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PeerJ 2024Bolt's Farm is the name given to a series of non-hominin bearing fossil sites that have often been suggested to be some of the oldest Pliocene sites in the Cradle of...
Bolt's Farm is the name given to a series of non-hominin bearing fossil sites that have often been suggested to be some of the oldest Pliocene sites in the Cradle of Humankind, South Africa. This article reports the results of the first combined Uranium-Series and Electron Spin Resonance (US-ESR) dating of bovid teeth at Milo's Cave and Aves Cave at Bolt's Farm. Both tooth enamel fragments and tooth enamel powder ages were presented for comparison. US-ESR, EU and LU models are calculated. Overall, the powder ages are consistent with previous uranium-lead and palaeomagnetic age estimates for the Aves Cave deposit, which suggest an age between ~3.15 and 2.61 Ma and provide the first ages for Milo's Cave dates to between ~3.1 and 2.7 Ma. The final ages were not overly dependent on the models used (US-ESR, LU or EU), which all overlap within error. These ages are all consistent with the biochronological age estimate (<3.4->2.6 Ma) based on the occurrence of Stage I . Preliminary palaeomagnetic analysis from Milo's Cave indicates a reversal takes place at the site with predominantly intermediate directions, suggesting the deposit may date to the period between ~3.03 and 3.11 Ma within error of the ESR ages. This further suggests that there are no definitive examples of palaeocave deposits at Bolt's Farm older than 3.2 Ma. This research indicates that US-ESR dating has the potential to date fossil sites in the Cradle of Humankind to over 3 Ma. However, bulk sample analysis for US-ESR dating is recommended for sites over 3 Ma.
Topics: South Africa; Fossils; Electron Spin Resonance Spectroscopy; Uranium; Radiometric Dating; Animals; Caves; Tooth; Dental Enamel
PubMed: 38952976
DOI: 10.7717/peerj.17478 -
RSC Advances Jun 2024Endowing implanted biomaterials with better hemocompatibility, anticoagulation, antioxidant and antiplatelet adhesion is necessary because of their potential to trigger...
Endowing implanted biomaterials with better hemocompatibility, anticoagulation, antioxidant and antiplatelet adhesion is necessary because of their potential to trigger activation of multiple reactive mechanisms including coagulation cascade and potentially causing serious adverse clinical events like late thrombosis. Active ingredients from natural sources including , , and have the ability to inhibit the coagulation cascade and thrombus formation around biomedical implants. These properties are of interest for the development of a novel drug for biomedical implants to potentially solve the current blood clotting and coagulation problems which lead to stent thrombosis. The objective of this study was to incorporate different anticoagulants from natural sources into a degradable matrix of chitosan with varying concentrations ranging from 5% to 15% and a composite containing all three drugs. The presence of anticoagulant constituents was identified using GC-MS. Subsequently, all the compositions were characterized principally by using Fourier transform infrared spectroscopy and scanning electron microscopy while the drug release profile was determined using UV-spectrometry for a 30 days immersion period. The results indicated an initial burst release which was subsequently followed by the sustained release pattern. Compared to heparin loaded chitosan, DPPH and hemolysis tests revealed better blood compatibility of natural drug loaded films. Moreover, the anticoagulation activity of natural drugs was equivalent to the heparin loaded film; however, through docking, the mechanism of inhibition of the coagulation cascade of the novel drug was found to be through blocking the extrinsic pathway. The study suggested that the proposed drug composite expresses an optimum composition which may be a practicable and appropriate candidate for biomedical implant coatings.
PubMed: 38952927
DOI: 10.1039/d4ra00796d -
Frontiers in Physiology 2024Several fluorescent proteins (FPs) and chromoproteins (CPs) are present in anthozoans and play possible roles in photoprotection. Coral tissues in massive corals often...
