Miracle-dz/UniFAR-FTUs huggingface dataset:
CD8 T cell epitope generation toward the continually mutating SARS-CoV-2 spike protein in genetically diverse human population: Implications for disease control and prevention

The ongoing pandemic of SARS-CoV-2 has brought tremendous crisis on global health care systems and industrial operations that dramatically affect the economic and social life of numerous individuals worldwide. Understanding anti-SARS-CoV-2 immune responses in population with different genetic backgrounds and tracking the viral evolution are crucial for successful vaccine design. In this study, we reported the generation of CD8 T cell epitopes by a total of 80 alleles of three major class I HLAs using NetMHC 4.0 algorithm for the spike protein of SARS-CoV-2, a key antigen that is targeted by both B cells and T cells. We found diverse capacities of S protein specific epitope presentation by different HLA alleles with very limited number of predicted epitopes for HLA-B*2705, HLA-B*4402 and HLA-B*4403 and as high as 132 epitopes for HLA-A*6601. Our analysis of 1000 S protein sequences from field isolates collected globally over the past few months identified three recurrent point mutations including L5F, D614G and G1124V. Differential effects of these mutations on CD8 T cell epitope generation by corresponding HLA alleles were observed. Finally, our multiple alignment analysis indicated the absence of seasonal CoV induced cross-reactive CD8 T cells to drive these mutations. Our findings provided molecular explanations for the observation that individuals with certain HLA alleles such as B*44 are more prone to SARS-CoV-2 infection. Studying anti-S protein specific CD8 T cell immunity in diverse genetic background is critical for better control and prevention of the SARS-CoV-2 pandemic.
DyNeuMo Mk-1: A Fully-Implantable, Motion-Adaptive Neurostimulator with Configurable Response Algorithms

There is growing interest in using adaptive neuro-modulation to provide a more personalized therapy experience that might improve patient outcomes. This paper describes the design of the ‘DyNeuMo Mk-1’, a fully-implantable, motion-adaptive research stimulator that titrates stimulation based on the patient’s movement state (e.g. posture, activity, shock, free-fall). The design leverages off-the-shelf consumer technology that provides inertial sensing with low-power, high reliability and modest cost. We used a three-axis accelerometer and its embedded digital motion processor to enable real-time stimulation adaption based on configurable motion parameters. The algorithm configurability and expanded stimulation parameter space allows for a number of applications to be explored in both central and peripheral applications. The implantable system was designed, prototyped and verified using ISO 13485 design controls, including ISO 14971 risk management techniques to ensure patient safety, while enabling novel algorithms. With the design controls in place, first-in-human research trials are now being prepared to explore the utility of automated motion-adaptive algorithms. The design highlights how consumer electronics technology can be leveraged for efficient and reliable medical device development. The implantable system automatically provides activity- and posture-based responsive stimulation which can be configured by the clinician to optimize therapy. Intended applications include adaptive stimulation for movement disorders, synchronizing stimulation with circadian patterns, and reacting to transient inertial events such as shocks for urinary incontinence.
High-Throughput Discovery and Characterization of Human Transcriptional Effectors

Thousands of proteins localize to the nucleus; however, it remains unclear which contain transcriptional effectors. Here, we develop HT-recruit - a pooled assay where protein libraries are recruited to a reporter, and their transcriptional effects are measured by sequencing. Using this approach, we measure gene silencing and activation for thousands of domains. We find a relationship between repressor function and evolutionary age for the KRAB domains, discover Homeodomain repressor strength is collinear with Hox genetic organization, and identify activities for several Domains of Unknown Function. Deep mutational scanning of the CRISPRi KRAB maps the co-repressor binding surface and identifies substitutions that improve stability/silencing. By tiling 238 proteins, we find repressors as short as 10 amino acids. Finally, we report new activator domains, including a divergent KRAB. Together, these results provide a resource of 600 human proteins containing effectors and demonstrate a scalable strategy for assigning functions to protein domains.
Sex differences in the amplification of responding to an alcohol-predictive cue by an alcohol-associated context

