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Background: Ruminal microbial communities enriched on lignocellulosic biomass have shown considerable promise for the discovery of microorganisms and enzymes involved in digesting cell wall compounds, a key bottleneck in the development of second-generation biofuels and bioproducts, enabling a circular bioeconomy. Cardoon (Cynara cardunculus) is a promising inedible energy crop for current and future cellulosic biorefineries and the emerging bioenergy and bioproducts industries. The rumen microbiome can be considered an anaerobic "bioreactor", where the resident microbiota carry out the depolymerization and hydrolysis of plant cell wall polysaccharides (PCWPs) through the catalytic action of fibrolytic enzymes. In this context, the rumen microbiota represents a potential source of microbes and fibrolytic enzymes suitable for biofuel production from feedstocks. In this study, metatranscriptomic and 16S rRNA sequencing were used to profile the microbiome and to investigate the genetic features within the microbial community adherent to the fiber fractions of the rumen content and to the residue of cardoon biomass incubated in the rumen of cannulated cows. Results: The metatranscriptome of the cardoon and rumen fibre-adherent microbial communities were dissected in their functional and taxonomic components. From a functional point of view, transcripts involved in the methanogenesis from CO2 and H2, and from methanol were over-represented in the cardoon-adherent microbial community and were affiliated with the Methanobrevibacter and Methanosphaera of the Euryarchaeota phylum. Transcripts encoding glycoside hydrolases (GHs), carbohydrate-binding modules (CBMs), carbohydrate esterases (CEs), polysaccharide lyases (PLs), and glycoside transferases (GTs) accounted for 1.5% (6,957) of the total RNA coding transcripts and were taxonomically affiliated to major rumen fibrolytic microbes, such as Oscillospiraceae, Fibrobacteraceae, Neocallimastigaceae, Prevotellaceae, Lachnospiraceae, and Treponemataceae. The comparison of the expression profile between cardoon and rumen fiber-adherent microbial communities highlighted that specific fibrolytic enzymes were potentially responsible for the breakdown of cardoon PCWPs, which was driven by specific taxa, mainly Ruminococcus, Treponema, and Neocallimastigaceae. Conclusions: Analysis of 16S rRNA and metatranscriptomic sequencing data revealed that the cow rumen microbiome harbors a repertoire of new enzymes capable of degrading PCWPs. Our results demonstrate the feasibility of using metatranscriptomics of enriched microbial RNA as a potential approach for accelerating the discovery of novel cellulolytic enzymes that could be harnessed for biotechnology. This research contributes a relevant perspective towards degrading cellulosic biomass and providing an economical route to the production of advanced biofuels and high-value bioproducts. [ABSTRACT FROM AUTHOR]

Bats are efficient reservoirs of a number of viruses with zoonotic potential, and are involved directly in the transmission cycle of many zoonoses. In the present study, which is part of a larger project that is documenting the viromes of the bat species found in the Mid-North states of Maranhão and Piauí, we analyzed 16 pooled samples obtained from four species of bat of the genus Artibeus—Artibeus obscurus, Artibeus cinereus, Artibeus lituratus and Artibeus planirostris. We describe and identify a Hepatovirus, denominated Hepatovirus H isolate sotense, which was found in a pool of internal organs (liver and lungs) extracted from a specimen of A. planirostris, a frugivorous bat, collected in the Cerrado biome of Maranhão state. This material was analyzed using new generation sequencing, which produced a contig of 7390 nucleotides and presented a degree of identity with a number of existing Hepatovirus sequences available for bats (amino acid identity of 61.5% with Bat hepatovirus C of Miniopterus cf. manavi, 66.6% with Bat hepatovirus G of Coleura afra, 67.4% with Hepatovirus G2 of Rhinolophus landeri, and 75.3% with Hepatovirus H2 of Rhinolophus landeri). The analysis of the functional domains of this contig confirmed a pattern consistent with the characteristics of the genus Hepatovirus (Picornaviridae). In the phylogenetic tree with several other Hepatovirus species, this genome also grouped in a monophyletic clade with Hepatovirus H (HepV-H1; HepV-H2, and HepV-H3) albeit on an external branch, which suggests that it may be a distinct genotype within this species. This is the first isolate of Hepatovirus H identified in bats from South America, and represents an important discovery, given that most studies of viruses associated with bats in the state of Maranhão have focused on the family Rhabdoviridae. [ABSTRACT FROM AUTHOR]

Background: Dendrobium huoshanense, a traditional medicinal and food plant, has a rich history of use. Recently, its genome was decoded, offering valuable insights into gene function. However, there is no comprehensive gene functional analysis platform for D. huoshanense. Result: To address this, we created a platform for gene function analysis and comparison in D. huoshanense (DhuFAP). Using 69 RNA-seq samples, we constructed a gene co-expression network and annotated D. huoshanense genes by aligning sequences with public protein databases. Our platform contained tools like Blast, gene set enrichment analysis, heatmap analysis, sequence extraction, and JBrowse. Analysis revealed co-expression of transcription factors (C2H2, GRAS, NAC) with genes encoding key enzymes in alkaloid biosynthesis. We also showcased the reliability and applicability of our platform using Chalcone synthases (CHS). Conclusion: DhuFAP (www.gzybioinformatics.cn/DhuFAP) and its suite of tools represent an accessible and invaluable resource for researchers, enabling the exploration of functional information pertaining to D. huoshanense genes. This platform stands poised to facilitate significant biological discoveries in this domain. [ABSTRACT FROM AUTHOR]

Background: Lumbrosacral spondylolisthesis is a common spinal ailment affecting 4-6% of the population. It occurs when the morphology of the neural foramen changes, trapping nerve roots in a restricted area. Lower back pain can range from moderate to severe and can present with or without radiculopathy. Surgical methods like posterior instrumented interbody fusion (PLF), posterior lumbar interbody fusion (PLIF), and transforaminal lumbar interbody fusion (TLIF) are commonly used. However, high-level evidence on the best surgical method is still lacking. The primary focus of this study is to evaluate the surgical outcomes and documenting any complications. Methods: This prospective observational study enrolled 40 consecutive patients at a tertiary care hospital in Ongole, Andhra Pradesh, who were scheduled for surgical intervention for a low-grade degenrative spondylolisthesis. The study excluded patients with long-term medications, facet tenderness, previous spinal surgery, diabetic neuropathy, or vascular claudication. Data was collected through radiological assessments, operative time, blood loss, technique, and intraoperative complications, with post-operative normalization assessed using VAS scores and Oswestry Disability Index. Results: The study involved 11 men and 29 women with low-back pain, neurological claudication, and radiating pain in the lower extremities. The most common radiographic finding was decreased disc space (72.5%) and loss of lumbar lordosis (17.5%). Surface-level wound infection was seen in 11 patients, but it was effectively treated with oral antibiotics. The mean follow-up period was 8.5 months. The neurological and functional recovery of patients showed significant improvement throughout the follow-up period. Lower grades of radiological fusion were associated with higher VAS scores for pain. Conclusion: Surgery for symptomatic low- and midgrade spondylolisthesis has demonstrated superior functional clinical outcomes and enhanced pain control. Opting for posterior decompression and spinal fusion can result in a successful fusion process with few complications. A higher pelvic incidence may be crucial in the progression of developing spondylolisthesis. [ABSTRACT FROM AUTHOR]

