Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Trisomic iPSCs from Down Syndrome Fibroblasts Manifest Mitochondrial Alterations Early during Neuronal Differentiation

Simple Summary Down Syndrome, which is due to the presence of three copies of chromosome 21, always presents with mental retardation, possibly caused by defects in the development of neurons. In recent years, it has been shown that cells and tissues in Down syndrome manifest alterations in the function of mitochondria, the organelles that provide energy to cells. We hypothesized that mitochondrial dysfunction might contribute to the defect in neuronal cell development. To test this hypothesis, we generated a model of stem cells that, upon specific treatments, are capable of giving rise to neuronal cells, as evidenced by the synthesis of specific proteins. We observed that stem cells derived from Down syndrome individuals, after 21 days of growth in an artificial system, had an abnormal tendency to develop as glial cells, compared with control cells. As early as day 7 of culture, the trisomic cells also exhibited defects in mitochondrial function, such as anomalies in their calcium level, oxygen free radicals, oxygen consumption, and synthesis of ATP, a molecule that is critical in energy conversions. These results indicate that alterations in neuronal development and mitochondrial function occur early in this model, which we think is suitable for answering further questions. Abstract Background: The presence of mitochondrial alterations in Down syndrome suggests that it might affect neuronal differentiation. We established a model of trisomic iPSCs, differentiating into neural precursor cells (NPCs) to monitor the occurrence of differentiation defects and mitochondrial dysfunction. Methods: Isogenic trisomic and euploid iPSCs were differentiated into NPCs in monolayer cultures using the dual-SMAD inhibition protocol. Expression of pluripotency and neural differentiation genes was assessed by qRT-PCR and immunofluorescence. Meta-analysis of expression data was performed on iPSCs. Mitochondrial Ca2+, reactive oxygen species (ROS) and ATP production were investigated using fluorescent probes. Oxygen consumption rate (OCR) was determined by Seahorse Analyzer. Results: NPCs at day 7 of induction uniformly expressed the differentiation markers PAX6, SOX2 and NESTIN but not the stemness marker OCT4. At day 21, trisomic NPCs expressed higher levels of typical glial differentiation genes. Expression profiles indicated that mitochondrial genes were dysregulated in trisomic iPSCs. Trisomic NPCs showed altered mitochondrial Ca2+, reduced OCR and ATP synthesis, and elevated ROS production. Conclusions: Human trisomic iPSCs can be rapidly and efficiently differentiated into NPC monolayers. The trisomic NPCs obtained exhibit greater glial-like differentiation potential than their euploid counterparts and manifest mitochondrial dysfunction as early as day 7 of neuronal differentiation.
Estimation of Soil Surface Roughness Using Stereo Vision Approach

Soil roughness is one of the most challenging issues in the agricultural domain and plays a crucial role in soil quality. The objective of this research was to develop a computerized method based on stereo vision technique to estimate the roughness formed on the agricultural soils. Additionally, soil till quality was investigated by analyzing the height of plow layers. An image dataset was provided in the real conditions of the field. For determining the soil surface roughness, the elevation of clods obtained from tillage operations was computed using a depth map. This map was obtained by extracting and matching corresponding keypoints as super pixels of images. Regression equations and coefficients of determination between the measured and estimated values indicate that the proposed method has a strong potential for the estimation of soil shallow roughness as an important physical parameter in tillage operations. In addition, peak fitting of tilled layers was applied to the height profile to evaluate the till quality. The results of this suggest that the peak fitting is an effective method of judging tillage quality in the fields.
Structure solution and refinement from powder or single-crystal diffraction data? Pros and cons: An example of the high-pressure β′-polymorph of glycine