Background In male rats, physical contexts that are associated with alcohol can invigorate responding to a discrete, alcohol-predictive conditioned stimulus (CS), and amplify priming-induced reinstatement. Here, we examined these effects as a function of biological sex. Methods Male and female Long-Evans rats were acclimated to drinking ethanol (EtOH, 15% v/v) in their home cages. Next, they were trained to associate an auditory CS (10 s; white noise; 15 trials per session) with EtOH delivery (0.2 ml per CS; 3.0 ml per session) into a fluid port for oral intake. Training occurred in a distinctive context containing specific visual, olfactory, and tactile stimuli. During alternating sessions rats were exposed to a second context where they did not receive EtOH. At test, CS presentations occurred in both contexts without EtOH delivery. Rats then underwent extinction using repeated unreinforced presentations of the CS in both contexts. An alcohol-primed reinstatement test was then conducted, in which 0.2 ml of EtOH was presented both at the start of the session and during the first CS presentation, after which no EtOH was delivered for the remainder of the session. Results At both test and reinstatement, male rats made significantly more CS port-entries in the context associated with alcohol delivery than in the context in which alcohol was never experienced. Unlike males, female rats made a similar number of CS port-entries at test in both the alcohol context and the neutral context. The reinstatement observed in female rats was not affected by context. Conclusions These findings identify novel sex differences in the capacity of an alcohol-associated context to modulate responding to a discrete, alcohol-predictive cue.
The chromosomal passenger complex establishes chromosome biorientation via two parallel localization pathways

Chromosome biorientation is established by the four-member chromosomal passenger complex (CPC) through phosphorylation of incorrect kinetochore-microtubule attachments. During chromosome alignment, the CPC localizes to the inner centromere, the inner kinetochore and spindle microtubules. Here we show that a small region of the CPC subunit INCENP/Sli15 is required to target the complex to all three of these locations in budding yeast. This region, the SAH, is essential for phosphorylation of outer kinetochore substrates, chromosome segregation, and viability. By restoring the CPC to each of these three locations individually, we found that inner centromere localization is sufficient to establish chromosome biorientation and viability independently of the other two targeting mechanisms. Remarkably, although neither the inner kinetochore nor microtubule binding activities was able to rescue viability individually, they were able to do so when combined. We have therefore identified two parallel pathways by which the CPC can promote chromosome biorientation and proper completion of mitosis.
Nicotinamide mononucleotide (NMN) deamidation by the gut microbiome and evidence for indirect upregulation of the NAD+metabolome

Treatment with nicotinamide mononucleotide (NMN) is a prominent strategy to address the age-related decline in nicotinamide adenine dinucleotide (NAD+) levels for maintaining aspects of late-life health. It is assumed that exogenous NMN is directly incorporated into NAD+in mammals by the canonical recycling pathway, however the need for NAD+is conserved across evolution, including bacteria in the gut microbiome, which can deamidate NMN to nicotinic acid mononucleotide (NaMN). Here, we use strategic isotope labelling studies to demonstrate a role for the gut microbiome in deamidating orally delivered NMN into NaMN prior to its uptake and incorporation in mammals. Microbiome depletion increased the overall abundance of NAD metabolites, suggesting a competition relationship. Strikingly, treatment with labelled NMN increased the production of unlabelled NAD precursors, with a greater than 3-fold increase in endogenous NR levels in the gut of antibiotics treated animals upon labelled NMN treatment. These data suggest that exogenous NMN impacts the NAD metabolome through indirect means, rather than through its direct incorporation, including through the production of endogenous NR via an as-yet unidentified pathway, and demonstrate an important role for the gut microbiome in the assimilation of orally delivered NMN.
Dissociable components of oscillatory activity underly information encoding in human perception

