Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessment of Lactic Acid Bacteria Isolated from Chakka : An Indian Fermented Dairy Product

Objective: The objective of this study was to isolate, identify and characterize the lactic acid bacteria (LAB) from a domestic food (Chakka) and to evaluate their properties for application as starter cultures in fermented dairy products.Methods: LAB were isolated using standard MRS/M17 media and characterized phenotypically and identified by 16SrDNA sequencing and Whole Genome Sequencing and their evolutionary relationships were plotted using MEGA X. Culture conditions were optimized in a shaker incubator and different media formulations using Skimmed Milk Powder, Yeast Extract, Glucose, and Casein Enzyme Hydrolysate were designed and tested. Subsequently, the isolates were grown in a 1 L bioreactor under controlled conditions to study their total viable count and the growth rates. Lactic acid production was quantified in MRS and laboratory formulated M2 media under optimized growth conditions. The recovery, quantification and total yield of exopolysaccharides (EPS) produced by the isolated strains was also done.Results: The isolates were grouped as bacilli (C2, C4, C5, C12, and P1) and cocci(Q1, and Q2). The bacilli were identified as subspecies of Lactobacillus delbrueckii and cocci were identified as Streptococcus thermophilus. M2 media was found to be a viable alternative to standard media. Bacilli and cocci were found to produce L and D-lactic acid, respectively, and bacilli were better lactic acid producers than cocci. Similarly, bacilli were found to be better EPS producers in M2 media.Conclusion: The results suggest of this study suggest that strains isolated from Chakka could be potential starter cultures for use in yogurt manufacturing. The critical understanding about the metabolism of these LAB would be helpful for the maintenance of strains and their exploitation as starter cultures.
Regeneration of dorsal spinal cord neurons after injury via in situ NeuroD1-mediated astrocyte-to-neuron conversion

Spinal cord injury (SCI) often leads to impaired motor and sensory functions, partially because the injury-induced neuronal loss cannot be easily replenished through endogenous mechanisms. In vivo neuronal reprogramming has emerged as a novel technology to regenerate neurons from endogenous glial cells by forced expression of neurogenic transcription factors. We have previously demonstrated successful astrocyte-to-neuron conversion in mouse brains with injury or Alzheimer’s disease by overexpressing a single neural transcription factor NeuroD1 via retroviruses. Here we demonstrate regeneration of dorsal spinal cord neurons from reactive astrocytes after SCI via adeno-associated virus (AAV), a more clinically relevant gene delivery system. We find that NeuroD1 converts reactive astrocytes into neurons in the dorsal horn of stab-injured spinal cord with high efficiency (∼95%). Interestingly, NeuroD1-converted neurons in the dorsal horn mostly acquire glutamatergic neuronal subtype, expressing spinal cord-specific markers such as Tlx3 but not brain-specific markers such as Tbr1, suggesting that the astrocytic lineage and local microenvironment affect the cell fate of conversion. Electrophysiological recordings show that the NeuroD1-converted neurons can functionally mature and integrate into local spinal cord circuitry by displaying repetitive action potentials and spontaneous synaptic responses. We further show that NeuroD1-mediated neuronal conversion can occur in the contusive SCI model, allowing future studies of evaluating this reprogramming technology for functional recovery after SCI. In conclusion, this study may suggest a paradigm shift for spinal cord repair using in vivo astrocyte-to-neuron conversion technology to generate functional neurons in the grey matter.
The antimalarial natural product salinipostin A identifies essential α/β serine hydrolases involved in lipid metabolism in P. falciparum parasites

