Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutagénesis, selección y caracterización nutricional de una cepa nativa de Saccharomyces cerevisiae para la producción de isobutanol

Con el proposito de obtener una cepa de Saccharomyces cerevisiae con mayor produccion de isobutanol durante el proceso de fermentacion, se evaluo una coleccion de levaduras de esta especie y se selecciono la cepa 209-2-8. Esta cepa produjo isobutanol en una concentracion de 301.7 mg/L al emplear mieles de cana suplementadas con fosfato diacido de amonio como sustrato. Esta levadura fue sometida a un proceso de mutagenesis con N-metil N-nitro nitrosoguanidina, acoplado a la seleccion en un medio con sulfometuron metil. De este proceso se obtuvo la levadura S. cerevisiae Q1, la cual presento una produccion de isobutanol 1.92 veces mayor que la de la cepa parental alcanzando una concentracion de 580.8 mg/L. La produccion de alcohol isoamilico por parte de la cepa mutante fue 1.3 veces mayor respecto a la cepa parental. Posteriormente, mediante un proceso de mutagenesis con etil metano sulfonato y un enriquecimiento con nistatina se obtuvo la cepa Q1m que presenta auxotrofia para L-leucina. Esta cepa alcanzo una produccion de isobutanol de 811.0 mg/L en mieles suplementadas con L-leucina, mientras redujo su produccion de alcohol isoamilico. La productividad alcanzada fue de 16.4 mg/Lh, la cual fue determinada mediante una evaluacion preliminar en biorreactor. Por otro lado, se realizo un diseno experimental Plackett-Burman, empleando un medio de referencia quimicamente definido. Con este diseno se encontro que la concentracion de fosfato diacido de potasio y la de biotina, y el nivel de pH son los factores que influencian la produccion de isobutanol.
Muller’s ratchet as a mechanism of frailty and multimorbidity

Mutation accumulation has been proposed as a cause of senescence. In this process, both constitutional and recurrent mutations accumulate gradually and differentially among differentiating cells, tissues and organs, in relation to stage and age, analogous to Muller’s ratchet in asexually reproducing organisms. Latent and cascading deleterious effects of mutations might initiate steady “accumulation of deficits” in cells, leading to cellular senescence, and functional decline of tissues and organs, and ultimately manifest as frailties and disease. We investigated a few of these aspects in cell populations through modeling and simulation using the Moran birth-death process, under varied scenarios of mutation accumulation. Our results agree with the principle of Muller’s ratchet. The ratchet speed in a given tissue depends on the population size of cells, mutation rate, and selection coefficient. Additionally, deleterious mutations seem to rapidly accumulate particularly early in the life-course, during which the rate of cell division is high, thereby exerting a greater effect on cellular senescence. The speed of the ratchet afterward varies greatly between cells nested in tissues and tissues within organs due to heterogeneity in the life span and turnover rate of specific cell types. Importantly, the ratchet accelerates with age, resulting in a synergistic fitness decay in cell populations. We extend Fisher’s average excess concept and rank order scale to interpret differential phenotypic effects of mutation load in a given tissue. We conclude that classical evolutionary genetic models could explain partially, the origins of frailty, subclinical conditions, morbidity and health consequences of senescence. Significance Frailty is defined as physiological and functional decline of organs and organ systems, due to deficit accumulation from stochastic damages within the organism with advanced age. Equivalently, with age, both constitutional and somatic mutations accumulate gradually and differentially among cells, cell lineages, tissues, and organs. Since most mutations are deleterious, accumulation of random and recurrent mutations could create a “load,” on the genome and contextually express in the epigenome and phenotype spaces. Here we extend Muller’s ratchet principle to explain frailty and multi-morbidity using the Moran model and simulations. Our results agree with the Muller’s ratchet principle. We emphasize the need for considering cumulative effects of the entire spectrum of mutations for explaining the origin of frailty, sub-clinical conditions, and morbidity.
Molecular Basis of Carotenoid Accumulation in Horticultural Crops

