Miracle-dz/UniFAR-FTUs huggingface dataset:
BDNF Overexpression in the Ventral Hippocampus Promotes Antidepressant- and Anxiolytic-Like Activity in Serotonin Transporter Knockout Rats

Brain-derived neurotrophic factor is one of the most studied proteins playing a pivotal role in neuroplasticity events and vulnerability and resilience to stress-related disorders. Most importantly, BDNF is decreased in depressive patients, and increased after antidepressant treatment. Additionally, BDNF was found to be reduced in a genetic subset of depression susceptible patients carrying the human polymorphism in the serotonin transporter promoter region (5-HTTLPR). The serotonin knockout rat (SERT-/-) is one of the animal models used to investigate the underlying molecular mechanisms behind the genetic susceptibility to depression in humans. SERT-/- rats present decreased BDNF levels, especially BDNF exon IV, in the prefrontal cortex (PFC) and ventral hippocampus (vHIP), and display anxiety- and depression-like behavior. To investigate whether upregulating BDNF in the vHIP would meliorate the phenotype of SERT-/- rats, we overexpressed BDNF locally into the rat brain by means of stereotaxic surgery and submitted the animals to behavioral challenges, including the sucrose consumption, the open field, and forced swim tests. Additionally, we measured hypothalamus-pituitary-adrenal (HPA)-axis reactivity. The results showed that lentivirus-induced BDNF IV overexpression in the vHIP of SERT-/- rats promoted higher sucrose preference and sucrose intake, on the first day of the sucrose consumption test, indicative for decreased anhedonia-like behavior. Moreover, it decreased immobility time in the forced swim test, suggesting adaptive passive coping. Additionally, BDNF upregulation increased the time spent in the center of a novel environment, implying decreased novel-induced anxiety-like behavior. Finally, it promoted a stronger decrease in plasma corticosterone levels 60 minutes after restraint stress. In conclusion, modulation of BDNF IV levels in the vHIP of SERT-/- rats led to a positive behavioral outcome placing BDNF upregulation in the vHIP as a potential candidate for the development new therapeutic approaches targeting the improvement of depressive symptoms.
A simple and highly efficient method for multi-allelic CRISPR-Cas9 editing in primary cell cultures

Background CRISPR-Cas9-based technologies have revolutionized experimental manipulation of mammalian genomes. None-the-less, limitations of the delivery and efficacy of these technologies restrict their application in primary cells. Aims To create an optimized protocol for penetrant, reproducible, and fast targeted insertiondeletion mutation (indel) formation in cell cultures derived from primary cells, using patient-derived glioblastoma (GBM) stem-like cells (GSCs) and human neural stem/progenitor cells (NSCs) for proof-of-concept experiments. Methods We employed transient nucleofection of Cas9:sgRNA ribonucleoprotein complexes using chemically synthesized 2’-O-methyl 3’phosphorothioate-modified sgRNAs and purified Cas9 protein. Indel frequency and size distribution were measured via computational deconvolution of Sanger sequencing trace data. Western blotting was used to evaluate protein loss. RNA-seq in edited NSCs was used to assess gene expression changes resulting from knockout of tumor suppressors commonly altered in GBM. Results We found that with this optimized technique, we can routinely achieve >90% indel formation in only 3 days, without the need to create clonal lines for simple loss-of-function experiments. We observed near-total protein loss of target genes in cell pools. Additionally, we found that this approach allows for the creation of targeted genomic deletions. We also demonstrated the utility of this method for quickly creating a series of gene knockouts that allow for the study of oncogenic activities. Conclusion Our data suggest that this relatively simple method can be used for highly efficient and fast gene knockout, as well as for targeted genomic deletions, even in hyperdiploid cells (such as GSCs). This represents an extremely useful tool for the cancer research community when wishing to inactivate not only coding genes, but also non-coding RNAs, UTRs, enhancers, and promoters. This method can be readily applied to diverse cell types by varying the nucleofection conditions.
Genetic analysis of SARS-CoV-2 strains collected from North Africa: viral origins and mutational spectrum