Brain decoding can predict visual perception from non-invasive electrophysiological data by combining information across multiple channels. However, decoding methods typically confound together the multi-faceted and distributed neural processes underlying perception, so it is unclear what specific aspects of the neural computations involved in perception are reflected in this type of macroscale data. Using MEG data recorded while participants viewed a large number of naturalistic images, we analytically separated the brain signal into a slow 1/f drift (<5Hz) and a oscillatory response in the theta frequency band. Combined with a method for capturing between-trial variability in the way stimuli are processed, this analysis revealed that there are at least three dissociable components that contain distinct stimulus-specific information: a 1/f component, reflecting the temporally stable aspect of the stimulus representation; a global phase shift of the theta oscillation, related to differences in the speed of processing between the stimuli; and differential patterns of theta phase across channels, likely related to stimulus-specific computations. We demonstrate that common cognitive interpretations of decoding analysis can be flawed if the multicomponent nature of the signal is ignored, and suggest that, by acknowledging this fact, we can provide a more accurate interpretation of commonly observed phenomena in the study of perception.
Phylogeographic model selection using convolutional neural networks

The field of phylogeography has evolved rapidly in terms of the analytical toolkit to analyze the ever-increasing amounts of genomic data. Despite substantial advances, researchers have not fully explored all potential analytical tools to tackle the challenge posed by the huge size of genomic datasets. For example, deep learning techniques, such as convolutional neural networks (CNNs), widely employed in image and video classification, are largely unexplored for phylogeographic model selection. In non-model organisms, the lack of information about their ecology, natural history, and evolution can lead to uncertainty about which set of demographic models should be considered. Here we investigate the utility of CNNs for assessing a large number of competing phylogeographic models using South American lizards as an example, and approximate Bayesian computation (ABC) to contrast the performance of CNNs. First, we evaluated three demographic scenarios (constant, expansion, and bottleneck) for each of four recovered lineages and found that the overall model accuracy was higher than 98% for all lineages. Next, we evaluated a set of 26 models that accounted for evolutionary relationships, gene flow, and changes in effective population size among these lineages and recovered an overall accuracy of 87%. In contrast, ABC was unable to single out a best fit model among 26 competing models. Finally, we used the CNN model to investigate the evolutionary history of two South American lizards. Our results indicate the presence of hidden genetic diversity, gene flow between non-sister populations, and changes in effective population sizes through time, likely in response to Pleistocene climatic oscillations. Our results demonstrate that CNNs can be easily and usefully incorporated into the phylogeographer’s toolkit.
A visual pathway for skylight polarization processing in Drosophila

Many insects use patterns of polarized light in the sky to orient and navigate. Here we functionally characterize neural circuitry in the fruit fly, Drosophila melanogaster, that conveys polarized light signals from the eye to the central complex, a brain region essential for the fly’s sense of direction. Neurons tuned to the angle of polarization of ultraviolet light are found throughout the anterior visual pathway, connecting the optic lobes with the central complex via the anterior optic tubercle and bulb, in a homologous organization to the ‘sky compass’ pathways described in other insects. We detail how a consistent, map-like organization of neural tunings in the peripheral visual system is transformed into a reduced representation suited to flexible processing in the central brain. This study identifies computational motifs of the transformation, enabling mechanistic comparisons of multisensory integration and central processing for navigation in the brains of insects.
Human trans-editing enzyme displays tRNA acceptor-stem specificity and relaxed amino acid selectivity

Accurate translation of genetic information into proteins is vital for cell sustainability. ProXp-ala prevents proteome-wide Pro-to-Ala mutations by hydrolyzing misacylated Ala-tRNAPro, which is synthesized by prolyl-tRNA synthetase. Bacterial ProXp-ala was previously shown to combine a size-based exclusion mechanism with conformational and chemical selection for the recognition of the alanyl moiety, whereas tRNAPro is selected via recognition of tRNA acceptor-stem elements G72 and A73. The identity of these critical bases changed during evolution with eukaryotic cytosolic tRNAPro possessing a cytosine at the corresponding positions. The mechanism by which eukaryotic ProXp-ala adapted to these changes remains unknown. In this work, recognition of the aminoacyl moiety and tRNA acceptor stem by human (Homo sapiens, or Hs) ProXp-ala was examined. Enzymatic assays revealed that Hs ProXp-ala requires C72 and C73 in the context of Hs cytosolic tRNAPro for efficient deacylation of mischarged Ala-tRNAPro. The strong dependence on these bases prevents cross-species deacylation of bacterial Ala-tRNAPro or of Hs mitochondrial Ala-tRNAPro by the human enzyme. Similar to the bacterial enzyme, Hs ProXp-ala showed strong tRNA acceptor-stem recognition but differed in its amino acid specificity profile relative to bacterial ProXp-ala. Changes at conserved residues in both the Hs and bacterial ProXp-ala substrate-binding pockets modulated this specificity. These results illustrate how the mechanism of substrate selection diverged during the evolution of the ProXp-ala family, providing the first example of a trans-editing domain whose specificity evolved to adapt to changes in its tRNA substrate.
Effect of pre-treatment on quality of minimally processed culinary banana cv. Kachkal (ABB group)

