Miracle-dz/UniFAR-FTUs huggingface dataset:
Cortical tension regulates Hippo signaling via Par-1-mediated Kibra degradation

The Hippo pathway is an evolutionarily conserved regulator of tissue growth. Multiple Hippo signaling components are regulated via proteolytic degradation. However, how these degradation mechanisms are themselves modulated remains unexplored. Kibra is a key upstream pathway activator that promotes its own ubiquitin-mediated degradation upon assembling a Hippo signaling complex. Here, we demonstrate that Hippo complex-dependent Kibra degradation is modulated by cortical tension. Using classical genetic, osmotic, and pharmacological manipulations of myosin activity and cortical tension, we show that increasing cortical tension leads to Kibra degradation, whereas decreasing cortical tension increases Kibra abundance. Our study also implicates Par-1 in regulating Kib abundance downstream of cortical tension. We demonstrate that Par-1 promotes ubiquitin-mediated Kib degradation in a Hippo complex-dependent manner and is required for tension-induced Kib degradation. Collectively, our results reveal a previously unknown molecular mechanism by which cortical tension affects Hippo signaling and provide novel insights into the role of mechanical forces in growth control.
intI1 primer selection for class 1 integron integrase gene and transcript quantification – validation and application for monitoring intl1 gene abundance within septic tanks in Thailand

Antimicrobial resistance (AMR) poses serious global public health threat and wastewater treatment (WWT), including septic tanks, are a significant source of AMR genes to the environment. Environmental monitoring of broad-range AMR genes remains a challenge. The class-1 integron-integrase (intI1) gene has been proposed as a proxy for overall AMR abundance, but there is no consensus on the qPCR primer set to use. A systematic review of the literature found 65 primer sets. The coverage and specificity of each, including newly designed MGB-TaqMan primer-probe, was evaluated against a database of clinical and environmental intl1, intl1-like and non-intl1 sequences. Three primer sets were selected, laboratory validated for DNA and mRNA quantification and used to quantity intl1 gene abundance from household and healthcare conventional septic tanks (CST) and novel household Solar Septic Tanks (SST) in Thailand. Specificity of the intl1 septic tank amplicons showed that no primer set could distinguish between intl1 and intl-1 like sequences. Each primer set showed the same trends across septic tanks, with highest gene abundance in influent>sludge>effluent. There was no statistical difference between the same sample quantified by the three primer sets. However, when comparing gene abundances from the same primer set across septic tanks, statistical differences between different sample types were observed for one primer set but not the others. This may lead to different interpretation of risk associated with each reactor in spreading intl1 to the environment. Comparing reactor types, intI1 abundance in the effluent was lowest in the SST-household<CST-household<CST-healthcare. Depending on primer set used, 31 to 42% of intI1 was removed from effluent of the CST-household tank with accessible influent. Our study provided insight into the importance of intl1 primer choice. We propose the use of the validated set (F3-R3) for optimal intI1 quantification and towards the goal of achieving standardisation across environmental studies.
Small RNA Sequencing Reveals a Distinct MicroRNA Signature between Glucocorticoid Responder and Glucocorticoid Non-Responder Primary Human Trabecular Meshwork Cells after Dexamethasone Treatment