In Morocco two waves of SARS-CoV-2 infections have been recorded. The first one occurred from March 02, 2020 with infections mostly imported from Europe and the second one dominated by local infections. At the time of writing, the genetic diversity of Moroccan isolates of SARS-CoV-2 has not yet been reported. The present study aimed to analyze first the genomic variation of the twenty-eight Moroccan strains of SARS-CoV-2 isolated from March 03, 2020 to May 15, 2020, to compare their distributions with twelve other viral genomes from North Africa as well as to identify their possible sources. Our finding revealed 61 mutations in the Moroccan genomes of SARS-CoV-2 compared to the reference sequence Wuhan-Hu-1/2019, of them 23 (37.7%) were present in two or more genomes. Focusing on non-synonymous mutations, 29 (47.54%) were distributed in five genes (ORF1ab, spike, membrane, nucleocapsid and ORF3a) with variable frequencies. The non-structural protein coding regions nsp3-Multi domain and nsp12-RdRp of the ORF1ab gene harbored more mutations, with six for each. The comparison of genetic variants of fourty North African strains revealed that two non-synonymous mutations D614G (in spike) and Q57H (in ORF3a) were common in four countries (Morocco, Tunisia, Algeria and Egypt), with a prevalence of 92.5% (n = 37) and 42.5% (n = 17), respectively, of the total genomes. Phylogenetic analysis showed that the Moroccan and Tunisian SARS-CoV-2 strains were closely related to those from different origins (Asia, Europe, North and South America) and distributed in different distinct subclades. This could indicate different sources of infection with no specific strain dominating yet in in these countries. These results have the potential to lead to new comprehensive investigations combining genomic data, epidemiological information and the clinical characteristics of patients with SARS-CoV-2.
Behavioral and neural fusion of expectation with sensation

Humans perceive expected stimuli faster and more accurately. However, the mechanism behind the integration of expectations with sensory information during perception remains unclear. We investigated the hypothesis that such integration depends on ‘fusion’ — the weighted averaging of different cues informative about stimulus identity. We first trained participants to map a range of tones onto faces spanning a male-female continuum via associative learning. These two features served as expectation and sensory cues to sex, respectively. We then tested specific predictions about the consequences of fusion by manipulating the congruence of these cues in psychophysical and fMRI experiments. Behavioral judgments and patterns of neural activity in auditory association regions revealed fusion of sensory and expectation cues, providing evidence for a precise computational account of how expectations influence perception.
Impact of parasitic lifestyle and different types of centromere organization on chromosome and genome evolution in the plant genus Cuscuta

The parasitic genus Cuscuta (Convolvulaceae) is exceptional among plants with respect to centromere organization, including both monocentric and holocentric chromosomes, and substantial variation in genome size and chromosome number. We investigated 12 species representing the diversity of the genus in a phylogenetic context to reveal the molecular and evolutionary processes leading to diversification of their genomes. We measured genome sizes and investigated karyotypes and centromere organization using molecular cytogenetic techniques. We also performed low-pass whole genome sequencing and comparative analysis of repetitive DNA composition. A remarkable 102-fold variation in genome sizes (342–34,734 Mbp/1C) was detected for monocentric Cuscuta species, while genomes of holocentric species were of moderate sizes (533–1,545 Mbp/1C). The genome size variation was primarily driven by the differential accumulation of repetitive sequences. The transition to holocentric chromosomes in the subgenus Cuscuta was associated with loss of histone H2A phosphorylation and elimination of centromeric retrotransposons. In addition, the basic chromosome number (x) decreased from 15 to 7, presumably due to chromosome fusions. We demonstrated that the transition to holocentricity in Cuscuta was accompanied by significant changes in epigenetic marks, chromosome number and the repetitive DNA sequence composition.
HIF-stabilization prevents delayed fracture healing