Salinipostin A (Sal A) is a potent antimalarial marine natural product with an undefined mechanism of action. Using a Sal A-derived activity-based probe, we identify its targets in the Plasmodium falciparum parasite. All of the identified proteins contain α/β serine hydrolase domains, and several are essential for parasite growth. One of the essential targets displays high homology to human monoacylglycerol lipase (MAGL) and is able to process lipid esters including a MAGL acylglyceride substrate. This Sal A target is inhibited by the anti-obesity drug Orlistat, which disrupts lipid metabolism and produces disorganized and stalled schizonts similar to Sal A. Resistance selections yielded parasites that showed only minor reductions in sensitivity and that acquired mutations in a protein linked to drug resistance in Toxoplasma gondii. This inability to evolve efficient resistance mechanisms combined with the non-essentiality of human homologs makes the serine hydrolases identified here promising antimalarial targets.
Evaluating Bayesian stable isotope mixing models of wild animal diet and the effects of trophic discrimination factors and informative priors

Ecologists quantify animal diets using direct and indirect methods, including analysis of faeces, pellets, prey items and gut contents. For stable isotope analyses of diet, Bayesian stable isotope mixing models (BSIMMs) are increasingly used to infer the relative importance of food sources to consumers. Although a powerful approach, it has been hard to test BSIMM performance for wild animals because precise, direct dietary data are difficult to collect. We evaluated the performance of BSIMMs in quantifying animal diets when using δ13C and δ15N stable isotope ratios from the feathers and red blood cells of common buzzard Buteo buteo chicks. We analysed mixing model outcomes with various trophic discrimination factors (TDFs), with and without informative priors, and compared these to direct observations of prey provisioned to chicks by adults at nests, using remote cameras. Although BSIMMs with different TDFs varied markedly in their performance, the statistical package SIDER generated TDFs for both feathers and blood that resulted in model outputs that accorded well with direct observations of prey provisioning. Using feather TDFs derived from captive peregrines Falco peregrinus resulted in estimates of diet composition that were also similar to provisioned prey, although blood TDFs from the same study performed poorly. The inclusion of informative priors, based on conventional analysis of pellet and prey remains, markedly reduced model performance. BSIMMs can provide accurate assessments of diet in wild animals. TDF estimates from the SIDER package performed well. The inclusion of informative priors from conventional methods in Bayesian mixing models can transfer biases into model outcomes, leading to erroneous results.
Platinum chemotherapy induces lymphangiogenesis to prime tissues for tumor metastasis

Chemotherapy has been used to inhibit cancer growth for decades, but emerging evidence shows it can affect the tumor stroma unintentionally promoting cancer malignancy. After treatment of primary tumors, remaining drug drains via lymphatics. Though all drugs interact with the lymphatics, we know little of their impact on them. Here, we show a previously unknown effect of platinums, a widely used chemotherapeutic, to directly induce systemic VEGFR3-dependent lymphangiogenesis. These changes are dose-dependent, long-lasting, and occur in healthy and cancerous tissue in multiple mouse models of breast cancer. We saw similar effects in human ovarian and breast cancer patients whose treatment regimens included platinums. Carboplatin treatment results in lymphatic hyperplasia and secretion of pro-chemotactic factors in lymph nodes. Carboplatin treatment of healthy mice prior to mammary tumor inoculation increases cancer metastasis. These findings have broad-reaching implications for cancer patients receiving platinums and support the inclusion of anti-VEGFR3 therapy into treatment regimens.Platinum chemotherapy induces lymphangiogenesis priming tissues for metastasis of breast cancer. Inhibition of VEGFR3 via antibody blockade can reverse these effects.
Inferring foraging locations and water masses preferred by spotted seals Phoca largha and bearded seals Erignathus barbatus

