bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth and population structure of bloody cockles Senilia senilis at Banc d’Arguin and Bijagós with different environmental conditions and harvesting regimes
Authors: El-Hacen EM , Lemrabott SYC , Meijer KJ , Piersma T , Govers LL , van Gils JA , Olff H
Published: March 2023

In addition to density-dependent (i.e. food availability) and independent (i.e. abiotic gradients) forces, size-selective harvests of organisms often induce changes to their life history, demography, and reproduction. Shellfish are increasingly overexploited worldwide, and the effect of size-selective harvest on their populations is unclear. The African bloody cockleSenilia senilisis a dominant bivalve in most West African coastal systems, where it is an important source of protein. Here, we studied its population structure (abundance, biomass, and size) and life history traits (age, annual growth rate, and size for age) under contrasting harvesting conditions at the 2 largest intertidal systems in the region: the Bijagós archipelago in Guinea-Bissau (harvested) and Banc d’Arguin in Mauritania (unexploited). To account for local ecological context, we assessed environmental variables that could also affect the abundance and size ofS. senilisat these sites. We found that theS. senilispopulation at Bijagós is significantly denser and older, with lower standing biomass and smaller-sized shells than the population from Banc d’Arguin. In Bijagós, the annual growth is 3-fold lower, and the size-for-age is half of that at Banc d’Arguin. At both sites,S. senilisdensities and sizes were correlated with habitat quality indicators: mangrove and mudflat productivity at Bijagós and seagrass and sediment characteristics at Banc d’Arguin. The smaller-sized mature individuals, denser populations, and lower standing biomass at Bijagós compared to Banc d’Arguin are indications of considerable size-selection pressure at Bijagós.
Dipyridamole inhibits hydroxylamine augmented nitric oxide (NO) production by activated polymorphonuclear neutrophils through an adenosine-independent mechanism.
Authors: Wykretowicz A , Filipiak A , Szczepanik A , Wysocki H
Published: March 2023

Polymorphonuclear neutrophils (PMN) are thought to play a role in reperfusion injury and ischemia. These effects are partly mediated by toxic oxygen species (superoxide anion, hydrogen peroxide and hydroxyl radical) acting at the level of the endothelium. It was demonstrated recently that the superoxide anion reacts with nitric oxide (NO) and that interaction leads to the generation of highly toxic peroxynitrite. Several drugs were tested so far in order to affect PMN function. It was demonstrated that dipyridamole (2,6-bis-diethanolamino-4,8-dipiperidinopyrimido-(5,4-d)-pyrimidine) can influence neutrophil function by inhibiting adenosine uptake. However, this action can not fully explain all of the observed effects of dipyridamole action on PMN metabolism. The aim of our study was to evaluate the influence of dipyridamole on nitric oxide production by activated polymorphonuclear neutrophils. Incubation of PMNs with hydroxylamine (HA) and phorbol myristate acetate (PMA) generated nitrite (36.4+/-4.2 nmol/h 2x10(6) PMN), dipyridamole at 100 micromol/l, 50 micromol/l and 10 micromol/l caused a considerable drop in nitrite production (11.8+/-1.8, 19.7+/-2.7 and 27.4+/-3.2 nmol/h, respectively). Neither adenosine nor the adenosine analogue could mimic the dipyridamole effect. Moreover theophylline, an adenosine inhibitor could not reverse the dipirydamole action on PMN metabolism. We also found that dipyridamole inhibited hydrogen peroxide release from neutrophils. Catalase that scavenges hydrogen peroxide also largely abolished nitric oxide release from PMN. It is evident that dipyridamole inhibits hydroxylamine-augmented nitric oxide production by activated polymorphonuclear neutrophils through an adenosine-independent mechanism.
Diaphorase can metabolize some vasorelaxants to NO and eliminate NO scavenging effect of 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (PTIO).
Authors: Bartík P , Chalupský K , Muller B , Stoclet J-C , Entlicher G
Published: March 2023

Diaphorase was studied as a possible oxidoreductase participating in NO production from some vasorelaxants. In the presence of NADH or NADPH, diaphorase can convert selected NO donors, glycerol trinitrate (GTN) and formaldoxime (FAL) to nitrites and nitrates with NO as an intermediate. This activity of diaphorase was inhibited by diphenyleneiodonium (DPI) (inhibitor of some NADPH-dependent flavoprotein oxidoreductases), while it remained uninhibited by NG-nitro-L-arginine methyl ester (inhibitor of NO synthase) 7-Ethoxyresorufin (inhibitor of cytochrome P-450 1A1 and cytochrome P-450 NADPH-dependent reductase) inhibited the conversion of GTN only. Existence of NO as an intermediate of the reaction was supported by results of electron paramagnetic resonance spectroscopy. In addition to its ability to affect the above mentioned NO donors, diaphorase was able to reduce 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (PTIO) and thus to eliminate its NO scavenging effect. This activity of diaphorase could also be inhibited by DPI. The reaction of diaphorase with GTN and PTIO was not affected by superoxide dismutase (SOD) or catalase. Reaction of FAL with diaphorase was lowered with SOD by 38 % indicating the partial participation of superoxide anion probably generated by the reaction of diaphorase with NADH or NADPH. Catalase had no effect. Diaphorase could apparently be one of the enzymes participating in the metabolism of studied NO donors to NO. The easy reduction and consequent elimination of PTIO by diaphorase could affect its use as an NO scavenger in biological tissues.
Effects of acute hypoxia on the estimation of the lactate threshold from ventilatory gas exchange indices during an incremental exercise test.
Authors: Ozcelik O , Kelestimur H
Published: March 2023

