Miracle-dz/UniFAR-FTUs huggingface dataset:
An EMG-assisted Muscle-Force Driven Finite Element Analysis Pipeline to Investigate Joint- and Tissue-Level Mechanical Responses in Functional Activities: Towards a Rapid Assessment Toolbox

Joint tissue mechanics (e.g., stress and strain) are believed to have a major involvement in the onset and progression of musculoskeletal disorders, e.g., knee osteoarthritis (KOA). Accordingly, considerable efforts have been made to develop musculoskeletal finite element (MS-FE) models to estimate highly-detailed tissue mechanics that predict cartilage degeneration. However, creating such models is time-consuming and requires advanced expertise. This limits these complex, yet promising MS-FE models to research applications with few participants and making the models impractical for clinical assessments. Also, these previously developed MS-FE models are not assessed for any activities other than the gait. This study introduces and validates a semi-automated rapid state-of-the-art MS-FE modeling and simulation toolbox incorporating an electromyography (EMG) assisted MS model and a muscle-force driven FE model of the knee with fibril-reinforced poro(visco)elastic cartilages and menisci. To showcase the usability of the pipeline, we estimated joint- and tissue-level knee mechanics in 15 KOA individuals performing different daily activities. The pipeline was validated by comparing the estimated muscle activations and joint mechanics to existing experimental data. Also, to examine the importance of EMG-assisted MS analyses, results were compared against outputs from the same FE models but driven by static-optimization-based MS models. The EMG-assisted MS-FE pipeline bore a closer resemblance to experiments, compared to the static-optimization-based MS-FE pipeline. More importantly, the developed pipeline showed great potentials as a rapid MS-FE analysis toolbox to investigate multiscale knee mechanics during different activities of individuals with KOA.
GCN5 maintains muscle integrity by acetylating YY1 to promote dystrophin expression

This work identifies a novel role for the acetyltransferase GCN5 in regulating muscle integrity through inhibition of DNA binding activity of the transcriptional repressor YY1. Here we report that in mice a muscle-specific knockout of GCN5 (Gcn5skm-/-) reduces the expression of key structural muscle proteins, including dystrophin, resulting in myopathy. Supporting our observation, a meta-analysis between the differential transcriptome of Gcn5skm-/- muscle and all available open-access data sets identified top correlations with musculoskeletal diseases in humans. GCN5 was found to acetylate YY1 at two residues (K392 and K393), which disrupts the interaction between the YY1 zinc-finger region and DNA. De/acetylation mimics for these YY1 post-translational modifications modulated muscle structural gene expression and DNA binding. Analysis of human GTEx data also found positive and negative correlations between fiber diameter and GCN5 and YY1 respectively. Collectively, our results demonstrate that GCN5 acetyltransferase activity regulates YY1 DNA binding and expression of dystrophin to modulate muscle integrity.
A constitutively expressed fluorescence ubiquitin cell cycle indicator (FUCCI) in axolotls for studying tissue regeneration

Regulation of cell cycle progression is essential for cell proliferation during regeneration following injury. After appendage amputation, the axolotl (Ambystoma mexicanum) regenerates missing structures through an accumulation of proliferating cells known as the blastema. To study cell division during blastema growth, we generated a transgenic line of axolotls that ubiquitously expresses a bicistronic version of the Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI). We demonstrate near-ubiquitous expression of FUCCI expression in developing and adult tissues and validate these expression patterns with DNA synthesis and mitosis phase markers. We demonstrate the utility of FUCCI for live and whole-mount imaging, showing the predominantly local contribution of cells during limb and tail regeneration. We also show that spinal cord amputation results in increased proliferation at least 5 mm from the injury. Finally, we use multimodal staining to provide cell type information for cycling cells by combining fluorescence in-situ hybridization, EdU click-chemistry, and immunohistochemistry on a single FUCCI tissue section. This new line of animals will be useful for studying cell cycle dynamics using in-situ endpoint assays and in-vivo imaging in developing and regenerating animals. Summary statement We generated a ubiquitous transgenic fluorescence ubiquitin cell cycle indicator (FUCCI) axolotl line for examination of cell cycle dynamics during tissue regeneration.
To catch a hijacker: abundance, evolution and genetic diversity of P4-like bacteriophage satellites