Herpesviruses replicate by cleaving concatemeric dsDNA into single genomic units that are packaged through an oligomeric portal present in preformed procapsids. In contrast to what is known about phage portal proteins, details concerning herpesvirus portal structure and function are not as well understood. A panel of 65 Varicella-Zoster virus (VZV) recombinant portal proteins with five amino acid in-frame insertions were generated by random transposon mutagenesis of the VZV portal gene, ORF54. Subsequently, 65 VZVLUC recombinant viruses (TNs) were generated via recombineering. Insertions were mapped to predicted portal domains (clip, wing, stem, wall, crown, and β-hairpin tunnel-loop) and recombinant viruses were characterized for plaque morphology, replication kinetics, pORF54 expression, and classified based on replication in non-complementing (ARPE19) or complementing (ARPE54C50) cell lines. The N- and C-termini were tolerant to insertion mutagenesis, as were certain clip sub-domains. The majority of mutants mapping to the wing, wall, β-hairpin tunnel loop, and stem domains were lethal. Elimination of the predicted ORF54 start codon revealed that the first 40 amino acids of the N-terminus were not required for viral replication. Stop codon insertions in the C-terminus showed that the last 100 amino acids were not required for viral replication. Lastly, a putative protease cleavage site was identified in the C-terminus of pORF54. Cleavage was likely orchestrated by a viral protease; however, processing was not required for DNA encapsidation and viral replication. The panel of recombinants should prove valuable in future studies to dissect mammalian portal structure and function. IMPORTANCE Though nucleoside analogs and a live-attenuated vaccine are currently available to treat some human herpesvirus family members, alternate methods of combating herpesvirus infection could include blocking viral replication at the DNA encapsidation stage. The approval of Letermovir provided proof of concept regarding the use of encapsidation inhibitors to treat herpesvirus infections in the clinic. We propose that small-molecule compounds could be employed to interrupt portal oligomerization, assembly into the capsid vertex, or affect portal function/dynamics. Targeting portal at any of these steps would result in disruption of viral DNA packaging and a decrease or absence of mature infectious herpesvirus particles. The oligomeric portals of herpesviruses are structurally conserved, and therefore, it may be possible to find a single compound capable of targeting portals from one or more of the herpesvirus subfamilies. Drug candidates from such a series would be effective against viruses resistant to the currently available antivirals. [ABSTRACT FROM AUTHOR]

In areas ranging from neuroimaging to climate science, advances in data storage and sensor technology have led to a proliferation in multidimensional functional datasets. A common approach to analyzing functional data is to first map the discretely observed functional samples into continuous representations, and then perform downstream statistical analysis on these smooth representations. It is well known that many of the traditional approaches used for 1D functional data representation are plagued by the curse of dimensionality and quickly become intractable as the dimension of the domain increases. In this article, we propose a computational framework for learning continuous representations from a sample of multidimensional functional data that is immune to several manifestations of the curse. The representations are constructed using a set of separable basis functions that are defined to be optimally adapted to the data. We show that the resulting estimation problem can be solved efficiently by the tensor decomposition of a carefully defined reduction transformation of the observed data. Roughness-based regularization is incorporated using a class of differential operator-based penalties. Relevant theoretical properties are also discussed. The advantages of our method over competing methods are thoroughly demonstrated in simulations. We conclude with a real data application of our method to a clinical diffusion MRI dataset. for this article are available online. [ABSTRACT FROM AUTHOR]

In the steelmaking process, inaccurate composition of raw materials, experimental process parameter control, and other factors bring about large statistical uncertainty to the phosphorus content prediction of molten steel. Meanwhile, lots of models mainly predict the end‐point phosphorus content, but the composition change during the whole production process is still in the gray box condition, where the exact refining state is unknown. These two problems increase the difficulty in process parameter optimization and control. In order to improve the phosphorus content control in the steelmaking process, this work proposes the functional relevance vector machine (FRVM) method. This method smooths the time series of process parameters to continuous functions by functional data analysis to predict the phosphorus content change during the whole production process, and estimates the probabilistic distributions of regression weights based on the Bayesian framework to directly output the probabilistic confidence interval of the phosphorus content. The real‐world steelmaking dataset validates that the mean relative prediction error of phosphorus content by the FRVM method is less than 18.04% during the whole production process and the end‐point hit rate is 86.46% when the prediction error is within ±0.005 wt%. [ABSTRACT FROM AUTHOR]

Apicomplexan parasites are aetiological agents of numerous diseases in humans and livestock. Functional genomics studies in these parasites enable the identification of biological mechanisms and protein functions that can be targeted for therapeutic intervention. Recent improvements in forward genetics and whole‐genome screens utilising CRISPR/Cas technology have revolutionised the functional analysis of genes during Apicomplexan infection of host cells. Here, we highlight key discoveries from CRISPR/Cas9 screens in Apicomplexa or their infected host cells and discuss remaining challenges to maximise this technology that may help answer fundamental questions about parasite–host interactions. [ABSTRACT FROM AUTHOR]

Human and viral microRNAs (miRNAs) are involved in the regulation of gene transcription, and the establishment of their profiles in acute (AHI) and chronic (CHI) HIV infections may shed light on the pathogenetic events related to different phases of HIV disease. Next-generation sequencing (NGS) of miRNA libraries was performed, and the reads were used to analyze miRNA differential expression in the plasma with AHI and CHI. Functional analysis was then undertaken to investigate the biological processes characterizing the two phases of HIV infection. Except for hsa-miR-122-5p, which was found in 3.39% AHI vs. 0.18% CHI, the most represented human miRNAs were similarly represented in AHI and CHI. However, when considering the overall detected miRNAs in AHI and CHI, 15 displayed differential expression (FDR p < 0.05). Functional analysis identified 163 target mRNAs involved in promoting angiogenesis activation in AHI versus CHI through the action of hsa-miR10b-5p, hsa-miR1290, hsa-miR1-3p, and hsa-miR296-5p. The viral miRNAs detected, all belonging to herpesviruses, accounted for only 0.014% of total reads. The present data suggest that AHI patients exhibit strong innate immune activation through the upregulation of hsa-miR-122-5p and early activation of angiogenesis. More specific investigations are needed to study the role of viral miRNAs in HIV pathogenesis. [ABSTRACT FROM AUTHOR]

Humans and mammals need to ingest essential amino acids (EAAs) for protein synthesis. In addition to their importance as nutrients, EAAs are involved in brain homeostasis. However, elderly people are unable to efficiently consume EAAs from their daily diet due to reduced appetite and variations in the contents of EAAs in foods. On the other hand, strains of the yeast Saccharomyces cerevisiae that accumulate EAAs would enable elderly people to intakegest adequate amounts of EAAs and thus might slow down the neurodegenerative process, contributing to the extension of their healthy lifespan. In this study, we isolated a mutant (strain HNV-5) that accumulates threonine, an EAA, derived from a diploid laboratory yeast by conventional mutagenesis. Strain HNV-5 carries a novel mutation in the HOM3 gene encoding the Ala462Thr variant of aspartate kinase (AK). Enzymatic analysis revealed that the Ala462Thr substitution significant ly decreased the sensitivity of AK activity to threonine feedback inhibition even in the presence of 50 mM threonine. Interestingly, Ala462Thr substitution did not affect the catalytic ability of Hom3, in contrast to previously reported amino acid substitutions that resulted in reduced sensitivity to threonine feedback inhibition. Furthermore, yeast cells expressing the Ala462Thr variant showed an approximately threefold increase in intracellular threonine content compared to that of the wild-type Hom3. These findings will be useful for the development of threonine-accumulating yeast strains that may improve the quality of life in elderly people. IMPORTANCE For humans and mammals, essential amino acids (EAAs) play an important role in maintaining brain function. Therefore, increasing the intake of EAAs by using strains of the yeast Saccharomyces cerevisiae that accumulate EAAs may inhibit neurodegeneration in elderly people and thus contribute to extending healthy lifespan and improving their quality of life. Threonine, an EAA, is synthesized from aspartate. Aspartate kinase (AK) catalyzes the first step in threonine biosynthesis and is subject to allosteric regulation by threonine. Here, we isolated a threonine-accumulating mutant of S. cerevisiae by conventional mutagenesis and identified a mutant gene encoding a novel variant of AK. In contrast to previously isolated variants, the Hom3 variant exhibited AK activity that was insensitive to feedback inhibition by threonine but retained its catalytic ability. This resulted in increased production of threonine in yeast. These findings open up the possibility for the rational design of AK to increase threonine productivity in yeast. [ABSTRACT FROM AUTHOR]