The purpose of this study was to investigate the validity of non-invasive lactate threshold estimation using ventilatory and pulmonary gas exchange indices under condition of acute hypoxia. Seven untrained males (21.4+/-1.2 years) performed two incremental exercise tests using an electromagnetically braked cycle ergometer: one breathing room air and other breathing 12 % O2. The lactate threshold was estimated using the following parameters: increase of ventilatory equivalent for O2 (VE/VO2) without increase of ventilatory equivalent for CO2 (VE/VCO2). It was also determined from the increase in blood lactate and decrease in standard bicarbonate. The VE/VO2 and lactate increase methods yielded the respective values for lactate threshold: 1.91+/-0.10 l/min (for the VE/VO2) vs. 1.89+/-0.1 l/min (for the lactate). However, in hypoxic condition, VE/VO2 started to increase prior to the actual threshold as determined from blood lactate response: 1.67+/-0.1 l/min (for the lactate) vs. 1.37+/-0.09 l/min (for the VE/VO2) (P=0.0001), i.e. resulted in pseudo-threshold behavior. In conclusion, the ventilatory and gas exchange indices provide an accurate lactate threshold. Although the potential for pseudo-threshold behavior of the standard ventilatory and gas exchange indices of the lactate threshold must be concerned if an incremental test is performed under hypoxic conditions in which carotid body chemosensitivity is increased.
AI Ethics as Subordinated Innovation Network
Authors: Steinhoff James
Published: March 2023

AI ethics is proposed, by the Big Tech companies which lead AI research and development, as the cure for diverse social problems posed by the commercialization of data-intensive technologies. It aims to reconcile capitalist AI production with ethics. However, AI ethics is itself now the subject of wide criticism; most notably, it is accused of being no more than “ethics washing” - a cynical means of dissimulation for Big Tech, while it continues its business operations unchanged. This paper aims to critically assess, and go beyond the ethics washing thesis. I argue that AI ethics is indeed ethics washing, but not only that. It has a more significant economic function for Big Tech. To make this argument I draw on the theory of intellectual monopoly capital. I argue that ethics washing is better understood as a subordinated innovation network: a dispersed network of contributors beyond Big Tech’s formal employment whose research is indirectly planned by Big Tech, which also appropriates its results. These results are not intended to render AI more ethical, but rather to advance the business processes of intellectual monopoly capitals. Because the parameters of AI ethics are indirectly set in advance by Big tech, the ostensible goal that AI ethics sets for itself-to resolve the contradiction between business and ethics-is in fact insoluble. I demonstrate this via an analysis of the latest trend in AI ethics: the operationalization of ethical principles.
Solar System Wave Packet and its Achievements
Authors: Soltani Abolfazl
Published: March 2023

If Titius-Bode Law (TBL) was only a relation between three, four or even five planets, then we could call it a coincidence, but when it is true for seven planets, plus Ceres and Pluto (nine objects), there is definitely a reason for it. Here, we show that, probably, the existence of a standing and cosinusoidal wave packet in solar system, with the wavelength = 0.6 AU (AU represents the distance of Earth from the sun) and the phase constant ∅0=π/6, is the reason for TBL. In this article we obtain the equation of this wave packet. In this article we prove that without Solar System Wave Packet (SSWP), it is not possible to reach to the TBL from the protoplanetary disk of solar system. In the following of the article, based on the theory of SSWP, we will enter into the atomic field and arrive to a new atomic model.
Comparative physiological, morphological, histological, and AQP2 immunohistochemical analysis of the Arabian camels (Camelus dromedarius) and oxen kidney: Effects of adaptation to arid environments
Authors: El-Hady Enas , Behairy Amany , Goda Nehal A. , Abdelbaset-Ismail Ahmed , Ahmed Ahmed E. , Al-Doaiss Amin A. , Abd El-Rahim Ibrahim , Alshehri Mohammed A. , Aref Mohamed
Published: March 2023

