Miracle-dz/UniFAR-FTUs huggingface dataset:
Ex Vivo Systems to Study Chondrogenic Differentiation and Cartilage Integration

Articular cartilage injury and repair is an issue of growing importance. Although common, defects of articular cartilage present a unique clinical challenge due to its poor self-healing capacity, which is largely due to its avascular nature. There is a critical need to better study and understand cellular healing mechanisms to achieve more effective therapies for cartilage regeneration. This article aims to describe the key features of cartilage which is being modelled using tissue engineered cartilage constructs and ex vivo systems. These models have been used to investigate chondrogenic differentiation and to study the mechanisms of cartilage integration into the surrounding tissue. The review highlights the key regeneration principles of articular cartilage repair in healthy and diseased joints. Using co-culture models and novel bioreactor designs, the basis of regeneration is aligned with recent efforts for optimal therapeutic interventions.
Deficient hand washing facilities in public toilets in the time of the COVID-19 pandemic: A survey in one high-income country

Aims: To identify the extent of the provision of water and soap for hand washing in public toilets at the time of the COVID-19 pandemic. To also make comparisons with a pre-pandemic survey that included a sample of the same facilities. Methods: We collected data from 400 toilets that were open to the public; all those in three contiguous city council territories (228) and a further convenience sample of 172 around the rest of New Zealand. Comparisons were made with the data on the same facilities included in a 2012/2013 survey. Results: For all the toilets in this survey, 2.5% had no water for hand washing and 14.8% had no soap. There was COVID-19 related health messaging signage in 19.5% of toilets, with posters of the COVID-19 QR code used to facilitate contact tracing in 12.3%, and generic hand washing signage in 1.8%. The hand washing water had 'no touch' activation at 28.0% of toilets and at 18.5% for toilet bowl flushing. Toilet bowl lids were not present at 32.8%, and 2.3% of toilets had damage which would impair their functionality (eg, broken toilet seats). For the 128 sites that had also been examined in the previous survey, this new survey found significantly increased provision of soap (risk ratio = 1.47; 95%CI: 1.25 to 1.72), but no increased provision of water. Conclusions: Despite the serious threat of the COVID-19 pandemic, the majority of hand washing facilities in public toilets sampled required tap touching, and did not have health messaging. Nevertheless there has been some modest improvements in soap (but not water) provision since the previous survey eight years before.
Dynamic supramolecular poly(isobutylene)s for self-healing materials

Mono- and bifunctional supramolecular poly(isobutylene)s (PIBs) bearing hydrogen-bonding motifs (barbituric acid or a Hamilton wedge) are prepared by a combination of living carbocationic polymerization (LCCP) and azide–alkyne “click” reactions to investigate their dynamics and self-healing behaviour. Barbituric acid (7) or Hamilton wedge (8) functionalized polymers (3a–c, 4a–d, 5a–c, 6a) with molecular weights of ∼3000 up to 30 000 g mol−1 exhibit complete end group transformation as proven by NMR and MALDI methods. Temperature-dependent rheology in the melt reveals thermoreversible formation of supramolecular clusters. Stoichiometric mixing of the polymers by solution blending affects the extent of clustering by specifically interacting barbituric acid/Hamilton wedge moieties. Frequency-dependent measurements on bifunctional barbituric acid functionalized PIBs reveal a strong rubbery plateau and terminal flow, caused by the formation of dynamically bridged clusters. In addition, fluorescence recovery after photobleaching (FRAP) measurements on the same supramolecular polymers reveal a multitude of different chain dynamics. Small discs of these polymers show self-healing at room temperature after being cut and brought into contact at the fractured surface.
A Whole-Brain Functional Connectivity Model of Alzheimers Disease Pathology