INTRODUCTION
Several fluorescent proteins (FPs) and chromoproteins (CPs) are present in anthozoans and play possible roles in photoprotection. Coral tissues in massive corals often display discoloration accompanied by inflammation. Incidences of the pink pigmentation response (PPR) in massive , described as inflammatory pink lesions of different shapes and sizes, has recently increased worldwide. FPs are reported to be present in PPR lesions, wherein a red fluorescent protein (RFP) appears to play a role in reducing reactive oxygen species. However, to date, the biochemical characterization and possible roles of the pigments involved are poorly understood. The present study aimed to identify and characterize the proteins responsible for pink discoloration in massive colonies displaying PPRs, as well as to assess the differential distribution of pigments and the antioxidant properties of pigmented areas.
METHOD
CPs were extracted from PPR lesions using gel-filtration chromatography and identified via genetic analysis using liquid chromatography-tandem mass spectrometry. The coexistence of CPs and RFP in coral tissues was assessed using microscopic observation. Photosynthetic antivity and hydrogen peroxide-scavenging activitiy were measured to assess coral stress conditions.
RESULTS
The present study revealed that the same CP (plut2.m8.16902.m1) isolated from massive was present in both the pink spot and patch morphologies of the PPR. CPs were also found to coexist with RFP in coral tissues that manifested a PPR, with a differential distribution (coenosarc or tip of polyps' tentacles). High hydrogen peroxide-scavenging rates were found in tissues affected by PPR.
DISCUSSION AND CONCLUSION
The coexistence of CPs and RFP suggests their possible differential role in coral immunity. CPs, which are specifically expressed in PPR lesions, may serve as an antioxidant in the affected coral tissue. Overall, this study provides new knowledge to our understanding of the role of CPs in coral immunity.
PubMed: 38952870
DOI: 10.3389/fphys.2024.1339907 -
Journal of Biomedical Optics Jun 2024Biomanufacturing utilizes modified microbial systems to sustainably produce commercially important biomolecules for use in agricultural, energy, food, material, and... (Review)
Review
SIGNIFICANCE
Biomanufacturing utilizes modified microbial systems to sustainably produce commercially important biomolecules for use in agricultural, energy, food, material, and pharmaceutical industries. However, technological challenges related to non-destructive and high-throughput metabolite screening need to be addressed to fully unlock the potential of synthetic biology and sustainable biomanufacturing.
AIM
This perspective outlines current analytical screening tools used in industrial cell strain development programs and introduces label-free vibrational spectro-microscopy as an alternative contrast mechanism.
APPROACH
We provide an overview of the analytical instrumentation currently used in the "test" portion of the design, build, test, and learn cycle of synthetic biology. We then highlight recent progress in Raman scattering and infrared absorption imaging techniques, which have enabled improved molecular specificity and sensitivity.
RESULTS
Recent developments in high-resolution chemical imaging methods allow for greater throughput without compromising the image contrast. We provide a roadmap of future work needed to support integration with microfluidics for rapid screening at the single-cell level.
CONCLUSIONS
Quantifying the net expression of metabolites allows for the identification of cells with metabolic pathways that result in increased biomolecule production, which is essential for improving the yield and reducing the cost of industrial biomanufacturing. Technological advancements in vibrational microscopy instrumentation will greatly benefit biofoundries as a complementary approach for non-destructive cell screening.
Topics: Spectrum Analysis, Raman; Vibration; Bacteria
PubMed: 38952688
DOI: 10.1117/1.JBO.29.S2.S22711 -
Frontiers in Psychiatry 2024The aim of this study was to examine some psychometric characteristics of the Chilean-adapted version of the Quantitative Checklist for Autism in Toddlers (Q-CHAT-24)...
BACKGROUND
The aim of this study was to examine some psychometric characteristics of the Chilean-adapted version of the Quantitative Checklist for Autism in Toddlers (Q-CHAT-24) (24) in a group of unselected children (community sample). This version was administered remotely through an online version during the pandemic period to caregivers of children, aged 18-24 months, registered in four primary care polyclinics of the Health Service Araucanía Sur, Chile.