Compared to other mammals, Arabian camels are ideal models for exploring the structural adaptations that enable camels to survive in arid environments. Thus, this study aimed to explore how evolutionary adaptation to arid conditions modifies the characteristics of the kidneys in Arabian camels (Camelus dromedarius) compared to oxen. Urine samples were physically and chemically analyzed. Harvested kidneys were subjected to topographical and fast spin echo magnetic resonance (FSE-MR) imaging. Histology, histomorphometry, and Aquaporin-2 (AQP2) expression by immunohistochemistry were also performed. Here, in dromedaries, sodium and potassium values in the urine were much higher (p=0.001, for both), whereas chloride was much lower (p=0.004) than the values of oxen. Compared with oxen, the level of the hormone aldosterone in serum was significantly lower (p=0.002), whereas creatinine and urea were significantly higher (p=0.005 and p=0.001, respectively). Uric acid in dromedaries and oxen did not differ significantly (p=0.349). Like sodium levels (p=0.001) in dromedary serum, chloride was also much higher (p=0.002) than in oxen. The average value of potassium was much lower (p=0.009) than that of oxen. Morphologically, anatomical and FSE MRI studies revealed that minor and major calyces were not found in dromedary kidneys. The renal pelvis was not found in oxen, and the major calyx was directly connected to the ureter. The dromedary kidney contained a wider medullary portion as well as increased diameters for renal corpuscles (RCs), proximal convoluted tubules (PCTs), and collecting tubules (CTs, p<0.05) compared with the oxen. We also noted that AQP2 was significantly expressed in dromedary nephron components, except for RCs, compared with oxen as shown by immunohistochemistry. Overall, these data strongly suggest that the dromedary has a greater ability to adapt to harsh desert conditions in terms of producing highly concentrated urine than oxen.
Immobilizing lead and copper in aqueous solution using microbial- and enzyme-induced carbonate precipitation
Authors: Wang Lin , Cheng Wen-Chieh , Xue Zhong-Fei , Rahman Md Mizanur , Xie Yi-Xin , Hu Wenle
Published: March 2023

Inappropriate irrigation could trigger migration of heavy metals into surrounding environments, causing their accumulation and a serious threat to human central nervous system. Traditional site remediation technologies are criticized because they are time-consuming and featured with high risk of secondary pollution. In the past few years, the microbial-induced carbonate precipitation (MICP) is considered as an alternative to traditional technologies due to its easy maneuverability. The enzyme-induced carbonate precipitate (EICP) has attracted attention because bacterial cultivation is not required prior to catalyzing urea hydrolysis. This study compared the performance of lead (Pb) and copper (Cu) remediation using MICP and EICP respectively. The effect of the degree of urea hydrolysis, mass and species of carbonate precipitation, and chemical and thermodynamic properties of carbonates on the remediation efficiency was investigated. Results indicated that ammonium ion (NH4+) concentration reduced with the increase in lead ion (Pb2+) or copper ion (Cu2+) concentration, and for a given Pb2+ or Cu2+ concentration, it was much higher under MICP than EICP. Further, the remediation efficiency against Cu2+ is approximately zero, which is way below that against Pb2+ (approximately 100%). The Cu2+ toxicity denatured and even inactivated the urease, reducing the degree of urea hydrolysis and the remediation efficiency. Moreover, the reduction in the remediation efficiency against Pb2+ and Cu2+ appeared to be due to the precipitations of cotunnite and atacamite respectively. Their chemical and thermodynamic properties were not as good as calcite, cerussite, phosgenite, and malachite. The findings shed light on the underlying mechanism affecting the remediation efficiency against Pb2+ and Cu2+.
CRISPR-mediated optogene expression from a cell-specific endogenous promoter in retinal ON-bipolar cells to restore vision
Authors: Maddalena A. , Kleinlogel S.
Published: March 2023

Retinitis pigmentosa, an inherited form of retinal degeneration, is characterized by a progressive loss of rods and subsequent degeneration of cones, leading to blindness. However, the remaining neural portion of the retina (bipolar and ganglion cells) remains anatomically and functionally intact for an extended time. A possible treatment to restore the light sensitivity of the retina consists of rendering the remaining retinal cells photosensitive using optogenetic tools like, for example, Opto-mGluR6, a light-sensitive mGluR6 receptor. We have previously demonstrated that AAV vector-mediated expression of Opto-mGluR6 in ON-bipolar cells restores visual function in otherwise blind mice. However, classical gene supplementation therapy still suffers from high off-target expression rates and uncontrollable target gene expression levels that may lead to either cytotoxicity or lack of functional restoration. To address these issues and achieve cell-specific and endogenously controlled Opto-mGluR6 expression, we employed the CRISPR/Cas technology—in particular, homology-independent targeted integration (HITI) and microhomology-dependent targeted integration (MITI)—to knock-in the Opto-mGluR6 gene behind the ON-bipolar cell-specific GRM6 promoter. We compared four Cas systems in vitro and show that SpCas9 for HITI and LbCpf1 for MITI are well suited to promoting knock-in. As AAV2-mediated ON-bipolar cell transduction resulted in inefficiency, we evaluated Exo-AAVs as delivery vehicles and found Exo-AAV1 efficient for targeting ON-bipolar cells. We demonstrate that intravitreal injection of Exo-AAV1 carrying vectors that promote MITI significantly improved visual acuity in otherwise blind rd1 mice. We conclude by confirming and providing a qualitative evaluation of the MITI-mediated knock-in in the correct genomic locus.
Association of multiple blood metals with thyroid function in general adults: A cross−sectional study
Authors: Ye Yanshi , Li Ye , Ma Qintao , Li Ying , Zeng Huixian , Luo Yaosheng , Liang Yongqian , Liu Lan , Liu Lingling , Lin Xu , Yu Genfeng , Song Cheng , Wan Heng , Shen Jie
Published: March 2023

Introduction

Thyroid function has a large impact on humans’ metabolism and is affected by iodine levels, but there is a scarcity of studies that elucidate the association between thyroid function and other elements.

