology was validated in brain autopsy samples from patients. We report that upregulation of cathepsin L is an important process in the induction of nuclear lamina damage, shown by lamin B1 cleavage, and is associated with epigenetic modifications in AD pathophysiology. More importantly, pharmacological targeting and genetic knock out of cathepsin L mitigated Aβ42 induced lamin B1 degradation and downstream structural and molecular changes. Affirming these findings, overexpression of cathepsin L alone was sufficient to induce lamin B1 cleavage. The proteolytic activity of cathepsin L on lamin B1 was confirmed using mass spectrometry. Our research identifies cathepsin L as a newly identified lamin B1 protease and mediator of laminopathy observed in AD. These results uncover a new aspect in the pathophysiology of AD that can be pharmacologically prevented, raising hope for potential therapeutic interventions.