: Spotted seals Phoca largha and bearded seals Erignathus barbatus are ice-associated seals that have overlapping range in the Beaufort, Chukchi, and Bering Seas, but have different foraging ecologies. The link between foraging behaviour and specific oceanographic variables is not well understood for these species, nor is the influence of different dive metrics when modelling their foraging behaviour. To explore the value of different dive metrics to estimate foraging behaviour, and the relationships between foraging and water bodies/oceanographic variables, we tagged 3 spotted seals and 2 bearded seals with satellite telemetry tags that recorded movement and oceanographic data. To infer foraging behaviour, we included dive metrics in Bayesian state-space switching models, and found that models that included depth-corrected dive duration were more parsimonious than models that included dive shape. The addition of vertical movements to the model enabled better determination of foraging areas (inferred from area-restricted searches) and provided insights into the probabilities of switching between foraging and transiting behaviours. The collection of oceanographic data in situ at a scale relevant to seals helped identify water masses, and how they were used, and potential oceanographic cues used by seals to identify foraging locations. Fine-scale spatiotemporal clustering analysis revealed spotted and bearded seal foraging ‘hotspots’ in the Chukchi and Bering Seas that overlap with hotspots identified for other marine mammals and marine birds.
Metabolic remodeling by TIGAR overexpression is a therapeutic target in esophageal squamous-cell carcinoma

Whole-genome sequencing has identified many amplified genes in esophageal squamous-cell carcinoma (ESCC); however, their roles and the clinical relevance have yet elucidated. Here we show TP53-induced glycolysis and apoptosis regulator (TIGAR) is a major player in ESCC progression and chemoresistance. TIGAR reprograms glucose metabolism from glycolysis to the glutamine pathway through AMP-activated kinase, and its overexpression is correlated with poor disease outcomes. Tigar knockout mice have reduced ESCC growth and tumor burden. Treatment of TIGAR-overexpressed ESCC cell xenografts and patient-derived tumor xenografts in mice with combination of glutaminase inhibitor and chemotherapeutic agents achieves significant more efficacy than chemotherapy alone. These findings shed light on an important role of TIGAR in ESCC and provide evidence for targeted treatment of TIGAR-overexpressed ESCC. Significance Effective and target therapies are required for ESCC, one of the most common types of digestive OR cancer. Little has been known about the biology of ESCC progression or potential molecular targets OR for treatment. Whole-genome sequencing and RNA sequencing studies in ESCC have identified OR many recurrent copy number gain genes; however, the roles and druggable relevance of these OR genes remains poorly understood. Herein we demonstrate that TIGAR overexpression leads to OR metabolic remodeling, promoting ESCC progression and resistance to chemotherapeutic agents. OR Inhibiting the glutamine pathway significantly represses TIGAR-overexpressing ESCC growth and OR enhances tumor cell sensitization to cytotoxic agents. These findings might provide the rationale OR for clinical trials testing glutamine pathway inhibitors in combination with chemotherapy in OR TIGAR-expressing ESCC.
Testing gene-environment interactions for rare and/or common variants in sequencing association studies

The risk of many complex diseases is determined by a complex interplay of genetic and environmental factors. Advanced next generation sequencing technology makes identification of gene-environment (GE) interactions for both common and rare variants possible. However, most existing methods focus on testing the main effects of common and/or rare genetic variants. There are limited methods developed to test the effects of GE interactions for rare variants only or rare and common variants simultaneously. In this study, we develop novel approaches to test the effects of GE interactions of rare and/or common risk, and/or protective variants in sequencing association studies. We propose two approaches: 1) testing the effects of an optimally weighted combination of GE interactions for rare variants (TOW-GE); 2) testing the effects of a weighted combination of GE interactions for both rare and common variants (variable weight TOW-GE, VW-TOW-GE). Extensive simulation studies based on the Genetic Analysis Workshop 17 data show that the type I error rates of the proposed methods are well controlled. Compared to the existing interaction sequence kernel association test (ISKAT), TOW-GE is more powerful when there are GE interactions’ effects for rare risk and/or protective variants; VW-TOW-GE is more powerful when there are GE interactions’ effects for both rare and common risk and protective variants. Both TOW-GE and VW-TOW-GE are robust to the directions of effects of causal GE interactions. We demonstrate the applications of TOW-GE and VW-TOW-GE using an imputed data from the COPDGene Study.
North Atlantic right whale (Eubalaena glacialis) and its food: (II) interannual variations in biomass of Calanus spp. on western North Atlantic shelves