Methods

We performed a cross-sectional study on 1,067 adults to evaluate the associations of the common essential metals with thyroid function in adults living in an iodine-adequate area of China. Serum free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH), and blood metals (zinc, iron, copper, magnesium, manganese, and calcium) were measured. Further, the thyroid hormone sensitivity indexes, FT3:FT4 ratio, and thyrotropin T4 resistance index (TT4RI) were calculated. Linear regression, quantile g-computation, and Bayesian kernel machine regression methods were used to explore the association of metals with thyroid function.

Results

We found that the TSH levels correlated with copper (negative) and zinc (positive). Iron and copper were positively associated with FT3 and FT4 levels, respectively. Iron (positive) and copper (negative) were correlated with the FT3:FT4 ratio. Furthermore, we found that manganese was inversely correlated with TT4RI, while zinc was positively correlated.

Discussion

Our findings suggest that manganese, iron, copper, and zinc levels were strongly correlated with thyroid function, and patients with thyroid disorders are recommended to measure those metals levels.
Dissolved oxygen shapes the archaeal communities in the seawater of Changjiang Estuary
Authors: Wang Jianxin , Tian Chunmiao , Wu Dongmei , Wang Rixin
Published: March 2023

Archaea play a significant role in regulating the biogeochemical processes of marine ecosystems. In this study, the high-throughput sequencing was used to explore the archaeal communities in the seawater from the hypoxic and non-hypoxic zones of the Changjiang Estuary. Thaumarchaeota dominated the archaeal communities in the hypoxic zones (bottom water), and Euryarchaeota were mainly distributed in the non-hypoxic zones (surface water). However, the diversity and richness of the archaeal communities showed no obvious difference in the hypoxic and non-hypoxic zones. Moreover, Thaumarchaeota and Nitrosopumilales were positively correlated with salinity, but negatively correlated with dissolved oxygen (DO) and temperature. Temperature, phosphorus, and dissolved oxygen had significant correlations with archaeal richness, while ammonia nitrogen was correlated with archaeal diversity. The networks of archaeal communities possessed a high proportion of positive interspecific interaction and revealed that the Marine Group II species may play distinct roles in both hypoxic and non-hypoxic zones. The current work assessed the influence of dissolved oxygen on the archaeal community patterns and network interaction, thereby illumining the community structure shift of archaea caused by the hypoxia phenomenon in the Changjiang Estuary, which laid a foundation for the future studies on the ecological functions of archaea in estuary ecosystems.
Screening ANLN and ASPM as bladder urothelial carcinoma-related biomarkers based on weighted gene co-expression network analysis
Authors: Yang Tenghao , Chi Zepai , Liu Guoyuan , Hong Xuwei , Cao Sizhe , Cheng Kequan , Zhang Yonghai
Published: March 2023

Introduction: Bladder cancer (BLCA) is one of the most common malignancies in the urinary system with a poor prognosis and high treatment costs. Identifying potential prognostic biomarkers is significant for exploring new therapeutic and predictive targets of BLCA.

Methods: In this study, we screened differentially expressed genes using the GSE37815 dataset. We then performed a weighted gene co‐expression network analysis (WGCNA) to identify the genes correlated with the histologic grade and T stage of BLCA using the GSE32548 dataset. Subsequently, Kaplan Meier survival analysis and Cox regression were used to further identify prognosis‐related hub genes using the datasets GSE13507 and TCGA‐BLCA. Moreover, we detected the expression of the hub genes in 35 paired samples, including BLCA and paracancerous tissue, from the Shantou Central Hospital by qRT‐polymerase chain reaction.

Results: This study showed that Anillin (ANLN) and Abnormal spindle-like microcephaly-associated gene (ASPM) were prognostic biomarkers for BLCA. High expression of ANLN and ASPM was associated with poor overall survival.The qRT‐PCR results revealed that ANLN and ASPM genes were upregulated in BLCA, and there was a correlation between the expression of ANLN and ASPM in cancer tissues and paracancerous tissue. Additionally, the increasing multiples in the ANLN gene was obvious in high-grade BLCA.

Discussion: In summary, this preliminary exploration indicated a correlation between ANLN and ASPM expression. These two genes, serving as the risk factors for BLCA progression, might be promising targets to improve the occurrence and progression of BLCA.
A framework for real-time monitoring, analysis and adaptive sampling of viral amplicon nanopore sequencing
Authors: Munro Rory , Holmes Nadine , Moore Christopher , Carlile Matthew , Payne Alexander , Tyson John R. , Williams Thomas , Alder Christopher , Snell Luke B. , Nebbia Gaia , Santos Roberto , Loose Matt
Published: March 2023

The ongoing SARS-CoV-2 pandemic demonstrates the utility of real-time sequence analysis in monitoring and surveillance of pathogens. However, cost-effective sequencing requires that samples be PCR amplified and multiplexed via barcoding onto a single flow cell, resulting in challenges with maximising and balancing coverage for each sample. To address this, we developed a real-time analysis pipeline to maximise flow cell performance and optimise sequencing time and costs for any amplicon based sequencing. We extended our nanopore analysis platform MinoTour to incorporate ARTIC network bioinformatics analysis pipelines. MinoTour predicts which samples will reach sufficient coverage for downstream analysis and runs the ARTIC networks Medaka pipeline once sufficient coverage has been reached. We show that stopping a viral sequencing run earlier, at the point that sufficient data has become available, has no negative effect on subsequent down-stream analysis. A separate tool, SwordFish, is used to automate adaptive sampling on Nanopore sequencers during the sequencing run. This enables normalisation of coverage both within (amplicons) and between samples (barcodes) on barcoded sequencing runs. We show that this process enriches under-represented samples and amplicons in a library as well as reducing the time taken to obtain complete genomes without affecting the consensus sequence.
Deciphering the complete human-monkeypox virus interactome: Identifying immune responses and potential drug targets
Authors: Kataria Raghav , Kaur Simardeep , Kaundal Rakesh
Published: March 2023