Bacteriophages (phages) are bacterial parasites that can themselves be parasitized by phage satellites. The molecular mechanisms used by satellites to hijack phages are sometimes understood in great detail, but the origins, abundance, distribution, and composition of these elements are poorly known. Here, we show that P4-like elements are present in more than 10% of the genomes of Enterobacterales, and in almost half of those of Escherichia coli, sometimes in multiple distinct copies. We identified over 1000 P4-like elements with very conserved genetic organization of the core genome and a few hotspots with highly variable genes. These elements are never found in plasmids and have very little homology to known phages, suggesting an independent evolutionary origin. Instead, they are scattered across chromosomes, possibly because their integrases are often exchanged with other elements. The rooted phylogenies of hijacking functions are correlated and suggest longstanding co-evolution. They also reveal broad host ranges in P4-like elements, since almost identical elements can be found in distinct bacterial genuses. Our results show that P4-like phage satellites constitute a very distinct, widespread and ancient family of mobile genetic elements. They pave the way for studying the molecular evolution of antagonistic interactions between phages and their satellites.
Seizures initiate in zones of relative hyperexcitation in a zebrafish epilepsy model

Seizures are thought to arise from an imbalance of excitatory and inhibitory neuronal activity. While most classical studies suggest excessive excitatory neural activity plays a generative role, some recent findings challenge this view and instead argue that excessive activity in inhibitory neurons initiates seizures. We investigated this question of imbalance in a zebrafish seizure model with multi-regional two-photon imaging of excitatory and inhibitory neuronal activity using a nuclear-localized calcium sensor. We found that seizures consistently initiated in circumscribed zones of the midbrain before propagating to other brain regions. Excitatory neurons were both more prevalent and more likely to be recruited than inhibitory neurons in initiation as compared with propagation zones. These findings support a mechanistic picture whereby seizures initiate in a region of hyper-excitation, then propagate more broadly once inhibitory restraint in the surround is overcome. Teaser We uncover the roles of excitation and inhibition during seizures, thus opening a path to more targeted therapy of epilepsy.
Unconventional Translation Initiation Factor EIF2A is required for Drosophila spermatogenesis

The eukaryotic initiation factor EIF2A is an unconventional translation factor required for initiation of protein synthesis from non-AUG codons from a variety of transcripts, including oncogenes and stress related genes in mammalian cells. Its function in multicellular organisms has not been reported. Here, we identify and characterize mutant alleles of the CG7414 gene, which encodes the Drosophila EIF2A ortholog. We identified that CG7414 undergoes sex-specific splicing that regulates its male-specific expression. We characterized a Mi{Mic} transposon insertion that disrupts the coding regions of all predicted isoforms and is a genetic null allele, and a PBac transposon insertion into an intron, which is a hypomorph. The Mi{Mic} allele is homozygous lethal, while the viable progeny from the hypomorphic PiggyBac allele are male sterile and female fertile. In dEIF2A mutant flies, sperm failed to individualize due to defects in F-actin cones and failure to form and maintain cystic bulges, ultimately leading to sterility. These results demonstrate that EIF2A is essential in a multicellular organism, both for normal development and spermatogenesis, and provide an entree into the elucidation of the role of EIF2A and unconventional translation in vivo.
Synthesis of Novel Polycationic Quaternary Di‐ and Trispirocyclic Benzenes

Abstract Treatment of hexakis(bromomethyl)benzene with a cyclic amine {morpholine, 1‐methylpiperazine, 1‐(2‐hydroxyethyl)piperazine, isonipecotamide, 4‐hydroxypiperidine, 4‐[3‐(4‐piperidyl)propyl]‐1‐piperidineethanol} gave a range of di‐ and trispirocyclic ammonium salts in satisfactory yields (22–62%). Presumably, the electrostatic and repulsion forces play an important role in their formation. The structure in solution and the protonation site have been investigated by NMR and IR spectroscopy.
Parameters affecting the grafting reaction and side reactions involved in the free-radical melt grafting of maleic anhydride onto high-density polyethylene