The structure of a high-pressure polymorph of glycine (the β′-polymorph formed reversibly at 0.8 GPa from the β-polymorph) was determined from high-resolution X-ray powder diffraction data collected in situ in a diamond anvil cell at nine pressure points up to 2.6 GPa. X-ray powder diffraction study gave a structural model of at least the same quality as that obtained from a single-crystal diffraction experiment. The difference between the powder-diffraction and the single-crystal models is related to the orientation of the NH3-tails and the structure of the hydrogen-bonds network. The phase transition between the β- and β′-polymorphs is reversible and preserves a single crystal intact. No transformations were observed between the β-, α-, and β′-polymorphs on compression and decompression, although the α- and β′-polymorphs belong to the same space group (P21/c). The instability of the β- and γ-forms with pressure can be predicted easily when considering the densities of their structures versus pressure. The direction of the transformation (i.e., which of the high-pressure polymorphs is formed) is determined by structural filiation between the parent and the high-pressure phases because of the kinetic control of the transformations.
Exosomal microRNA let-7-5p from Taenia pisiformis Cysticercus Prompted Macrophage to M2 Polarization through Inhibiting the Expression of C/EBP δ

Cysticercus pisiformis, the larval stage of Taenia pisiformis, causes serious illness in rabbits that severely impacts the rabbit breeding industry. An inhibitive Th2 immune response can be induced by let-7-enriched exosomes derived from T. pisiformis cysticercus. However, the underlying molecular mechanisms are not completely understood. Here, we report that exosomal miR-let-7-5p released by T. pisiformis cysticercus played a critical role in the activation of M2 macrophages. We found that overexpression of let-7-5p in M1 macrophages decreased M1 phenotype expression while promoting polarization to the M2 phenotype, which is consistent with experimental data in exosome-treated macrophages alone. In contrast, knockdown of let-7-5p in exosome-like vesicles promoted M1 polarization and decreased M2 phenotype expression. Furthermore, down-regulation of transcription factor CCAAT/enhancer-binding protein (C/EBP)-δ resulted in the decrease of M1 phenotype markers and increase of M2 phenotype markers. These results suggested that let-7 enriched in exosome-like vesicles from T. pisiformis metacestodes can induce M2 macrophage polarization via targeting C/EBP δ, which may be involved in macrophage polarization induced by T. pisiformis metacestodes. The finding helps to expand our knowledge of the molecular mechanism of immunosuppression and Th2 immune response induced by metacestodes.
Within-person changes in basal cortisol and caregiving modulate executive attention across infancy

Abstract One pathway by which environments of socioeconomic risk are thought to affect cognitive development is through stress physiology. The biological systems underpinning stress and attention undergo a sensitive period of development during infancy. Psychobiological theory emphasizes a dynamic pattern of context-dependent development, however, research has yet to examine how basal cortisol and attention dynamically covary across infancy in ecologically valid contexts. Thus, to address these gaps, we leveraged longitudinal, multilevel analytic methods to disentangle between- from within-person associations of hypothalamic–pituitary–adrenal (HPA) axis activity and executive attention behaviors across infancy. We use data from a large longitudinal sample (N = 1,292) of infants in predominantly low-income, nonurban communities at 7-, 15-, and 24-months of age. Using multilevel models, we investigated longitudinal associations of infant attention and basal cortisol levels and examined caregiving behaviors as moderators of this relationship. Results indicated a negative between- and within-person association between attention and cortisol across infancy and a within-person moderation by caregiver responsiveness. In other words, on the within-person level, higher levels of cortisol were concomitantly associated with lower infant attention across the first 2 years of life. However, variation in the caregiver's level of responsiveness either buffered or sensitized the executive attention system to the negative effects of physiological stress.
Interventions to optimise nutrition in older people in hospitals and long‐term care: Umbrella review