Monkeypox virus (MPXV) is a dsDNA virus, belonging to Poxviridae family. The outbreak of monkeypox disease in humans is critical in European and Western countries, owing to its origin in African regions. The highest number of cases of the disease were found in the United States, followed by Spain and Brazil. Understanding the complete infection mechanism of diverse MPXV strains and their interaction with humans is important for therapeutic drug development, and to avoid any future epidemics. Using computational systems biology, we deciphered the genome-wide protein-protein interactions (PPIs) between 22 MPXV strains and human proteome. Based on phylogenomics and disease severity, 3 different strains of MPXV: Zaire-96-I-16, MPXV-UK_P2, and MPXV_USA_2022_MA001 were selected for comparative functional analysis of the proteins involved in the interactions. On an average, we predicted around 92,880 non-redundant PPIs between human and MPXV proteomes, involving 8014 host and 116 pathogen proteins from the 3 strains. The gene ontology (GO) enrichment analysis revealed 10,624 common GO terms in which the host proteins of 3 strains were highly enriched. These include significant GO terms such as platelet activation (GO:0030168), GABA-A receptor complex (GO:1902711), and metalloendopeptidase activity (GO:0004222). The host proteins were also significantly enriched in calcium signaling pathway (hsa04020), MAPK signaling pathway (hsa04010), and inflammatory mediator regulation of TRP channels (hsa04750). These significantly enriched GO terms and KEGG pathways are known to be implicated in immunomodulatory and therapeutic role in humans during viral infection. The protein hubs analysis revealed that most of the MPXV proteins form hubs with the protein kinases and AGC kinase C-terminal domains. Furthermore, subcellular localization revealed that most of the human proteins were localized in cytoplasm (29.22%) and nucleus (26.79%). A few drugs including Fostamatinib, Tamoxifen and others were identified as potential drug candidates against the monkeypox virus disease. This study reports the genome-scale PPIs elucidation in human-monkeypox virus pathosystem, thus facilitating the research community with functional insights into the monkeypox disease infection mechanism and augment the drug development.
New insights into the germline genes and CDR3 repertoire of the TCRβ chain in Chiroptera
Authors: Zhou Hao , Li Jun , Zhou Dewei , Wu Yingjie , Wang Xingliang , Zhou Jiang , Ma Qingqing , Yao Xinsheng , Ma Long
Published: March 2023

Introduction

Bats are recognized as natural reservoirs for many viruses, and their unique immune system enables them to coexist with these viruses without frequently exhibiting disease symptoms. However, the current understanding of the bat adaptive immune system is limited due to the lack of a database or tool capable of processing T-cell receptor (TCR) sequences for bats.

Methods

We performed germline gene annotation in three bat species using homologous genes and RSSs (Recombinational Signal Sequences) scanning method. Then we used the conserved C gene to construct the TCRβ chain receptor library of the Intermediate Horseshoe Bat. Bats' TCRβ data will be analyzed using MiXCR and constructed reference library.

Results

Regarding the annotation results, we found that the Pale Spear-nosed Bat has 37 members in the TRBV12 family, which is more than the total number of TRBV genes in the Greater Horseshoe Bat. The average number of unique TCRβ chain receptor sequences in each Intermediate Horseshoe Bat sample reached 24,904.

Discussion

The distinct variations in the distribution of TRBV genes among the three types of bats could have a direct impact on the diversity of the TCR repertoire, as evidenced by the presence of conserved amino acids that indicate the T-cell recognition of antigens in bats is MHC-restricted. The bats’ TCRβ repertoire is formed through the rearrangement of the V-D-J-C genes, with D-J/V-D deletions and insertions resulting in high diversity.
Large-eddy simulation of a 15 GW wind farm: Flow effects, energy budgets and comparison with wake models
Authors: Maas Oliver
Published: March 2023

Planned offshore wind farm clusters have a rated capacity of more than 10 GW. The layout optimization and yield estimation of wind farms is often performed with computationally inexpensive, analytical wake models. As recent research results show, the flow physics in large (multi-gigawatt) offshore wind farms are more complex than in small (sub-gigawatt) wind farms. Since analytical wake models are tuned with data of existing, sub-gigawatt wind farms they might not produce accurate results for large wind farm clusters. In this study the results of a large-eddy simulation of a 15 GW wind farm are compared with two analytical wake models to demonstrate potential discrepancies. The TurbOPark model and the Niayifar and Porté-Agel model are chosen because they use a Gaussian wake profile and a turbulence model. The wind farm has a finite size in the crosswise direction, unlike as in many other large-eddy simulation wind farm studies, in which the wind farm is effectively infinitely wide due to the cyclic boundary conditions. The results show that new effects like crosswise divergence and convergence occur in such a finite-size multi-gigawatt wind farm. The comparison with the wake models shows that there are large discrepancies of up to 40% between the predicted wind farm power output of the wake models and the large-eddy simulation. An energy budget analysis is made to explain the discrepancies. It shows that the wake models neglect relevant kinetic energy sources and sinks like the geostrophic forcing, the energy input by pressure gradients and energy dissipation. Taking some of these sources and sinks into account could improve the accuracy of the wake models.
Women’s contribution in understanding how topoisomerases, supercoiling, and transcription control genome organization
Authors: Martin Laura , Neguembor Maria Victoria , Cosma Maria Pia
Published: March 2023