METHODS
An intentional non-probabilistic sampling was used. Three hundred and thirteen toddlers were examined. Participants completed an online version of the Q-CHAT-24 which was disseminated through the REDCap platform. Evidence of reliability through internal consistency and evidence of predictive validity through ROC curve analysis were realized.
RESULTS
The mean age of the children evaluated was 21.16 months. The Shapiro-Wilk test revealed that Q-CHAT-24 scores was normally distributed. 71 cases (23.12%) scored 38 points or more on the Q-CHAT-24, qualifying as Autistic Risk. 48 cases (15.63%) were confirmed as autistic through the ADOS-2 Module T. All items were positively correlated with Q-CHAT-24 total score. All items were positively correlated with Q-CHAT-24 total score. Internal consistency was acceptable for the Q-CHAT-24 (Cronbach ´s α=0.78). The internal consistencies were analyzed for the Q-CHAT-24 Factors, and they were good for factor 1 "Communication and Social Interaction" (Cronbach ´s α=0.85) and acceptable for factor 2 "Restrictive and Repetitive Patterns" (Cronbach ´s α=0.74). Receiver operating characteristic (ROC) curve analyses were performed. The AUC values were 0.93 with statistical significance (p<0.01). For the cut-off point of 38, the Sensitivity, Specificity and Youden index values were 0.89, 0.8 and 0.7, respectively. The Positive Predictive Value (PPV) was 86% and the Negative Predictive Value (NPV) was 85%.
CONCLUSIONS
In accordance with the objectives of this study, evidence of reliability and predictive validity was demonstrated for the Q-CHAT-24 in this Chilean population. More importantly, this study provides Sensitivity and Specificity data for a remote application version of an autism screening tool already validated in Chile. The implications of this have to do with the possibility of establishing a remote assessment system for children at risk of autism on a population scale.
PubMed: 38952633
DOI: 10.3389/fpsyt.2024.1363976 -
Frontiers in Oncology 2024Erythropoietin-producing human hepatocellular (Eph) receptors stand out as the most expansive group of receptor tyrosine kinases (RTKs). Accumulating evidence suggests...
BACKGROUND
Erythropoietin-producing human hepatocellular (Eph) receptors stand out as the most expansive group of receptor tyrosine kinases (RTKs). Accumulating evidence suggests that within this expansive family, the EphA subset is implicated in driving cancer cell progression, proliferation, invasion, and metastasis, making it a promising target for anticancer treatment. Nonetheless, the extent of EphA family involvement across diverse cancers, along with its intricate interplay with immunity and the tumor microenvironment (TME), remains to be fully illuminated.
METHODS
The relationships between EphA gene expression and patient survival, immunological subtypes, and TME characteristics were investigated based on The Cancer Genome Atlas (TCGA) database. The analyses employed various R packages.
RESULTS
A significant difference in expression was identified for most EphA genes when comparing cancer tissues and non-cancer tissues. These genes independently functioned as prognostic factors spanning multiple cancer types. Moreover, a significant correlation surfaced between EphA gene expression and immune subtypes, except for EphA5, EphA6, and EphA8. EphA3 independently influenced the prognosis of papillary renal cell carcinoma (KIRP). This particular gene exhibited links with immune infiltration subtypes and clinicopathologic parameters, holding promise as a valuable biomarker for predicting prognosis and responsiveness to immunotherapy in patients with KIRP.
CONCLUSION
By meticulously scrutinizing the panorama of EphA genes in a spectrum of cancers, this study supplemented a complete map of the effect of EphA family in Pan-cancer and suggested that EphA family may be a potential target for cancer therapy.
PubMed: 38952552
DOI: 10.3389/fonc.2024.1378087 -
Frontiers in Microbiology 2024Weeds are significant factors that detrimentally affect crop health and hinder optimal herbage yield. Rhizosphere microorganisms play crucial roles in plant growth,...
