bluuebunny/crossref_metadata_2025 huggingface dataset:
A convergent malignant phenotype in B-cell acute lymphoblastic leukemia involving the splicing factor SRRM1
Authors: Closa Adria , Reixachs-Solé Marina , Fuentes-Fayos Antonio C. , Hayer Katharina E. , Melero Juan Luis , Adriaanse Fabienne R. S. , Bos Romy S. , Torres-Diz Manuel , Hunger Stephen , Roberts Kathryn G. , Mullighan Charles , Stam Ronald W. , Thomas-Tikhonenko Andrei , Castaño Justo P. , Luque Raúl M. , Eyras Eduardo
Published: December 2021

A significant proportion of infant B-cell acute lymphoblastic leukemia (B-ALL) patients remains with a dismal prognosis due to yet undetermined mechanisms. We performed a comprehensive multicohort analysis of gene expression, gene fusions, and RNA splicing alterations to uncover molecular signatures potentially linked to the observed poor outcome. We identified 87 fusions with significant allele frequency across patients and shared functional impacts, suggesting common mechanisms across fusions. We further identified a gene expression signature that predicts high risk independently of the gene fusion background and includes the upregulation of the splicing factorSRRM1. Experiments in B-ALL cell lines provided further evidence for the role of SRRM1 on cell survival, proliferation, and invasion. Supplementary analysis revealed that SRRM1 potentially modulates splicing events associated with poor outcomes through protein-protein interactions with other splicing factors. Our findings reveal a potential convergent mechanism of aberrant RNA processing that sustains a malignant phenotype independently of the underlying gene fusion, and that could potentially complement current clinical strategies in infant B-ALL.
A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A
Authors: Simon Matthew , Yang Jiping , Gigas Jonathan , Earley Eric J. , Schaff Tory M. , Zhang Lei , Zagorulya Maria , Tombline Greg , Gilbert Michael , Yuen Samantha L. , Pope Alexis , Meter Michael Van , Emmrich Stephan , Han Jeehae , Ryu Seungjin , Tare Archana , Zhu Yizhou , Hudgins Adam , Atzmon Gil , Barzilai Nir , Wolfe Aaron , Moody Kelsey , Garcia Benjamin A. , Thomas David D. , Robbins Paul D. , Vijg Jan , Seluanov Andrei , Suh Yousin , Gorbunova Vera
Published: December 2021

Sirtuin 6 (SIRT6) is a deacylase and mono-ADP ribosyl transferase (mADPr) enzyme involved in multiple cellular pathways implicated in the regulation of aging and metabolism. Targeted sequencing identified a SIRT6 allele containing two linked substitutions (N308K/A313S) as enriched in Ashkenazi Jewish (AJ) centenarians as compared to AJ control individuals. Characterization of this SIRT6 (centSIRT6) allele demonstrated it to be a stronger suppressor of LINE1 retrotransposons, confer enhanced stimulation of DNA double strand break repair, and more robust cancer cell killing compared to the wild type. Surprisingly, centSIRT6 displayed weaker deacetylase activity, but stronger mADPr activity, over a range of NAD+concentrations and substrates. Additionally, centSIRT6 displayed a stronger interaction with Lamin A/C (LMNA), which correlated with enhanced ribosylation of LMNA. Our results suggest that enhanced SIRT6 function contributes to human longevity by improving genome maintenance via increased mADPr activity and enhanced interaction with LMNA.
Metabolic properties of murine kidney mitochondria
Authors: Panov Alexander V. , Mayorov Vladimir I. , Dikalov Sergey I.
Published: December 2021