The parameters affecting the grafting reaction and side reactions in free-radical melt grafting of maleic anhydride (MA) onto high-density polyethylene with the aid of 2,5-dimethyl-2,5-di(t-butyl peroxy)hexane peroxide(DTBPH) have been studied using an internal mixer. MA grafting degree of the maleated samples was measured with titrometry and FTIR spectroscopy methods. The extent of chain-branching/crosslinking side reactions was evaluated with gel content and MFI determination. The flow behavior and melt viscoelastic properties of the samples were measured using a rheometric mechanical spectrometer. DTBPH and MA concentrations, reaction temperature, rotor speed, the type and concentration of coagents were among the studied parameters. The results show that MA and DTBPH concentration has a major role on the grafting reaction, chain-branching/crosslinking side reactions and also the grafts microstructure in the final product. The reaction temperature has a complex effect on the maleation reaction. Increasing the rotor speed causes an increase in MA grafting degree of the samples and reduces the competitive side reactions. By using Gaylord additives, gel formation reduces at the expense of a dramatic decrease in the grafting degree. MA grafting degree is increased by the use of comonomers in the reaction and this is accompanied with a decrease in crosslinking side reaction when the vinyl type styrene comonomer is used. The results of processing torque in combination with the measurements of the melt viscoelastic property and gel content of the samples provide a great insight into understanding the gel formation mechanism. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
EHMT2 Controls Transcriptional Noise and the Developmental Switch after Gastrulation in the Mouse Embryo

Embryos that carry zygotic or parental mutations in Ehmt2, the gene encoding the main euchromatic histone H3K9 methyltransferase, EHMT2, exhibit variable developmental delay. We asked the question whether the delayed embryo is different transcriptionally from the normally developing embryo when they reach the same developmental stage. We collected embryos carrying a series of genetic deficiencies in the Ehmt2 gene and performed total RNA sequencing of somite stage-matched individual embryos. We applied novel four-way comparisons to detect differences between normal versus deficient embryos, and between 12-somite and 6-somite embryos. Importantly, we also identified developmental changes in transcription that only occur during the development of the normal embryo. We found that at the 6-somite stage, gastrulation-specific genes were not precisely turned off in the Ehmt2−/− embryos, and genes involved in organ growth, connective tissue development, striated muscle development, muscle differentiation, and cartilage development were not precisely switched on in the Ehmt2−/− embryos. Zygotic EHMT2 reduced transcriptional variation of developmental switch genes and at some repeat elements at the six-somite stage embryos. Maternal EHMT2-mutant embryos also displayed great transcriptional variation consistent with their variable survival, but transcription was normal in developmentally delayed parental haploinsufficient embryos, consistent with their good prospects. Global profiling of transposable elements in the embryo revealed that specific repeat classes responded to EHMT2. DNA methylation was specifically targeted by EHMT2 to LTR repeats, mostly ERVKs. Long noncoding transcripts initiated from those misregulated ‘driver’ repeats in Ehmt2−/− embryos, and extended to several hundred kilobases, encompassing a multitude of additional, similarly misexpressed ‘passenger repeats. ’ These findings establish EHMT2 as an important regulator of the transition between gastrulation programs and organ specification programs and of variability.
Little evidence that Eurasian jays (Garrulus glandarius) protect their caches by responding to cues about a conspecific’s desire and visual perspective