One of the biggest paradoxes in biology is that human genome is roughly 2 m long, while the nucleus containing it is almost one million times smaller. To fit into the nucleus, DNA twists, bends and folds into several hierarchical levels of compaction. Still, DNA has to maintain a high degree of accessibility to be readily replicated and transcribed by proteins. How compaction and accessibility co-exist functionally in human cells is still a matter of debate. Here, we discuss how the torsional stress of the DNA helix acts as a buffer, regulating both chromatin compaction and accessibility. We will focus on chromatin supercoiling and on the emerging role of topoisomerases as pivotal regulators of genome organization. We will mainly highlight the major breakthrough studies led by women, with the intention of celebrating the work of this group that remains a minority within the scientific community.
Comparison of different gene-therapy methods to treat Leber hereditary optic neuropathy in a mouse model
Authors: Velmurugan Sindhu , Chou Tsung-Han , Eastwood Jeremy D. , Porciatti Vittorio , Liu Yuan , Hauswirth William W. , Guy John , Yu Hong
Published: March 2023

Introduction

Therapies for Leber hereditary optic neuropathy (LHON), in common with all disorders caused by mutated mitochondrial DNA, are inadequate. We have developed two gene therapy strategies for the disease: mitochondrial-targeted and allotopic expressed and compared them in a mouse model of LHON.

Methods

A LHON mouse model was generated by intravitreal injection of a mitochondrialtargeted Adeno-associated virus (AAV) carrying mutant human NADH dehydrogenase 4 gene (hND4/m.11778G>A) to induce retinal ganglion cell (RGC) degeneration and axon loss, the hallmark of the human disease. We then attempted to rescue those mice using a second intravitreal injection of either mitochondrial-targeted or allotopic expressed wildtype human ND4. The rescue of RGCs and their axons were assessed using serial pattern electroretinogram (PERG) and transmission electron microscopy.

Results

Compared to non-rescued LHON controls where PERG amplitude was much reduced, both strategies significantly preserved PERG amplitude over 15 months. However, the rescue effect was more marked with mitochondrial-targeted therapy than with allotopic therapy (p = 0.0128). Post-mortem analysis showed that mitochondrial-targeted human ND4 better preserved small axons that are preferentially lost in human LHON.

Conclusions

These results in a pre-clinical mouse model of LHON suggest that mitochondrially-targeted AAV gene therapy, compared to allotopic AAV gene therapy, is more efficient in rescuing the LHON phenotype.
Synergistic structural and functional alterations in the medial prefrontal cortex of patients with high-grade gliomas infiltrating the thalamus and the basal ganglia
Authors: Yan Zheng , Tang Jun , Ge Honglin , Liu Dongming , Liu Yong , Liu Hongyi , Zou Yuanjie , Hu Xinhua , Yang Kun , Chen Jiu
Published: March 2023

Background

High-grade gliomas (HGGs) are characterized by a high degree of tissue invasion and uncontrolled cell proliferation, inevitably damaging the thalamus and the basal ganglia. The thalamus exhibits a high level of structural and functional connectivity with the default mode network (DMN). The present study investigated the structural and functional compensation within the DMN in HGGs invading the thalamus along with the basal ganglia (HITBG).

Methods

A total of 32 and 22 healthy controls were enrolled, and their demographics and neurocognition (digit span test, DST) were assessed. Of the 32 patients, 18 patients were involved only on the left side, while 15 of them were involved on the right side. This study assessed the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), gray matter (GM) volume, and functional connectivity (FC) within the DMN and compared these measures between patients with left and right HITBG and healthy controls (HCs).

Result

The medial prefrontal cortex (mPFC) region existed in synchrony with the significant increase in ALFF and GM volume in patients with left and right HITBG compared with HCs. In addition, patients with left HITBG exhibited elevated ReHo and GM precuneus volumes, which did not overlap with the findings in patients with right HITBG. The patients with left and right HITBG showed decreased GM volume in the contralateral hippocampus without any functional variation. However, no significant difference in FC values was observed in the regions within the DMN. Additionally, the DST scores were significantly lower in patients with HITBG, but there was no significant correlation with functional or GM volume measurements.