We show that mitochondria from the kidney of mice (MKM), rat brain (RBM), and heart (RHM) oxidize long-chain fatty acids at high rates in all metabolic states only in the presence of any other mitochondrial metabolites: succinate, glutamate, or pyruvate. All supporting substrates increased several folds the respiration rates in State 4 and State 3. The stimulations of the State 3 respiration with palmitoyl-carnitine + malate oxidation (100%) were: with succinate in MKM 340%, RBM 370%, and RHM 340%; with glutamate - MKM 200%, RBM 270%, and RHM 270%; and with pyruvate - MKM 150%, RBM 260%, and RHM 280%. The increases in O2 consumption in State 4 were due to increased leakage of electrons to produce superoxide radicals (O2•). Earlier, we have shown that the brain and heart mitochondria possess a strong intrinsic inhibition of succinate oxidation to prevent the excessive O2• production at diminished functional loads. We show that kidney mitochondria lack the intrinsic inhibition of SDH. The new methodology to study β-oxidation of LCFAs opens the opportunity to study energy metabolism under normal and pathological conditions, particularly in the organs that utilize LCFAs as the main energy source.
Single cell genome sequencing of laboratory mouse microbiota improves taxonomic and functional resolution of this model microbial community
Authors: Lyalina Svetlana , Stepanauskas Ramunas , Wu Frank , Sanjabi Shomyseh , Pollard Katherine S.
Published: December 2021

Laboratory mice are widely studied as models of mammalian biology, including the microbiota. However, much of the taxonomic and functional diversity of the mouse gut microbiome is missed in current metagenomic studies, because genome databases have not achieved a balanced representation of the diverse members of this ecosystem. Towards solving this problem, we used flow cytometry and low-coverage sequencing to capture the genomes of 764 single cells from the stool of three laboratory mice. From these, we generated 298 high-coverage microbial genome assemblies, which we annotated for open reading frames and phylogenetic placement. These genomes increase the gene catalog and phylogenetic breadth of the mouse microbiota, adding 135 novel species with the greatest increase in diversity to the Muribaculaceae and Bacteroidaceae families. This new diversity also improves the read mapping rate, taxonomic classifier performance, and gene detection rate of mouse stool metagenomes. The novel microbial functions revealed through our single-cell genomes highlight previously invisible pathways that may be important for life in the murine gastrointestinal tract.
Comparison of biological features of wild European rabbit mesenchymal stem cells derived from different tissues
Authors: Calle Alexandra , Zamora-Ceballos María , Bárcena Juan , Blanco Esther , Ramírez Miguel Ángel
Published: December 2021

Although the European rabbit is an “endangered” species and a notorious biological model, the analysis and comparative characterization of new tissue sources of rabbit mesenchymal stem cells (rMSCs) has not been well studied. Here we report for the first time the isolation and characterization of rMSCs derived from an animal belonging to a natural rabbit population within the species native region. New rMSC lines were isolated from different tissues: oral mucosa (rOM-MSC), dermal skin (rDS-MSC), subcutaneous adipose tissue (rSCA-MSC), ovarian adipose tissue (rOA-MSC), oviduct (rO-MSC), and mammary gland (rMG-MSC). The six rMSC lines showed plastic adhesion with fibroblast-like morphology and were all shown to be positive for CD44 and CD29 expression (characteristic markers of MSCs), and negative for CD34 or CD45 expression. In terms of pluripotency features, all rMSC lines expressed NANOG, OCT4, and SOX2. Furthermore, all rMSC lines cultured under osteogenic, chondrogenic, and adipogenic conditions showed differentiation capacity. In conclusion, this study describes the isolation and characterization of new rabbit cell lines from different tissue origins, with a clear mesenchymal pattern. We show that rMSC do not exhibit differences in terms of morphological features, expression of the cell surface, and intracellular markers of pluripotency and in vitro differentiation capacities, attributable to their tissue of origin.
Gross anatomy of the gluteal and posterior thigh muscles in koalas based on their innervations
Authors: Tojima Sayaka , Anetai Hidaka , Koike Kaito , Anetai Saori , Tokita Kounosuke , Leigh Chris , Kumaratilake Jaliya
Published: December 2021