Early detection of Alzheimers disease (AD) is a necessity as prognosis is poor upon symptom onset. Although previous work diagnosing AD from protein-based biomarkers has been encouraging, cerebrospinal (CSF) biomarker measurement of AD proteins requires invasive lumbar puncture, whereas assessment of direct accumulation requires radioactive substance exposure in positron emission tomography (PET) imaging. Functional magnetic resonance imaging (fMRI)-based neuromarkers, offers an alternative, especially those built by capitalizing on variance distributed across the entire human connectome. In this study, we employed connectome-based predictive modeling (CPM) to build a model of functional connections that would predict CSF p-tau/A{beta}42 (PATH-fc model) in individuals diagnosed with Mild Cognitive Impairment (MCI) and AD dementia. fMRI, CSF-based biomarker data, and longitudinal data from neuropsychological testing from the Alzheimers Disease NeuroImaging Initiative (ADNI) were utilized to build the PATH-fc model. Our results provide support for successful in-sample fit of the PATH-fc model in predicting AD pathology in MCI and AD dementia individuals. The PATH-fc model, distributed across all ten canonical networks, additionally predicted cognitive decline on composite measures of global cognition and executive functioning. Our highly distributed pathology-based model of functional connectivity disruptions had a striking overlap with the spatial affinities of amyloid and tau pathology, and included the default mode network as the hub of such network-based disruptions in AD. Future work validating this model in other external datasets, and to midlife adults and older adults with no known diagnosis, will critically extend this neuromarker development work using fMRI.
Determination of Vitamin C and Organic Acids in Various Fruits by HPLC

Liquid chromatographic methodology for determination of vitamin C and organic acids in different fruits (whortleberry, blackberry, red currant, black currant, raspberry, babaco, feijoa, kiwano, passion fruit, red and yellow tamarillos, medlar, and persimmon) cultivated in Galicia, Spain are developed. Both methods use a C18 column and an RP-18 precolumn for the stationary phase. High-performance-liquid-chromatographic-(HPLC-) grade water is brought to pH 2.2 with sulphuric acid for the mobile phase. The flow rate is 0.4 mL/min, and UV detection is at 254 nm for vitamin C and 214 nm for organic acids. Coefficients of variation of 1.84, 1.20, 1.00, and 2.60% are obtained for the vitamin C, quinic acid, malic acid and citric acid, respectively.
The cortical origin and initial spread of medial temporal tauopathy in Alzheimer’s disease assessed with positron emission tomography

An automated method to quantify TAU PET detected initial cortical tauopathy in Alzheimer’s disease and tracked subsequent amyloid-related TAU spread. Targeting TAU where it originates Positron emission tomography (PET) has been shown to be effective in detecting TAU depositions in the brain of patients with Alzheimer’s disease (AD). Now, Sanchez et al. applied an automated method to quantify TAU progression in patients with AD at different stages. The authors found that TAU signal emerges first in the rhinal cortex independently of Aβ. Subsequent TAU elevation in the temporal neocortex was associated with age, Aβ, and APOE status. Longitudinal data in a subgroup of patients confirmed the TAU trajectory and showed that baseline TAU was associated with subsequent TAU spread. Targeting TAU in the temporal lobe might slow TAU spread and disease progression in patients with AD. Advances in molecular positron emission tomography (PET) have enabled anatomic tracking of brain pathology in longitudinal studies of normal aging and dementia, including assessment of the central model of Alzheimer’s disease (AD) pathogenesis, according to which TAU pathology begins focally but expands catastrophically under the influence of amyloid-β (Aβ) pathology to mediate neurodegeneration and cognitive decline. Initial TAU deposition occurs many years before Aβ in a specific area of the medial temporal lobe. Building on recent work that enabled focus of molecular PET measurements on specific TAU-vulnerable convolutional temporal lobe anatomy, we applied an automated anatomic sampling method to quantify TAU PET signal in 443 adult participants from several observational studies of aging and AD, spanning a wide range of ages, Aβ burdens, and degrees of clinical impairment. We detected initial cortical emergence of tauopathy near the rhinal sulcus in clinically normal people and, in a subset with longitudinal 2-year follow-up data (n = 104), tracked Aβ-associated spread of TAU from this site first to nearby neocortex of the temporal lobe and then to extratemporal regions. Greater rate of TAU spread was associated with baseline measures of both global Aβ burden and medial temporal lobe TAU. These findings are consistent with clinicopathological correlation studies of Alzheimer’s tauopathy and enable precise tracking of AD-related TAU progression for natural history studies and prevention therapeutic trials.
Thermodynamics of CuAlO2 and CuAl2O4 and Phase Equilibria in the System Cu2O‐CuO‐Al2O3