Introduction: Asthma is a common chronic inflammatory respiratory disease worldwide. The long non-coding RNA (lncRNA) BCYRN1 has been shown to function in the inhibition of smooth muscle cell differentiation and vascular development, but its function and potential molecular mechanisms of lncRNA BCYRN1 in bronchial smooth muscle cells (BSMCs) in asthma remain unknown. Methods: Quantitative real-time polymerase chain reaction (RT-qPCR) was performed to detect the expression level of lncRNA BCYRN1 in blood and sputum of asthma patients. The effects of lncRNA BCYRN1 on the proliferation and migration of BSMCs were explored by cell counting kit-8, Transwell, colony formation, and flow cytometry analysis. Differentially expressed genes between lncRNA BCYRN1 overexpression and knockdown cells were identified using RNA-seq and verified using RT-qPCR. Results: LncRNA BCYRN1 was upregulated in asthma patients. Overexpression of lncRNA BCYRN1 significantly promoted the proliferation and migration of BSMCs, inhibited cell apoptosis and affected cell cycle arrest, promoting DNA replication. These effects were reversed after lncRNA BCYRN1 inhibition. RNA-seq identified 434 common differentially expressed genes in the lncRNA BCYRN1 overexpression and knockdown groups and verified their expression levels by RT-qPCR. Gene ontology, Kyoto Encyclopedia of Genes and Genomes and Gene set enrichment analysis indicated that these genes were mainly involved in external stimulus, cell cycle, growth factor activity, cytokine interactions, and inflammatory response. Conclusion: The identification of the highly expressed lncRNA BCYRN1 in patients with asthma, combined with functional experiments and transcriptional data, suggests that lncRNA BCYRN1 can mediate the development of asthma and can be used as a promising diagnostic and prognostic biomarker for asthma. Plain Language Summary: Asthma is a common chronic inflammatory respiratory disease worldwide. The lncRNA BCYRN1 has been shown to function in the inhibition of smooth muscle cell differentiation and vascular development, but its function and potential molecular mechanisms of lncRNA BCYRN1 in bronchial smooth muscle cells (BSMCs) in asthma remain unknown. In this study, the expression of lncRNA BCYRN1 was found to be upregulated in the blood and sputum of patients with asthma. Cell counting kit-8, colony formation and flow cytometric analysis revealed that overexpression of lncRNA BCYRN1 significantly promoted the proliferation and migration of BSMCs, inhibited cell apoptosis and affected cell cycle arrest, promoting DNA replication. These effects were reversed after lncRNA BCYRN1 inhibition. RNA-seq identified 434 common differentially expressed genes in the lncRNA BCYRN1 overexpression and knockdown groups, and verified their expression levels by RT-qPCR. Gene ontology, Kyoto Encyclopedia of Genes and Genomes and Gene set enrichment analysis indicated that these genes were mainly involved in external stimulus, cell cycle, growth factor activity, cytokine interactions, and inflammatory response. The identification of the highly expressed lncRNA BCYRN1 in patients with asthma, combined with functional experiments and transcriptional data, suggests that lncRNA BCYRN1 can mediate the development of asthma and can be used as a promising diagnostic and prognostic biomarker for asthma. [ABSTRACT FROM AUTHOR]

The purpose of this study is to demonstrate clustering methods within a functional data analysis (FDA) framework for identifying subgroups of individuals that may be exhibiting categories of misfit. Person response functions (PRFs) estimated within a FDA framework (FDA-PRFs) provide graphical displays that can aid in the identification of persons that have responded unexpectedly to items comprising an achievement test. Typical person fit statistics are also useful for detecting unexpected response patterns, but they do not provide insight into the underlying behaviors responsible for those responses. However, different responding behaviors tend to produce FDA-PRFs of different shapes, and may provide additional information regarding the reasons for misfit. Functional clustering methods are useful for categorizing respondents into subgroups based on the shapes of their FDA-PRFs. In this study, a small simulation illustrates the potential of clustering FDA-PRFs for identifying persons displaying common types of responding behaviors. The methodology is also applied to data from a high school biology assessment and a mathematics achievement test. Clustering FDA-PRFs offers a promising methodology for operationalizing person fit evaluations in large-scale assessments, and may be a valuable step in person fit assessment when used in conjunction with traditional indices of psychometric quality. [ABSTRACT FROM AUTHOR]

Microplastics are widespread pollutants, but few studies have linked field prevalence in organisms to laboratory uptakes. Aquatic filter feeders may be particularly susceptible to microplastic uptake, with the potential for trophic transfer to higher levels, including humans. Here, we surveyed microplastics from a model freshwater shrimp, common caraidina (Caridina nilotica) inhabiting the Crocodile River in South Africa to better understand microplastic uptake rates per individual. We then use functional response analysis (feeding rate as a function of resource density) to quantify uptake rates by shrimps in the laboratory. We found that microplastics were widespread in C. nilotica, with no significant differences in microplastic abundances among sampled sites under varying land uses, with an average abundance of 6.2 particles per individual. The vast majority of microplastics found was fibres (86.1%). Shrimp microplastic accumulation patterns were slightly higher in the laboratory than the field, where shrimp exhibited a hyperbolic Type II functional response model under varying exposure concentrations. Maximum feeding rates of 20 particles were found over a 6 h feeding period, and uptake evidenced at even the lowest laboratory concentrations (~10 particles per mL). These results highlight that microplastic uptake is widespread in field populations and partly density dependent, with field concentrations corroborating uptake rates recorded in the laboratory. Further research is required to elucidate trophic transfer from these taxa and to understand potential physiological impacts. [ABSTRACT FROM AUTHOR]

Bacterial–algal interactions strongly influence marine ecosystems. Bacterial communities in cultured dinoflagellates of the family Symbiodiniaceae have been characterized by metagenomics. However, little is known about whole‐genome analysis of marine bacteria associated with these dinoflagellates. We performed in silico analysis of four bacterial genomes from cultures of four dinoflagellates of the genera Symbiodinium, Breviolum, Cladocopium and Durusdinium. Comparative analysis showed that the former three contain the alphaproteobacterial family Parvibaculaceae and that the Durusdinium culture includes the family Sphingomonadaceae. There were no large genomic reductions in the alphaproteobacteria with genome sizes of 2.9–3.9 Mb, implying they are not obligate intracellular bacteria. Genomic annotations of three Parvibaculaceae detected the gene for diacetylchitobiose deacetylase (Dac), which may be involved in the degradation of dinoflagellate cell surfaces. They also had metabolic genes for dissimilatory nitrate reduction to ammonium (DNRA) in the nitrogen (N) cycle and cobalamin (vitamin B12) biosynthetic genes in the salvage pathway. Those three characters were not found in the Sphingomonadaceae genome. Predicted biosynthetic gene clusters for secondary metabolites indicated that the Parvibaculaceae likely produce the same secondary metabolites. Our study suggests that the Parvibaculaceae is a major resident of Symbiodiniaceae cultures with antibiotics. [ABSTRACT FROM AUTHOR]

This paper deals with a singular two dimensional initial boundary value problem for a Caputo time fractional parabolic equation supplemented by Neumann and non-local boundary conditions. The well posedness of the posed problem is demonstrated in a fractional weighted Sobolev space. The used method based on some functional analysis tools has been successfully showed its efficiency in proving the existence, uniqueness and continuous dependence of the solution upon the given data of the considered problem. More precisely, for proving the uniqueness of the solution of the posed problem, we established an energy inequality for the solution from which we deduce the uniqueness. For the existence, we proved that the range of the operator generated by the considered problem is dense. [ABSTRACT FROM AUTHOR]

