Structure-function Research Articles

Melatonin alleviates palmitic acid-induced mitochondrial dysfunction by reducing oxidative stress and enhancing autophagy in bovine endometrial epithelial cells

BackgroundNegative energy balance (NEB) typically occurs in dairy cows after delivery. Cows with a high yield are more likely to experience significant NEB. This type of metabolic imbalance could cause ketosis, which is often accompanied by a decline in reproductive performance. However, the molecular mechanisms underlying NEB have yet to be fully elucidated. During excessive NEB, the body fat is extensively broken down, resulting in the abnormal accumulation of non-esterified fatty acids (NEFAs), represented by palmitic acid (PA), within the uterus. Such an abnormal accumulation has the potential to damage bovine endometrial epithelial cells (BEECs), while the molecular mechanisms underlying its involvement in the PA-induced injury of BEECs remains poorly understood. Melatonin (MT) is recognized for its regulatory role in maintaining the homeostasis of mitochondrial reactive oxygen species (mitoROS). However, little is known as to whether MT could ameliorate the damage incurred by BEECs in response to PA and the molecular mechanism involved.ResultsAnalysis showed that 0.2 mmol/L PA stress increased the level of cellular and mitochondrial oxidative stress, as indicated by increased reactive oxygen species (ROS) level. In addition, we observed mitochondrial dysfunction, including abnormal mitochondrial structure and respiratory function, along with a reduction in mitochondrial membrane potential and mitochondrial copy number, and the induction of apoptosis. Notably, we also observed the upregulation of autophagy proteins (PINK, Parkin, LC3B and Ubiquitin), however, the P62 protein was also increased. As we expected, 100 μmol/L of MT pre-treatment attenuated PA-induced mitochondrial ROS and restored mitochondrial respiratory function. Meanwhile, MT pretreatment reversed the upregulation of P62 induced by PA and activated the AMPK-mTOR-Beclin-1 pathway, contributing to an increase of autophagy and decline apoptosis.ConclusionsOur findings indicate that PA can induce mitochondrial dysfunction and enhance autophagy in BEECs. In addition, MT is proved to not only reduce mitochondrial oxidative stress but also facilitate the clearance of damaged mitochondria by upregulating autophagy pathways, thereby safeguarding the mitochondrial pool and promoting cellular viability. Our study provides a better understanding of the molecular mechanisms underlying the effect of an excess of NEB on the fertility outcomes of high yielding dairy cows.

Identification, Molecular Characterization and Preliminary Functional Analysis of Three SLC27A Full-CDS cDNAs from Water Buffalo (Bubalus bubalis)

Background: Solute carrier family 27 family (SLC27As) have been identified to be involved in long chain fatty acid uptake in various tissues and cells, but their function in buffalo is unclear. Buffalo is an important dairy animal in some parts of the world. Buffalo milk contains more fat, protein, lactose and minerals than cow’s milk. The objective of this study was to identify the buffalo SLC27A1, 2 and 6 genes and to describe their characteristics, structure and basic function. Methods: The full-length coding sequences (CDSs) of SLC27A1, 2 and 6 were isolated from Binglangjiang buffalo and bioinformatics analyses were used to provide insights into the physicochemical characteristics, structure and function of their encoded proteins. Result: The CDSs of buffalo SLC27A1, 2 and 6 were 1941 bp, 1863 bp and 1905 bp in length, respectively, encoding 646, 620 and 634 amino acid residues accordingly. Their proteins FATP1, 2 and 6 have no signal peptide but a transmembrane helix with the N-terminus located outside the membrane and the C-terminus located in cytoplasmic side. All three proteins contain AMP-binding domains that belonged to AFD_class_I superfamily and may play a crucial role in the transport of fatty acids. The amino acid sequences of buffalo FATP1, 2 and 6 showed more than 88.6% identity with other species of Bovidae and more than 76.4% identity with other species of mammals. The phylogenetic tree showed that buffalo FATP1, 2 and 6 clustered in their respective clades and buffalo was more closely genetically related to other species of the Bovidae family. These findings suggest that buffalo FATPs are more similar in function to other species. The present study will provide a theoretical basis for further investigation of the functions of FATP1, 2 and 6 in buffalo lipid metabolism, especially milk fat metabolism.