The North Atlantic right whale (NARW), Eubalaena glacialis, feeds on zooplankton, particularly copepods of the genus Calanus. We quantified interannual variation in anomalies of abundance and biomass of Calanus spp. and near-surface and near-bottom ocean temperature and salinity from 19 subregions spanning the Gulf of Maine–Georges Bank (GoM–GBK), Scotian Shelf (SS), Gulf of St. Lawrence (GSL) and Newfoundland and Labrador Shelves. We analyzed time series from 1977 to 2016 in GoM–GBK, 1982 to 2016 in southwest GSL and 1999 to 2016 in remaining areas. Calanus finmarchicus dominated abundance and biomass, except in the GSL where Calanus hyperboreus was abundant. The biomass of Calanus spp. declined in many subregions over years 1999–2016 and was negatively correlated with sea surface temperature in GoM–GBK and on the SS. We detected ``regime shifts” to lower biomass of Calanus spp. in the GoM–GBK in 2010 and on the SS in 2011. In the GoM–GBK, shifts to lower biomass of C. finmarchicus coincided with shifts to warmer ocean temperature and with published reports of changes in spatial distribution and reduced calving rate of NARW. We hypothesize that warming has negatively impacted population levels of Calanus spp. near their southern range limit, reducing the availability of prey to NARW.
Annulohypoxylon sp. FPYF3050 produces volatile organic compounds against the pine wood nematode, Bursaphelenchus xylophilus

Natural volatiles released by the fungus, Annulohypoxylon sp. FPYF3050, were evaluated against the pine wood nematode (PWN), Bursaphelenchus xylophilus. Our results showed that volatile organic compounds (VOCs) caused 64.1 and 58.4% mortality of second-stage juveniles (J2) and mixed-stages (eggs, J2, third- and fourth-stage juveniles, and adults) of populations of PWN, but no inhibitive effects were detected on nematode eggs in the experiment. Analysis of the gases within the Petri plate by gas chromatography-mass spectrometry (GC-MS) showed a yield of an unique volatile with dominant 1,8-cineole in 77.4% relative area (RA) after 72 h treatment of nematodes with Annulohypoxylon sp. FPYF3050 and Botrytis cinerea. The commercial 1,8-cineole at concentrations of 2, 5, 10 and 15 μl ml−1 was applied to examine nematicidal activity. The results showed that 1,8-cineole had a 40-100% inhibition on the nematode eggs during 48 h treatment, more than 82.9% mortality of J2 after 24 h, 48 h and 96 h, and 18.7-91.9% mortality of the mixed-stage population, depending on the period after exposure. This result indicates that 1,8-cineole in the volatile gas emissions of Annulohypoxylon sp. FPYF3050 may play a crucial inhibitory effect on the pine wood nematode The nematicidal volatile gas from fungi may provide a useful biocontrol agent for controlling B. xylophilus.
LAMBDR: Long-range amplification and Nanopore sequencing of the Mycobacterium bovis direct-repeat region. A novel method for in-silico spoligotyping of M. bovis directly from badger faeces

The environment is an overlooked source of Mycobacterium bovis, the causative agent of bovine TB. Long read, end to end sequencing of variable repeat regions across the M. bovis genome was evaluated as a method of acquiring rapid strain level resolution directly from environmental samples. Eight samples of M. bovis, two BCG strains (Danish and Pasteur), and a single M. tuberculosis type culture (NCTC 13144) were used to generate data for this method. Long range PCR amplification of the direct repeat region was used to synthesize ∼5kb template DNA for onward sequence analysis. This has permitted culture independent identification of M. bovis spoligotypes present in the environment. Sequence level analysis of the direct repeat region showed that spoligotyping may underestimate strain diversity due to the inability to identify both SNPs and primer binding mutations using a biotinylated hybridisation approach.
The Draft Genome of Deladenus siricidicola