The standard Gibbs free energies of formation of CuAlO2 and CuAl2O4 were determined in the range 700° to 1100°C, using emf measurements on the galvanic cells (1) Pt,CuO +] Cu2O/CaO-ZrO2/O2,Pt; (2) Pt,Cu +] CuAlO2+] Al2O3/CaO-ZrO2/ Cu +] Cu2O,Pt; and (3) Pt,CuAl2O4+] CuAlO2+]Al2O3/CaO-ZrO2/O2,Pt. The results are compared with published information on the stability of these compounds. The entropy of transformation of CuO from tenorite to the rock-salt structure is evaluated from the present results and from earlier studies on the entropy of formation of spinels from oxides of the rock-salt and corundum structures. The temperatures corresponding to 3-phase equilibria in the system Cu2O-CuO-Al2O3 at specified O2 pressures calculated from the present results are discussed in reference to available phase diagrams.
Cognitive Reserve in Model Systems for Mechanistic Discovery: The Importance of Longitudinal Studies

The goal of this review article is to provide a resource for longitudinal studies, using animal models, directed at understanding and modifying the relationship between cognition and brain structure and function throughout life. We propose that forthcoming longitudinal studies will build upon a wealth of knowledge gleaned from prior cross-sectional designs to identify early predictors of variability in cognitive function during aging, and characterize fundamental neurobiological mechanisms that underlie the vulnerability to, and the trajectory of, cognitive decline. Finally, we present examples of biological measures that may differentiate mechanisms of the cognitive reserve at the molecular, cellular, and network level.
Ectonucleotidase Modulation of Lymphocyte Function in Gut and Liver

Imbalance between regulatory and effector T lymphocytes contributes to loss of immunotolerance and plays a permissive role in the initiation, perpetuation, and progression of chronic inflammatory diseases and autoimmune disorders. Regulatory/effector cell balance is governed by the CD39 ectonucleotidase, the prototype member of the NTPDase family that hydrolyzes ATP and ADP into AMP, subsequently converted into adenosine by CD73. Generation of adenosine impacts T-cell function as it contributes to the mechanism of suppression of Tregs and confers regulatory properties to pathogenic Th17-cells. CD39 cell distribution, mechanism of regulation and impact on inflammatory and regulatory signaling pathways are also discussed here. Innovative therapeutic strategies to boost CD39 levels and activity by either administering soluble ADPases or interfering with CD39 inhibitory signals are reviewed. Restoration of CD39 levels and function has enormous translational and clinical implications and should be regarded as an additional form of treatment to be deployed in the chronic inflammatory setting. The key role of CD39 in immunoregulation in the context of Crohn's disease, one of the most frequent manifestations of inflammatory bowel disease, and autoimmune hepatitis, an autoimmune disorder of the liver, is reviewed and discussed here.
Comparative Transcriptome Analysis During the Seven Developmental Stages of Channel Catfish (Ictalurus punctatus) and Tra Catfish (Pangasianodon hypophthalmus) Provides Novel Insights for Terrestrial Adaptation

Tra catfish (Pangasianodon hypophthalmus), also known as striped catfish, is a facultative air-breather that uses its swim bladder as an air-breathing organ (ABO). A related species in the same order (Siluriformes), channel catfish (Ictalurus punctatus), does not possess an ABO and thus cannot breathe in the air. Tra and channel catfish serve as great comparative models for investigating possible genetic underpinnings of aquatic to land transitions, as well as for understanding genes that are crucial for the development of the swim bladder and the function of air-breathing in tra catfish. In this study, hypoxia challenge and microtomy experiments collectively revealed critical time points for the development of the air-breathing function and swim bladder in tra catfish. Seven developmental stages in tra catfish were selected for RNA-seq analysis based on their transition to a stage that could live at 0 ppm oxygen. More than 587 million sequencing clean reads were generated, and a total of 21,448 unique genes were detected. A comparative genomic analysis between channel catfish and tra catfish revealed 76 genes that were present in tra catfish, but absent from channel catfish. In order to further narrow down the list of these candidate genes, gene expression analysis was performed for these tra catfish-specific genes. Fourteen genes were inferred to be important for air-breathing. Of these, HRG, GRP, and CX3CL1 were identified to be the most likely genes related to air-breathing ability in tra catfish. This study provides a foundational data resource for functional genomic studies in air-breathing function in tra catfish and sheds light on the adaptation of aquatic organisms to the terrestrial environment.
The Combined Impact of Gender and Age on Post-traumatic Stress Symptoms, Depression, and Insomnia During COVID-19 Outbreak in China