Corvids appear to be capable of adjusting their behaviour according to another’s perspective, knowledge and desire. For example, Eurasian jays have been found to employ a variety of cache protection strategies to minimise cache loss by responding to cues about the visual perspective or current desire of an observing conspecific. However, it is not known whether these jays (or any other corvid) can integrate multiple cues about different mental states and perform the optimal response accordingly. Across five experiments, we found little evidence that our Eurasian jays responded to either the visual perspective or current desire of another agent. In Experiments 1 and 2 we investigated whether Eurasian jays can limit the risk of cache loss by responding simultaneously to cues about the desire and perspective of a potential conspecific pilferer. Building on established paradigms, we used opaque and clear barriers to manipulate the observer’s visual access to cache locations, and specific satiety to manipulate the observer’s desire towards different types of food. Across both experiments the jays’ caching pattern provided no evidence that they could integrate information about the observer’s desire and perspective. Moreover, the results were also inconsistent with the previously reported effects that jays protect their caches by responding to either the visual access or specific satiety of the observer independently. To gain further insight into these unexpected results, we conducted three more experiments. In Experiments 3 and 4, we attempted to replicate the previous finding that Eurasian jays prefer to cache behind an opaque barrier over a clear barrier when observed by a conspecific than when caching in private. In Experiment 5, we further investigated the previous finding that jays preferentially cache a type of food that had been eaten to satiety by a conspecific over a food that had not been eaten by the conspecific. Experiments 3, 4 and 5 found no significant effects in the direction of the previously reported effects, questioning their robustness. We conclude by discussing the implications of our study for the field of corvid cognition and highlight several key issues that affect the reliability of comparative cognition research.
Studies of sulfosalts of copper; V, Phases and phase relations in the system Cu-Sb-As-S between 350 degrees and 500 degrees C

Phase relations have been determined for the system Cu-Sb-As-S between 350 degrees C and 500 degrees C. A new compound, Cu 4 (As,Sb) 2 S 5 , the only quaternary phase synthesized in this study, has not yet been reported as a mineral. It is not stable in either the Cu-Sb-S or Cu-As-S ternary system yet is ideally a ternary compound because Sb and As replace each other freely by solid solution. The compound ranges in composition from Cu 4 (Sb (sub 0.26) As (sub 0.74) ) 2 S 5 to Cu 4 (Sb (sub 0.55) As (sub 0.45) ) 2 S 5 . The d values (A) and intensities of the four strongest X-ray diffraction lines are 2.99(10), 2.59(4), 1.83(8), and 1.56(7) for the composition Cu 4 (Sb (sub 0.391) As (sub 0.609) ) 2 S 5 . The X-ray pattern resembles that of tennantite in its strongest lines. Because the phase is demonstrably stable down to 350 degrees C, and is apparently stable to even lower temperatures, it is probable that it will be discovered as a mineral.Phase relations are controlled by extensive substitutions of As for Sb in phases that appear on the ternary faces Cu-Sb-S and Cu-As-S. The important compounds are enargite, Cu 3 (As,Sb)S 4 ; famatinite, Cu 3 (Sb,As)S 4 ; luzonite Cu 3 (As,Sb)S 4 ; chalcostibite, Cu(Sb,As)S 2 ; high-skinnerite, Cu 3 (Sb,As)S 3 ; compound A, Cu 24 (As,Sb) 12 S 31 ; and the solid solution series tennantite-tetrahedrite, Cu (sub 12+X) (As,Sb) (sub 4+Y) S 13 . The composition volume for tennantite-tetrahedrite is complex and continuous from the pure As to the pure Sb end-member compositions. Compositions in the quaternary are always less sulfur rich than the ideal formula Cu 12 (As,Sb) 4 S 13 . Besides extensive substitution of As for Sb, the dominant controls on phase relations are (1) a set of tie lines between Cu 2 S and the continuous As-Sb binary solid solution and (2) a large liquid field centered on the ternary face Sb-As-S that extends far out into the quaternary.
Lysophophatidyl-choline 16:0 mediates persistent joint pain through Acid-Sensing Ion Channel 3: preclinical and clinical evidences