There are not many descriptions of the muscle morphology of marsupials, despite the fact that they should show diversity according to the adaptation and dispersal to a variety of environments. Most of the previous studies regarding the gross anatomy of marsupials were conducted in the 1800 - 1900’s, and many issues still remain that need to be reexamined. For instance, the muscle identification had been performed based only on their attachments and thus, muscle descriptions are often inconsistent among the studies. These classic studies often do not include figures or photographs, so the discrepancies in the descriptions of the muscles could only be verified by performing the muscle identification again with a more reliable method. This problem can be solved by performing muscle identification by innervation. This method, which focuses on the ontogenic origin of the muscle as opposed to the attachment site, is prone to individual and interspecies variation and is a common technique in recent anatomical research. This technique is more reliable than previous methods and is suitable for comparison with other taxa (i.e., eutherians). In this study, we first conducted muscle identification based on innervation in the gluteal and posterior thighs of koalas in order to reorganize the anatomical knowledge of marsupials. This is because the gluteus and posterior thighs of koalas are the areas where previous studies have been particularly inconsistent. We dissected five individual koalas and clarified discrepancies in previous studies, as well as investigated the unique muscle morphology and their function in koalas. Specifically, the koala’s gluteal muscle group is suitable for abduction, while the posterior thigh muscles are particularly suitable for flexion. In the future, we will update the anatomical findings of marsupials in the same way to clarify the adaptive dissipation process of marsupials, as well as to contribute to the understanding of the evolutionary morphology of mammals.
Genome edited colorectal cancer organoid models reveal distinct microRNA activity patterns across different mutation profiles
Authors: Villanueva Jonathan W. , Kwong Lawrence , Han Teng , Martinez Salvador Alonso , Shanahan Michael T. , Kanke Matt , Dow Lukas E. , Danko Charles G. , Sethupathy Praveen
Published: December 2021

Somatic mutations drive colorectal cancer (CRC) by disrupting gene regulatory mechanisms. Distinct combinations of mutations can result in unique changes to regulatory mechanisms leading to variability in the efficacy of therapeutics. MicroRNAs are important regulators of gene expression, and their activity can be altered by oncogenic mutations. However, it is unknown how distinct combinations of CRC-risk mutations differentially affect microRNAs. Here, using genetically-modified mouse intestinal organoid (enteroid) models, we identify 12 different modules of microRNA expression patterns across distinct combinations of mutations common in CRC. We also show that miR-24-3p is aberrantly upregulated in genetically-modified mouse enteroids irrespective of mutational context. Furthermore, we identify an enrichment of miR-24-3p predicted targets in downregulated gene lists from various mutational contexts compared to WT. In follow-up experiments, we demonstrate that miR-24-3p promotes CRC cell survival in multiple cell contexts. Our novel characterization of genotype-specific patterns of miRNA expression offer insight into the mechanisms that drive inter-tumor heterogeneity and highlight candidate microRNA therapeutic targets for the advancement of precision medicine for CRC.
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

Base 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

Probing 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 Statement

Little 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

Neuroblastoma 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.
Crystal structure of N,N,N′,N′-tetramethylethanediamine
Authors: Schrimpf Tobias , Otte Felix , Strohmann Carsten
Published: December 2021

The title compound N,N,N′,N′-tetramethylethanediamine, C6H16N2, is a bidentate amine ligand commonly used in organolithium chemistry for deaggregation. Crystals were grown at 243 K from n-pentane solution. The complete molecule is generated by a crystallographic center of symmetry and the conformation of the diamine is antiperiplanar. To investigate the intermolecular interactions, a Hirshfeld surface analysis was performed. It showed that H...H (van der Waals) interactions dominate with a contact percentage of 92.3%.
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

Purpose

This 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/approach

The 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.

Findings

This 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/value

This 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

Purpose

This 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/approach

This paper is about WECS using PMSG and is connected to a grid of two serial converters with common DC connections.

Findings

This 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/value

This 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

Purpose

Even 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/approach

In 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.

Findings

The 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/implications

The 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 implications

These outcomes provide some implications for policymakers.

Originality/value

Even 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

Purpose

The 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/approach

Tensile/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.

