Mitofusin-mediated contacts between mitochondria and peroxisomes regulate mitochondrial fusion.

Mitofusins are large GTPases that trigger fusion of mitochondrial outer membranes. Similarly to the human mitofusin Mfn2, which also tethers mitochondria to the endoplasmic reticulum (ER), the yeast mitofusin Fzo1 stimulates contacts between Peroxisomes and Mitochondria when overexpressed. Yet, the physiological significance and function of these "PerMit" contacts remain unknown. Here, we demonstrate that Fzo1 naturally localizes to peroxisomes and promotes PerMit contacts in physiological conditions. These contacts are regulated through co-modulation of Fzo1 levels by the ubiquitin-proteasome system (UPS) and by the desaturation status of fatty acids (FAs). Contacts decrease under low FA desaturation but reach a maximum during high FA desaturation. High-throughput genetic screening combined with high-resolution cellular imaging reveal that Fzo1-mediated PerMit contacts favor the transit of peroxisomal citrate into mitochondria. In turn, citrate enters the TCA cycle to stimulate the mitochondrial membrane potential and maintain efficient mitochondrial fusion upon high FA desaturation. These findings thus unravel a mechanism by which inter-organelle contacts safeguard mitochondrial fusion.

Crystal structure of heliorhodopsin.

Heliorhodopsins (HeRs) are a family of rhodopsins that was recently discovered using functional metagenomics1. They are widely present in bacteria, archaea, algae and algal viruses2,3. Although HeRs have seven predicted transmembrane helices and an all-trans retinal chromophore as in the type-1 (microbial) rhodopsin, they display less than 15% sequence identity with type-1 and type-2 (animal) rhodopsins. HeRs also exhibit the reverse orientation in the membrane compared with the other rhodopsins. Owing to the lack of structural information, little is known about the overall fold and the photoactivation mechanism of HeRs. Here we present the 2.4-Å-resolution structure of HeR from an uncultured Thermoplasmatales archaeon SG8-52-1 (GenBank sequence ID LSSD01000000). Structural and biophysical analyses reveal the similarities and differences between HeRs and type-1 microbial rhodopsins. The overall fold of HeR is similar to that of bacteriorhodopsin. A linear hydrophobic pocket in HeR accommodates a retinal configuration and isomerization as in the type-1 rhodopsin, although most of the residues constituting the pocket are divergent. Hydrophobic residues fill the space in the extracellular half of HeR, preventing the permeation of protons and ions. The structure reveals an unexpected lateral fenestration above the ß-ionone ring of the retinal chromophore, which has a critical role in capturing retinal from environment sources. Our study increases the understanding of the functions of HeRs, and the structural similarity and diversity among the microbial rhodopsins.

Bayesian approaches to smooth pursuit of random dot kinematograms: effects of varying RDK noise and the predictability of RDK direction.

Smooth pursuit eye movements respond on the basis of both immediate and anticipated target motion, where anticipations may be derived from either memory or perceptual cues. To study the combined influence of both immediate sensory motion and anticipation, subjects pursued clear or noisy random dot kinematograms (RDKs) whose mean directions were chosen from Gaussian distributions with SDs = 10° (narrow prior) or 45° (wide prior). Pursuit directions were consistent with Bayesian theory in that transitions over time from dependence on the prior to near total dependence on immediate sensory motion (likelihood) took longer with the noisier RDKs and with the narrower, more reliable, prior. Results were fit to Bayesian models in which parameters representing the variability of the likelihood either were or were not constrained to be the same for both priors. The unconstrained model provided a statistically better fit, with the influence of the prior in the constrained model smaller than predicted from strict reliability-based weighting of prior and likelihood. Factors that may have contributed to this outcome include prior variability different from nominal values, low-level sensorimotor learning with the narrow prior, or departures of pursuit from strict adherence to reliability-based weighting. Although modifications of, or alternatives to, the normative Bayesian model will be required, these results, along with previous studies, suggest that Bayesian approaches are a promising framework to understand how pursuit combines immediate sensory motion, past history, and informative perceptual cues to accurately track the target motion that is most likely to occur in the immediate future.NEW & NOTEWORTHY Smooth pursuit eye movements respond on the basis of anticipated, as well as immediate, target motions. Bayesian models using reliability-based weighting of previous (prior) and immediate target motions (likelihood) accounted for many, but not all, aspects of pursuit of clear and noisy random dot kinematograms with different levels of predictability. Bayesian approaches may solve the long-standing problem of how pursuit combines immediate sensory motion and anticipation of future motion to configure an effective response.