Conclusion

The observed pattern of synchrony between structure and function was present in the neuroplasticity of the mPFC and the precuneus. However, patients with HITBG may have a limited capacity to affect the connectivity within the regions of the DMN. Furthermore, the contralateral hippocampus in patients with HITBG exhibited atrophy. Thus, preventing damage to these regions may potentially delay the progression of neurological function impairment in patients with HGG.
Euglena gracilis-derived β-glucan paramylon entrains the peripheral circadian clocks in mice
Authors: Ryan Conn , Cao Siyuan , Sekiguchi Masataka , Haraguchi Atsushi , Murata Ako , Nakashima Ayaka , Suzuki Kengo , Shibata Shigenobu
Published: March 2023

Paramylon, a β-1,3-glucan storage polysaccharide derived from Euglena gracilis, has various health benefits, such as anti-obesity effects and modulation of immune function. However, whether paramylon intake affects the circadian clock remains unknown. In this study, we examined the effect of paramylon intake on the circadian clock. The results showed that the paramylon intake regulated peripheral clocks in mice. Furthermore, cecal pH and short-chain fatty acid concentrations after paramylon intake were measured. The correlation between changes in the expression of clock-related genes and alterations in the intestinal environment was confirmed. In addition, peripheral clock entrainment by paramylon intake was not observed in antibiotic-treated mice whose gut microbiota was weakened. These findings suggest that the regulation of the circadian clock by paramylon intake was mediated by changes in gut microbiota. In addition, the entraining effect of paramylon intake was also confirmed in mice bred under conditions mimicking social jetlag, which implies that paramylon intake may contribute to recovery from social jetlag. Thus, the appropriate consumption of paramylon may have a beneficial effect on health from a chrono-nutritional perspective.
Effect of megarectum on postoperative defecation of female patients with congenital rectovestibular fistula or rectoperineal fistula
Authors: Liu Chunxiang , Wang Song , Dai Jinyu , Li Jian , Wu Xiaoxia , Liu Yong , Yao Zhiwei , Ma Lushun , Sun Xiaobing , Sun Daqing
Published: March 2023

Background

To assess the effect of megarectum on postoperative defecation of female patients with congenital rectovestibular fistula or rectoperineal fistula.

Methods

From March 2013 to February 2021, 74 female patients with congenital rectovestibular fistula or rectoperineal fistula were treated. The age of patients ranged from 3 months to 1 year. Barium enema and spinal cord MRI were performed in all children. 4 patients were removed from the study because of spinal cord and sacral agenesis. Finally, 70 patients underwent one-stage anterior sagittal anorectoplasty (ASARP). Anal endoscopy and anorectal pressure measurement were performed 1 year after surgery. All patients were divided into two groups depending on the presence of megarectum (+) and (−) and observed for constipation and anal sphincter function.

Results

16 patients (4 months to 1 year) were complicated with megarectum, and 5 patients (3 months to 9 months) were without megarectum. The incision infection was seen in 3 patients. All patients were followed up for 1 year to 5 years. Fecal soiling was seen in 2 patients and constipation in 14 patients. Among 16 patients with megarectum, soiling was seen in 1 patient and the constipation in 12 patients. Among 54 patients without megarectum, soiling was seen in 1 patient and constipation in 2 patients. There was a significant difference in the incidence of postoperative constipation between the two groups (megarectum (+) 75% vs. megarectum (−) 3.7% (P < 0.05)). However, there was no significant difference in the score of anal sphincters between the two groups (P < 0.05). And there was no significant difference in anal resting pressure (P = 0.49) and length of anal high pressure area (P = 0.76). 7 patients with constipation and megarectum acquired normal anal function after the dilated rectum was resected.

Conclusion

Megarectum increases the possibility of difficult postoperative defecation in the patients with congenital rectovestibular fistula or rectoperineal fistula. However, constipation was not associated with ASARP postoperative effects on sphincter function. Resection of megarectum is helpful to the improvement of constipation.
Gut metabolomics and 16S rRNA sequencing analysis of the effects of arecoline on non-alcoholic fatty liver disease in rats
Authors: Zhu Lingping , Li Duo , Yang Xuefeng
Published: March 2023

Introduction: Non-alcoholic fatty liver disease (NAFLD) has gradually become the primary cause of fatty liver disease. Betel nuts have been used to treat gastrointestinal diseases.

Methods: In the present study, we analyzed the pathology, serology, gut flora, and metabolites in a rat model of NAFLD, with and without betel nut alkaloid treatment, using an integrated approach involving pathology, serological testing, 16S rRNA gene sequencing, and ultra-performance liquid chromatography-mass spectrometry metabolomics.

Results: Two rats were used for model validation. Thirty SD rats were included and divided into the normal group (C group), NAFLD model group (M group), low-dose group, medium-dose group (T group), and high-dose group with intraperitoneal injection of arecoline. The expression of blood lipids was significantly downregulated at all three arecoline concentrations (p < 0.05). Alpha-diversity analysis of the intestinal flora showed significant differences among the three groups, with a significant reduction in population diversity in the M group and a recovery of population diversity after arecoline treatment. At the phylum level, the relative abundance of Firmicutes was significantly higher in the T group and Proteobacteria in the M group. The KEGG metabolic pathways included polyketide sugar unit biosynthesis and hypertrophic cardiomyopathy. Thirty-three significantly different metabolites were identified among the groups. Significantly different metabolites between groups T and M included indolepyruvate, 2-deoxystreptamine, sakuranetin, glycyl-leucine, and riboflavin. The KEGG metabolic pathway suggested a potential role for arachidonic acid metabolism, serotonergic synapses, neuroactive ligand-receptor interactions, tyrosine metabolism, and regiomelanin. Vitamin digestion and absorption, as well as regulation of lipolysis in adipocytes, were the main metabolic pathways that distinguished the T vs. M groups. PGE2 is involved in several metabolic pathways. Correlation analysis showed that 29 bacterial species were significantly associated with PGE2 levels in the M and T groups. Vagococcus, Lawsonia, Christensenella, unidentified Erysipelotrichaceae, unidentified Coriobacteriaceae, and five other bacterial groups are unique in the PGE2 metabolic pathway regulated by arecoline.