Findings

The 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/value

The 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

The 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

Cosmetics 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

Despite 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

Wastewater‐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

Experimental 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.
Growth differentiation factor 11 accelerates liver senescence through the inhibition of autophagy
Authors: Sun Jian , Li Ying , Yang Xiao , Dong Wei , Yang Jiankun , Hu Qi , Zhang Cuntai , Fang Haoshu , Liu Anding
Published: December 2021

The “rejuvenating” effect of growth differentiation factor 11 (GDF11) is called into question recently, and its role, as well as plausible signaling mechanisms in liver senescence, is unclear. To overexpress or knockdown GDF11, aged male mice are injected with a single dose of adeno‐associated viruses‐GDF11 or adenovirus‐small hairpin RNA‐GDF11, respectively. GDF11 overexpression significantly accelerates liver senescence in aged mice, whereas GDF11 knockdown has opposite effects. Concomitantly, autophagic flux is impaired in livers from GDF11 overexpression mice. Conversely, GDF11 knockdown increases autophagic flux. Moreover, rapamycin successfully restores the impaired autophagic flux and alleviates liver senescence in GDF11 overexpression mice, while the GDF11 knockdown‐mediated benefits are abolished by the autophagy inhibitor bafilomycin A1. GDF11 leads to a drop in lysosomal biogenesis resulting in defective autophagic flux at autophagosome clearance step. Mechanistically, GDF11 significantly activates mammalian target of rapamycin complex 1 (mTORC1) and subsequently represses transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy. Inhibition of mTORC1 or TFEB overexpression rescues the GDF11‐impaired autophagic flux and cellular senescence. Hepatocyte‐specific deletion of GDF11 does not alter serum GDF11 levels and liver senescence. Collectively, suppression of autophagic activity via mTORC1/TFEB signaling may be a critical molecular mechanism by which GDF11 exacerbates liver senescence. Rather than a “rejuvenating” agent, GDF11 may have a detrimental effect on liver senescence.
COVID‐19 and geriatric medicine in Australia and New Zealand
Authors: Ischia Liesl , Naganathan Vasi , Waite Louise M. , Le Couteur David G. , Thillainadesan Janani
Published: December 2021

Objective

To investigate geriatricians’ views about issues facing geriatric medicine, and the preparedness of the health‐care system during the COVID‐19 pandemic.

Methods

An online survey of heads of geriatric medicine departments in hospitals in Australia and New Zealand undertaken in May 2020.

Results

The majority of hospitals had admitted one or more patients with suspected COVID‐19. Most geriatricians believed their hospital was ‘adequately’ or ‘well prepared’ for the pandemic. Inpatient capacity increased to manage acute, post‐acute and rehabilitative care of older patients with COVID‐19. Non‐inpatient services for older people were reduced and telehealth‐instituted widely. Increases in work hours, on‐call and staffing levels were reported. Geriatricians voiced major concerns about the preparedness of residential aged care facilities to manage the pandemic.

Conclusions

The COVID‐19 pandemic impacted on geriatricians and the provision of geriatric medicine services. Many issues that subsequently affected older people were predicted in advance.
The impact of diabetes mellitus type 1 on male fertility: Systematic review and meta‐analysis
Authors: Facondo Paolo , Di Lodovico Elena , Delbarba Andrea , Anelli Valentina , Pezzaioli Letizia Chiara , Filippini Erica , Cappelli Carlo , Corona Giovanni , Ferlin Alberto
Published: December 2021

Background

Some evidence suggests that diabetes mellitus type 1 (DM1) could affect male fertility, gonadal axis, semen parameters, and spermatogenesis because of effects of hyperglycemia and insulin deficiency. Anyhow, the exact impact of DM1 on male fertility is unclear.

Objectives

To review the studies evaluating paternity rate, male gonadal axis, and semen parameters in men with DM1.

Materials and methods

A review of relevant literature from January 1980 to December 2020 was performed. Only studies published in English reporting data on fatherhood (rate of children by natural fertility), hormonal and seminal parameters were included. Out of 14 retrieved articles, the eight studies evaluating semen parameters were meta‐analyzed.