Inhibition of high-fat diet-induced miRNA ameliorates tau toxicity in Drosophila.

Alzheimer's disease (AD), caused by amyloid beta (Aß) plaques and Tau tangles, is a neurodegenerative disease characterized by progressive memory impairment and cognitive dysfunction. High-fat diet (HFD), which induces type 2 diabetes, exacerbates Aß plaque deposition in the brain. To investigate the function of HFD in Tau-mediated AD, we fed an HFD to the Drosophila Tau model and found that HFD aggravates Tau-induced neurological phenotypes. Since microRNAs (miRNAs) are biomarkers for diabetes and AD, we evaluated the expression levels of common miRNAs of HFD and AD in HFD-fed Tau model fly brains. Among the common miRNAs, the expression levels of Let-7 and miR-34 were increased. We found that the inhibition of these miRNAs alleviates Tau-mediated AD phenotypes. Our research provides valuable insights into how HFD accelerates tau toxicity. Additionally, our work highlights the therapeutic potential of targeting Let-7 and miR-34 to develop innovative treatment approaches for AD.

KLF2 enhancer variant rs4808485 increases lupus risk by modulating inflammasome machinery and cellular homoeostasis.

OBJECTIVE: A recent genome-wide association study linked KLF2 as a novel Asian-specific locus for systemic lupus erythematosus (SLE) susceptibility. However, the underlying causal functional variant(s), cognate target gene(s) and genetic mechanisms associated with SLE risk are unknown. METHODS: We used bioinformatics to prioritise likely functional variants and validated the best candidate with diverse experimental techniques, including genome editing. Gene expression was compared between healthy controls (HCs) and patients with SLE with or without lupus nephritis (LN+, LN-). RESULTS: Through bioinformatics and expression quantitative trait locus analyses, we prioritised rs4808485 in active chromatin, predicted to modulate KLF2 expression. Luciferase reporter assays and chromatin immunoprecipitation-qPCR demonstrated differential allele-specific enhancer activity and binding of active histone marks (H3K27ac, H3K4me3 and H3K4me1), Pol II, CTCF, P300 and the transcription factor PARP1. Chromosome conformation capture-qPCR revealed long-range chromatin interactions between rs4808485 and the KLF2 promoter. These were directly validated by CRISPR-based genetic and epigenetic editing in Jurkat and lymphoblastoid cells. Deleting the rs4808485 enhancer in Jurkat (KO) cells disrupted NLRP3 inflammasome machinery by reducing KLF2 and increasing CASPASE1, IL-1ß and GSDMD levels. Knockout cells also exhibited higher proliferation and cell-cycle progression than wild type. RNA-seq validated interplay between KLF2 and inflammasome machinery in HC, LN+ and LN-. CONCLUSIONS: We demonstrate how rs4808485 modulates the inflammasome and cellular homoeostasis through regulating KLF2 expression. This establishes mechanistic connections between rs4808485 and SLE susceptibility.

A distinct abundant group of microbial rhodopsins discovered using functional metagenomics.