Abstract Background Inpatients have a high need for protein‐energy intake because of increased physical stress metabolism due to illnesses. Protein‐energy undernutrition in older patients increases the risk of complications such as falls, pressure ulcers and even death. An overview of effective interventions addressing this complex issue of malnutrition in older people is missing. Aims To give an overview of effective interventions to optimise nutrition in older people in hospitals and long‐term care. Design An umbrella review, according to the Joanna Briggs Institute and PRISMA statement, was conducted in April 2020. Methods A systematic search of publications from 2010 until 2020 was conducted in CINAHL, PubMed and Cochrane Database. Included were studies reporting nutrition interventions that involved nurses or the interprofessional team in optimising older hospitalised people's nutrition. Excluded were studies investigating the effects of parenteral nutrition, certain food supplements or tube feeding and research from intensive, community or palliative care. Components of interventions were classified according to the intervention Nutrition management: Patients’ assistance, patients’ instruction, foodservice, environment for meals and nutrient‐dense snacks. Findings Included were 13 reviews from 19 countries of the continents Asia, Australia, Europe and North America from hospitals and long‐term care settings. An interprofessional food promoting culture, including staff training as part of a multi‐component measure, has shown to be a successful element in implementing activities of Nutrition Management. Conclusion Several studies synthesised that optimising nutrition in older people in hospitals and long‐term care is achievable. Interventions were effective if—on a meta‐level—staff training was addressed as part of a multi‐component measure to reach an interprofessional food promoting culture. Implications for practice Interventions to optimise older people's nutrition have to consider an interprofessional food promoting culture, including staff training about the importance of nutrition, patients’ assistance and an appropriate environment for meals.
Synonymous Codon Pair Recoding of the HIV-1 env Gene Affects Virus Replication Capacity

Synonymous codon pair deoptimization is an efficient strategy for virus attenuation; however, the underlying mechanism remains controversial. Here, we optimized and deoptimized the codon pair bias (CPB) of the human immunodeficiency virus type 1 (HIV-1) envelope (env) gene to investigate the influence of env synonymous CPB recoding on virus replication capacity, as well as the potential mechanism. We found that env CPB deoptimization did not always generate attenuation, whereas CPB optimization attenuated virus replication in MT-4 cells. Furthermore, virus attenuation correlated with reduced Env protein production but not with decreased viral RNA synthesis. Remarkably, in our model, increasing the number of CpG dinucleotides in the 5′ end of env did not reduce the replication capacity of HIV-1. These results indicate that factors other than CPB or CpG content may have impacted the viral fitness of the synonymously recoded study variants. Our findings provide evidence that CPB recoding-associated attenuation can affect translation efficiency. Moreover, we demonstrated that an increased number of CpGs in the 5′ end of HIV-1 env is not always associated with reduced virus replication capacity.
Implications of Circadian Rhythm in Stroke Occurrence: Certainties and Possibilities

Stroke occurrence is not randomly distributed over time but has circadian rhythmicity with the highest frequency of onset in the morning hours. This specific temporal pattern is valid for all subtypes of cerebral infarction and intracerebral hemorrhage. It also correlates with the circadian variation of some exogenous factors such as orthostatic changes, physical activity, sleep-awake cycle, as well as with endogenous factors including dipping patterns of blood pressure, or morning prothrombotic and hypofibrinolytic states with underlying cyclic changes in the autonomous system and humoral activity. Since the internal clock is responsible for these circadian biological changes, its disruption may increase the risk of stroke occurrence and influence neuronal susceptibility to injury and neurorehabilitation. This review aims to summarize the literature data on the circadian variation of cerebrovascular events according to physiological, cellular, and molecular circadian changes, to survey the available information on the chronotherapy and chronoprophylaxis of stroke and its risk factors, as well as to discuss the less reviewed impact of the circadian rhythm in stroke onset on patient outcome and functional status after stroke.
A Descriptive Analysis of Transitions from Smoking to Electronic Nicotine Delivery System (ENDS) Use: A Daily Diary Investigation