INTRODUCTION
Weeds are significant factors that detrimentally affect crop health and hinder optimal herbage yield. Rhizosphere microorganisms play crucial roles in plant growth, development, and nutrient uptake. Therefore, research focusing on weed control through the lens of microorganisms has emerged as a prominent area of study. The oil-producing fungus , which is known for its numerous agricultural benefits, has garnered significant attention in recent years.
METHODS
In this study, we conducted inoculation experiments in a controlled artificial culture climate chamber to investigate the effects of differential hormones and differentially expressed genes in the stems and leaves of using Liquid Chromatography Tandem Mass Spectrometry and RNA-seq techniques, respectively. Additionally, Pearson's correlation analysis was used to establish correlations between differential hormones and growth indicators of .
RESULTS AND DISCUSSION
The results demonstrated that inoculation with sp. MXBP304 effectively suppressed aboveground biomass and plant height in . Furthermore, there was significant upregulation and downregulation in the expression of genes involved in the synthesis and metabolism of phenylalanine and L-phenylalanine. Conversely, the expression of genes related to tryptophan, L-tryptophan, and indole was significantly downregulated. The addition of sp. MXBP304 can influence the gene expression associated with phenylalanine and tryptophan synthesis and metabolism during growth, subsequently reducing the relative contents of phenylalanine and tryptophan, thereby directly inhibiting growth.
PubMed: 38952443
DOI: 10.3389/fmicb.2024.1385992 -
Acta Biochimica Et Biophysica Sinica Jul 2024Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1/programmed cell death ligand-1 (PD-1/PD-L1) have significantly prolonged the survival of...
Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1/programmed cell death ligand-1 (PD-1/PD-L1) have significantly prolonged the survival of advanced/metastatic patients with lung cancer. However, only a small proportion of patients can benefit from ICIs, and clinical management of the treatment process remains challenging. Glycosylation has added a new dimension to advance our understanding of tumor immunity and immunotherapy. To systematically characterize anti-PD-1/PD-L1 immunotherapy-related changes in serum glycoproteins, a series of serum samples from 12 patients with metastatic lung squamous cell carcinoma (SCC) and lung adenocarcinoma (ADC), collected before and during ICIs treatment, are firstly analyzed with mass-spectrometry-based label-free quantification method. Second, a stratification analysis is performed among anti-PD-1/PD-L1 responders and non-responders, with serum levels of glycopeptides correlated with treatment response. In addition, in an independent validation cohort, a large-scale site-specific profiling strategy based on chemical labeling is employed to confirm the unusual characteristics of IgG N-glycosylation associated with anti-PD-1/PD-L1 treatment. Unbiased label-free quantitative glycoproteomics reveals serum levels' alterations related to anti-PD-1/PD-L1 treatment in 27 out of 337 quantified glycopeptides. The intact glycopeptide EEQFN STYR (H3N4) corresponding to IgG4 is significantly increased during anti-PD-1/PD-L1 treatment (FC=2.65, =0.0083) and has the highest increase in anti-PD-1/PD-L1 responders (FC=5.84, =0.0190). Quantitative glycoproteomics based on protein purification and chemical labeling confirms this observation. Furthermore, obvious associations between the two intact glycopeptides (EEQFN STYR (H3N4) of IgG4, EEQYN STFR (H3N4F1) of IgG3) and response to treatment are observed, which may play a guiding role in cancer immunotherapy. Our findings could benefit future clinical disease management.
PubMed: 38952341
DOI: 10.3724/abbs.2024110 -
Veterinary Medicine and Science Jul 2024Acute flaccid paralysis (AFP) is a complex clinical syndrome with various aetiologies. If untreated, AFP may lead to death due to failure of respiratory muscles. Tick...