Many organisms capture or sense sunlight using rhodopsin pigments1,2, which are integral membrane proteins that bind retinal chromophores. Rhodopsins comprise two distinct protein families 1 , type-1 (microbial rhodopsins) and type-2 (animal rhodopsins). The two families share similar topologies and contain seven transmembrane helices that form a pocket in which retinal is linked covalently as a protonated Schiff base to a lysine at the seventh transmembrane helix2,3. Type-1 and type-2 rhodopsins show little or no sequence similarity to each other, as a consequence of extensive divergence from a common ancestor or convergent evolution of similar structures 1 . Here we report a previously unknown and diverse family of rhodopsins-which we term the heliorhodopsins-that we identified using functional metagenomics and that are distantly related to type-1 rhodopsins. Heliorhodopsins are embedded in the membrane with their N termini facing the cell cytoplasm, an orientation that is opposite to that of type-1 or type-2 rhodopsins. Heliorhodopsins show photocycles that are longer than one second, which is suggestive of light-sensory activity. Heliorhodopsin photocycles accompany retinal isomerization and proton transfer, as in type-1 and type-2 rhodopsins, but protons are never released from the protein, even transiently. Heliorhodopsins are abundant and distributed globally; we detected them in Archaea, Bacteria, Eukarya and their viruses. Our findings reveal a previously unknown family of light-sensing rhodopsins that are widespread in the microbial world.

Role of Autophagy and AMPK in Cancer Stem Cells: Therapeutic Opportunities and Obstacles in Cancer.

Cancer stem cells represent a resilient subset within the tumor microenvironment capable of differentiation, regeneration, and resistance to chemotherapeutic agents, often using dormancy as a shield. Their unique properties, including drug resistance and metastatic potential, pose challenges for effective targeting. These cells exploit certain metabolic processes for their maintenance and survival. One of these processes is autophagy, which generally helps in energy homeostasis but when hijacked by CSCs can help maintain their stemness. Thus, it is often referred as an Achilles heel in CSCs, as certain cancers tend to depend on autophagy for survival. Autophagy, while crucial for maintaining stemness in cancer stem cells (CSCs), can also serve as a vulnerability in certain contexts, making it a complex target for therapy. Regulators of autophagy like AMPK (5' adenosine monophosphate-activated protein kinase) also play a crucial role in maintaining CSCs stemness by helping CSCs in metabolic reprogramming in harsh environments. The purpose of this review is to elucidate the interplay between autophagy and AMPK in CSCs, highlighting the challenges in targeting autophagy and discussing therapeutic strategies to overcome these limitations. This review focuses on previous research on autophagy and its regulators in cancer biology, particularly in CSCs, addresses the remaining unanswered questions, and potential targets for therapy are also brought to attention.

Comprehensive Overview of Alzheimer's Disease: Etiological Insights and Degradation Strategies.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and affects millions of individuals globally. AD is associated with cognitive decline and memory loss that worsens with aging. A statistical report using U.S. data on AD estimates that approximately 6.9 million individuals suffer from AD, a number projected to surge to 13.8 million by 2060. Thus, there is a critical imperative to pinpoint and address AD and its hallmark tau protein aggregation early to prevent and manage its debilitating effects. Amyloid-ß and tau proteins are primarily associated with the formation of plaques and neurofibril tangles in the brain. Current research efforts focus on degrading amyloid-ß and tau or inhibiting their synthesis, particularly targeting APP processing and tau hyperphosphorylation, aiming to develop effective clinical interventions. However, navigating this intricate landscape requires ongoing studies and clinical trials to develop treatments that truly make a difference. Genome-wide association studies (GWASs) across various cohorts identified 40 loci and over 300 genes associated with AD. Despite this wealth of genetic data, much remains to be understood about the functions of these genes and their role in the disease process, prompting continued investigation. By delving deeper into these genetic associations, novel targets such as kinases, proteases, cytokines, and degradation pathways, offer new directions for drug discovery and therapeutic intervention in AD. This review delves into the intricate biological pathways disrupted in AD and identifies how genetic variations within these pathways could serve as potential targets for drug discovery and treatment strategies. Through a comprehensive understanding of the molecular underpinnings of AD, researchers aim to pave the way for more effective therapies that can alleviate the burden of this devastating disease.

Molecular Chaperonin HSP60: Current Understanding and Future Prospects.