A framework for player movement analysis in team sports

Player movement is a fundamental component of evaluating performance in most team sports. Movement can be evaluated across multiple scales, referring to the function of anatomical structures through various planes of motion or an individual regulating their field position based on the movement of opposition players. Developments in commercially available tracking systems have afforded end users the ability to investigate the spatiotemporal features of movement in fine detail. These advancements, in conjunction with overlaid contextual information, have provided insights into the strategies adopted by players in relation to their movement. Understanding movement beyond its semantic value allows practitioners to make informed decisions surrounding performance evaluation and training design. This investigation proposes a framework to guide the analysis of player movement within team sports environments. The framework describes how operational standards for assessing movement can be designed in reference to theory and a set training philosophy. Such practice allows for the spatial and temporal complexities within team sports to be described and could potentially lead to better-applied outcomes through greater interdisciplinary collaboration and an improved holistic understanding of movement. To inform its development, this study evaluates the current research and identifies several open questions to guide future investigations.

Enzymes of sphingolipid metabolism as transducers of metabolic inputs.

Sphingolipids (SLs) constitute a discrete subdomain of metabolism, and they display both structural and signaling functions. Accumulating evidence also points to intimate connections between intermediary metabolism and SL metabolism. Given that many SLs exhibit bioactive properties (i.e. transduce signals), these raise the possibility that an important function of SLs is to relay information on metabolic changes into specific cell responses. This could occur at various levels. Some metabolites are incorporated into SLs, whereas others may initiate regulatory or signaling events that, in turn, modulate SL metabolism. In this review, we elaborate on the former as it represents a poorly appreciated aspect of SL metabolism, and we develop the hypothesis that the SL network is highly sensitive to several specific metabolic changes, focusing on amino acids (serine and alanine), various fatty acids, choline (and ethanolamine), and glucose.

Role of mitochondria-endoplasmic reticulum contacts in neurodegenerative, neurodevelopmental and neuropsychiatric conditions.

Mitochondria-endoplasmic reticulum contacts (MERCs) mediate a close and continuous communication between both organelles that is essential for the transfer of calcium and lipids to mitochondria, necessary for cellular signalling and metabolic pathways. Their structural and molecular characterisation has shown the involvement of many proteins that bridge the membranes of the two organelles and maintain the structural stability and function of these contacts. The crosstalk between the two organelles is fundamental for proper neuronal function and is now recognised as a component of many neurological disorders. In fact, an increasing proportion of MERC proteins take part in the molecular and cellular basis of pathologies affecting the nervous system. Here we review the alterations in MERCs that have been reported for these pathologies, from neurodevelopmental and neuropsychiatric disorders to neurodegenerative diseases. Although mitochondrial abnormalities in these debilitating conditions have been extensively attributed to the high energy demand of neurons, a distinct role for MERCs is emerging as a new field of research. Understanding the molecular details of such alterations may open the way to new paths of therapeutic intervention.

Benchmark of deep-inelastic-scattering structure functions at Oαs3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\mathcal {O}\\left( \\alpha _s ^3\\right) $$\\end{document}

We present a benchmark comparison of the massless inclusive deep-inelastic-scattering (DIS) structure functions up to O(αs3)\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\mathcal {O}(\\alpha _s ^3)$$\\end{document} in perturbative QCD. The comparison is performed using the codes apfel++ and hoppet within the framework of the variable-flavour-number scheme and over a broad kinematic range relevant to the extraction of parton distribution functions. We provide results for both the single structure functions and the reduced cross sections in both neutral- and charged-current DIS. Look-up tables for future reference are included, and we also release the code used for the benchmark.

Age changes in the gastric mucosa of male albino rat: histological, immunohistochemical, histomorphometric and biochemical study.