Calving interval (CI) measures the number of days between two consecutive calves of the same cow, and previous studies based on phenotype and pedigree data reported low heritability for this trait. However, the genetic architecture of CI in the Nellore breed was not evaluated based on genomic data. Thus, this study aimed to estimate the heritability based on genomic data and carry out a genome-wide association study (GWAS) for CI in the Nellore breed, using 12,599 pedigree records, 5078 CI records, and 3818 animals genotyped with 50k SNPchip panel. Both quality control and GWAS were performed in BLUPF90 family packages, which use the single-step genomic best linear unbiased predictor (ssGBLUP) method. The average CI was 427.6 days, with a standard deviation of 106.9 and a total range of 270–730 days. The heritability estimate was 0.04 ± 0.04. The p-values of GWAS analysis resulted in a genomic inflation factor (lambda) of 1.08. The only significant SNP (rs136725686) at the genome-wide level (p-value = 1.53E-06) was located on BTA13. Other 19 SNPs were significant at the chromosome-wide level, distributed on BTA1, 2, 3, 6, 10, 13, 14, 17, 18, 22, and 26. Functional annotation analysis found thirty-six protein-coding genes, including genes related to cell cycle (RAD21 , BCAR3), oocyte function (LHX8 , CLPX , UTP23), immune system (TXK , TEC , NFATC2), endocrine function (LRRFIP2 , GPR158), estrous cycle (SLC38A7), and female fertility (CCK , LYZL4 , TRAK1 , FOXP1 , STAC). Therefore, CI is a complex trait with small heritability in Nellore cattle, and various biological processes may be involved with the genetic architecture of CI in Nellore cattle. • This is the first GWAS analysis for the calving interval in a Zebu cattle breed. • GWAS analysis found 20 SNPs associated with calving interval. • 36 protein-coding genes were found near the SNPs associated with calving interval. • Various significant SNPs are in regions where 70 QTLs were previously reported. • Various significant SNPs are in signature selection reported for cattle. [ABSTRACT FROM AUTHOR]

Meso-diaminopimelate dehydrogenase (meso-DAPDH) from Corynebacterium glutamicum ATCC13032 (CgDAPDH) is a type I meso-DAPDH that shows obvious preference toward meso-diaminopimelate (meso-DAP) and exhibits almost no amination activity toward 2-keto acids. There are seven distinct conserved insertions and deletions (indels) between type I and type II meso-DAPDH. The current functional analysis of indels is not comprehensive in meso-DAPDH. Continuing from our previous work on these indels, we first examined the functions of the other indels shown as insertion residues in type I CgDAPDH. Alanine mutations in M216, T240, K289, and Q290 lost at least 40% of their activity, highlighting the importance of these four sites in CgDAPDH. Molecular dynamic analysis indicated that the four non-active sites altered the dynamic network of interactions within the protein. Subsequently, these four sites together with the previously identified indel-related residues R180, L176, and H193 were targeted by site-saturation mutagenesis to improve the amination ability of CgDAPDH toward pyruvic acid. The most significant improvement was observed with the mutant CgL176R, which showed a six-fold increase toward pyruvic acid in kcat/Km compared to wild-type CgDAPDH. Overall, our study provides new hotspots and ideas for the subsequent protein engineering of CgDAPDH, which may also be applied to other meso-DAPDHs. [ABSTRACT FROM AUTHOR]

One of the most promising applications of satellite data is providing users in charge of land and emergency management with information and data to support decision making for geohazard mapping, monitoring and early warning. In this work, we consider ground displacement data obtained via interferometric processing of satellite radar imagery, and we provide a novel post-processing approach based on a Functional Data Analysis paradigm capable of detecting precursors in displacement time series. The proposed approach appropriately accounts for the spatial and temporal dependencies of the data and does not require prior assumptions on the deformation trend. As an illustrative case, we apply the developed method to the identification of precursors to a mud volcano eruption in the Santa Barbara village in Sicily, southern Italy, showing the advantages of using a Functional Data Analysis framework for anticipating the warning signal. Indeed, the proposed approach is able to detect precursors of the paroxysmal event in the time series of the locations close to the eruption vent and provides a warning signal months before a scalar approach would. The method presented can potentially be applied to a wide range of geological events, thus representing a valuable and far-reaching monitoring tool. [ABSTRACT FROM AUTHOR]

A mathematical model of progressive disease of the nervous system also called multiple sclerosis (MS) is studied in this paper. The proposed model is investigated under the concept of the fractal-fractional order derivative (FFOD) in the Caputo sense. In addition, the tools of nonlinear functional analysis are applied to prove some qualitative results including the existence theory, stability, and numerical analysis. For the recommended results of the existence theory, Banach and Krassnoselski's fixed point theorems are used. Additionally, Hyers–Ulam (HU) concept is used to derive some results for stability analysis. Additionally, for numerical illustration of approximate solutions of various compartments of the considered model, the modified Euler method is utilized. The aforementioned results are displayed graphically for various values of fractal-fractional orders. [ABSTRACT FROM AUTHOR]

Variants that disrupt normal pre-mRNA splicing are increasingly being recognized as a major cause of monogenic disorders. The SCN1A gene, a key epilepsy gene that is linked to various epilepsy phenotypes, is no exception. Approximately 10% of all reported variants in the SCN1A gene are designated as splicing variants, with many located outside of the canonical donor and acceptor splice sites, and most have not been functionally investigated. However, given its restricted expression pattern, functional analysis of splicing variants in the SCN1A gene could not be routinely performed. In this study, we conducted a comprehensive analysis of all reported SCN1A variants and their potential to impact SCN1A splicing and conclude that splicing variants are substantially misannotated and under-represented. We created a splicing reporter system consisting of 18 splicing vectors covering all 26 protein-coding exons with different genomic contexts and several promoters of varying strengths in order to reproduce the wild-type splicing pattern of the SCN1A gene, revealing cis -regulatory elements essential for proper recognition of SCN1A exons. Functional analysis of 95 SCN1A variants was carried out, including all 68 intronic variants reported in the literature, located outside of the splice sites canonical dinucleotides; 21 exonic variants of different classes (synonymous, missense, nonsense and in-frame deletion) and six variants observed in patients with epilepsy. Interestingly, almost 20% of tested intronic variants had no influence on SCN1A splicing, despite being reported as causative in the literature. Moreover, we confirmed that the majority of predicted exonic variants affect splicing unravelling their true molecular mechanism. We used functional data to perform genotype-phenotype correlation, revealing distinct distribution patterns for missense and splice-affecting 'missense' variants and observed no difference in the phenotype severity of variants leading to in-frame and out-of-frame isoforms, indicating that the Nav1.1 protein is highly intolerant to structural variations. Our work demonstrates the importance of functional analysis in proper variant annotation and provides a tool for high-throughput delineation of splice-affecting variants in SCN1A in a whole-gene manner. [ABSTRACT FROM AUTHOR]

Carotenoids are essential nutrients for humans and animals, and carotenoid coloration represents an important meat quality parameter for many farmed animals. Increasingly, studies have demonstrated that vertebrate carotenoid cleavage oxygenases (CCOs) are essential enzymes in carotenoid metabolism and are therefore potential candidate genes for improving carotenoid deposition. However, our understanding of carotenoid bioavailability and CCOs functions in invertebrates, particularly marine species, is currently quite limited. We previously identified that a CCO homolog, PyBCO-like 1, was the causal gene for carotenoid coloration in the 'Haida golden scallop', a variety of Yesso scallop (Patinopecten yessoensis) characterized by carotenoid enrichment. Here, we found that another CCO-encoding gene named PyBCO2 (β-carotene oxygenase 2) was widely expressed in P. yessoensis organs/tissues, with the highest expression in striated muscle. Inhibiting BCO2 expression in P. yessoensis through RNA interference led to increased carotenoid (pectenolone and pectenoxanthin) deposition in the striated muscle, and the color of the striated muscle changed from white to light orange. Our results indicate that PyBCO2 might be a candidate gene used for improving carotenoid content in normal Yesso scallops, and also in 'Haida golden scallops'. [ABSTRACT FROM AUTHOR]