Molecular chaperones are highly conserved across evolution and play a crucial role in preserving protein homeostasis. The 60 kDa heat shock protein (HSP60), also referred to as chaperonin 60 (Cpn60), resides within mitochondria and is involved in maintaining the organelle's proteome integrity and homeostasis. The HSP60 family, encompassing Cpn60, plays diverse roles in cellular processes, including protein folding, cell signaling, and managing high-temperature stress. In prokaryotes, HSP60 is well understood as a GroEL/GroES complex, which forms a double-ring cavity and aids in protein folding. In eukaryotes, HSP60 is implicated in numerous biological functions, like facilitating the folding of native proteins and influencing disease and development processes. Notably, research highlights its critical involvement in sustaining oxidative stress and preserving mitochondrial integrity. HSP60 perturbation results in the loss of the mitochondria integrity and activates apoptosis. Currently, numerous clinical investigations are in progress to explore targeting HSP60 both in vivo and in vitro across various disease models. These studies aim to enhance our comprehension of disease mechanisms and potentially harness HSP60 as a therapeutic target for various conditions, including cancer, inflammatory disorders, and neurodegenerative diseases. This review delves into the diverse functions of HSP60 in regulating proteo-homeostasis, oxidative stress, ROS, apoptosis, and its implications in diseases like cancer and neurodegeneration.

Heat Shock Response and Heat Shock Proteins: Current Understanding and Future Opportunities in Human Diseases.

The heat shock response is an evolutionarily conserved mechanism that protects cells or organisms from the harmful effects of various stressors such as heat, chemicals toxins, UV radiation, and oxidizing agents. The heat shock response triggers the expression of a specific set of genes and proteins known as heat shock genes/proteins or molecular chaperones, including HSP100, HSP90, HSP70, HSP60, and small HSPs. Heat shock proteins (HSPs) play a crucial role in thermotolerance and aiding in protecting cells from harmful insults of stressors. HSPs are involved in essential cellular functions such as protein folding, eliminating misfolded proteins, apoptosis, and modulating cell signaling. The stress response to various environmental insults has been extensively studied in organisms from prokaryotes to higher organisms. The responses of organisms to various environmental stressors rely on the intensity and threshold of the stress stimuli, which vary among organisms and cellular contexts. Studies on heat shock proteins have primarily focused on HSP70, HSP90, HSP60, small HSPs, and ubiquitin, along with their applications in human biology. The current review highlighted a comprehensive mechanism of heat shock response and explores the function of heat shock proteins in stress management, as well as their potential as therapeutic agents and diagnostic markers for various diseases.

Leveraging Data Locality in Quantum Convolutional Classifiers.

Quantum computing (QC) has opened the door to advancements in machine learning (ML) tasks that are currently implemented in the classical domain. Convolutional neural networks (CNNs) are classical ML architectures that exploit data locality and possess a simpler structure than a fully connected multi-layer perceptrons (MLPs) without compromising the accuracy of classification. However, the concept of preserving data locality is usually overlooked in the existing quantum counterparts of CNNs, particularly for extracting multifeatures in multidimensional data. In this paper, we present an multidimensional quantum convolutional classifier (MQCC) that performs multidimensional and multifeature quantum convolution with average and Euclidean pooling, thus adapting the CNN structure to a variational quantum algorithm (VQA). The experimental work was conducted using multidimensional data to validate the correctness and demonstrate the scalability of the proposed method utilizing both noisy and noise-free quantum simulations. We evaluated the MQCC model with reference to reported work on state-of-the-art quantum simulators from IBM Quantum and Xanadu using a variety of standard ML datasets. The experimental results show the favorable characteristics of our proposed techniques compared with existing work with respect to a number of quantitative metrics, such as the number of training parameters, cross-entropy loss, classification accuracy, circuit depth, and quantum gate count.

A Novel Color Switch of Microbial Rhodopsin.

Function of animal and microbial rhodopsins starts by light absorption of the retinal chromophore. The absorption maximum wavelength (λmax) of rhodopsins is determined by the energy gap between the electronically ground (S0) and first excited (S1) state of the retinal chromophore, and the color tuning mechanism is one of the central topics in rhodopsin research. "Color switches", color-determining residues, are red- and blue-shifting amino acids at the same position in two rhodopsins, whose exchange causes spectral blue- and red-shifts, respectively, in each rhodopsin. As mutation easily destroys elaborate chromophore-protein interactions, the known color switches in microbial rhodopsins are limited; the L/Q switch in C-helix (TM3), the A/TS switch in G-helix (TM7), and the G/P switch in F-helix (TM6). Here, we report a novel color switch of microbial rhodopsins, which is located in D-helix (TM4). In this color switch, the red- and blue-shifting amino acids are Asn (N) and Leu (L)/Ile (I), respectively. As Asn and Leu/Ile are polar and nonpolar amino acids, respectively, and the position is located near the ß-ionone ring, the N/LI switch matches the general rule of color tuning by polarity. The N/LI switch is also useful for optogenetics, as many ion-transporting rhodopsins contain blue-shifting amino acids, such as L and I, at that position.