Carotenoids are isoprenoid pigments, which are widely distributed in nature. In fruits and flowers, carotenoids are responsible for bright yellow, orange, and red colors and provide a substrate to form flavor compounds, which attract pollinators and seed dispersers. In leaves, carotenoids play an essential role in photosynthesis. When carotenoids are ingested in the diet, they play a vital role in human nutrition and health as a precursor of vitamin A, antioxidants, and anti-inflammatory agents. It is therefore important to control carotenoid accumulation to improve the commercial value of horticultural crops. Carotenoid accumulation is regulated by flux through the carotenoid biosynthetic pathway, and also by degradation and sequestration into plastids, which function as sink organelles. These processes are mostly controlled at the transcriptional levels of relevant genes. In this review, we summarize recent advances in studies on the molecular mechanisms that regulate carotenoid accumulation in vegetables, fruits, and ornamental flowers.
The loss of V0-ATPase induces Microvillus inclusion-like disease in C. elegans

Food absorption relies on the strong polarity of intestinal epithelial cells and the array of microvilli forming a brush border at their luminal pole. Recent discovery of the genes associated with rare genetic absorption disorders such as Microvillus inclusion disease (MVID) enlightened a major role of membrane trafficking in the maintenance of both the enterocyte polarity and the integrity of the brush border. However, how membrane trafficking defects can lead to food malabsorption in MVID patients is still poorly understood. Combining genetic RNAi screen and in vivo super-resolution imaging in C. elegans intestine, we uncovered that depletion of the V0 sector of the V-ATPase (V0-ATPase) fully recapitulates the severe structural, polarity and trafficking defects observed in enterocytes from patients with MVID. Furthermore, we show that V0-ATPase specifically controls an apical trafficking step involving RAB-11 endosomes and the SNARE SNAP-29. Finally, this new in vivo MVID model allowed to follow the dynamics of microvillus inclusions and to characterize the potential rescue of MVID phenotype by cholesterol complementation. Hence, we describe a new function for the V0-ATPase in apical trafficking and epithelial polarity maintenance and the promising use of C. elegans intestine as an in vivo model to better understand the molecular mechanisms of rare genetic enteropathies. Author Summary Maintenance of the strong polarity of intestinal epithelial cells and the array of microvilli forming a brush border at their luminal pole is essential to food absorption. Recent studies on rare genetic absorption disorders such as Microvillus inclusion disease (MVID) identified a major, albeit ill-defined, role of membrane trafficking in the maintenance of both the enterocyte polarity and the integrity of the brush border. Combining systematic depletion of trafficking genes by RNAi and in vivo super-resolution imaging in C. elegans intestine, we uncovered that depletion of the V0 sector of the V-ATPase complex (V0-ATPase) fully recapitulates the severe structural, polarity and trafficking defects observed in enterocytes from patients with MVID. Using this new in vivo MVID-like model, we characterized a new pathway of polarity maintenance, studied the dynamics of microvillus inclusions as well as identified the potentcy of cholesterol complementation to correct V0-ATPase depletion-induced polarity and structural defects. Thus, we describe here both a new cellular function of the V0-ATPase and a new in vivo model to study the mechanisms of MVID.
The Grapevine Calmodulin-Like Protein Gene CML21 Is Regulated by Alternative Splicing and Involved in Abiotic Stress Response

Calmodulin-like proteins (CMLs) represent a large family of plant calcium sensor proteins involved in the regulation of plant responses to environmental cues and developmental processes. In the present work, we identified four alternatively spliced mRNA forms of the grapevine CML21 gene that encoded proteins with distinct N-terminal regions. We studied the transcript abundance of CML21v1, CML21v2, CML21v3, and CML21v4 in wild-growing grapevine Vitis amurensis Rupr. in response to desiccation, heat, cold, high salinity, and high mannitol stress using quantitative real-time RT-PCR. The levels of all four splice variants of VaCML21 were highly induced in response to cold stress. In addition, VaCML21v1 and VaCML21v2 forms were highly modulated by all other abiotic stress treatments. Constitutive expression of VaCML21v2 and VaCML21v4 improved biomass accumulation of V. amurensis callus cell cultures under prolonged low temperature stress. Heterologous expression of the grapevine CML21v2 and VaCML21v4 splice variants in Arabidopsis improved survival rates of the transgenic plants after freezing. The VaCML21v2 overexpression enhanced activation of the cold stress-responsive marker genes AtDREB1A and AtDREB2A, while VaCML21v4 overexpression—AtCOR47, AtRD29A, AtRD29B, and AtKIN1 genes after freezing stress in the transgenic Arabidopsis. The results indicate that the grapevine CML21 gene acts as a positive regulator in the plant response to cold stress. The detected variety of CML21 transcripts and their distinct transcriptional responses suggested that this expansion of mRNA variants could contribute to the diversity of grapevine adaptive reactions.
Effect of evening light exposure on sleep in bipolar disorder: A longitudinal analysis for repeated measures in the APPLE cohort

