Miracle-dz/UniFAR-FTUs huggingface dataset:
A sodium-dependent communication pathway across class A G-protein coupled receptors

G-protein-coupled receptors (GPCRs) are membrane proteins that transmit signals across the cell membrane by activating intracellular effector proteins in response to extracellular ligand interaction. A large majority of GPCRs are characterized by an evolutionarily conserved activation mechanism, involving the reorientation of helices and residue side chains, rearrangement of an internal hydrogen bonding network, and the expulsion of a sodium ion from an ionizable binding site in the transmembrane region. However, how sodium, internal water, and protein residues interplay to determine the overall receptor state remains elusive. Here, we employed information theory to trace signal transmission pathways through the receptors and identify their concerted response to sodium binding and protonation. Applying our methodology, ‘State Specific Information’, to all-atom molecular dynamics simulations of pharmaceutically important GPCRs, we discovered a conserved communication pathway that enabled the exchange of information between the sodium binding site and the distal G-protein binding region, connecting the most highly conserved ionizable residues in the receptors. Reorientation of internal water molecules was essential for the coupling of conformational state changes of protein residues along this pathway, which ultimately reconfigured the conformation of the G-protein binding site. The presence of sodium disconnected this pathway. By inhibiting protonation, sodium was found to serve as a master switch that determined the molecular state of GPCRs during the receptors’ transition to activation.
Novel inhibitors of E. coli lipoprotein diacylglyceryl transferase are insensitive to resistance caused by lpp deletion

Lipoprotein diacylglyceryl transferase (Lgt) catalyzes the first step in the biogenesis of Gram-negative bacterial lipoproteins which play crucial roles in bacterial growth and pathogenesis. We demonstrate that Lgt depletion in a clinical uropathogenic Escherichia coli strain leads to permeabilization of the outer membrane and increased sensitivity to serum killing and antibiotics. Importantly, we identify the first ever described Lgt inhibitors that potently inhibit Lgt biochemical activity in vitro and are bactericidal against wild-type Acinetobacter baumannii and E. coli strains. Unlike inhibition of other steps in lipoprotein biosynthesis, deletion of the major outer membrane lipoprotein, lpp, is not sufficient to rescue growth after Lgt depletion or provide resistance to Lgt inhibitors. Our data validate Lgt as a novel druggable antibacterial target and suggest that inhibition of Lgt may not be sensitive to one of the most common resistance mechanisms that invalidate inhibitors of downstream steps of bacterial lipoprotein biosynthesis and transport.
Environmental flexibility does not explain metabolic robustness

Cells show remarkable resilience against genetic and environmental perturbations. However, its evolutionary origin remains obscure. In order to leverage methods of systems biology for examining cellular robustness, a computationally accessible way of quantification is needed. Here, we present an unbiased metric of structural robustness in genome-scale metabolic models based on concepts prevalent in reliability engineering and fault analysis. The probability of failure (PoF) is defined as the (weighted) portion of all possible combinations of loss-of-function mutations that disable network functionality. It can be exactly determined if all essential reactions, synthetic lethal pairs of reactions, synthetic lethal triplets of reactions etc. are known. In theory, these minimal cut sets (MCSs) can be calculated for any network, but for large models the problem remains computationally intractable. Herein, we demonstrate that even at the genome scale only the lowest-cardinality MCSs are required to efficiently approximate the PoF with reasonable accuracy. Building on an improved theoretical understanding, we analysed the robustness of 489 E. coli, Shigella, Salmonella, and fungal genome-scale metabolic models (GSMMs). In contrast to the popular “congruence theory”, which explains the origin of genetic robustness as a byproduct of selection for environmental flexibility, we found no correlation between network robustness and the diversity of growth-supporting environments. On the contrary, our analysis indicates that amino acid synthesis rather than carbon metabolism dominates metabolic robustness.
Development of a Species Diagnostic Molecular Tool for an Invasive Pest, Mythimna loreyi, Using LAMP

The Mythimna loreyi (Duponchel) is one of the well-known a noctuid pest in Africa, Australia, and many Asian countries. This species has recently emerged as an invasive pest of some cereal crops in Korea. However, it is extremely difficult to identify the morphologically similar species, Mythimna separate, which occur at the cornfield in the larvae stage. Therefore, it is hard to accurately investigate invasive pests. In this study, the LAMP assay was developed for rapid, simple, effective species identification. By analyzing the mt genome, the species-specific sequence was found at the coding region of the NADH dehydrogenase subunit 5 gene. Based on this unique sequence, four LAMP primers and two loop primers were designed. The F3 and B3 primers were able to diagnose species-specific in general and multiplex PCR, and specifically reacted within the inner primers in LAMP assay. The optimal incubation condition of the LAMP assay was 61 □ for 60 minutes with four LAMP primers, though additional loop primer, BF and LF, did not significantly shorten the amplification time. The broad range of DNA concentration was workable in LAMP assay, in which the minimum detectable DNA concentration was 100 pg. Here, DNA releasing method was applied which took five minutes of incubation at 95 □ without the DNA extraction process, and only some pieces of tissue from larvae and adult samples were needed. The incidence of invasive pests is gradually diversifying, therefore, this simple and accurate LAMP assay possibly applied in the intensive field monitoring for the invasive pests and integrated management of Mythimna loreyi.
Distribution, genetic differentiation, and assortative mating of distinct morphotypes of Diaulula sandiegensis, a nudibranch with high dispersal potential