The initial phase of fracture healing decides on success of bone regeneration and is characterized by an inflammatory milieu and low oxygen tension (hypoxia). Negative interference with or prolongation of this fine-tuned initiation phase will ultimately lead to a delayed or incomplete healing such as non-unions which then requires an effective and gentle therapeutic intervention. Common reasons include a dysregulated immune response, immunosuppression or a failure in cellular adaptation to the inflammatory hypoxic milieu of the fracture gap and a reduction in vascularizing capacity by environmental noxious agents (e.g. rheumatoid arthritis, smoking). The hypoxia-inducible factor (HIF)-1α is responsible for the cellular adaptation to hypoxia, activating angiogenesis and supporting cell attraction and migration to the fracture gap. Here, we hypothesized that stabilizing HIF-1α could be a cost-effective and low-risk prevention strategy of fracture healing disorders. Therefore, we combined a well-known HIF-stabilizer – deferoxamine (DFO) – and a less known HIF-enhancer – macrophage migration inhibitory factor (MIF) – to synergistically induce improved fracture healing. Stabilization of HIF-1α enhanced calcification and osteogenic differentiation of MSCs in vitro. In vivo, the application of DFO with or without MIF during the initial healing phase accelerated callus mineralization and vessel formation in a clinically relevant mouse-osteotomy-model in a compromised healing setting. Our findings provide support for a promising preventive strategy towards bone healing disorders in patients with a higher risk due to e.g. delayed neovascularization by accelerating fracture healing using DFO and MIF to stabilize HIF-1α.
A fast numerical method for oxygen supply in tissue with complex blood vessel network

Oxygen field evaluation is important in modeling and simulation of many important physiological processes of animals, such as angiogenesis. However, numerical simulation of the oxygen field in animal tissue is usually limited by the unusual coupling of different mechanisms, the nonlinearity of the model, and the complex geometry of refined blood vessel networks. In this work, a fast numerical method is designed for the simulation of oxygen supply in tissue with a large-scale complex vessel network. This method employs an implicit finite-difference scheme to compute the oxygen field. By virtue of an oxygen source distribution technique from vessel center lines to mesh points and a corresponding post-processing technique that eliminate the local numerical error induced by source distribution, square mesh with relatively large mesh sizes can be applied while sufficient numerical accuracy is maintained. The new method has computational complexity which is slightly higher than linear with respect to the number of mesh points and has a convergence order which is slightly lower than second order with respect to the mesh size. As an example, the oxygen field of a tissue irrigated by a blood vessel network with more than four thousand blood vessels can be accurately computed within one minute with our new method. The new method will definitely promote further researches based on evaluation of oxygen field, such as modeling of angiogenesis and pathogenesis of many cardiovascular diseases.
MetaFunPrimer: primer design for targeting genes observed in metagenomes

High throughput primer design is needed to simultaneously design primers for multiple genes of interest, such as a group of functional genes. We have developed MetaFunPrimer, a bioinformatic pipeline to design primer targets for genes of interests, with a prioritization based on ranking the presence of gene targets in references, such as metagenomes. MetaFunPrimer takes inputs of protein and nucleotide sequences for gene targets of interest accompanied by a set of reference metagenomes or genomes for determining genes of interest. Its output is a set of primers that may be used to amplify genes of interest. To demonstrate the usage and benefits of MetaFunPrimer, a total of 78 HT-qPCR primer pairs were designed to target observed ammonia monooxygenase subunit A (amoA) genes of ammonia-oxidizing bacteria (AOB) in 1,550 soil metagenomes. We demonstrate that these primers can significantly improve targeting of amoA-AOB genes in soil metagenomes compared to previously published primers. IMPORTANCE Amplification-based gene characterization allows for sensitive and specific quantification of functional genes. Often, there is a large diversity of genes represented for a function of interest, and multiple primers may be necessary to target associated genes. Current primer design tools are limited to designing primers for only a few genes of interest. MetaFunPrimer allows for high throughput primer design for functional genes of interest and also allows for ranking gene targets by their presence and abundance in environmental datasets. This tool enables high throughput qPCR approaches for characterizing functional genes.
Assessment of genetic diversity in French bean (Phaseolus vulgaris L) based on RAPD marker