Age related changes in the stomach are associated with alterations in the structure and secretory function of the gastric glands. The present study aimed to investigate histological, histomorphometric and biochemical changes in the gastric mucosa of rats with age. Eighty adult male albino rats were randomly divided into four age groups, 20 rats in each (prepubertal, adolescent, adult, and senile). The gastric specimens were subjected to light microscopic examination using haematoxylin and eosin, PAS and Masson's trichrome stains. Immunohistochemical staining for caspase-3 and inducible nitric oxide synthase (iNOS) was carried out. Measurement of superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA) activity in gastric tissue homogenates was performed using ELISA. Quantitative analysis of vascular endothelial growth factor (VEGF) gene expression was done by real-time polymerase chain reaction (PCR). Light microscopic examination of gastric mucosa of senile rats revealed distortion of gastric glands and erosions. Surface mucous cells, mucous neck cells, parietal and chief cells exhibited cytoplasmic destruction, nuclear degeneration, apoptosis and oxidative damage. There was a significant decrease in the mean gastric mucosal thickness, increase in collagen content and decrease in mucous content with the advance of age. These morphological changes were associated with a significant decrease in SOD and GPx activity and increase in MDA activity, in addition to decreased VEGF gene expression. Gastric mucosa of aged rats showed histological and immunohistochemical alterations. These changes were associated with oxidative stress, decreased antioxidant capacity and decreased angiogenesis.

Genomic insights into cytokinin oxidase/dehydrogenase (CKX) gene family, identification, phylogeny and synteny analysis for its possible role in regulating seed number in Pigeonpea (Cajanus cajan (L.) Millsp.)

Cytokinin oxidase/dehydrogenase (CKX) regulates cytokinin levels in plants which are vital for plant growth and development. However, there is a paucity of evidence regarding their role in controlling embryo/seed development in pigeonpea. This comprehensive study provides information on the identification and characterization of CKX genes in pigeonpea. A genome-wide analysis identified 18 CKX genes, each with distinct structure, expression patterns, and possible diverse functions. Domain analysis revealed the presence of the sequences including FAD and CK-Binding domain, and subcellular localization analysis showed that almost 50 % of them reside within the nucleus. They were observed to be located unevenly on chromosome numbers 2, 4, 6, 7, and 11 with a majority of them present on the scaffolds. The 8 homologous pairs and various orthologous gene pairs provided further insights into their evolution pattern. Further, SNP/Indels variation in CKX genes and haplotype groups among contrasting genotypes for SNPP (seed number per pod) were analyzed. Spatiotemporal expression analysis revealed the significant expression pattern of CcCKX15, CcCKX17, and CcCKX2 in genotypes carrying low SNPP reiterating their possible role as negative regulators. These genes can be potential targets to undertake seed and biomass improvement in pigeonpea.

Baker’s yeast beta glucan supplementation was associated with an improved innate immune mRNA expression response after exercise

Beta glucans are found in many natural sources, however, only Baker’s Yeast Beta Glucan (BYBG) has been well documented to have structure–function effects that are associated with improved innate immune response to stressors (e.g., exercise, infection, etc.). The purpose was to identify a BYBG-associated mRNA expression pattern following exercise. Participants gave IRB-approved consent and were randomized to BYBG (Wellmune®; N=9) or Placebo (maltodextrin; N=10) for 6-weeks prior to performing 90 min of whole-body exercise. Paxgene blood samples were collected prior to exercise (PRE), after exercise (POST), two hours after exercise (2H), and four hours after exercise (4H). Total RNA was isolated and analyzed for the expression of 770 innate immune response mRNA (730 mRNA targets; 40 housekeepers/controls; Nanostring nCounter). The raw data were normalized against housekeeping controls and expressed as Log2 fold change from PRE for a given condition. Significance was set at p < 0.05 with adjustments for multiple comparisons and false discovery rate. We identified 47 mRNA whose expression was changed after exercise with BYBG and classified them to four functional pathways: 1) Immune Cell Maturation (8 mRNA), 2) Immune Response and Function (5 mRNA), 3) Pattern Recognition Receptors and DAMP or PAMP Detection (25 mRNA), and 4) Detection and Resolution of Tissue Damage (9 mRNA). The identified mRNA whose expression was altered after exercise with BYBG may represent an innate immune response pattern and supports previous conclusions that BYBG improves immune response to a future sterile inflammation or infection.