Camellia is an important plant genus that includes well-known species such as C. sinensis, C. oleifera, and C. japonica. The C. sinensis cultivar 'Sangmok', one of Korea's standard types of tea landraces, is a small evergreen tree or shrub. Genome annotation has shown that Korean tea plants have special and unique benefits and superior components, such as catechin. The genome of Camellia sinensis cultivar 'Sangmok' was assembled on the chromosome level, with a length of 2678.62 Mbp and GC content of 38.16%. Further, 15 chromosome-scale scaffolds comprising 82.43% of the assembly (BUSCO completeness, 94.3%) were identified. Analysis of 68,151 protein-coding genes showed an average of 5.003 exons per gene. Among 82,481 coding sequences, the majority (99.06%) were annotated by Uniprot/Swiss-Prot. Further analysis revealed that 'Sangmok' is closely related to C. sinensis, with a divergence time of 60 million years ago. A total of 3336 exclusive gene families in 'Sangmok' were revealed by gene ontology analysis to play roles in auxin transport and cellular response mechanisms. By comparing these exclusive genes with 551 similar catechin genes, 17 'Sangmok'-specific catechin genes were identified by qRT-PCR, including those involved in phytoalexin biosynthesis and related to cytochrome P450. The 'Sangmok' genome exhibited distinctive genes compared to those of related species. This comprehensive genomic investigation enhances our understanding of the genetic architecture of 'Sangmok' and its specialized functions. The findings contribute valuable insights into the evolutionary and functional aspects of this plant species. [ABSTRACT FROM AUTHOR]

This document is a special issue of the journal Axioms titled "Topology and Functional Analysis" in honor of María Jesús Chasco's 65th birthday. It includes papers on topological groups, topological semi-groups, and topological vector spaces, highlighting the interaction between topology and functional analysis. The papers cover various topics such as factorization of groups into thin subsets, extensions of characters defined on subgroups, distinguished subgroups of compact Abelian groups, preservation of min-subgroup structure under aggregation functions, bounded sets in topological spaces subject to the action of a monoid, and the distinguished property in tensor products and weak* dual spaces. María Jesús Chasco is recognized for her contributions to mathematics, particularly in the field of duality in topological groups. [Extracted from the article]

Functional analysis (FA) methodology has been deemed the best practice in the field of applied behavior analysis. The data collected in an FA allows behavior analysts to develop the most effective and ethical behavior interventions. With the diagnosis for individuals with autism on the rise along with the forecast of adults who will need support, it may be time to take stock of the available literature. The purpose of this review was to evaluate the behavior analytic research over the last 25 years (1997–2022) on FA and treatment for adults who engage in severe problem behavior. Utilizing specific inclusion and exclusion criteria resulted in the identification of 28 articles. These articles were examined across participant characteristics, target behavior, FA type, FA settings, interventions, generalization, and maintenance. Implications on adult FA and treatment are discussed along with recommendations for practitioners who desire to support this population. [ABSTRACT FROM AUTHOR]

Introduction: Human African trypanosomiasis, commonly known as sleeping sickness, is a vector-borne parasitic disease prevalent in sub-Saharan Africa and transmitted by the tsetse fly. Suramin, a medication with a long history of clinical use, has demonstrated varied modes of action against Trypanosoma brucei. This study employs a comprehensive workflow to investigate the metabolic effects of suramin on T. brucei, utilizing a multimodal metabolomics approach. Objectives: The primary aim of this study is to comprehensively analyze the metabolic impact of suramin on T. brucei using a combined liquid chromatography-mass spectrometry (LC–MS) and nuclear magnetic resonance spectroscopy (NMR) approach. Statistical analyses, encompassing multivariate analysis and pathway enrichment analysis, are applied to elucidate significant variations and metabolic changes resulting from suramin treatment. Methods: A detailed methodology involving the integration of high-resolution data from LC–MS and NMR techniques is presented. The study conducts a thorough analysis of metabolite profiles in both suramin-treated and control T. brucei brucei samples. Statistical techniques, including ANOVA-simultaneous component analysis (ASCA), principal component analysis (PCA), ANOVA 2 analysis, and bootstrap tests, are employed to discern the effects of suramin treatment on the metabolomics outcomes. Results: Our investigation reveals substantial differences in metabolic profiles between the control and suramin-treated groups. ASCA and PCA analysis confirm distinct separation between these groups in both MS-negative and NMR analyses. Furthermore, ANOVA 2 analysis and bootstrap tests confirmed the significance of treatment, time, and interaction effects on the metabolomics outcomes. Functional analysis of the data from LC–MS highlighted the impact of treatment on amino-acid, and amino-sugar and nucleotide-sugar metabolism, while time effects were observed on carbon intermediary metabolism (notably glycolysis and di- and tricarboxylic acids of the succinate production pathway and tricarboxylic acid (TCA) cycle). Conclusion: Through the integration of LC–MS and NMR techniques coupled with advanced statistical analyses, this study identifies distinctive metabolic signatures and pathways associated with suramin treatment in T. brucei. These findings contribute to a deeper understanding of the pharmacological impact of suramin and have the potential to inform the development of more efficacious therapeutic strategies against African trypanosomiasis. [ABSTRACT FROM AUTHOR]

Many folding enzymes use separate domains for the binding of substrate proteins and for the catalysis of slow folding reactions such as prolyl isomerization. FKBP12 is a small prolyl isomerase without a chaperone domain. Its folding activity is low, but it could be increased by inserting the chaperone domain from the homolog SlyD of E. coli near the prolyl isomerase active site. We inserted two other chaperone domains into human FKBP12: the chaperone domain of SlpA from E. coli, and the chaperone domain of SlyD from Thermococcus sp. Both stabilized FKBP12 and greatly increased its folding activity. The insertion of these chaperone domains had no influence on the FKBP12 and the chaperone domain structure, as revealed by two crystal structures of the chimeric proteins. The relative domain orientations differ in the two crystal structures, presumably representing snapshots of a more open and a more closed conformation. Together with crystal structures from SlyD-like proteins, they suggest a path for how substrate proteins might be transferred from the chaperone domain to the prolyl isomerase domain. [ABSTRACT FROM AUTHOR]

This paper is dedicated to the memory of the esteemed Serbian mathematician Slaviša B. Prešić (1933–2008). The primary aim of this survey paper is to compile articles on Prešić-type mappings published since 1965. Additionally, it introduces a novel class of symmetric contractions known as Prešić–Menger and Prešić–Ćirić–Menger contractions, thereby enriching the literature on Prešić-type mappings. The paper endeavors to furnish young researchers with a comprehensive resource in functional and nonlinear analysis. The relevance of Prešić's method, which generalizes Banach's theorem from 1922, remains significant in metric fixed point theory, as evidenced by recent publications. The overview article addresses the growing importance of Prešić's approach, coupled with new ideas, reflecting the ongoing advancements in the field. Additionally, the paper establishes the existence and uniqueness of fixed points in Menger spaces, contributing to the filling of gaps in the existing literature on Prešić's works while providing valuable insights into this specialized domain. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease, causing impaired mobility. There are currently no effective therapies other than palliative treatment. Mesenchymal stromal cells (MSCs) and their secreted extracellular vesicles (MSC-EVs) have shown promise in attenuating OA progression, promoting chondral regeneration, and modulating joint inflammation. However, the precise molecular mechanism of action driving their beneficial effects has not been fully elucidated. In this study, we analyzed MSC-EV-treated human OA chondrocytes (OACs) to assess viability, proliferation, migration, cytokine and catabolic protein expression, and microRNA and mRNA profiles. We observed that MSC-EV-treated OACs displayed increased metabolic activity, proliferation, and migration compared to the controls. They produced decreased proinflammatory (Il-8 and IFN-γ) and increased anti-inflammatory (IL-13) cytokines, and lower levels of MMP13 protein coupled with reduced expression of MMP13 mRNA, as well as negative microRNA regulators of chondrogenesis (miR-145-5p and miR-21-5p). In 3D models, MSC-EV-treated OACs exhibited enhanced chondrogenesis-promoting features (elevated sGAG, ACAN, and aggrecan). MSC-EV treatment also reversed the pathological impact of IL-1β on chondrogenic gene expression and extracellular matrix component (ECM) production. Finally, MSC-EV-treated OACs demonstrated the enhanced expression of genes associated with cartilage function, collagen biosynthesis, and ECM organization and exhibited a signature of 24 differentially expressed microRNAs, associated with chondrogenesis-associated pathways and ECM interactions. In conclusion, our data provide new insights on the potential mechanism of action of MSC-EVs as a treatment option for early-stage OA, including transcriptomic analysis of MSC-EV-treated OA, which may pave the way for more targeted novel therapeutics. [ABSTRACT FROM AUTHOR]