RAPD molecular markers were used to evaluate the genetic diversity in the fourteen varieties of French bean ( Phaseolus vulgaris ) of three eco-geographical regions of Bangladesh. Out of the 20 primers only, 6 yielded polymorphic banding patterns. In total, 40 different DNA bands were reproducibly obtained, out of which 28 (70%) were polymorphic. The polymorphisms were scored and used in band-sharing analysis to identify genetic relationships. Cluster analysis based on Jaccard’s similarity coefficient using UPGMA grouped all the 14 genotypes into two major groups. Pair-wise variety comparison of the varieties showed that inter-variety similarity indices for PV004 versus PV005 (98.51) was higher than all other varietals pairs. On the other hand, inter-cultivar similarity index for BARI 01 versus PV009 (59.58) cultivar was lower than all other cultivar pairs. Therefore, the inherent simplicity and efficiency of RAPD analyses will be to facilitate the construction of RAPD-based genetic linkage maps in French bean. Key words: RAPD, French bean, polymorphism.
Brain-Machine Neurofeedback: Robotics or Electrical Stimulation?

Neurotechnology such as brain-machine interfaces (BMI) are currently being investigated as training devices for neurorehabilitation, when active movements are no longer possible. When the hand is paralyzed following a stroke for example, a robotic orthosis, functional electrical stimulation (FES) or their combination may provide movement assistance; i.e., the corresponding sensory and proprioceptive neurofeedback is given contingent to the movement intention or imagination, thereby closing the sensorimotor loop. Controlling these devices may be challenging or even frustrating. Direct comparisons between these two feedback modalities (robotics vs. FES) with regard to the workload they pose for the user are, however, missing. Twenty healthy subjects controlled a BMI by kinesthetic motor imagery of finger extension. Motor imagery-related sensorimotor desynchronization in the EEG beta frequency-band (17–21 Hz) was turned into passive opening of the contralateral hand by a robotic orthosis or FES in a randomized, cross-over block design. Mental demand, physical demand, temporal demand, performance, effort, and frustration level were captured with the NASA Task Load Index (NASA-TLX) questionnaire by comparing these workload components to each other (weights), evaluating them individually (ratings), and estimating the respective combinations (adjusted workload ratings). The findings were compared to the task-related aspects of active hand movement with EMG feedback. Furthermore, both feedback modalities were compared with regard to their BMI performance. Robotic and FES feedback had similar workloads when weighting and rating the different components. For both robotics and FES, mental demand was the most relevant component, and higher than during active movement with EMG feedback. The FES task led to significantly more physical (p = 0.0368) and less temporal demand (p = 0.0403) than the robotic task in the adjusted workload ratings. Notably, the FES task showed a physical demand 2.67 times closer to the EMG task, but a mental demand 6.79 times closer to the robotic task. On average, significantly more onsets were reached during the robotic as compared to the FES task (17.22 onsets, SD = 3.02 vs. 16.46, SD = 2.94 out of 20 opportunities; p = 0.016), even though there were no significant differences between the BMI classification accuracies of the conditions (p = 0.806; CI = −0.027 to −0.034). These findings may inform the design of neurorehabilitation interfaces toward human-centered hardware for a more natural bidirectional interaction and acceptance by the user.
Complement Inhibition in Coronavirus Disease (COVID)-19: A Neglected Therapeutic Option