Amine-decorated metal-organic frameworks MIL-53(Al) on titanosilicate zeolite ETS-10 for radioactive iodine entrapment

The storage/disposal of the hazardous fission product iodine (I2) from waste of nuclear industries has caused worldwide concerns because of its severely negative impacts on organisms and environments. Therefore, searching for appropriate adsorbent is of great importance for effective capture of radioactive I2. Herein, a series of novel hierarchical adsorbents, composed of the nanoscale Materials of Institute Lavoisier-53(Al) (MIL-53(Al)) or its amine functionalized derivative NH2-MIL-51(Al) onto a supporter Engelhard Titanosilicate-10 (ETS-10) were successfully synthesized via a wet impregnation method. The performance for I2 removal of the absorbents (MIL-53(Al), NH2-MIL-51(Al) and NH2-MIL-51(Al)@ETS-10) were studied as functions of loading amount, morphology and pore structure, respectively. The NH2-MIL-51(Al)@ETS-10 represents the best adsorption performance due to its good cooperative effects including larger surface area, higher load capacity, strong affinity of charge-transfer complexes with I2 (-NH2 or –NH with I). The adsorption capacity of NH2-MIL-51(Al)@ETS-10 could be reached to 1.16 g·g−1 and is ∼ 2.5 and 5 times higher than the NH2-MIL-51(Al) and MIL-51(Al), respectively. The kinetics and isotherms for adsorption could be fitted via pseudo-second-order and Langmuir models, respectively, indicating the strong monolayer chemisorption interactions. The study manifests that the designed material has certain potential for application in I2 entrapment.

The functions of leg muscles, structures and mechanisms in running.

The actions of the major human leg muscles are well established; however, the functions of these muscle actions during steady running remain unclear. Here, leg structures and mechanisms are considered in terms of their functions in meeting the task of a vehicle acting as an effective machine, supporting body weight during translation with low mechanical work demand and in supplying mechanical work economically. Legs are modelled as a sequence of linkages that predict muscle actions and reveal the varying muscle functions within the integrated leg. Work avoidance is achieved with isometric muscles and linkages that promote a sliding of the hip over the ground contact, resulting in an approximately horizontal path of the centre of mass. Economical work supply requires, for muscle with constrained power, shortening over the entire stance duration; this function is achieved by the hamstrings without disrupting the linkages resulting in work avoidance. In late stance, the two functions occur through coactivation of antagonistic muscles, providing one answer to Lombard's paradox. Quadriceps and hamstring tensions result in opposing moments about both hip and knee joints, but by doing so perform the independent yet complementary roles of work avoidance during translating weight support and economical work supply.

Association of birthweight and risk of incident dementia: a prospective cohort study.

Given the epidemiological studies investigating the relationship between birthweight and dementia are limited. Our study aimed to explore the association between birthweight and the risk of dementia, cognitive function, and brain structure. We included 275,648 participants from the UK Biobank, categorizing birthweight into quartiles (Q1 ≤ 2.95 kg; Q2 > 2.95 kg, ≤ 3.32 kg; Q3 > 3.32 kg, ≤ 3.66 kg; Q4 > 3.66 kg), with Q3 as the reference. Cox regression models and restricted cubic splines estimated the relationship between birthweight and the risk of all causes of dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VD). Multivariable linear regression models assessed the relationship between birthweight, cognitive function, and MRI biomarkers. Over a median follow-up of 13.0 years, 3103 incident dementia cases were recorded. In the fully adjusted model, compared to Q3 (> 3.32 kg, ≤ 3.66 kg), lower birthweight in Q1 (≤ 2.95 kg) was significantly associated with increased risk of ACD (HR = 1.18, 95%CI 1.06-1.30, P = 0.001) and VD (HR = 1.32, 95%CI 1.07-1.62, P = 0.010), but no significant association with AD was found. Continuous birthweight showed a U-shaped nonlinear association with dementia. Lower birthweight was associated with worse performance in cognitive tasks, including reaction time, fluid intelligence, numeric, and prospective memory. Additionally, certain brain structure indices were identified, including brain atrophy and reductions in area, thickness, and volume of regional subcortical areas. Our study emphasizes the association between lower birthweight and increased dementia risk, correlating cognitive function and MRI biomarkers of brain structure, suggesting that in utero or early-life exposures might impact cognitive health in adulthood.