A study was undertaken to assess the suitable pre-treatment for maintaining quality of minimally processed culinary banana. The experiment was laid out in factorial CRD with nine treatments replicated three times. The minimally processed banana slices were subjected to pretreatments like Calcium chloride (2%); Calcium chloride (3%); Ascorbic acid (2%); Ascorbic acid (3%); Citric acid (2%); Citric acid (3%); KMS (2%); KMS (3%) and distilled water (control), packed in areca nut leaf sheath and polystyrene packages which were wrapped with cling film and stored in refrigerated conditions till it remains in good condition. The TSS, acidity, ascorbic acid, calcium, starch and phenols showed decreasing trend with the increase in storage period. However, TSS retention was more in KMS treated samples (5%)) with least browning, while higher ascorbic acid (11.37mg/100g) and phenol (17.04mg/100 g) contents were observed in ascorbic acid treated samples. Similarly, citric acid treatment showed higher acidity (0.168%) in the samples. Maximum starch (0.35%) and calcium (10meq/100g) contents were recorded in calcium chloride treated samples. The maximum degree of browning was observed in control as compared to other treatments and the least browning was observed in the samples treated with KMS. Among the treatments, highest PLW was observed in control and minimum in ascorbic acid treated samples. At the end of the storage period, overall score obtained for the minimally processed cooked banana was highest in KMS treated samples. Thus, it might be concluded from the study that minimally processed culinary banana pre-treated with KMS (2% or 3%) could be stored in refrigerated condition up to maximum of 10 days without quality deterioration as compared to other treatment.
Equilibrium and Thermodynamic Studies on Adsorption of Hexavalent Chromium from Aqueous Solution onto Low Cost Activated Carbon

The removal of hexavalent chromium [Cr(VI)] is a challenging task due to its acute toxicity even at low concentration. In the present study, a low-cost activated carbon (LAC) was prepared from desert date seed shell by chemical activation with H3PO4 and utilized for the removal of hexavalent chromium from aqueous solution. Batch experiments were conducted to investigate the influence of operating variables such as pH, contact time, adsorbent dosage, initial concentration, co-existing ions and temperature. The amount of Cr(VI) adsorbed was found to vary with solution pH and maximum adsorption was observed at a pH value of 2.0. The extent of chromium uptake (mg g) was found to increase with increase in initial concentration and contact time. The applicability of the four isotherm models for the present equilibrium data follows the sequence: Freundlich > Temkin > Langmuir > Dubinin-Radushkevich. The mean free energy from the Duninin-Radushkevic isotherm model hinted that the adsorption of Cr(VI) onto the adsorbent surface follows physisorption mechanism. Thermodynamic parameters related to adsorption, Gibbs free energy change (∆G°), enthalpy change (∆H°), entropy change (∆S°), were also calculated and the negative value of ∆H° indicates the exothermic nature of the adsorption process. The considerable adsorption capacity of 99.09 mg g is a signifier of the suitability of the prepared adsorbent for commercial application. The findings implicated that the adsorbent can be employed in the treatment of Cr-bearing water and wastewater.
Fraxinus parryi, nom. nov., of NW Baja California, Mexico