The fatal outcome from coronavirus disease 2019 (COVID-19) is attributed to terminal respiratory failure secondary to bilateral pneumonia from severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) infection (1–3). However, a subset of younger patients with severe COVID-19 suffer from uncontrolled hyperinflammation and succumb to acute organ failure and cardiac arrest while still being adequately oxygenated (4–7). The “cytokine storm” or “cytokine release syndrome” (CRS) has been implicated in adverse patient outcomes, with interleukin-6 (IL-6) representing a key inflammatory mediator and surrogate marker of CRS (8, 9). The U.S. Food and Drug Administration (FDA) approved the expanded access to a recombinant monoclonal antibody against human IL-6 receptors (tocilizumab), and a randomized controlled phase 3 clinical trial on tocilizumab in adult patients suffering from severe COVID-19 is currently ongoing (10–13). The available empirical treatment modalities include a wide spectrum of off-label indications for antirheumatic agents, including cytokine inhibitors, corticosteroids, intravenous immunoglobulin, and other novel anti-inflammatory molecules (13–15). However, the exact mechanisms of hyperinflammation and hypercoagulation in COVID-19 patients remain enigmatic and poorly understood.
The Effects of Palm Oil on Plasma and Serum Lipid Parameters: A Systematic Review on Animal Intervention Studies

Background: Accumulative evidences on the beneficial effects of palm oil are progressively reported; however, there are still several controversies related to their effects on the risks of cardiovascular disease (CVD). This review explores the effects of palm oil and its liquid fraction namely palm olein, which is commonly used as cooking oil on four lipid parameters; total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C), which play an important role as CVD-related biomarkers. A systematic review of the literature was conducted to identify the relevant studies on palm oil and the lipid parameters specifically focusing on the in-vivo animal model. Methods: A comprehensive search was conducted in Medline via EBSCOhost, Medline via OVID and Scopus. Studies were limited to the English language published between the years of 2000 and 2019. The main inclusion criteria were as follows: (1) Study with in-vivo animal experiments [the animal should be limited to mammals] (2) Study should have evaluated the effects of palm oil or palm olein on plasma or serum lipid parameter (3) Study should have used palm oil or palm olein in the form of pure or refined oil (4) The treatment of palm oil or palm olein was assessed using the following outcomes: plasma or serum TC, TG, HDL-C, and LDL-C concentration (5) Study should have control group and (6) studies on specific fatty acid, fraction enriched tocotrienol and tocopherol, crude palm oil, kernel oil, red palm oil, thermally oxidized palm oil, hydrogenated palm oil, and palm oil or palm olein based products namely margarine, palm milk, butter and cream were excluded. The quality and the risk of bias on the selected studies were assessed using the ARRIVE Guideline and SYRCLE's Risk of Bias tools, respectively. Results: The literature search successfully identified 17 potentially relevant articles, whereby nine of them met the inclusion criteria. All research articles included in this review were in vivo studies comprising seven rats, one hamster and one mice model. Conclusion: Significant positive outcomes were observed in several lipid parameters such as TC and LDL-C. The evidence from this review supported that palm oil and palm olein possess high potential as lipid-lowering agents.
Stimulus-dependent contrast sensitivity asymmetries around the visual field

Asymmetries in visual performance at isoeccentric locations are known as performance fields. At a fixed eccentricity, visual performance is best along the horizontal, intermediate along the lower vertical, and poorest along the upper vertical meridian. These performance fields are pervasive across a range of visual tasks, including those mediated by contrast sensitivity. However, contrast performance fields have not been characterized with a systematic manipulation of stimulus spatial frequency, eccentricity, and size; three parameters that constrain contrast sensitivity. Further, individual differences in performance fields measurements have not been assessed. Here, we use an orientation discrimination task to characterize the pattern of contrast sensitivity across four isoeccentric locations along the cardinal meridians, and to examine whether and how this asymmetry pattern changes with systematic manipulation of stimulus spatial frequency (4 cpd to 8 cpd), eccentricity (4.5° to 9°), and size (3° visual angle to 6° visual angle). Our data demonstrate that contrast sensitivity is highest along the horizontal, intermediate along the lower vertical, and poorest along the upper vertical meridian. This pattern is consistent across stimulus parameter manipulations, even though they cause profound shifts in contrast sensitivity. Eccentricity-dependent decreases in contrast sensitivity can be compensated for by scaling stimulus size alone. Moreover, we find that individual variability in the strength of performance field asymmetries is consistent across conditions. This study is the first to systematically and jointly manipulate, and compare, contrast performance fields across spatial frequency, eccentricity, and size, and to address individual variability in performance fields.