Rheumatic diseases are often associated to debilitating chronic joint pain, which remains difficult to treat and requires new therapeutic strategies. Here, we describe increased content of lysophosphatidyl-choline (LPC) 16:0 in the knee synovial fluids of two independent cohorts of patients with painful joint diseases. If LPC16:0 levels correlated with pain in patients with osteoarthritis (OA), they do not appear to be the hallmark of a particular joint disease. We found that intra-articular injections of LPC16:0 in mouse produce chronic pain and anxiety-like behaviors in both males and females with no apparent inflammation, peripheral nerve sprouting and damage, nor bone alterations. LPC16:0-induced persistent pain state is dependent on peripheral Acid-Sensing Ion Channel 3 (ASIC3), ultimately leading to central sensitization. LPC16:0 and ASIC3 thus appear as key players of chronic joint pain with potential implications in OA and possibly across others rheumatic diseases.
A projectome of the bumblebee central complex

Insects have evolved diverse and remarkable strategies for navigating in various ecologies all over the world. Regardless of species, insects share the presence of a group of morphologically conserved neuropils known collectively as the central complex (CX). The CX is a navigational hub, involved in sensory integration and coordinated motor activity. Despite the fact that our understanding of navigational behavior comes predominantly from ants and bees, most of what we know about the underlying neural circuitry of such behavior comes from work in fruit flies. Here we aim to close this gap, by providing the first comprehensive map of all major columnar neurons and their projection patterns in the CX of a bee. We find numerous components of the circuit that appear to be highly conserved between the fly and the bee, but also highlight several key differences which are likely to have important functional ramifications.
A machine-learning algorithm correctly classifies cortical evoked potentials from both natural retinal stimulation and electrical stimulation of the optic nerve

Objective Optic nerve’s intraneural stimulation is an emerging neuroprosthetic approach to provide artificial vision to totally blind patients. An open question is the possibility to evoke individual non-overlapping phosphenes via selective intraneural optic nerve stimulation. To begin answering this question, first, we aim at showing in preclinical experiments with animals that each intraneural electrode could evoke a distinguishable activity pattern in the primary visual cortex. Approach We performed both patterned visual stimulation and patterned electrical stimulation in healthy rabbits while recording evoked cortical activity with an electrocorticogram array in the primary visual cortex. Electrical stimulation was delivered to the optic nerve with the intraneural array OpticSELINE. We used a support vector machine algorithm paired to a linear regression model to classify cortical responses originating from visual stimuli located in different portions of the visual field and electrical stimuli from the different electrodes of the OpticSELINE. Main results Cortical activity induced by visual and electrical stimulation could be classified with nearly 100% accuracy relative to the specific location in the visual field or electrode in the array from which it originated. For visual stimulation, the accuracy increased with the separation of the stimuli and reached 100% for separation higher than 7 degrees. For electrical stimulation, at low current amplitudes, the accuracy increased with the distance between electrodes, while at higher current amplitudes, the accuracy was nearly 100% already for the shortest separation. Significance Optic nerve’s intraneural stimulation with the OpticSELINE induced discernible cortical activity patterns. These results represent a leap forward for intraneural optic nerve stimulation towards artificial vision.
Removal of Hexachlorobenzene and Phenanthrene from Clayey Soil by Surfactant- and Ultrasound-Assisted Electrokinetics

Removal of nonpolar contaminants such as most organic compounds are transported primarily by electroosmosis in electrokinetic remediation, thus the process is effective only if the contaminants are soluble in pore fluid. Hydrophobic organic compounds such as hexachlorobenzene (HCB) and phenanthrene (PHE) can adsorb strongly to clayey soil. Therefore, in this study, enhancements were done by adding 2-hydroxylpropyl-β-cyclodextrin surfactant and ultrasonication comparably to assist the electrokinetic treatment in improving the mobility of these hydrophobic compounds. The results show that HCB and PHE were mobilized and removed in both cases. But HCB is more difficult to remove than PHE, because of its highly stable nature and low water-solubility property. Ultrasound-assisted test performed better PHE reduction than surfactant-assisted test, because ultrasound can degrade the contaminant through oxidation by free radicals.