Results

The rate of children (four studies) was lower than controls among men affected by DM1, especially in men with a longer duration of disease. The data of gonadal hormonal profile in DM1 men (six studies) are very heterogeneous and a neutral effect of DM1 or a condition of subclinical hypogonadism could not be concluded. Meta‐analysis showed that men with DM1 (n = 380), compared with controls (n = 434), have significantly lower normal sperm morphology [‐0.36% (‐0.66; ‐0.06), p < 0.05, six studies] and sperm progressive motility [33.62% (‐39.13; ‐28.11), p < 0.001, two studies] and a trend toward a lower seminal volume [‐0.51 (‐1.03; 0.02), p = 0.06, eight studies], without difference in total sperm count and concentration. Data on scrotal ultrasound and sperm DNA fragmentation are too few. No study evaluated other factors of male infertility, such as transrectal ultrasound, semen infections, sperm auto‐antibodies, and retrograde ejaculation.

Discussion

DM1 might impair male fertility and testis functions (endocrine, spermatogenesis), but definition of its actual impact needs further studies.

Conclusion

Men with DM1 should be evaluated with a complete hormonal, seminal, and ultrasound workup to better define their fertility potential and need for follow up of testis functions.
Is delirium associated with negative outcomes in older patients with hip fracture: analysis of the 4904 patients 2017–2018 from the Australian and New Zealand hip fracture registry
Authors: Oberai Tarandeep , Woodman Richard , Laver Kate , Crotty Maria , Kerkhoffs Gino , Jaarsma Ruurd
Published: December 2021

Aim

To determine associations between delirium and health outcomes using the Australia and New Zealand population‐based hip fracture patient registry (ANZHFR).

Methods

We performed a retrospective cohort study using data from the ANZHFR among hip‐fracture surgery patients admitted to and discharged from hospital between 1 January 2017 and 31 December 2018.

Results

Of the 4904 patients with complete data and included in the analysis, 1789 (36.5%) experienced delirium during their hospital stay. Patients with delirium also had a higher rate of in‐hospital mortality (adjusted HR = 1.76; 95% CI = 1.24, 2.49; P < 0.001), a higher rate of long‐term mortality (adjusted HR = 1.30; 95% CI = 1.15, 1.48; P < 0.001) and a higher odds of discharge to an aged care facility (adjusted OR = 1.24; 95% CI = 1.04, 1.48; P = 0.019).

Conclusion

A high rate of postoperative delirium exists among Australian and New Zealand hip fracture patients. Rates of hospital mortality, length of hospital stay and discharge to residential aged care are considerably worse in these patients.
Anthropocenic Discards: Embodied Infrastructures and Uncanny Exposures at Dakar’s Dump
Authors: Fredericks Rosalind
Published: December 2021

This article examines ethnographically the embodied infrastructures of waste picking labour at Dakar’s dump, Mbeubeuss, as a lens into the material politics of disposability in the Anthropocene. Through examining the lifeworlds threatened with erasure by a World Bank‐funded project to modernise the dump, it interrogates the shifting dialectics of waste and value in an era of disposability urbanism. Specifically, the article examines the material, social, and spiritual infrastructures of waste picking to trace how the pickers forge value through their craft, expertise, and toil. Living with toxins allows them to pursue the good life and stake claims to an urban commons—but with violently uneven bodily burdens. It then explores the uncanny, often violent, consequences of state efforts to “valorise” dump economies as they enclose the commons and disrupt pickers’ ritual practices. The research extends understandings of infrastructure and offers new provocations for how socio‐material relationships may be revalued in the Anthropocene.
Psychological well‐being and worries among pregnant women in the first trimester during the early phase of the COVID‐19 pandemic in Denmark compared with a historical group: A hospital‐based cross‐sectional study
Authors: Broberg Lotte , Rom Ane L. , de Wolff Mie G. , Høgh Stinne , Nathan Nina O. , Paarlberg Louise D. , Christensen Karl B. , Damm Peter , Hegaard Hanne Kristine
Published: December 2021

Introduction

A pandemic may negatively influence psychological well‐being in the individual. We aimed to assess the potential influence of the first national lockdown in Denmark (March to June 2020) due to the COVID‐19 pandemic on psychological well‐being and the content and degree of worries among pregnant women in early pregnancy.