Underwater quantitative thickness mapping through marine growth for corrosion measurement using shear wave EMAT with high lift-off performance

Underwater inspection is important to ensure the safety, integrity and functionality of underwater structures. Although numerous conventional methods have been adopted for underwater inspection, successful application of most methods relies on the surface condition of the object, which, however, is typically covered by marine growth. Consequently, routine inspection requires thorough cleaning of marine growth, which is time-consuming and costly. Hence a method which can inspect objects without the need for extensive surface cleaning is necessary. Two methods have the potential to achieve this: pulse eddy current (PEC) and electromagnetic acoustic transducer (EMAT). PEC attains a significant lift-off distance, enabling inspection through marine growth. However, it suffers from high sensitivity to environmental conditions and low inspection accuracy due to ‘relative’ property which means its results are interpreted by comparing received signals to reference values. In contrast to PEC, EMAT provides ‘absolute’ measurements, ensuring precise results in the inspection. But it is limited by a small lift-off distance (<2∼3 mm), rendering it unsuitable for underwater applications with marine growth. Therefore, if the lift-off distance can be enhanced to a specific value, this method may offer a superior solution for underwater inspections. In this paper, a quantitative measurement method is proposed through employing a shear wave EMAT with high lift-off performance. A repelling configuration of magnets is introduced to achieve a significantly improved maximum effective lift-off distance of up to 5 mm in both air and seawater conditions with only 400 Vpp applied. This EMAT is then demonstrated to measure thickness through marine growth, showing excellent underwater performance in quantitative thickness mapping for corrosion inspection.

Aided Porous Medium Emulsification for Functional Hydrogel Microparticles Synthesis.

Despite the substantial advancement in developing various hydrogel microparticle (HMP) synthesis methods, emulsification through porous medium to synthesize functional hybrid protein-polymer HMPs has yet to be addressed. Here, the aided porous medium emulsification for hydrogel microparticle synthesis (APME-HMS) system, an innovative approach drawing inspiration from porous medium emulsification is introduced. This method capitalizes on emulsifying immiscible phases within a 3D porous structure for optimal HMP production. Using the APME-HMS system, synthesized responsive bovine serum albumin (BSA) and polyethylene glycol diacrylate (PEGDA) HMPs of various sizes are successfully synthesized. Preserving protein structural integrity and functionality enable the formation of cytochrome c (cyt c) - PEGDA HMPs for hydrogen peroxide (H2O2) detection at various concentrations. The flexibility of the APME-HMS system is demonstrated by its ability to efficiently synthesize HMPs using low volumes (≈50µL) and concentrations (100µm) of proteins within minutes while preserving proteins' structural and functional properties. Additionally, the capability of the APME-HMS method to produce a diverse array of HMP types enriches the palette of HMP fabrication techniques, presenting it as a cost-effective, biocompatible, and scalable alternative for various biomedical applications, such as controlled drug delivery, 3D printing bio-inks, biosensing devices, with potential implications even in culinary applications.

A Convolutional Neural Network with Multifrequency and Structural Similarity Loss Functions for Electromagnetic Imaging

A Convolutional Neural Network with Multifrequency and Structural Similarity Loss Functions for Electromagnetic Imaging

Probing the Topological Effects on Stability Enhancement and Therapeutic Performance of Protein Bioconjugates: Tadpole, Macrocycle versus Figure-of-Eight.