The mental health problems might have been increased owing to the COVID-19 pandemic with the commencement of the year 2020, therefore, an epidemiological survey appraising the burden of mental health issues among the general population is imperative. This cross-sectional study attempts to reveal the underlying mental health conditions, such as Post-Traumatic Stress Symptoms (PTSS), depression, and insomnia, relating to the pandemic situation, and to further examine the combined effects of gender and age on the COVID-19 related mental health consequences. An online survey was conducted among 2,992 adults in China from February 1st 2020 to February 10th 2020. The study uses binary logistic regression to analyze the potential factors associated with PTSD, depression, and insomnia. The results indicate that the prevalence of PTSS, depression, and insomnia are 19.5, 26.9, and 19.6% respectively during the COVID-19. Men and women show different rates of PTSS and depression, whereas no insomnia is found in both males and females. The females above 50 years of age have a lower level of depressive symptoms (OR = 0.448, 95%CI: 0.220–0.911, Cohen's d = −0.443) as compared with females aged 18–25; while the highest effect sizes for PTSS (OR = 2.846, 95%CI: 1.725–4.695, Cohen's d = 0.537) and the depression (OR = 2.024, 95%CI: 1.317–3.111, Cohen's d = 0.314) are seen in males aged 26 to 30. Besides gender, education, living conditions, direct exposure to COVID-19, the post mental and the physical health condition is related to PTSS, depression, and insomnia. Our study suggests that high-risk groups, especially those having two or more related factors and young men, should be the focus of mental health intervention.
Right to Life or Right to Die in Advanced Dementia: Physician-Assisted Dying

“A mind that could be so alive one moment with thought and feeling building toward the next step and then someone erases the blackboard. It’s all gone and I can’t even reconstruct what the topic was. It’s just gone. And I sit with the dark, the blank. ” As the eminent American psychologist, Sandra Bem mused so eloquently in her writings, immediately after receiving a diagnosis of Alzheimer’s (1). This anecdote very poignantly summarizes the harrowing effect dementia has on the individual person. There have beenmassive improvements in the health sector over the previous decades, and as a consequence people have been able to live longer and healthier lives. However, concurrently, there has also been an increase in the cases of non-communicable diseases, which includes dementia. In 2015 itself, dementia affected 47 million people worldwide; corresponding to roughly 5% of the world’s elderly population (2, 3). Extensive research has been done for early and moderate stage dementia, but severe dementia is relatively neglected with very few evidence-based treatment options available. The later stages are very important because they harbor unique characteristics and events that affect not only the lives of the patients, but also their caregivers. In advanced stages, patients suffer from gradual deterioration in cognitive ability and functional impairments, which imposes a heavy burden on the public health system and families. Both direct and indirect costs of institutionalization are staggeringly large (4). These factors require a need for revision of existing health advisory and the below-mentioned concerns should be appropriately addressed before devising further health policy.
Unravelling the Role of Rumen Microbial Communities, Genes, and Activities on Milk Fatty Acid Profile Using a Combination of Omics Approaches