Material and methods

In this hospital‐based cross‐sectional study based on self‐reported data we compared psychological well‐being and worries among women who were pregnant during the first phase of the pandemic (COVID‐19 group) (n = 685), with women who were pregnant the year before (Historical group) (n = 787). Psychological well‐being was measured by the five‐item World Health Organization Well‐being Index (WHO‐5), using a score ≤50 as indicator of reduced psychological well‐being. Differences in WHO‐5 mean scores and in the prevalence of women with score ≤50 were assessed using general linear and log‐binomial regression analyses. The Cambridge Worry Scale was used to measure the content and degree of major worries. To detect differences between groups, Pearson’s Chi‐square test was used.

Results

We found no differences in mean WHO‐5 score between groups (mean difference) 0.1 (95% CI −1.5 to 1.6) or in the prevalence of women with WHO‐5 score ≤50 (prevalence ratio 1.04, 95% CI 0.83–1.29) in adjusted analyses. A larger proportion of women in the COVID‐19 group reported major worries about Relationship with husband/partner compared with the Historical group (3% [n = 19] vs 1% [n = 6], p = 0.04), and 9.2% in the COVID‐19 group worried about the possible negative influence of the COVID‐19 restrictions.

Conclusions

Our findings indicate that national restrictions due to the COVID‐19 pandemic did not influence the psychological well‐being or the content and degree of major worries among pregnant women. However, a larger proportion of women in the COVID‐19 group reported major worries concerning Relationship with husband/partner compared with the Historical group and 9.2% in the COVID‐19 group worried about the possible negative influence of the COVID‐19 restrictions.
Impact of left ventricular inspection employing cardiopulmonary bypass on outcome after implantation of left ventricular assist device
Authors: Lewin Daniel , Nersesian Gaik , Roehrich Luise , Mueller Marcus , Mulzer Johanna , Stein Julia , Kukucka Marian , Starck Christoph , Schoenrath Felix , Falk Volkmar , Ott Sascha , Potapov Evgenij V.
Published: December 2021

Background

Cardiopulmonary bypass (CPB) during left ventricular assist device (LVAD) implantation provides circulatory support and allows for safe inspection of the left ventricle (LV), whereas circulatory support by veno‐arterial extracorporeal life support (va‐ECLS) or off‐pump implantation may reduce postoperative bleeding and inflammatory response.

Methods

Retrospective analysis of 616 consecutive adult patients who received an LVAD via median sternotomy between January 1, 2015 and December 31, 2019. All patients undergoing concomitant intracardiac procedures other than closure of persistent foramen ovale or atrial septal defect and redo surgeries were excluded from the analysis. The remaining patients (n = 222) were divided into two groups and 1:1 propensity score‐matched regarding preoperative parameters: patients who underwent LVAD implantation with LV inspection employing CPB (CPB group, n = 62) and without LV inspection on va‐ECLS or off‐pump (non‐CPB group, n = 62).

Results

The groups were well balanced with regard to preoperative baseline characteristics (standard difference <0.1). Patients in the CPB group required more blood transfusions (median 2 vs. 0 units, p = 0.031) during surgery and in the first 24 h afterwards. The median intensive care unit stay was longer in the CPB group (18 vs. 11 days, p = 0.021). The CPB group showed an absence of perioperative stroke and a smaller number of events per patient‐year for postoperative ischemic stroke (0.02 vs. 0.12, p = 0.003). 30‐day survival (87% vs. 87.1%) and 1‐year survival (80.3% vs. 74%) were similar in both groups (p = 0.78).

Conclusion

Visual LV inspection on CPB may reduce the risk of postoperative ischemic stroke. Despite the negative effects of employing CPB in lieu of other intraoperative strategies, survival was similar in both groups.