Type III polyketide synthases (type III PKSs) are single homodimeric enzymes that produce diverse products such as phloroglucinol, pyrones, resorcinols and chalcones which are biotechnologically important molecules. In an attempt to identify new type III PKS from extreme environments, the deep-sea sediment metagenome from Bay of Bengal was screened for type III PKS genes. BLASTX analyses of Nanopore sequence derived metagenome with the in-house created PKS database revealed a full length type III PKS from a 5 kb fragment. The annotated full length type III PKS, S9PKS showed 25–30 % sequence identity towards previously characterized enzymes. To functionally characterize the gene, it was synthesized, cloned into pET28a and pColdI vectors under T7 and csp promoters, respectively, and expressed in Escherichia coli Rosetta(DE3) pLysS. The optimized PKS (OptiPKS) was expressed as inclusion bodies under both promoters. The inclusion bodies were successfully solubilised using low concentration of urea, refolded and purified using Ni-NTA Agarose resin. The purified OptiPKS was tested for functionality using fatty acyl-CoA substrates at various temperatures. High performance liquid chromatography (HPLC) analyses revealed that OptiPKS produced tri and tetraketide pyrones using C 4 to C 10 acyl-CoA starter substrates. Further characterization and mutation of the enzyme would reveal its functional significance. Thus, the study could be a lead for the annotation and functional characterization of putative type III PKS from environmental metagenome data. [Display omitted] [ABSTRACT FROM AUTHOR]

The relationship between the early‐age activity of Mediterranean fruit flies (medflies) or other fruit flies and their lifespan has not been much studied, in contrast to the connections between lifespan and diet, sexual signaling, and reproduction. The objective of this study is to assess intra‐day and day‐to‐day activity profiles of female Mediterranean fruit flies and their role as biomarker of longevity as well as to explore the relationships between these activity profiles, diet, and age‐at‐death throughout the lifespan. We use advanced statistical methods from functional data analysis (FDA). Three distinct patterns of activity variations in early‐age activity profiles can be distinguished. A low‐caloric diet is associated with a delayed activity peak, while a high‐caloric diet is linked with an earlier activity peak. We find that age‐at‐death of individual medflies is connected to their activity profiles in early life. An increased risk of mortality is associated with increased activity in early age, as well as with a higher contrast between daytime and nighttime activity. Conversely, medflies are more likely to have a longer lifespan when they are fed a medium‐caloric diet and when their daily activity is more evenly distributed across the early‐age span and between daytime and nighttime. The before‐death activity profile of medflies displays two characteristic before‐death patterns, where one pattern is characterized by slowly declining daily activity and the other by a sudden decline in activity that is followed by death. [ABSTRACT FROM AUTHOR]

Considering the context of functional data analysis, we developed and applied a new Bayesian approach via the Gibbs sampler to select basis functions for a finite representation of functional data. The proposed methodology uses Bernoulli latent variables to assign zero to some of the basis function coefficients with a positive probability. This procedure allows for an adaptive basis selection since it can determine the number of bases and which ones should be selected to represent functional data. Moreover, the proposed procedure measures the uncertainty of the selection process and can be applied to multiple curves simultaneously. The methodology developed can deal with observed curves that may differ due to experimental error and random individual differences between subjects, which one can observe in a real dataset application involving daily numbers of COVID-19 cases in Brazil. Simulation studies show the main properties of the proposed method, such as its accuracy in estimating the coefficients and the strength of the procedure to find the true set of basis functions. Despite having been developed in the context of functional data analysis, we also compared the proposed model via simulation with the well-established LASSO and Bayesian LASSO, which are methods developed for non-functional data. [ABSTRACT FROM AUTHOR]

Simple Summary: Mating behavior plays a crucial role in the survival and reproduction of insect populations. The fruitless (fru) gene, recognized for regulating male mating behaviors in Drosophila melanogaster, acts as a central "tuner", shaping courtship behavior through sex-specific expression patterns within the courtship neural circuit. While fru homologs and sex-specific isoforms have been identified in other holometabolan insects, controlling mating behavior, hemimetabolous insects show the generation of non-sex-specific mRNAs by the fru gene, suggesting potential functional differences. This study focuses on fru homologs (Nlfru) in the Hemiptera species Nilaparvata lugens, utilizing RNAi-mediated knockdown to explore Nlfru functions in male mating behavior and tissue development. Our research contributes to understanding the regulation of mating behavior in N. lugens and sheds light on the evolution of the fru gene across insect species. The fruitless (fru) gene functions as a crucial "tuner" in male insect courtship behavior through distinct expression patterns. In Nilaparvata lugens, our previous research showed doublesex (dsx) influencing male courtship songs, causing mating failures with virgin females. However, the impact of fru on N. lugens mating remains unexplored. In this study, the fru homolog (Nlfru) in N. lugens yielded four spliceosomes: Nlfru-374-a/b, Nlfru-377, and Nlfru-433, encoding proteins of 374aa, 377aa, and 433aa, respectively. Notably, only Nlfru-374b exhibited male bias, while the others were non-sex-specific. All NlFRU proteins featured the BTB conserved domain, with NlFRU-374 and NlFRU-377 possessing the ZnF domain with different sequences. RNAi-mediated Nlfru or its isoforms' knockdown in nymph stages blocked wing-flapping behavior in mating males, while embryonic knockdown via maternal RNAi resulted in over 80% of males losing wing-flapping ability, and female receptivity was reduced. Nlfru expression was Nldsx-regulated, and yet courtship signals and mating success were unaffected. Remarkably, RNAi-mediated Nlfru knockdown up-regulated the expression of flightin in macropterous males, which regulated muscle stiffness and delayed force response, suggesting Nlfru's involvement in muscle development regulation. Collectively, our results indicate that Nlfru functions in N. lugens exhibit a combination of conservation and species specificity, contributing insights into fru evolution, particularly in Hemiptera species. [ABSTRACT FROM AUTHOR]

We show that the biharmonic Hilbert complex with mixed boundary conditions on bounded strong Lipschitz domains is closed and compact. The crucial results are compact embeddings that follow by abstract arguments using functional analysis together with particular regular decompositions. Higher Sobolev order results are also proved. [ABSTRACT FROM AUTHOR]

The insect gustatory system participates in identifying potential food sources and avoiding toxic compounds. During this process, gustatory receptors (GRs) recognize feeding stimulant and deterrent compounds. However, the GRs involved in recognizing stimulant and deterrent compounds in the red imported fire ant, Solenopsis invicta, remain unknown. Therefore, we conducted a study on the genes SinvGR1, SinvGR32b, and SinvGR28a to investigate the roles of GRs in detecting feeding stimulant and deterrent compounds. In this current study, we found that sucrose and fructose are feeding stimulants and the bitter compound quinine is a feeding deterrent. The fire ant workers showed significant behavior changes to avoid the bitter taste in feeding stimulant compounds. Reverse transcription quantitative real‐time polymerase chain reaction results from developmental stages showed that the SinvGR1, SinvGR32b, and SinvGR28a genes were highly expressed in fire ant workers. Tissue‐specific expression profiles indicated that SinvGR1, SinvGR32b, and SinvGR28a were specifically expressed in the antennae and foreleg tarsi of workers, whereas SinvGR32b gene transcripts were also highly accumulated in the male antennae. Furthermore, the silencing of SinvGR1 or SinvGR32b alone and the co‐silencing of both genes disrupted worker stimulation and feeding on sucrose and fructose. The results also showed that SinvGR28a is required for avoiding quinine, as workers with knockdown of the SinvGR28a gene failed to avoid and fed on quinine. This study first identified stimulant and deterrent compounds of fire ant workers and then the GRs involved in the taste recognition of these compounds. This study could provide potential target gustatory genes for the control of the fire ant. [ABSTRACT FROM AUTHOR]