Objective: Sleep disturbance, a core feature of bipolar disorder, is associated with residual mood symptoms, mood episode recurrence and suicide ideation. We investigated the effect of evening light exposure on sleep in patients with bipolar disorder. Methods: In this longitudinal analysis, we measured the sleep parameters of 207 outpatients with bipolar disorder using actigraphy at their homes for seven consecutive nights. We measured the white-light illuminance and the irradiance of each wavelength during the 4 hours before each participant’s bedtime. We used mixed-effect linear regression analysis for repeated measures to evaluate the effect of evening light exposure on subsequent sleep parameters. Results: The median white-light illuminance was 25.8 lux (interquartile range, 12.9–50.1 lux). In a multivariable model adjusted for potential confounders, we found higher white-light illuminance to be significantly associated with lower sleep efficiency (per log lux: 95% confidence interval = [−1.328, −0.133]; p = 0.017), prolonged sleep-onset latency (95% confidence interval = [0.006, 0.172]; p = 0.035) and longer wake after sleep onset (95% confidence interval = [1.104, 4.459]; p = 0.001). This effect size was larger in the younger age group (aged < 44 years) stratified by median age. Higher irradiance of the blue wavelength range was significantly associated with longer wake after sleep onset, a result similar to those for the green and red wavelength ranges. Conclusion: We observed significant associations between evening light exposure and subsequent sleep in patients with bipolar disorder. The effects of various light wavelengths on sleep in bipolar disorder require further investigation.
Targeted Therapy Recommendations for Therapy Refractory Solid Tumors—Data from the Real-World Precision Medicine Platform MONDTI

Advanced therapy-refractory solid tumors bear a dismal prognosis and constitute a major challenge in offering effective treatment strategies. In this real-world retrospective analysis of our precision medicine platform MONDTI, we describe the molecular profile of 554 patients diagnosed with 17 different types of advanced solid tumors after failure of all standard treatment options. In 304 cases (54.9% of all patients), a molecular-driven targeted therapy approach could be recommended, with a recommendation rate above 50% in 12 tumor entities. The three highest rates for therapy recommendation per tumor classification were observed in urologic malignancies (90.0%), mesothelioma (78.6%), and male reproductive cancers (71.4%). Tumor type (p = 0.46), expression of p-mTOR (p = 0.011), expression of EGFR (p = 0.046), and expression of PD-L1 (p = 0.023) had a significant impact on the targeted therapy recommendation rate. Therapy recommendations were significantly more often issued for men (p = 0.015) due to gender-specific differences in the molecular profiles of patients with head and neck cancer and malignant mesothelioma. This analysis demonstrates that precision medicine was feasible and provided the basis for molecular-driven therapy recommendations in patients with advanced therapy refractory solid tumors.
Bovines Harbor a Diverse Array of Vector-Borne Pathogens in Northeast Algeria

Arthropod-borne hemoparasites represent a serious health problem in livestock, causing significant production losses. Currently, the evidence of Anaplasma spp. , Theileria spp. , Babesia spp. , and hemotropic Mycoplasma spp. in Algeria remains limited to a few scattered geographical regions. In this work, our objectives were to study the prevalence of these vector-borne pathogens and to search other agents not yet described in Algeria as well as the identification of statistical associations with various risk factors in cattle in the northeast of Algeria. Among the 205 cattle blood samples tested by PCR analysis, 42.4% positive results were obtained for at least one pathogen. The overall rates of Anaplasma spp. , Theileria/Babesia spp. , and Mycoplasma spp. in the cattle sampled were respectively 30.7%, 18.5%, and 2.9%; co-infections with multiple species was also detected. Anaplasma spp. and Theileria/Babesia spp. were detected at a higher rate in cattle under 3 years old, according to univariate analysis. Anaplasma spp. DNA was detected more frequently in our sample in cattle living in semi extensive farming. Our study provides additional data about Anaplasma spp. , Theileria/Babesia spp. and reveals for the first time that Mycoplasma wenyonii and ‘Candidatus Mycoplasma hemobos are present in cattle in Northeast Algeria.
Evaluation of NMU-Induced Breast Cancer Treated with Sirolimus and Sunitinib on Breast Cancer Growth