Milk products are an important component of human diets, with beneficial effects for human health, but also one of the major sources of nutritionally undesirable saturated fatty acids (SFA). Recent discoveries showing the importance of the rumen microbiome on dairy cattle health, metabolism and performance highlight that milk composition, and potentially milk SFA content, may also be associated with microorganisms, their genes and their activities. Understanding these mechanisms can be used for the development of cost-effective strategies for the production of milk with less SFA. This work aimed to compare the rumen microbiome between cows producing milk with contrasting FA profile and identify potentially responsible metabolic-related microbial mechanisms. Forty eight Holstein dairy cows were fed the same total mixed ration under the same housing conditions. Milk and rumen fluid samples were collected from all cows for the analysis of fatty acid profiles (by gas chromatography), the abundances of rumen microbiome communities and genes (by whole-genome-shotgun metagenomics), and rumen metabolome (using 500 MHz nuclear magnetic resonance). The following groups: (i) 24 High-SFA (66.9–74.4% total FA) vs. 24 Low-SFA (60.2–66.6%% total FA) cows, and (ii) 8 extreme High-SFA (69.9–74.4% total FA) vs. 8 extreme Low-SFA (60.2–64.0% total FA) were compared. Rumen of cows producing milk with more SFA were characterized by higher abundances of the lactic acid bacteria Lactobacillus, Leuconostoc, and Weissella, the acetogenic Proteobacteria Acetobacter and Kozakia, Mycobacterium, two fungi (Cutaneotrichosporon and Cyphellophora), and at a lesser extent Methanobrevibacter and the protist Nannochloropsis. Cows carrying genes correlated with milk FA also had higher concentrations of butyrate, propionate and tyrosine and lower concentrations of xanthine and hypoxanthine in the rumen. Abundances of rumen microbial genes were able to explain between 76 and 94% on the variation of the most abundant milk FA. Metagenomics and metabolomics analyses highlighted that cows producing milk with contrasting FA profile under the same diet, also differ in their rumen metabolic activities in relation to adaptation to reduced rumen pH, carbohydrate fermentation, and protein synthesis and metabolism.
An Evolutionary Arms Race Between Burkholderia pseudomallei and Host Immune System: What Do We Know?

A better understanding of co-evolution between pathogens and hosts holds promise for better prevention and control strategies. This review will explore the interactions between Burkholderia pseudomallei, an environmental and opportunistic pathogen, and the human host immune system. B. pseudomallei causes “Melioidosis,” a rapidly fatal tropical infectious disease predicted to affect 165,000 cases annually worldwide, of which 89,000 are fatal. Genetic heterogeneities were reported in both B. pseudomallei and human host population, some of which may, at least in part, contribute to inter-individual differences in disease susceptibility. Here, we review (i) a multi-host—pathogen characteristic of the interaction; (ii) selection pressures acting on B. pseudomallei and human genomes with the former being driven by bacterial adaptation across ranges of ecological niches while the latter are driven by human encounter of broad ranges of pathogens; (iii) the mechanisms that generate genetic diversity in bacterial and host population particularly in sequences encoding proteins functioning in host—pathogen interaction; (iv) reported genetic and structural variations of proteins or molecules observed in B. pseudomallei—human host interactions and their implications in infection outcomes. Together, these predict bacterial and host evolutionary trajectory which continues to generate genetic diversity in bacterium and operates host immune selection at the molecular level.
Serine/threonine Kinases Play Important Roles in Regulating Polyunsaturated Fatty Acid Biosynthesis in Synechocystis sp. PCC6803

Serine/threonine kinases (STKs) play important roles in prokaryotic cellular functions such as growth, differentiation, and secondary metabolism. When the external environment changes, prokaryotes rely on signal transduction systems, including STKs that quickly sense these changes and alter gene expression to induce the appropriate metabolic changes. In this study, we examined the roles of the STK genes spkD and spkG in fatty acid biosynthesis in the unicellular cyanobacterium Synechocystis sp. PCC6803, using targeted gene knockout. The linoleic acid (C18: 2), γ-linolenic acid (C18: 3n6), α-linolenic acid (C18: 3n3), and stearidonic acid (C18: 4) levels were significantly lower in spkD and spkG gene knockout mutants than in the wild type at a culture temperature of 30°C and a light intensity of 40 μmol⋅m–2⋅s–1. The expression levels of fatty acid desaturases and STK genes differed between the spkD and spkG gene knockout mutants. These observations suggest that spkD and spkG may directly or indirectly affect the fatty acid composition in Synechocystis sp. PCC6803 by regulating the expression of fatty acid desaturases genes. Therefore, the STK genes spkD and spkG play important roles in polyunsaturated fatty acid biosynthesis in Synechocystis sp. PCC6803. These findings could facilitate the development of cyanobacteria germplasm resources that yield high levels of fatty acids. In addition, they provide a theoretical basis for the genetic engineering of cyanobacteria with improved yields of secondary metabolites and increased economic benefits.