Mycosynthesis of Zinc Oxide Nanoparticles Exhibits Fungal Species Dependent Morphological Preference.

Filamentous fungi can synthesize a variety of nanoparticles (NPs), a process referred to as mycosynthesis that requires little energy input, do not require the use of harsh chemicals, occurs at near neutral pH, and do not produce toxic byproducts. While NP synthesis involves reactions between metal ions and exudates produced by the fungi, the chemical and biochemical parameters underlying this process remain poorly understood. Here, the role of fungal species and precursor salt on the mycosynthesis of zinc oxide (ZnO) NPs is investigated. This data demonstrates that all five fungal species tested are able to produce ZnO structures that can be morphologically classified into i) well-defined NPs, ii) coalesced/dissolving NPs, and iii) micron-sized square plates. Further, species-dependent preferences for these morphologies are observed, suggesting potential differences in the profile or concentration of the biochemical constituents in their individual exudates. This data also demonstrates that mycosynthesis of ZnO NPs is independent of the anion species, with nitrate, sulfate, and chloride showing no effect on NP production. These results enhance the understanding of factors controlling the mycosynthesis of ceramic NPs, supporting future studies that can enable control over the physical and chemical properties of NPs formed through this "green" synthesis method.

Enhancing Electrochemical CO2 Reduction on Perovskite Oxide for Solid Oxide Electrolysis Cells through In Situ A-Site Deficiencies and Surface Carbonate Deposition Induced by Lithium Cation Doping and Exsolution.

Solid oxide electrolysis cells (SOECs) hold enormous potential for efficient conversion of CO2 to CO at low cost and high reaction kinetics. The identification of active cathodes is highly desirable to promote the SOEC's performance. This study explores a lithium-doped perovskite La0.6- x Lix Sr0.4 Co0.7 Mn0.3 O3-δ (x = 0, 0.025 0.05, and 0.10) material with in situ generated A-site deficiency and surface carbonate as SOEC cathodes  for CO2 reduction. The experimental results indicate that the SOEC with the La0.55 Li0.05 Sr0.4 Co0.7 Mn0.3 O3-δ cathode exhibits a current density of 0.991 A cm-2 at 1.5 V/800 °C, which is an improvement of ≈30% over the pristine sample. Furthermore, SOECs based on the proposed cathode demonstrate excellent stability over 300 h for pure CO2 electrolysis. The addition of lithium with high basicity, low valance, and small radius, coupled with A-site deficiency, promotes the formation of oxygen vacancy and modifies the electronic structure of active sites, thus enhancing CO2 adsorption, dissociation process, and CO desorption steps as corroborated by the experimental analysis and the density functional theory calculation. It is further confirmed that Li-ion migration to the cathode surface forms carbonate and consequently provides the perovskite cathode with an impressive anti-carbon deposition capability, as well as electrolysis activity.

Efficacy and safety of degludec U100 versus glargine U300 for the early postoperative management of patients with type 2 diabetes mellitus undergoing coronary artery bypass graft surgery: A non-inferiority randomized trial.