Objective: To analyze the effect of sirolimus and sunitinib in blocking the tumor growth and to evaluate the expressions of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2/neu) after treated with sirolimus and sunitinib. Methods: Thirty-two female Sprague Dawley rats at age 21-days old were administered intraperitoneally with N-Methyl-N-Nitroso Urea (NMU), dosed at 70mg/kg body weight. The rats were divided into 4 groups; Group 1 (Control, n=8), Group 2 (Sirolimus, n=8), Group 3 (Sunitinib, n=8) and Group 4 (Sirolimus+Sunitinib, n=8), being treated twice when the tumor reached the size of 14.5±0.5 mm and subsequently sacrificed after 5 days. The protein expressions of ER, PgR and HER2/neu of the tumor tissues were evaluated by using immunohistochemistry analysis. Results: Treatment with sirolimus alone lowered expressions of ER and PgR of breast cancer and reduced tumor size. There was no significant difference of ER and PgR expressions between control and sunitinib treated tumor. Sunitinib treated tumors reduce in diameter after the first treatment, however the diameter increases after the second treatment. Histologically, sunitinib treated tumor did not show any aggressive invasive carcinoma of no special type (NST) histological subtypes. In addition, all NMU-induced tumors are HER2/neu-negative scoring. Conclusion: Sirolimus is neither synergistic nor additive with sunitinib for breast cancer treatment.
Protecting the Herd: Why Pharmacists Matter in Mass Vaccination

Background: The COVID-19 pandemic is ongoing. The unprecedented challenges worldwide implore the urgent development of a safe and effective COVID-19 vaccine. Globally, pharmacists have been delivering important public health services as part of the COVID-19 response. It remains to be seen what role they will play once a vaccine is available. This review examines herd immunity and the potential role of the pharmacy profession in mass vaccination against COVID-19, particularly within the Australian context. Aim: A literature review was conducted to review the global development of COVID-19 vaccines, and the Australian healthcare workforce capability and existing policy for mass vaccination and the potential role of the pharmacist. Method: ScienceDirect, Scopus, The National Centre for Biotechnology Information (NCBI), Wiley Online Library, PubMed, and Google Scholar were used to search for relevant literature using keywords COVID-19, vaccines, immunisation, herd immunity, pandemic, pharmacist and Australian healthcare. Results: A large portion of the literature was journal articles, and information from governmental and international bodies such as the World Health Organisation were often referenced. Over 20 million Australians need to be immunised through vaccination or acquire immunity through natural infection for the country to achieve herd immunity for COVID-19. When examining state and territory pandemic plans, pharmacists are underutilised. Modifying legislation to allow pharmacists to administer approved COVID-19 vaccines will enable a trained and skilled workforce to be deployed to increase the rate of mass vaccination. Conclusion: In preparation for a successful COVID-19 vaccine, the Australian Government must consider various elements in their vaccination policy. This includes the estimated herd immunity threshold, methods of vaccine delivery, vaccine clinic locations, staffing arrangements and training, and strategies for vaccine prioritisation. Pharmacists can and should play a key role in the roll out of mass COVID-19 vaccination.
Reaction kinetics of hydrogen peroxide in teeth for teeth whitening applications