The present study aimed to understand the role of miRNAs in differential glucocorticoid (GC) responsiveness in human trabecular meshwork (HTM) cells using small RNA sequencing. For this, total RNA was extracted from cultured HTM cells with known GC responsiveness using Human organ-cultured anterior segment (HOCAS) (GC-responder GC-R; n=4) and GC-non-responder (GC-NR; n=4) after treatment with either 100nM dexamethasone (DEX) or ethanol (ETH) for 7 days. Differentially expressed miRNAs (DEMIRs) were compared among 5 groups and validated by RT-PCR. There were 13 and 21 DEMIRs identified in Group #1 (ETH vs DEX-treated GC-R) and Group #2 (ETH vs DEX-treated GC-NR) respectively. Seven miRNAs were found as common miRNAs dysregulated in both GC-R and GC-NR (Group #3). There were 6 and 14 unique DEMIRs were identified in GC-R (Gropu#4) and GC-NR (Group#5) HTM cells respectively. Ingenuity Pathway Analysis identified enriched pathways and biological processes associated with differential GC responsiveness in HTM cells. Integrative analysis of miRNA-mRNA of the same set of HTM cells revealed several molecular regulators for GC non-responsiveness. This is the first study revealed a unique miRNA signature between GC-R and GC-NR HTM cells which raises the possibility of developing new molecular targets for the management of steroid-OHT/glaucoma.
On the uncertainty of single-number quantities for rating airborne sound insulation

Single-number quantities are widely used to characterise acoustic properties of building products and buildings. The uncertainty of these values is now investigated by analysing a large amount of round robin results. Methods are developed to calculate the uncertainty of the single number rating from third-octave band sound insulations and the associated uncertainties. The Monte-Carlo method is used to verify the calculation methods. It turns out that correlation effects between third-octave bands significantly influence the uncertainty of the single number rating. Whereas an upper limit for the uncertainty can be calculated by assuming a full, positive correlation between all third-octave bands, the uncorrelated case does not provide a lower limit due to the occurrence of negative correlation. Since correlation effects cannot be predicted it is recommended to use the averaged uncertainties as derived from round robin tests until a deeper understanding of the governing mechanisms enables a calculation of the uncertainties.
Determinants and Potential of Trade Using the Gravity Model Approach: Empirical Evidence of Egyptian Rice Crop

The aim of this study is to examine the determinants of Egyptian trade in general and Egyptian rice trade in particular with 11 rice-importing partner countries (Libya, Lebanon, Syria, Saudi Arabia, Sudan, Jordan, Turkey, the United Kingdom, Ukraine, Belgium, and Romania). To reach the main goals of the study, the gravity model was used to figure out which factors had the most impact on Egypt’s exports and imports. Using annual data on Egypt’s foreign and agricultural trade during the period 2001–2020 and data on the period 2001–2016 of rice crops with the 11 trading partners, the study reached several important conclusions. Among these conclusions, the Egyptian GDP variable had a negative effect on the total value of Egyptian imports and agriculture by increasing the value of total exports, agricultural exports, and rice exports to Egypt. Egyptian imports, exports, and population growth were all hurt by the Egyptian population variable. The study also shows that a 1% increase in export prices leads to a 3.97% increase in shipments of Egyptian rice to partner countries. According to economic theory, higher transportation expenses reduce trade volumes for both exports and imports. The variable distance between capitals has a negative effect on Egyptian exports. The study was designed based on the results of the main investigation. Based on the main investigation, the study made several important recommendations, including the need to take several measures to deflect the pace of economic growth of both the Egyptian total and agricultural export variables and rice export value, focusing on countries with high monetary and real GDP and a close geographical distribution. Improve economic relations between Egypt and its trading partners and shift from import-export cooperation to strategic food security cooperation.
The long-term trend of uterine fibroid burden in China from 1990 to 2019: A Joinpoint and Age–Period–Cohort study