AIMS: To compare the efficacy and safety of degludec U100 versus glargine U300 for the early postoperative management of patients with type 2 diabetes mellitus (T2D) undergoing coronary artery bypass graft (CABG) surgery. METHODS: A total of 239 patients were randomly assigned (1:1) to receive a basal-bolus regimen in the early postoperative period using degludec U100 (n = 122) or glargine U300 (n = 117) as basal and glulisine before meals. The primary outcome was mean differences between groups in their daily BG concentrations. The major safety outcome was the occurrence of hypoglycemia. RESULTS: There were no differences in mean daily BG concentrations (157 vs. 162 mg/dl), mean percentage of readings within target BG of 70-180 mg/dl (74% vs. 73%), daily basal insulin dose (19 vs. 21 units/day), length of stay (median [IQR]: 9 vs. 9 days), or hospital complications (21.3% vs. 21.4%) between treatment groups. There were no differences in the proportion of patients with BG <70 mg/dl (15.6% vs. 23.1%) or <54 mg/dl (1.6% vs. 4.3%) between degludec-100 and glargine-300 groups. CONCLUSIONS: Treatment with degludec U100 is as effective and safe as glargine U300 for the early postoperative hospital management of patients with T2D undergoing CABG.

Therapeutic spectrum of piperine for clinical practice: a scoping review.

Translation of traditional knowledge of herbs into a viable product for clinical use is still an uphill task. Piperine, a pungent alkaloid molecule derived from Piper nigrum and Piper longum possesses diverse pharmacological effects. Traditionally, pepper is used for arthritis, bronchitis, gastritis, diarrhea, snake bite, menstrual pain, fever, and bacterial infections, etc. The anti-inflammatory, antioxidant and immunomodulatory actions of piperine are the possible mechanisms behind its therapeutic potential. Various in-silico and experimental studies have shown piperine as a possible promising molecule in coronavirus disease (COVID-19), ebola, and dengue due to its immunomodulatory and antiviral activities. The other important clinical applications of piperine are due to its bio enhancing effect on drugs, by modulating, absorption in the gastrointestinal tract, altering activities of transporters like p-glycoprotein substrates, and modulating drug metabolism by altering the expression of cytochrome P450 or UDP-glucuronosyltransferase enzymes. Piperine attracted clinicians in treating patients with arthritis, metabolic syndrome, diabetes, skin infections, gastric and liver disorders. This review focused on systematic, evidence-based insight into the use of piperine in clinical settings and mechanistic details behind its therapeutic actions. Also, highlights a number of clinical trials of piperine at various stages exploring its clinical application in cancer, neurological, respiratory, and viral disease, etc.

Specific zinc binding to heliorhodopsin.

Heliorhodopsins (HeRs), a recently discovered family of rhodopsins, have an inverted membrane topology compared to animal and microbial rhodopsins. The slow photocycle of HeRs suggests a light-sensor function, although the actual function remains unknown. Although HeRs exhibit no specific binding of monovalent cations or anions, recent ATR-FTIR spectroscopy studies have demonstrated the binding of Zn2+ to HeR from Thermoplasmatales archaeon (TaHeR) and 48C12. Even though ion-specific FTIR spectra were observed for many divalent cations, only helical structural perturbations were observed for Zn2+-binding, suggesting a possible modification of the HeR function by Zn2+. The present study shows that Zn2+-binding lowers the thermal stability of TaHeR, and slows back proton transfer to the retinal Schiff base (M decay) during its photocycle. Zn2+-binding was similarly observed for a TaHeR opsin that lacks the retinal chromophore. We then studied the Zn2+-binding site by means of the ATR-FTIR spectroscopy of site-directed mutants. Among five and four mutants of His and Asp/Glu, respectively, only E150Q exhibited a completely different spectral feature of the α-helix (amide-I) in ATR-FTIR spectroscopy, suggesting that E150 is responsible for Zn2+-binding. Molecular dynamics (MD) simulations built a coordination structure of Zn2+-bound TaHeR, where E150 and protein bound water molecules participate in direct coordination. It was concluded that the specific binding site of Zn2+ is located at the cytoplasmic side of TaHeR, and that Zn2+-binding affects the structure and structural dynamics, possibly modifying the unknown function of TaHeR.

Detection of the ß-lactoglobulin genotype in zebu cattle (Gangatiri) milk using high-resolution accurate mass spectroscopy.