Objectives: We aimed to examine patterns in smoking and electronic nicotine delivery system (ENDS) use over an extended period of time (up to 20 weeks) in people who smoked and who had never previously made a successful quit attempt using an ENDS. Design and setting: We conducted a longitudinal mixed-methods study in Dunedin, New Zealand, during 2018 and 2019. Participants: Purposively selected participants (N = 45; age (≥18 years), gender, ethnicities, cigarettes/day) who wished to quit smoking. Interventions: Participants were provided with a second-generation ENDS device (vape pen or starter “tank” device) at the start of their quit attempt, and asked to complete smartphone-based daily diary surveys assessing smoking and ENDS use. Outcome measures: Sunburst plots and a sequence plot were used to describe weekly and daily patterns of smoking and ENDS use (smoking only, ENDS use only, dual use, abstinent). Results: The most frequently reported movements among participants, classified according to their study week behaviour, occurred between dual use and exclusive ENDS use (and vice versa). A smaller group reported moving from dual use to exclusive smoking (and often back to dual use), and a small number reported moving between abstinence and different ENDS and smoked tobacco usage behaviours. Data visualisations focussing on those participants who had provided data during each of weeks 9–12 indicate that only a minority reported sustained dual use; instead, most participants indicated varied smoked tobacco and ENDS use, which included periods of dual use. Conclusions: The considerable variety observed within and between study participants suggests that high variability is typical rather than exceptional. Transitions from smoking to ENDS use may involve considerable periods of dual use, which is likely to be dynamic and potentially sustained over several months.
Pancreatic β Cells Inhibit Glucagon Secretion from α Cells: An In Vitro Demonstration of α–β Cell Interaction

Interactions between endocrine α and β cells are critical to their secretory function in vivo. The interactions are highly regulated, although yet to be fully understood. In this study, we aim to assess the impact of α and β cell co-culture on hormone secretion. Mouse clonal cell lines α-TC6-1 (α cell line) and MIN-6 (β cell line) were cultured independently or in combination in a medium containing 5.5, 11.1, or 25 mM glucose, respectively. After 72 h, hormone release was measured using insulin and glucagon secretion assays, the cell distribution was visualized by inverted microscopy and an immunocytochemistry assay, and changes in gene expressions were assessed using the RT-PCR technique. The co-culture of the two cell lines caused a decrease in glucagon secretion from α-TC1-6 cells, while no effect on insulin secretion from MIN-6 cells was revealed. Both types of cells were randomly scattered throughout the culture flask, unlike in mice islets in vivo where β cells cluster in the core and α cells are localized at the periphery. During the α–β cell co-culture, the gene expression of glucagon (Gcg) decreased significantly. We conclude that islet β cells suppress glucagon secretion from α cells, apparently via direct cell-to-cell contact, of which the molecular mechanism needs further verification.
Genotype Load Modulates Amyloid Burden and Anxiety-Like Patterns in Male 3xTg-AD Survivors despite Similar Neuro-Immunoendocrine, Synaptic and Cognitive Impairments

The wide heterogeneity and complexity of Alzheimer’s disease (AD) patients’ clinical profiles and increased mortality highlight the relevance of personalized-based interventions and the need for end-of-life/survival predictors. At the translational level, studying genetic and age interactions in a context of different levels of expression of AD-genetic-load can help to understand this heterogeneity better. In the present report, a singular cohort of long-lived (19-month-old survivors) heterozygous and homozygous male 3xTg-AD mice were studied to determine whether their AD-genotype load can modulate the brain and peripheral pathological burden, behavioral phenotypes, and neuro-immunoendocrine status, compared to age-matched non-transgenic controls. The results indicated increased amyloid precursor protein (APP) levels in a genetic-load-dependent manner but convergent synaptophysin and choline acetyltransferase brain levels. Cognitive impairment and HPA-axis hyperactivation were salient traits in both 3xTg-AD survivor groups. In contrast, genetic load elicited different anxiety-like profiles, with hypoactive homozygous, while heterozygous resembled controls in some traits and risk assessment. Complex neuro-immunoendocrine crosstalk was also observed. Bodyweight loss and splenic, renal, and hepatic histopathological injury scores provided evidence of the systemic features of AD, despite similar peripheral organs’ oxidative stress. The present study provides an interesting translational scenario to study further genetic-load and age-dependent vulnerability/compensatory mechanisms in Alzheimer’s disease.
On the Coupling between Mechanical Properties and Electrostatics in Biological Membranes