BACKGROUND
Acute flaccid paralysis (AFP) is a complex clinical syndrome with various aetiologies. If untreated, AFP may lead to death due to failure of respiratory muscles. Tick paralysis, which is a noninfectious neurologic syndrome of AFP, occurs following tick attachment, engorgement, and injection of tick saliva toxins. There is no specific diagnostic test for tick paralysis, and mortality increases as definitive diagnosis is delayed. Although metabolomic investigation of tick saliva was conducted, there is a lack of research on metabolomic evaluation of hosts affected by tick paralysis.
OBJECTIVES
Thus, the aim of this study is to investigate metabolomic changes in serum samples of dogs with tick paralysis due to Rhipicephalus sanguineus using NMR-based metabolomics and to identify potential diagnostic/prognostic markers.
MATERIALS AND METHODS
Forty dogs infested with R. sanguineus, with clinical findings compatible with AFP and with a confirmed tick paralysis diagnosis ex juvantibus, constituted the Paralysis Group. Ten healthy dogs, which were admitted either for vaccination and/or check-up purposes, constituted the Control Group. After the confirmation tick paralysis, medical history, vaccination and nutritional status, body surface area and estimated tick numbers of all the dogs were noted. Physical examination included body temperature, heart and respiratory rate, capillary refill time evaluation and Modified Glasgow Coma Scale calculation. Serum samples were extracted from venous blood samples of all the dogs and were prepared for NMR analysis, and NMR-based metabolomics identification and quantification were performed.
RESULTS
NMR-based serum metabolomics of the present study revealed distinct up/down-regulated expressions, presenting a promising avenue. Moreover, it was observed that energy metabolism and especially liver functions were impaired in dogs with tick paralysis, and not only the respiratory system but also the kidneys were affected.
CONCLUSION
It was concluded that the present approach may help to better understand the pathological mechanisms developing in cases of AFP due to tick paralysis.
Topics: Animals; Dogs; Tick Paralysis; Dog Diseases; Magnetic Resonance Spectroscopy; Metabolomics; Female; Male; Rhipicephalus sanguineus; Metabolome; Paralysis
PubMed: 38952268
DOI: 10.1002/vms3.1528 -
Aging Cell Jul 2024Alzheimer's disease (AD) is a neurodegenerative disorder associated with behavioral and cognitive impairments. Unfortunately, the drugs the Food and Drug Administration...
Alzheimer's disease (AD) is a neurodegenerative disorder associated with behavioral and cognitive impairments. Unfortunately, the drugs the Food and Drug Administration currently approved for AD have shown low effectiveness in delaying the progression of the disease. The focus has shifted to non-pharmacological interventions (NPIs) because of the challenges associated with pharmacological treatments for AD. One such intervention is environmental enrichment (EE), which has been reported to restore cognitive decline associated with AD effectively. However, the therapeutic mechanisms by which EE improves symptoms associated with AD remain unclear. Therefore, this study aimed to reveal the mechanisms underlying the alleviating effects of EE on AD symptoms using histological, proteomic, and neurotransmitter-related analyses. Wild-type (WT) and 5XFAD mice were maintained in standard housing or EE conditions for 4 weeks. First, we confirmed the mitigating effects of EE on cognitive impairment in an AD animal model. Then, histological analysis revealed that EE reduced Aβ accumulation, neuroinflammation, neuronal death, and synaptic loss in the AD brain. Moreover, proteomic analysis by liquid chromatography-tandem mass spectrometry showed that EE enhanced synapse- and neurotransmitter-related networks and upregulated synapse- and neurotransmitter-related proteins in the AD brain. Furthermore, neurotransmitter-related analyses showed an increase in acetylcholine and serotonin concentrations as well as a decrease in polyamine concentration in the frontal cortex and hippocampus of 5XFAD mice raised under EE conditions. Our findings demonstrate that EE restores cognitive impairment by alleviating AD pathology and regulating synapse-related proteins and neurotransmitters. Our study provided neurological evidence for the application of NPIs in treating AD.
PubMed: 38952076
DOI: 10.1111/acel.14231