【Objective】MYB305 as a member of the MYB R2R3 subfamily, plays an important role in plant nectary development, nectar protein expression, starch accumulation and hydrolysis, and flavonoid synthesis. Therefore, it is of great significance to study the expression profile and function of MYB305 for the molecular mechanism study of Liriodendron tulipifera floral nectary.【Method】Having floral nectary of nectariferous plant L. tulipifera as materials, the anthocyanidin content in five stages of floral nectary was detected by spectrophotometry, LtMYB305 gene was cloned via RACE（rapid-amplification of cDNA ends）technology, and relative expressions among different tissues were analyzed by RT-qPCR assay. Then, subcellular localization of LtMYB305 protein was verified using tobacco leaves as materials, and the function of LtMYB305 gene was studied by genetic transformation approaches of wild type Arabidopsis thaliana（col）.【Result】The anthocyanidin in the nectaries of L. tulipifera was accumulated from the late expanding stage, increased sharply at the early flowering stage, and reached the highest of 27.14 μg/g at the withering stage, which was consistent with the process of nectar secretion and coloring. The full-length of LtMYB305 was 931 bp encoding 198 amino acids and its protein was hydrophilic and non-transmembrane. LtMYB305 was expressed highly only in the nectary of L. tulipifera at anthesis stage, and hardly in other tissues. LtMYB305 protein was localized in the nucleus. After the overexpression of LtMYB305, the nectary groove of the lateral nectary disappeared and deepened, the expressions of AtMYB30, AtPIN, AtSWEET9 genes related to flower nectary were up-regulated, and the expressions of AtCRC, AtBOP1/2, AtMYB21, AtSWEET3/4/7 genes were down-regulated.【Conclusion】 The LtMYB305 has typical characteristics of transcription factor and is involved to the nectary development in L. tulipifera. [ABSTRACT FROM AUTHOR]

Cranioplasty involves the surgical reconstruction of cranial defects arising as a result of various factors, including decompressive craniectomy, cranial malformations, and brain injury due to road traffic accidents. Most of the modern decompressive craniectomies (DC) warrant a future cranioplasty surgery within 6–36 months. The conventional process of capturing the defect impression and polymethyl methacrylate (PMMA) flap fabrication results in a misfit or misalignment at the site of implantation. Equally, the intra-operative graft preparation is arduous and can result in a longer surgical time, which may compromise the functional and aesthetic outcomes. As part of a multicentric pilot clinical study, we recently conducted a cohort study on ten human subjects during 2019–2022, following the human ethics committee approvals from the participating institutes. In the current study, an important aspect of measuring the extent of bone remodelling during the time gap between decompressive craniectomy and cranioplasty was successfully evaluated. The sterilised PMMA bone flaps were implanted at the defect area during the cranioplasty surgery using titanium mini plates and screws. The mean surgery time was 90 ± 20 min, comparable to the other clinical studies on cranioplasty. No signs of intra-operative and post-operative complications, such as cerebrospinal fluid leakage, hematoma, or local and systemic infection, were clinically recorded. Importantly, aesthetic outcomes were excellent for all the patients, except in a few clinical cases, wherein the PMMA bone flap was to be carefully customized due to the remodelling of the native skull bone. The extent of physiological remodelling was evaluated by superimposing the pre-operative and post-operative CT scan data after converting the defect morphology into a 3D model. This study further establishes the safety and efficacy of a technologically better approach to fabricate patient-specific acrylic bone flaps with improved surgical outcomes. More importantly, the study outcome further demonstrates the strategy to address bone remodelling during the patient-specific implant design. [ABSTRACT FROM AUTHOR]

My main goal here is to develop a functional analysis of cheating and corruption in sports, and to differentiate cheating within the broader category of corruption. Whereas officials can act corruptly, they cannot cheat. In contrast, sports participants, since they occupy two roles, can do both. I argue that although acts of cheating are acts of corruption, not all corrupt acts by competitors are acts of cheating. I also respond to some skeptical challenges and criticisms of the concept of 'cheating' by providing some opposing arguments and a provisional definition. I argue that cheating in sports occurs in the context of a complex institutional practice. It transpires due to some failing in the efforts and/or limitations of sports officials to prohibit it. In central cases it consists in both the functional and ethical violation of the constitutional norms of a sport in the service of obtaining unearned victory for the cheater. [ABSTRACT FROM AUTHOR]

Accretive and monotone operator theory are central branches of nonlinear functional analysis and constitute the abstract study of certain set-valued mappings between function spaces. This paper deals with the computational properties of these accretive and (generalized) monotone set-valued operators. In particular, we develop (and extend) for this field the theoretical framework of proof mining, a program in mathematical logic that seeks to extract computational information from prima facie "non-computational" proofs from the mainstream literature. To this end, we establish logical metatheorems that guarantee and quantify the computational content of theorems pertaining to accretive and (generalized) monotone set-valued operators. On the one hand, our results unify a number of recent case studies, while they also provide characterizations of central analytical notions in terms of proof theoretic ones on the other, which provides a crucial perspective on needed quantitative assumptions in future applications of proof mining to these branches. [ABSTRACT FROM AUTHOR]

The therapeutic response to lithium in patients with bipolar disorder is highly variable and has a polygenic basis. Genome-wide association studies investigating lithium response have identified several relevant loci, though the precise mechanisms driving these associations are poorly understood. We aimed to prioritise the most likely effector gene and determine the mechanisms underlying an intergenic lithium response locus on chromosome 21 identified by the International Consortium on Lithium Genetics (ConLi+Gen). We conducted in-silico functional analyses by integrating and synthesising information from several publicly available functional genetic datasets and databases including the Genotype-Tissue Expression (GTEx) project and HaploReg. The findings from this study highlighted TMPRSS15 as the most likely effector gene at the ConLi+Gen lithium response locus. TMPRSS15 encodes enterokinase, a gastrointestinal enzyme responsible for converting trypsinogen into trypsin and thus aiding digestion. Convergent findings from gene-based lookups in human and mouse databases as well as co-expression network analyses of small intestinal RNA-seq data (GTEx) implicated TMPRSS15 in the regulation of intestinal nutrient absorption, including ions like sodium and potassium, which may extend to lithium. Although the findings from this study indicated that TMPRSS15 was the most likely effector gene at the ConLi+Gen lithium response locus, the evidence was circumstantial. Thus, the conclusions from this study need to be validated in appropriately designed wet-lab studies. The findings from this study are consistent with a model whereby TMPRSS15 impacts the efficacy of lithium treatment in patients with bipolar disorder by modulating intestinal lithium absorption. • TMPRSS15 is a novel regulator of lithium response in patients with bipolar disorder. • It is the most likely effector gene at a known lithium response locus. • The gene encodes enterokinase (ENTK), a key modulator of intestinal absorption. • ENTK likely impacts lithium response through the modulation of lithium absorption. [ABSTRACT FROM AUTHOR]

The structural dependence of nonlinear optical properties associated with ADP-doped PVA/PVP polymer composites is discussed in this work. Polymer composites are fabricated using the solution casting method. X-ray diffraction (XRD) was used to perform structural analysis on these samples whose average crystallite size increases with an increase in dopant concentration. Results from UV–Vis–NIR spectra show that the samples are transparent in the IR region. The Z-scan technique was established by following the method described by Sheik-Bahae et al. The shape of the open aperture plot suggests that the samples exhibit two-photon absorption. The NLO properties such as nonlinear absorption coefficient (β) , two-photon absorption cross-section ( σ 2) and the imaginary part of third-order nonlinear susceptibility (χ (3)) were investigated at 1064 nm and these values were found to be in the order of ∼ 1 0 − 7 W/cm, ∼ 1 0 − 2 0 cm4/GW and ∼ 1 0 − 1 4 esu, respectively. The open aperture Z-scan method yielded optical limiting data, from which the optical limiting threshold was calculated to be in the order of ∼ 1 0 1 3 W/m2. Functional data analysis uses a suitable basis representation to assess the functional correlation between global and local variables. [ABSTRACT FROM AUTHOR]