Abstract The nematode Deladenus siricidicola is used as biological control agent against the invasive woodwasp Sirex noctilio, a serious invasive pest of Pinus plantations globally. The draft genome of this ecologically and economically important entomoparasitic nematode was determined.
An artistic approach to neurofeedback for emotion regulation

Neurofeedback has been shown to be a promising tool for learning to regulate one’s own emotions in healthy populations and in neuropsychiatric disorders. While it has been suggested that neurofeedback performance improves when sensory feedback is related to the pathology under consideration, it is still difficult to represent in real time a proper feedback representative of our emotional state. Since emotion is a central part of people’s dealings with artworks, we have initiated a collaboration between neuroscientists and artists to develop a visual representation of emotions that can be used in neurofeedback experiences. As a result of this collaboration, emotions were represented as particles, moving in a white sphere according to valence and arousal levels. In this study, several possibilities for particle control were explored: direction of particles, their concentration in a specific place, or their gravity. 107 participants evaluated these performances, either in laboratory condition or at various scientific and artistic events. At the end of the experiment, questionnaires were distributed to participants who were asked to indicate on scales ranging from 0 to 5 how artistic the different representations were and could be used as a clinical activity, whether they thought they had successfully controlled the particles during the neurofeedback exercise, and whether they had appreciated the experience. We found that influing on the direction and concentration of particles was considered the most artistic with an average score around 3/5. 47% of the participants considered the concentration of particles as artistic. In addition, although this is not the purpose of this study, we found that participants could significantly control the direction of particles during this session. These encouraging results constitute a first step before evaluating the effectiveness of our emotional neurofeedback over several sessions in healthy, then pathological populations.
Incorporation of Internet Databases into Pharmacotherapy Coursework

The Internet is an international computer network that allows communication among institutions and individuals. The World-Wide Web (WWW) is the name of the system developed to facilitate the exploration and retrieval of information on the Internet. The availability of the WWW to access the Internet appears to be a major advance in communication and information technology. The purpose of this project was to assess and enhance student ability to access appropriate pharmacotherapy data using the Internet and to evaluate selected Internet sites as resources for our Pharmacotherapy of Neoplastic Diseases course. Students were assigned activities that required the use of Internet databases. The project evaluation administered at the conclusion of the course asked students to characterize their prior experience with the Internet and to respond to evaluative statements about the Internet assignments. These responses revealed that the class had very limited exposure to Internet sites dealing with biomedical sciences prior to this class. In addition, students consistently rated Internet assignments as positive learning experiences. Continued incorporation of Internet assignments into the curriculum of this course is planned.
MTHFR gene A1298C polymorphism and Alzheimer’s disease susceptibility

Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme involved in homocysteine/methionone metabolism. It catalyzes the conversion of 5,10methlenetetrahydrofolate in to 5methyltetrahydrofolate. A number of studies have examined the association of MTHFR A1298C polymorphism as risk factor for Alzheimer’s disease (AD), but the results were contradictory. To clarify the influence of MTHFR A1298C polymorphism on Alzheimer’s disease (AD), a meta-analysis of ten case-control studies was carried out. Four electronic databases were searched up to August, 2019 for suitable articles. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to evaluate the association. All statistical analyses were performed by MetaAnalyst program. The results of meta-analysis suggested that except allele contrast model, A1298C polymorphism is not risk for Alzheimer’s disease using overall comparisons in three genetic models (C vs. A: OR= 1.26, 95%CI= 0.912-1.76, p= 0.04; CC+AC vs. AA: OR= 1.43; 95%CI= 0.85-2.44; p=0.05; CC vs. AA: OR= 1.16, 95%CI= .88-1.55, p= 0.51; AC vs. AA: 1.55; 95%CI= 0.81-2.93,p=0.07). Publication bias was absent in all five genetic models. In conclusion, results of present meta-analysis showed no significant association between MTHFR A1298C polymorphism and AD risk.