Cell membrane structure is proposed as a lipid matrix with embedded proteins, and thus, their emerging mechanical and electrostatic properties are commanded by lipid behavior and their interconnection with the included and absorbed proteins, cytoskeleton, extracellular matrix and ionic media. Structures formed by lipids are soft, dynamic and viscoelastic, and their properties depend on the lipid composition and on the general conditions, such as temperature, pH, ionic strength and electrostatic potentials. The dielectric constant of the apolar region of the lipid bilayer contrasts with that of the polar region, which also differs from the aqueous milieu, and these changes happen in the nanometer scale. Besides, an important percentage of the lipids are anionic, and the rest are dipoles or higher multipoles, and the polar regions are highly hydrated, with these water molecules forming an active part of the membrane. Therefore, electric fields (both, internal and external) affects membrane thickness, density, tension and curvature, and conversely, mechanical deformations modify membrane electrostatics. As a consequence, interfacial electrostatics appears as a highly important parameter, affecting the membrane properties in general and mechanical features in particular. In this review we focus on the electromechanical behavior of lipid and cell membranes, the physicochemical origin and the biological implications, with emphasis in signal propagation in nerve cells.
A Review of the Effects and Production of Spore-Forming Probiotics for Poultry

Simple Summary Spore-forming probiotics are widely used in the poultry industry for their beneficial impact on host health. The main feature that separates spore-forming probiotics from the more common lactic acid probiotics is their high resistance to external and internal factors, resulting in higher viability in the host and correspondingly, greater efficiency. Their most important effect is the ability to confront pathogens, which makes them a perfect substitute for antibiotics. In this review, we cover and discuss the interactions of spore-forming probiotic bacteria with poultry as the host, their health promotion effects and mechanisms of action, impact on poultry productivity parameters, and ways to manufacture the probiotic formulation. The key focus of this review is the lack of reproducibility in poultry research studies on the evaluation of probiotics’ effects, which should be solved by developing and publishing a set of standard protocols in the professional community for conducting probiotic trials in poultry. Abstract One of the main problems in the poultry industry is the search for a viable replacement for antibiotic growth promoters. This issue requires a “one health” approach because the uncontrolled use of antibiotics in poultry can lead to the development of antimicrobial resistance, which is a concern not only in animals, but for humans as well. One of the promising ways to overcome this challenge is found in probiotics due to their wide range of features and mechanisms of action for health promotion. Moreover, spore-forming probiotics are suitable for use in the poultry industry because of their unique ability, encapsulation, granting them protection from the harshest conditions and resulting in improved availability for hosts’ organisms. This review summarizes the information on gastrointestinal tract microbiota of poultry and their interaction with commensal and probiotic spore-forming bacteria. One of the most important topics of this review is the absence of uniformity in spore-forming probiotic trials in poultry. In our opinion, this problem can be solved by the creation of standards and checklists for these kinds of trials such as those used for pre-clinical and clinical trials in human medicine. Last but not least, this review covers problems and challenges related to spore-forming probiotic manufacturing.
The Use of Natural Compounds as a Strategy to Counteract Oxidative Stress in Animal Models of Diabetes Mellitus

Diabetes mellitus (DM) is a chronic metabolic disease characterised by insulin deficiency, resulting in hyperglycaemia, a characteristic symptom of type 2 diabetes mellitus (DM2). DM substantially affects numerous metabolic pathways, resulting in β-cell dysfunction, insulin resistance, abnormal blood glucose levels, impaired lipid metabolism, inflammatory processes, and excessive oxidative stress. Oxidative stress can affect the body’s normal physiological function and cause numerous cellular and molecular changes, such as mitochondrial dysfunction. Animal models are useful for exploring the cellular and molecular mechanisms of DM and improving novel therapeutics for their safe use in human beings. Due to their health benefits, there is significant interest in a wide range of natural compounds that can act as naturally occurring anti-diabetic compounds. Due to rodent models’ relatively similar physiology to humans and ease of handling and housing, they are widely used as pre-clinical models for studying several metabolic disorders. In this review, we analyse the currently available rodent animal models of DM and their advantages and disadvantages and highlight the potential anti-oxidative effects of natural compounds and their mechanisms of action.