ii ACKNOWLEDGEMENTS . iv TABLE OF CONTENTS . v LIST OF TABLES . viii LIST OF FIGURES . x INTRODUCTION . 1 METHODS . 13 Study Organism Diaulula sandiegensis . Error! Bookmark not defined. Change in Spotting Pattern over Time . 13 Data acquisition field investigations . 17 Data acquisition – laboratory common garden experiment . 17 Laboratory set up . 19 Data analysis . 20 Distinct Morphotypes . 21 Data acquisition . 21 Data analysis . 21 Morphotypes of Diaulula sandiegensis Relative to Latitude and Depth . 23
Motif Analysis in k-mer Networks: An Approach towards Understanding SARS-CoV-2 Geographical Shifts

With an increasing number of SARS-CoV-2 sequences available day by day, new genomic information is getting revealed to us. As SARS-CoV-2 sequences highlight wide changes across the samples, we aim to explore whether these changes reveal the geographical origin of the corresponding samples. The k-mer distributions, denoting normalized frequency counts of all possible combinations of nucleotide of size upto k, are often helpful to explore sequence level patterns. Given the SARS-CoV-2 sequences are highly imbalanced by its geographical origin (relatively with a higher number samples collected from the USA), we observe that with proper under-sampling k-mer distributions in the SARS-CoV-2 sequences predict its geographical origin with more than 90% accuracy. The experiments are performed on the samples collected from six countries with maximum number of sequences available till July 07, 2020. This comprises SARS-CoV-2 sequences from Australia, USA, China, India, Greece and France. Moreover, we demonstrate that the changes of genomic sequences characterize the continents as a whole. We also highlight that the network motifs present in the sequence similarity networks have a significant difference across the said countries. This, as a whole, is capable of predicting the geographical shift of SARS-CoV-2.
Vascular origins of low‐frequency oscillations in the cerebrospinal fluid signal in resting‐state fMRI: Interpretation using photoplethysmography

Slow and rhythmic spontaneous oscillations of cerebral blood flow are well known to have diagnostic utility, notably frequencies of 0.008-0.03 Hz (B-waves) and 0.05-0.15Hz (Mayer waves or M waves). However, intracranial measurements of these oscillations have been difficult. Oscillations in the cerebrospinal fluid (CSF), which are influenced by the cardiac pulse wave, represent a possible avenue for non-invasively tracking these oscillations using resting-state functional MRI (rs-fMRI), and have been used to correct for vascular oscillations in rs-fMRI functional connectivity calculations. However, the relationship between low-frequency CSF and vascular oscillations is unclear. In this study, we investigate this relationship using fast simultaneous multi-slice rs-fMRI coupled with fingertip photoplethysmography (PPG). We not only extract B-wave and M-wave range spectral power from the PPG signal, but also derive the pulse-intensity ratio (PIR, a surrogate of slow blood-pressure oscillations), the second-derivative of the PPG (SDPPG, a surrogate of arterial stiffness) and heart-rate variability (HRV). The main findings of this study are: (1) signals in different CSF regions (ROIs) are not equivalent in their vascular contributions or in their associations with vascular and tissue rs-fMRI signals; (2) the PPG signal contains the highest signal contribution from the M-wave range, while PIR contains the highest signal contribution from the B-wave range; (3) in the low-frequency range, PIR is more strongly associated with rs-fMRI signal in the CSF than PPG itself, and than HRV and SDPPG; (4) PPG-related vascular oscillations only contribute to < 20% of the CSF signal in rs-fMRI, insufficient support for the assumption that low-frequency CSF signal fluctuations directly reflect vascular oscillations. These findings caution the use of CSF as a monolithic region for extracting physiological nuisance regressors in rs-fMRI applications. They also pave the way for using rs-fMRI in the CSF as a potential tool for tracking cerebrovascular health through, for instance the strong relationship between PIR and the CSF signal.
Proteomic analysis of microtubule inner proteins (MIPs) in Rib72 null Tetrahymena cells reveals functional MIPs

Motile cilia and flagella are built from stable populations of doublet microtubules that comprise their axonemes. Their unique stability is brought about, at least in part, by a network of Microtubule Inner Proteins (MIPs) found in the lumen of their doublet microtubules. Rib72A and Rib72B were identified as microtubule inner proteins (MIPs) in the motile cilia of Tetrahymena thermophila. Loss of these proteins leads to ciliary defects and loss of multiple MIPs. We performed mass spectrometry coupled with proteomic analysis and bioinformatics to identify the MIPs lost in RIB72A/B knockout (KO) Tetrahymena cells. From this analysis we identified a number of candidate MIPs and pursued one, Fap115, for functional characterization. We find that loss of Fap115 results in disrupted cell swimming and aberrant ciliary beating. Cryo-electron tomography reveals that Fap115 localizes to MIP6a in the A-tubule of the doublet microtubules. Overall, our results highlight the complex relationship between MIPs, ciliary structure, and ciliary function.
Transmembrane Polar Relay Drives the Allosteric Regulation for ABCG5/G8 Sterol Transporter