We studied the genetic polymorphism of beta-lactoglobulin (ß-Lg) whey protein in Gangatiri zebu cows for this Research Communication. The polymorphic nature of milk protein fractions and their association with milk production traits, composition and quality has attracted several efforts in evaluating the allelic distribution of protein locus as a potential dairy trait marker. Genetic variants of ß-Lg have highly significant effects on casein number (B > A) and protein recovery (B > A) and also determine the yield of cheese dry matter (B > A). Molecular techniques of polyacrylamide gel electrophoresis and high-resolution accurate mass-spectroscopy were applied to characterize the ß-Lg protein obtained from the Gangatiri breed milk. Sequence analysis of ß-Lg showed the presence of variant B having UniProt database accession number P02754, coded on the PAEP gene. Our study can provide reference and guidance for the selection of superior milk (having ß-LgB) from this indigenous breed that could potentially give a good yield of ß-Lg for industrial applications.

Probing of alpha, beta and kappa-caseins polymorphic variants in Gangatiri cow milk with the use of polyacrylamide gel electrophoresis and HRAMS.

This research communication aimed to probe the genetic polymorphisms of alpha, beta, and kappa caseins in Gangatiri cows (an indigenous Indian cattle). Detection of variants has received considerable research interest in the dairy industry and animal breeding in recent years as a source of good quality protein, but also of bioactive peptides that may be linked to health implications. The polymorphic nature of casein fractions and their association with milk production traits, composition, and quality also attracted several efforts in evaluating the allelic distribution of different casein locus as a potential dairy trait marker. Molecular techniques of polyacrylamide gel electrophoresis and high-resolution accurate mass-spectrometry have been applied to this probe. Sequence analysis of different casein types in the cows showed the presence of four specific variants.

PCL retention demonstrates better functional scores and gait patterns in total knee arthroplasty using a medial congruent insert-a prospective study.

PURPOSE: Despite Total Knee Arthroplasty (TKA) being one of the most successful procedures for end stage arthritis, nearly 20% of patients undergoing this procedure remain dissatisfied. Various design options have been introduced to reduce this cohort of patients. One such option has been the introduction of the medial congruent (MC) polyethylene design. This study was undertaken to evaluate outcome measures and gait analysis in patients undergoing bilateral single stage TKA where the posterior cruciate ligament (PCL) was retained or excised in contralateral knees. METHODS: 60 bilateral TKA's were performed by a single surgeon using a MC design option from July to Sep 2021. The study lots included patients between the ages of 55 and 70 years with fixed varus deformity of degenerative aetiology, and Kellgren Lawrence Grade 3 and 4 radiological changes. Exclusion criteria were previous surgery to the lower extremities, sero positive arthropathies, post traumatic arthritis, valgus deformity, flexion contractures > 20°, and any pre-existing pathology impacting gait, e.g., poliomyelitis, or neuromuscular disorders. The PCL was retained or sacrificed on contralateral sides for the purpose of this study. Functional scores, outcomes and gait analysis on level and gradient walking were evaluated at a follow-up of 18 months. RESULTS: At 18, months the Range of Motion (ROM) improved from a preoperative value of 97.3 ± 11.5 to 110.3 ± 6.1 on the PCL retained side (MC-PCL) and from 96.5 ± 10.8 to 113 ± 5.8 on the PCL excised side (MC-PCLX). Knee Society Score (KSS-2011) improved from a preoperative value of 21.2 ± 4.5 to 89.8 ± 3.4 at 18 months postoperatively on the MC-PCL side and from 21.5 ± 4 to 88.2 ± 3.7 on the MC-PCLX side. Forgotten Joint Score (FJS-12) was 8.8 ± 0.7 on the MC-PCL side and 8.1 ± 0.9 on the MC-PCLX side 18 months after surgery. Our gait analysis evaluation demonstrated a lower forefoot pressure in the MC-PCL group in comparison to the MC-PCLX group when subjects were made to walk on a 30° upward incline. This difference was found to be statistically significant. CONCLUSION: In this study, while ROM was greater in the MC-PCLX study lot, patient satisfaction was higher in the MC-PCL study lot. Gait assessment demonstrated lower forefoot pressure while ascending an incline of 30° in the MC-PCL study lot as compared to the MC-PCLX study lot approximating normal gait patterns. LEVEL OF EVIDENCE: II.