Chemical topology provides a unique dimension for making therapeutic protein bioconjugates with native structure and intact function, yet the effects of topology remain elusive. Herein, the design, synthesis, and characterization of therapeutic protein bioconjugates in three topologies (i.e., tadpole, macrocycle, and figure-of-eight), are reported. The interferon α2b (IFN) and albumin binding domain (ABD) are selected as the model proteins for bioconjugation and proof-of-concept. The biosynthesis of these topological isoforms is accomplished via direct expression in cells using SpyTag-SpyCatcher chemistry and/or split-intein-mediated ligation for topology diversification. The corresponding topologies are proven with combined techniques of LC-MS, SDS-PAGE, and controlled proteolytic digestion. While the properties of these topological isoforms are similar in most cases, the figure-of-eight-shaped bioconjugate, f8-IFN-ABD, exhibits the best thermal stability and anti-aggregation properties along with prolonged half-life and enhanced tumor retention relative to the tadpole-shaped control, tadp-IFN-ABD, and the macrocyclic control, c-IFN-ABD, showcasing considerable topological effects. The work expands the topological diversity of proteins and demonstrates the potential advantages of leveraging chemical topology for functional benefits beyond multi-function integration in protein therapeutics.

General relativistic effects and the near-infrared variability of Sgr A*

A systematic study, based on the third-moment structure function, of Sgr A*’s variability finds an exponential rise time, τ1,obs = 14.8−1.5+0.4 minutes, and decay time, τ2,obs = 13.1−1.4+1.3 minutes. This symmetry of the flux-density variability is consistent with earlier work, and we interpret it as being caused by the dominance of Doppler boosting, as opposed to gravitational lensing, in Sgr A*’s light curve. A relativistic, semi-physical model of Sgr A* confirms an inclination angle of i ≲ 45°. The model also shows that the emission of the intrinsic radiative process can have some asymmetry even though the observed emission does not. The third-moment structure function, which is a measure of the skewness of the light-curve increments, may be a useful summary statistic in other contexts of astronomy because it senses only temporal asymmetry; that is, it averages to zero for any temporally symmetric signal.

The Nonlinear Relationship Between High-Density Lipoprotein and Changes in Pulmonary Structure Function and Pulmonary Function in COPD Patients in China

The Nonlinear Relationship Between High-Density Lipoprotein and Changes in Pulmonary Structure Function and Pulmonary Function in COPD Patients in China

Solar wind data analysis aided by synthetic modeling: A better understanding of plasma frame variations from temporal data

Context. In situ measurements of the solar wind, a turbulent and anisotropic plasma flow originating at the Sun, are mostly carried out by single spacecraft, resulting in one-dimensional time series. Aims. The conversion of these measurements to the spatial frame of the plasma is a great challenge, but it is required for direct comparison of the measurements with magnetohydrodynamic turbulence theories. Methods. We present a tool kit based on the synthetic modeling of solar wind fluctuations as two-dimensional noise maps with adjustable spectral and power anisotropy that can help with the temporal-spatial conversion of real data. Specifically, by following the spacecraft trajectory through a noise map (relative velocity and angle relative to some mean magnetic field) with properties tuned to mimic those of the solar wind, the likelihood that the temporal data fluctuations represent parallel or perpendicular fluctuations in the plasma frame can be quantified by correlating structure functions of the noise map. Synthetic temporal data can also be generated, which can provide a testing ground for analysis applied to the solar wind data. Results. We demonstrate this tool by investigating Parker Solar Probe’s seventh encounter trajectory and data, and we showcase several possible ways in which it can be used. We find that whether temporal variations in the spacecraft frame come from parallel or perpendicular variations in the plasma frame strongly depends on the spectral and power anisotropy of the measured wind. Conclusions. Data analysis assisted by such underlying synthetic models as presented here could open up new ways to interpret measurements in the future, specifically in the more reliable determination of plasma frame quantities from temporal measurements.

Generalized Core Functions of Maximum Entropy Theory of Ecology

Core distributions of Maximum Entropy Theory of Ecology (METE) are the Spatial Structure Function (SSF) and the Ecosystem Structure Function (ESF). SSF is a by-species prediction of the clustering of individuals over space. ESF is a kind of container function that describes the probability space of how abundances are assigned to species and how metabolic energy is parti-tioned over individuals in a community. In this study, these core functions of METE are generalized by deriving the corresponding functions in the Tsallis q-entropy. Derivation used the method of Lagrange multipliers. The generalized SSF and ESF are expressed in terms of the q-exponential function. Numerical examples are provided to illustrate the generalized SSF.