Summary: Wholegrain composite flours are used for bakery products to enhance their nutritional value and to decrease the reliance on wheat importation as well as to ensure food security in most developing countries. This work aimed to optimise oat, maize, barley and wheat flour levels in the development of nutritionally enriched wholegrain pretzels. Composite flour blends were prepared by mechanical mixing of oat flour (OF), barley flour (BF), maize flour (MF) and wheat flour (WF) in the following proportion: WF (100%) (T0 – control), W:B (90:10) (T1), W:M (90:10) (T2), W:O (90:10) (T3), W:B:M:O (85:5:5:5) (T4), W:B:M:O (76:8:8:8) (T5) and W:B:M:O (70:10:10:10) (T6). Wholegrain composite flour mixes were analysed for their proximate composition and antioxidant properties. The fat, protein, ash and moisture content significantly changed (P < 0.05) in all treatments, while the fibre content increased. DPPH radical scavenging activity and total phenolic and flavonoid content showed significant changes compared to the control. A rapid visco analyser determined multigrain flour's rheological and pasting properties, and the values showed significant (P < 0.05) differences for peak viscosity, final viscosity and pasting temperature. The final product was analysed for proximate analysis, texture, colour and sensory evaluation. The increase in moisture, protein, fibre and ash content of the product was observed. Moisture, fat and fibre content of pretzels exhibited significant correlations (P < 0.05) with the sensory parameters. A grouping of the samples in function of the chemical and sensory characteristics was depicted from the principal component analysis. Texture and colour analysis showed significant differences (P < 0.05). Sensory evaluation results showed that the overall score for acceptability found for composite flour mix which contains 10% barley, 10% oat and 10% maize with wheat in a 30:70 ratio was accepted by the consumer. Consumption of wholegrain pretzels as snack food can contribute to a nutritious and balanced diet. [ABSTRACT FROM AUTHOR]

In this dissertation, we study the coupled system of q$$ q $$‐fractional Langevin differential equations involving q$$ q $$‐Caputo derivative having q$$ q $$‐fractional integral conditions. With the help of some adequate conditions, we investigate the uniqueness and existence of mild solution of the aforementioned system. We also analyze various kinds of Ulam's stability. Banach fixed point theorem and Leray–Schauder of cone type are used to illustrate the existence and uniqueness results. We also used non‐linear functional analysis methods to explore variety of stability types. An example is provided to clearly demonstrate our theoretical outcomes. [ABSTRACT FROM AUTHOR]

Marek Pokropski's "Mechanisms and Consciousness Integrating Phenomenology with Cognitive Science" reopens the question about the possibility of naturalization of phenomenology. The author adopts the position of nonreductive mechanistic integration, which, he claims, has offered new methodological perspectives for studying complex mental phenomena such as consciousness. In this paper, I outline the context of the discussions on the relationship between phenomenology and cognitive sciences, and (§2) discuss the approach proposed by Pokropski, pointing out the main arguments and the most important research achievements. Then I focus on some difficulties of this position. The first of these I associate with a procedure which I call a dismemberment of phenomenology (§3). The second (§4) concerns the concept of constraint, which is key to Pokropski's analyzes, and some consequences of its application and alternative reading. Finally, in §5 I draw attention to two difficulties. The first is whether it is possible to read phenomenology in terms of functional analysis; the second is related to the doubt whether psychological or phenomenological functional explanations can be treated as mechanistic (which is a strong premise of Pokropski's argument). In Conclusion I make an overall assessment of the presented approach. [ABSTRACT FROM AUTHOR]

Oligoasthenoteratozoospermia (OAT) is a common type of male infertility; however, its genetic causes remain largely unknown. Some of the genetic determinants of OAT are gene defects affecting spermatogenesis. BCORL1 (BCL6 corepressor like 1) is a transcriptional corepressor that exhibits the OAT phenotype in a knockout mouse model. A hemizygous missense variant of BCORL1 (c.2615T > G:p.Val872Gly) was reported in an infertile male patient with non‐obstructive azoospermia (NOA). Nevertheless, the correlation between BCORL1 variants and OAT in humans remains unknown. In this study, we used whole‐exome sequencing to identify a novel hemizygous nonsense variant of BCORL1 (c.1564G > T:p.Glu522*) in a male patient with OAT from a Han Chinese family. Functional analysis showed that the variant produced a truncated protein with altered cellular localization and a dysfunctional interaction with SKP1 (S‐phase kinase‐associated protein 1). Further population screening identified four BCORL1 missense variants in subjects with both OAT (1 of 325, 0.31%) and NOA (4 of 355, 1.13%), but no pathogenic BCORL1 variants among 362 fertile subjects. In conclusion, our findings indicate that BCORL1 is a potential candidate gene in the pathogenesis of OAT and NOA, expanded its disease spectrum and suggested that BCORL1 may play a role in spermatogenesis by interacting with SKP1. [ABSTRACT FROM AUTHOR]

We analyze the existence of solutions for a class of quasilinear parabolic equations with critical growth nonlinearities, nonlinear boundary conditions, and L¹ data. We formulate our problems in an abstract form, then using some techniques of functional analysis, such as Leray-Schauder's topological degree associated with the truncation method and very interesting compactness results, we establish the existence of weak solutions to the proposed models. [ABSTRACT FROM AUTHOR]

• XGBoost algorithm is first utilized to predict β-hydroxybutyrylation modification. • A novel predictor KbhbXG is proposed for β-hydroxybutyrylation modification. • Functional analyses reveal different organisms preferentially engaging in distinct biological processes and pathways. • Dataset and codes of KbhbXG can access at https://github.com/Lab-Xu/KbhbXG. Lysine β-hydroxybutyrylation is an important post-translational modification (PTM) involved in various physiological and biological processes. In this research, we introduce a novel predictor KbhbXG, which utilizes XGBoost to identify β-hydroxybutyrylation modification sites based on protein sequence information. The traditional experimental methods employed for the identification of β-hydroxybutyrylated sites using proteomic techniques are both costly and time-consuming. Thus, the development of computational methods and predictors can play a crucial role in facilitating the rapid identification of β-hydroxybutyrylation sites. Our proposed KbhbXG model first utilizes machine learning algorithm XGBoost to predict β-hydroxybutyrylation modification sites. On the independent test set, KbhbXG achieves an accuracy of 0.7457, specificity of 0.7771, and an impressive area under the curve (AUC) score of 0.8172. The high AUC score achieved by our method demonstrates its potential for effectively identifying novel β-hydroxybutyrylation sites, thereby facilitating further research and exploration of the β-hydroxybutyrylation process. Also, functional analyses have revealed that different organisms preferentially engage in distinct biological processes and pathways, which can provide valuable insights for understanding the mechanism of β-hydroxybutyrylation and guide experimental verification. To promote transparency and reproducibility, we have made both the codes and dataset of KbhbXG publicly available. Researchers interested in utilizing our proposed model can access these resources at https://github.com/Lab-Xu/KbhbXG. [ABSTRACT FROM AUTHOR]

Fast parameterized methods such as density-functional tight-binding (DFTB) facilitate realistic calculations of large molecular systems, which can be accelerated by the fragment molecular orbital (FMO) method. Fragmentation facilitates interaction analyses between functional parts of molecular systems. In addition to DFTB, other parameterized methods combined with FMO are also described. Applications of FMO methods to biochemical and inorganic systems are reviewed. [ABSTRACT FROM AUTHOR]

The analysis of stability in functional equations (FEs) within neutrosophic normed spaces is a significant challenge due to the inherent uncertainties and complexities involved. This paper proposes a novel approach to address this challenge, offering a comprehensive framework for investigating stability properties in such contexts. Neutrosophic normed spaces are a generalization of traditional normed spaces that incorporate neutrosophic logic. By providing a systematic methodology for addressing stability concerns in neutrosophic normed spaces, our approach facilitates enhanced understanding and control of complex systems characterized by indeterminacy and uncertainty. The primary focus of this research is to propose a novel class of Euler-Lagrange additive FE and investigate its Ulam-Hyers stability in neutrosophic normed spaces. Direct and fixed point techniques are utilized to achieve the required results. [ABSTRACT FROM AUTHOR]