Purpose: Uterine fibroids occur in 40%–60% of women and are symptomatic in 30% of the patients by causing abnormal uterine bleeding, pelvic pressure, pain, and infertility. The study aims to evaluate the long-term trend of uterine fibroids mortality and disability-adjusted life years (DALYs) in China and the relative risks of age, period, and birth cohort effects. Methods: The mortality and DALYs of uterine fibroids from 1990 to 2019 were derived from the Global Burden of Disease 2019. The annual percentage change and average annual percent change (AAPC) were assessed using the Joinpoint regression. The effects of age, period, and birth cohort on death and DALYs were analyzed by the Age–Period–Cohort framework. Results: The age-standardized rates were all on the ascending trend, with the greatest increase in the age-standardized mortality rate (AAPC, 1.53; 95% CI, 1.04–2.02). The net drift was found to be 3.51% (95% CI, 2.25%–4.78%) per year for mortality and 0.34% (95% CI, 0.14%–0.53%) per year for DALYs. Significant age, period, and birth cohort effects were found for mortality and DALYs (p < 0.001 for all). The mortality risk increased overall with age, but the DALYs risk increased first and then decreased with age. The period and birth cohort risks for mortality and DALYs showed different trends. Conclusion: These secular time trends and changes of mortality and DALYs reveal the socioeconomic alterations, reform of diagnosis and therapy, and changes in social lifestyles and behaviors. Uterine fibroids are still the most common benign gynecological tumors in women, and more epidemiological investigations and social health prevention and control should be applied.
Cortical type: a conceptual tool for meaningful biological interpretation of high-throughput gene expression data in the human cerebral cortex

The interpretation of massive high-throughput gene expression data requires computational and biological analyses to identify statistically and biologically significant differences, respectively. There are abundant sources that describe computational tools for statistical analysis of massive gene expression data but few address data analysis for biological significance. In the present article we exemplify the importance of selecting the proper biological context in the human brain for gene expression data analysis and interpretation. For this purpose, we use cortical type as conceptual tool to make predictions about gene expression in areas of the human temporal cortex. We predict that the expression of genes related to glutamatergic transmission would be higher in areas of simpler cortical type, the expression of genes related to GABAergic transmission would be higher in areas of more complex cortical type, and the expression of genes related to epigenetic regulation would be higher in areas of simpler cortical type. Then, we test these predictions with gene expression data from several regions of the human temporal cortex obtained from the Allen Human Brain Atlas. We find that the expression of several genes shows statistically significant differences in agreement with the predicted gradual expression along the laminar complexity gradient of the human cortex, suggesting that simpler cortical types may have greater glutamatergic excitability and epigenetic turnover compared to more complex types; on the other hand, complex cortical types seem to have greater GABAergic inhibitory control compared to simpler types. Our results show that cortical type is a good predictor of synaptic plasticity, epigenetic turnover, and selective vulnerability in human cortical areas. Thus, cortical type can provide a meaningful context for interpreting high-throughput gene expression data in the human cerebral cortex.
Potential utilization of oil shale as a stabilizing material for compressed Earth block

This research aims to produce a compressed Earth block (CEB) product locally from soil collected from North Jordan. The CEB mixture was further stabilized using oil shale (OS) and ordinary Portland cement (OPC). The CEB specimens were thoroughly characterized by studying their mechanical properties (compressive and flexural strength) and durability characteristics (erosion, absorption, and shrinkage tests). Eight mixtures were carried out for the CEB, one of which was the control mix. The other mixtures were carried out by replacing soil with OS, cement, and sand in different proportions. The results showed that higher compressive strength and flexural strength for CEB were obtained in the mixtures that contained 10% of OS and 10% of cement, resulting in an average compressive strength of 10.6 MPa and flexural strength of 0.25 MPa. The absorption increased when the OS increased in the soil. The consequent erosion test was related to the absorption test, where the higher the absorption, the more negative the results of the erosion test. Moreover, oil shale improved the shrinkage properties of the CEB, as the higher the proportion of oil shale in the CEB, the lower the shrinkage. Finally, using oil shale as a stabilizing agent in soil had a clear role in improving the mechanical properties, hiding the shrinkage cracks, and reducing the volume shrinkage value of the CEB.
Neurocognitive and cerebellar function in ADHD, autism and spinocerebellar ataxia