Discussion: Arecoline has lipid-lowering effects and may exert therapeutic effects in NAFLD through intestinal metabolites and intestinal flora, as well as through the Butyricicoccus/Christensenella/Coriobacteriaceae-COX2/PGE2 pathway. Thus, arecoline may represent a potential drug or target for NAFLD treatment.
Polyherbal formulation conjugated to gold nanoparticles induced ferroptosis in drug-resistant breast cancer stem cells through ferritin degradation
Authors: Chittineedi Prasanthi , Mohammed Arifullah , Abdul Razab Mohammad Khairul Azhar , Mat Nawi Norazlina , Pandrangi Santhi Latha
Published: March 2023

Aim: Due to their minimal side effects, the anti-cancer properties of the polyherbal formulation are being investigated. However, due to their low absorption potential, the administration of polyherbal formulations is restricted. Loading the polyherbal formulation into gold nanoparticles enhances the bioavailability of the polyherbal formulation (PHF) accompanied by reducing the concentration of doxorubicin (dox). Ferroptosis is one of the novel pathways that specifically target cancer stem cells due to high ferritin levels. Hence, in the present study, we conjugated polyherbal formulation with gold nanoparticles and studied its effect on inducing ferroptosis in drug-resistant breast cancer cell lines.

Materials and methods: PHF and dox conjugated to gold nanoparticles were characterized using FTIR, UV-Vis spectrophotometer, DLS, particle size analyzer, and XRD. The drug entrapment and efficiency studies were performed to assess the biodegradable potential of the synthesized gold nanoparticles. Paclitaxel-resistant breast cancer stem cells were generated, and an MTT assay was performed to evaluate the cytotoxicity potential of AuNP-PHF and AuNP-dox. Scratch assay and clonogenic assay were performed to assess the migration and proliferation of the cells after treatment with chosen drug combinations. The ability of PHF and dox conjugated to gold nanoparticles to induce ferritinophagy was evaluated by RT-PCR. Finally, image analysis was performed to check apoptosis and cellular ROS using inverted fluorescent microscope. The ability to induce cell cycle arrest was assessed by cell cycle analysis using flow cytometer.

Results and conclusion: PHF and dox conjugated to gold nanoparticles showed high stability and showed to induce ferritin degradation in drug resistant breast cancer stem cells through ferritin degradation. AuNP-PHF in combination with low dose of AuNP-Dox nanoconjugate could be used as an effective cancer therapeutic agent, by targeting the autophagy necroptosis axis.
Lactobacillus reuteri strain 8008 attenuated the aggravation of depressive-like behavior induced by CUMS in high-fat diet-fed mice through regulating the gut microbiota
Authors: Li Canye , Su Zuanjun , Chen Zhicong , Cao Jinming , Liu Xiufeng , Xu Feng
Published: March 2023

Objective: Gut microbiota play a key role in the pathogenesis of obesity and depression. Probiotics are a preventive strategy for obesity and a novel treatment for depression symptoms. However, the ameliorative or therapeutic effect of potential probiotic candidate Lactobacillus reuteri (L. reuteri) on obesity and depression comorbidity still remains unclear. We investigated the effects of chronic unpredictable mild stress (CUMS) in high-fat diet-fed mice and the effects of Lactobacillus reuteri strain 8008 on various disease indicators of obesity and depression comorbidity disease.

Methods: Forty male C57BL/6 mice were randomized into 2 groups: the normal control (NC) group (n = 10) and the high-fat diet (HFD) group (n = 30), being fed with normal diet (ND) or high-fat diet (HFD) for 8 weeks, respectively. Then the obese mice fed with HFD were randomly allocated into 3 sub-groups: the HFD group (n = 10); the HFD + CUMS group (n = 10); the HFD + CUMS + L.r group (n = 10). The latter 2 subgroups underwent CUMS for 4 weeks to build the obesity and depression comorbidity mice model. During the duration of treatment, mice were gavaged with 0.5 mL PBS solution or L. reuteri (2 × 109 CFU/mL) once a day, respectively. The body weight, food intake, organ weight, behavioral indicators, histology, blood lipids, levels of inflammatory cytokines and tight junction proteins and abundance of colonic contents bacteria were measured.

Results: The obesity and depression comorbidity mice model was successfully established after HFD feeding and chronic stress. The comorbid mice demonstrated inflammatory responses increase in liver and adipose tissues, worsened damage to the intestinal barrier as well as gut microbiota disorder. Gavaged with L. reuteri attenuated depressive-like behavior, improved blood lipids and insulin resistance, reduced inflammation in liver and adipose tissues, improved intestinal tight junctions as well as the microbiome dysbiosis in obesity and depression comorbidity mice.

Conclusion:Lactobacillus reuteri strain 8008 could alleviate depressive-like behaviors and related indicators of obesity disorders by regulating the gut microbiota in obesity and depression comorbid mice.