The common ash of NW Baja California is usually called Fraxinus trifoliata, as in Wiggins' (1980) flora of Baja California. That name is a misspelling of F. trifoliolata, which is a later homonym of F. trifoliolata W. W. Smith (1916). The Baja Californian ash is therefore renamed Fraxinus parryi. It has also been misidentified as F. jonesii. The common name is "crucecilla". This ash barely extends into San Diego County, California.
Grape and Wine Proteins of White Wine Varietals

To study the effect on stability of the various protein fractions present in wines a technique for purification and fractionation of the proteins was developed. This involved dialysis, gel filtration, and gel electrophoresis. Fermentation and heat had somewhat similar effects but had different mechanisms in that they generally resulted in a decrease in protein content, a decided shift in the amount of protein in the various fractions, and occasionally the appearance of entirely new fractions. Fermentation had one effect not noted in the heat treatment: an occasional increase in total protein content as determined by the Diemair and Maier procedure. This increase is due to peptides released by the yeast during fermentation. One interesting result was the finding that the yeast contributed no soluble heatunstable proteins to the wine. Ion-exchange chromatography on DEAE-cellulose produced four fractions, one of which was stable to heat. Therefore, determination of total protein as a measure of protein stability of a wine is valueless since the individual proteins behave differently in their sensitivity to heat denaturation.
Korean and Japanese Isolates of Viral Hemorrhagic Septicemia Virus from Olive Flounder are Pathogenic to Rainbow Trout Fry

We evaluated the pathogenicity of Korean and Japanese isolates of viral hemorrhagic septicemia virus (VHSV: genotype IVa) from olive flounder Paralichthys olivaceus using rainbow trout Oncorhynchus mykiss fry. The cumulative mortalities of fish challenged with FYeosu05 (Korean) and Obama25 (Japanese) isolates at 106.5 TCID50/fish were 64 and 48%, respectively. No mortality was observed among the fish challenged with either of the isolates at 105.5 TCID50/fish, or in mock-challenged fish. The affected fish exhibited darkening of the body, an expanded abdomen, pale gills, an enlarged spleen, and diffuse necrosis in the splenic and interstitial hematopoietic tissues. We re-isolated VHSV from all mortalities using cell culture and confirmed their presence by reverse transcription loop-mediated isothermal amplification (RT-LAMP). We thus concluded that Asian VHSV isolates from olive flounder are pathogenic to rainbow trout fry, although with low virulence.
A qualitative study exploring adolescents' experience of brief behavioural activation for depression and its impact on the symptom of anhedonia.

OBJECTIVES Anhedonia, the loss of interest and pleasure, is a core symptom of depression and is associated with deficits in reward processing. Behavioural Activation for depression may address this symptom due to its focus on identifying and increasing intrinsically rewarding activities. DESIGN This was a qualitative study employing reflexive thematic analysis (TA). METHODS Participants were eight treatment-seeking adolescents with a recent primary diagnosis of depression who had received eight sessions of Brief Behavioural Activation. Qualitative semi-structured interviews were conducted after treatment was completed. RESULTS Three main themes emerged: (1) connecting, reviewing, and taking action: 'focus on getting better rather than what you're feeling'; (2) struggles, restrictors, and motivators: 'it seemed really unachievable'; and (3) feeling, acting, or seeing things differently: 'looking forwards in a more healthy way'. CONCLUSIONS Both specific Brief Behavioural Activation strategies (e.g., connecting with values) and more generic therapeutic strategies (e.g., self-monitoring) may be helpful in treating the symptom of anhedonia in adolescent depression. Motivational aspects of anhedonia, as well as anxiety, fatigue, and academic pressures act as potential barriers to recovery. This highlights the need for psychological treatments for adolescent depression to include explicit and targeted strategies to enhance motivation. PRACTITIONER POINTS Young people reported that specific Brief Behavioural Activation strategies (e.g., connecting with values) and more generic therapeutic techniques (e.g., self-monitoring) had a role in treating anhedonia. Barriers to engaging in Brief BA included: motivational anhedonia, fatigue, and academic demands.