The cerebellum plays a major role in balance, motor control and sensorimotor integration, but also in cognition, language, and emotional regulation. Several neuropsychiatric disorders such as attention deficit-hyperactivity disorder (ADHD), autism spectrum disorder (ASD), as well as neurological diseases such as spinocerebellar ataxia type 3 (SCA3) are associated with differences in cerebellar function. Morphological abnormalities in different cerebellar subregions produce distinct behavioral symptoms related to the functional disruption of specific cerebro-cerebellar circuits. The specific contribution of the cerebellum to typical development may therefore involve the optimization of the structure and function of cerebro-cerebellar circuits underlying skill acquisition in multiple domains. Here, we review cerebellar structural and functional differences between healthy and patients with ADHD, ASD, and SCA3, and explore how disruption of cerebellar networks affects the neurocognitive functions in these conditions. We discuss how cerebellar computations contribute to performance on cognitive and motor tasks and how cerebellar signals are interfaced with signals from other brain regions during normal and dysfunctional behavior. We conclude that the cerebellum plays a role in many cognitive functions. Still, more clinical studies with the support of neuroimaging are needed to clarify the cerebellum’s role in normal and dysfunctional behavior and cognitive functioning.
Multi-generation study of heavy ion beam-induced mutations and agronomic trait variations to accelerate rice breeding

Heavy ion beam (HIB) is an effective physical mutagen that has been widely used in plant mutational breeding. Systemic knowledge of the effects caused by different HIB doses at developmental and genomic levels will facilitate efficient breeding for crops. Here we examined the effects of HIB systematically. Kitaake rice seeds were irradiated by ten doses of carbon ion beams (CIB, 25 – 300 Gy), which is the most widely used HIB. We initially examined the growth, development and photosynthetic parameters of the M1 population and found that doses exceeding 125 Gy caused significant physiological damages to rice. Subsequently, we analyzed the genomic variations in 179 M2 individuals from six treatments (25 – 150 Gy) via whole-genome sequencing (WGS). The mutation rate peaks at 100 Gy (2.66×10-7/bp). Importantly, we found that mutations shared among different panicles of the same M1 individual are at low ratios, validating the hypothesis that different panicles may be derived from different progenitor cells. Furthermore, we isolated 129 mutants with distinct phenotypic variations, including changes in agronomic traits, from 11,720 M2 plants, accounting for a 1.1% mutation rate. Among them, about 50% possess stable inheritance in M3. WGS data of 11 stable M4 mutants, including three lines with higher yields, reveal their genomic mutational profiles and candidate genes. Our results demonstrate that HIB is an effective tool that facilitates breeding, that the optimal dose range for rice is 67 – 90% median lethal dose (LD50), and that the mutants isolated here can be further used for functional genomic research, genetic analysis, and breeding.
The complete mitochondrial genome of Amorphophallus albus and development of molecular markers for five Amorphophallus species based on mitochondrial DNA

Introduction Amorphophallus albus is an herbaceous, cormous, perennial plant used as a food source and traditional medicine in Asia. Methods In this study, we assembled and annotated the complete mitochondrial genome (mitogenome) of A. albus. Then we analyzed the repeated elements and mitochondrial plastid sequences (MTPTs), predicted RNA editing sites in mitochondrial protein-coding genes (PCGs). Lastly, we inferred the phylogenetic relationships of A. albus and other angiosperms based on mitochondrial PCGs, and designed two molecular markers based on mitochondrial DNA. Results and discussion The complete mitogenome of A. albus consists of 19 circular chromosomes. And the total length of A. albus mitogenome is 537,044 bp, with the longest chromosome measuring 56,458 bp and the shortest measuring 12,040 bp. We identified and annotated a total of 36 protein-coding genes (PCGs), 21 tRNA genes, and 3 rRNA genes in the mitogenome. Additionally, we analyzed mitochondrial plastid DNAs (MTPTs) and identified 20 MTPTs between the two organelle genomes, with a combined length of 22,421 bp, accounting for 12.76% of the plastome. Besides, we predicted a total of 676 C to U RNA editing sites on 36 protein-coding genes of high confidence using Deepred-mt. Furthermore, extensive genomic rearrangement was observed between A. albus and the related mitogenomes. We conducted phylogenetic analyses based on mitochondrial PCGs to determine the evolutionary relationships between A. albus and other angiosperms. Finally, we developed and validated two molecular markers, Ai156 and Ai976, based on two intron regions (nad2i156 and nad4i976) respectively. The discrimination success rate was 100 % in validation experiments for five widely grown konjac species. Our results reveal the multi-chromosome mitogenome of A. albus, and the developed markers will facilitate molecular identification of this genus.
Mechanical effect of reconstructed shapes of autologous ossicles on middle ear acoustic transmission