Clinical parameters for dental whitening such as peroxide concentration and treatment time have been empirically derived. However, limited quantitative analyses examine reactivity of hydrogen peroxide on in vivo tooth stains under various catalytic settings. The wide range of possible activators and stains are challenging in creating a standardized tooth model to isolate various effects for clinical applications. This study uses three model systems to determine the effects of heat, light, metal catalysts, and pH on peroxide bleaching. By first using a model chemical stain, alkaline pH levels (7.4), 35°C heat treatment, and 490nm light activation were optimal for increasing overall bleaching efficacy. When the same conditions were applied to bleaching stained bovine teeth using liquid peroxide, only 35°C heat treatment showed catalytic effect, increasing overall luminosity and decreasing yellowness. A final evaluation of the activation parameters on teeth treated with commercially used gel peroxides revealed positive catalytic activity for heat alone. These results, in conjunction with future clinical studies, can provide the basis for optimizing clinical whitening parameters and ultimately control peroxide reactivity to enhance bleaching efficacy while minimizing undesired side-effects.
Effect of TiO2 Nanotube Pore Diameter on Human Mesenchymal Stem Cells and Human Osteoblasts

The pore diameter of uniformly structured nanotubes can significantly change the behaviour of cells. Recent studies demonstrated that the activation of integrins is affected not by only the surface chemistry between the cell-material interfaces, but also by the features of surface nanotopography, including nanotube diameter. While research has been carried out in this area, there has yet to be a single systemic study to date that succinctly compares the response of both human stem cells and osteoblasts to a range of TiO2 nanotube pore diameters using controlled experiments in a single laboratory. In this paper, we investigate the influence of surface nanotopography on cellular behaviour and osseointegrative properties through a systemic study involving human mesenchymal stem cells (hMSCs) and human osteoblasts (HOBs) on TiO2 nanotubes of 20 nm, 50 nm and 100 nm pore diameters using in-vitro assessments. This detailed study demonstrates the interrelationship between cellular behaviour and nanotopography, revealing that a 20 nm nanotube pore diameter is preferred by hMSCs for the induction of osteogenic differentiation, while 50 nm nanotubular structures are favourable by HOBs for osteoblastic maturation.
Fundamental Concepts of Human Thermoregulation and Adaptation to Heat: A Review in the Context of Global Warming

The international community has recognized global warming as an impending catastrophe that poses significant threat to life on earth. In response, the signatories of the Paris Agreement (2015) have committed to limit the increase in global mean temperature to <1.5 °C from pre-industry period, which is defined as 1850–1890. Considering that the protection of human life is a central focus in the Paris Agreement, the naturally endowed properties of the human body to protect itself from environmental extremes should form the core of an integrated and multifaceted solution against global warming. Scholars believe that heat and thermoregulation played important roles in the evolution of life and continue to be a central mechanism that allows humans to explore, labor and live in extreme conditions. However, the international effort against global warming has focused primarily on protecting the environment and on the reduction of greenhouse gases by changing human behavior, industrial practices and government policies, with limited consideration given to the nature and design of the human thermoregulatory system. Global warming is projected to challenge the limits of human thermoregulation, which can be enhanced by complementing innate human thermo-plasticity with the appropriate behavioral changes and technological innovations. Therefore, the primary aim of this review is to discuss the fundamental concepts and physiology of human thermoregulation as the underlying bases for human adaptation to global warming. Potential strategies to extend human tolerance against environmental heat through behavioral adaptations and technological innovations will also be discussed. An important behavioral adaptation postulated by this review is that sleep/wake cycles would gravitate towards a sub-nocturnal pattern, especially for outdoor activities, to avoid the heat in the day. Technologically, the current concept of air conditioning the space in the room would likely steer towards the concept of targeted body surface cooling. The current review was conducted using materials that were derived from PubMed search engine and the personal library of the author. The PubMed search was conducted using combinations of keywords that are related to the theme and topics in the respective sections of the review. The final set of articles selected were considered “state of the art,” based on their contributions to the strength of scientific evidence and novelty in the domain knowledge on human thermoregulation and global warming.
The Incidence of Vibrio Species in Louisiana and Maryland Oysters (Crassostrea Virginica).

x INTRODUCTION. 1 CHAPTER I Identification of Vibrio species in Louisiana oysters— discovery of a new Vibrio group. 7 Introduction. 8 Materials and Methods. 14 Results and Discussion. 34 CHAPTER II The specificity of Vibrio vulnificus anti-flagellar IgG and IgM monoclonal antibody coagglutination reagents. 59 Introduction. 60 Materials and Methods. 65 Results and Discussion. 79 LITERATURE CITED. 103 VITA. 114