Conductive hearing loss is caused by a variety of defects, such as chronic otitis media, osteosclerosis, and malformation of the ossicles. In such cases, the defective bones of the middle ear are often surgically reconstructed using artificial ossicles to increase the hearing ability. However, in some cases, the surgical procedure does not result in increased hearing, especially in a difficult case, for example, when only the footplate of the stapes remains and all of the other bones are destroyed. Herein, the appropriate shapes of the reconstructed autologous ossicles, which are suitable for various types of middle-ear defects, can be determined by adopting an updating calculation based on a method that combines numerical prediction of the vibroacoustic transmission and optimization. In this study, the vibroacoustic transmission characteristics were calculated for bone models of the human middle ear by using the finite element method (FEM), after which Bayesian optimization (BO) was applied. The effect of the shape of artificial autologous ossicles on the acoustic transmission characteristics of the middle ear was investigated with the combined FEM and BO method. The results suggested that the volume of the artificial autologous ossicles especially has a great influence on the numerically obtained hearing levels.
Evaluating normalization accounts against the dense vowel space of Central Swedish

Talkers vary in the phonetic realization of their vowels. One influential hypothesis holds that listeners overcome this inter-talker variability through pre-linguistic auditory mechanisms that normalize the acoustic or phonetic cues that form the input to speech recognition. Dozens of competing normalization accounts exist—including both accounts specific to vowel perception and general purpose accounts that can be applied to any type of cue. We add to the cross-linguistic literature on this matter by comparing normalization accounts against a new phonetically annotated vowel database of Swedish, a language with a particularly dense vowel inventory of 21 vowels differing in quality and quantity. We evaluate normalization accounts on how they differ in predicted consequences for perception. The results indicate that the best performing accounts either center or standardize formants by talker. The study also suggests that general purpose accounts perform as well as vowel-specific accounts, and that vowel normalization operates in both temporal and spectral domains.
Viewpoint: spinocerebellar ataxias as diseases of Purkinje cell dysfunction rather than Purkinje cell loss

Spinocerebellar ataxias (SCAs) are a group of hereditary neurodegenerative diseases mostly affecting cerebellar Purkinje cells caused by a wide variety of different mutations. One subtype, SCA14, is caused by mutations of Protein Kinase C gamma (PKCγ), the dominant PKC isoform present in Purkinje cells. Mutations in the pathway in which PKCγ is active, i.e., in the regulation of calcium levels and calcium signaling in Purkinje cells, are the cause of several other variants of SCA. In SCA14, many of the observed mutations in the PKCγ gene were shown to increase the basal activity of PKCγ, raising the possibility that increased activity of PKCγ might be the cause of most forms of SCA14 and might also be involved in the pathogenesis of SCA in related subtypes. In this viewpoint and review article we will discuss the evidence for and against such a major role of PKCγ basal activity and will suggest a hypothesis of how PKCγ activity and the calcium signaling pathway may be involved in the pathogenesis of SCAs despite the different and sometimes opposing effects of mutations affecting these pathways. We will then widen the scope and propose a concept of SCA pathogenesis which is not primarily driven by cell death and loss of Purkinje cells but rather by dysfunction of Purkinje cells which are still present and alive in the cerebellum.