The heterodimeric ATP-binding cassette (ABC) sterol transporter, ABCG5/G8, is responsible for the biliary and transintestinal secretion of cholesterol and dietary plant sterols. Missense mutations of ABCG5/G8 can cause sitosterolemia, a loss-of-function disorder characterized by plant sterol accumulation and premature atherosclerosis. A new molecular framework was recently established by a crystal structure of human ABCG5/G8 and reveals a network of polar and charged amino acids in the core of the transmembrane domains, namely polar relay. In this study, we utilize genetic variants to dissect the mechanistic role of this transmembrane polar relay in controlling ABCG5/G8 function. We demonstrated a sterol-coupled ATPase activity of ABCG5/G8 by cholesteryl hemisuccinate (CHS), a relatively water-soluble cholesterol memetic, and characterized CHS-coupled ATPase activity of three loss-of-function missense variants, R543S, E146Q, and A540F, which are respectively within, in contact with, and distant from the polar relay. The results established an in vitro phenotype of the loss-of-function and missense mutations of ABCG5/G8, showing significantly impaired ATPase activity and loss of energy sufficient to weaken the signal transmission from the transmembrane domains. Our data provide a biochemical evidence underlying the importance of the polar relay and its network in regulating the catalytic activity of ABCG5/G8 sterol transporter.
Joint evolution of mycorrhizal type, pollination, and seed dispersal mode in trees

Mycorrhizal type, pollination, and seed dispersal mode are key drivers of tree diversity, but because they are usually studied in isolation, their evolutionary relationships are poorly understood. We investigated the evolutionary relationships among mycorrhizal type (arbuscular mycorrhizal [AM], ectomycorrhizal [EM], and AM + EM), seed dispersal mode (anemochorous, endozoochorous, and unspecialized), and pollination mode (biotic and wind) in 821 tree species. We found evidence of joint evolution of all three features. Most AM-associated trees had endozoochorous seed dispersal and biotic pollination, whereas most EM-associated trees had anemochorous seed dispersal and wind pollination. Overall, mycorrhizal type, seed dispersal mode, and pollination mode were linked, emphasizing the importance joint study of these traits for understand of tree diversity.
Distinct default mode network subsystems show similarities and differences in the effect of task focus across reading and autobiographical memory

Semantic cognition can be both perceptually-coupled, for example, during reading, and decoupled, such as in daydreams. Mind-wandering, characterised by autobiographical memory retrieval, often interferes with externally-focussed tasks. This study investigated the neural basis of these states, when they occur in isolation and in competition, using fMRI. Participants were asked to read sentences, presented word-by-word, or to recall personal memories, as a proxy for mind-wandering. Task conflict was created by presenting sentences during memory recall, or memory cues before sentences. We found that different subsystems of the default mode network (DMN) do not fully dissociate across internally- and externally-oriented states, and they do not fully separate in terms of the effects of task focus; this depends on the task. The lateral temporal DMN subsystem, associated with semantic cognition, was activated across both tasks, and by sentence inputs even when they were task-irrelevant. In the core DMN subsystem, greater task focus corresponded to a selective pattern of activation during memory recall and deactivation during reading. Both DMN subsystems formed different patterns of functional coupling depending on the task. In this way, DMN supports both access to meaning from perceptual inputs and focussed internal cognitive states in the face of distracting external information.
Differential inhibition of GABA release from mouse hippocampal interneuron subtypes by the volatile anesthetic isoflurane

General anesthesia is critical to modern medicine and animal research, but the cellular and molecular actions of general anesthetics on the central nervous system remain poorly understood. Volatile anesthetics such as isoflurane disrupt synaptic transmission and inhibit synaptic vesicle release in a neurotransmitter-selective manner. For example, GABA release from interneurons is less sensitive to isoflurane inhibition than are glutamate or dopamine release. Hippocampal and cortical interneuron subpopulations have diverse neurophysiological and synaptic properties, and their individual subtype-specific responses to isoflurane are unknown. We used live-cell optical imaging of exocytosis using fluorescent biosensors expressed in transgenic mouse hippocampal neuron cultures to delineate interneuron subtype-specific effects of isoflurane on synaptic vesicle exocytosis. We found that a clinically relevant concentration of isoflurane (0.5 mM) differentially modulated action potential-mediated exocytosis from GABAergic interneurons: parvalbumin-expressing interneurons were inhibited to 83.1±11.7% of control, whereas somatostatin-expressing and interneurons glutamatergic neurons were inhibited to 58.6±13.3% and 64.5±8.5% of control, respectively. The role of presynaptic voltage-gated sodium channel (Nav) subtype expression in determining isoflurane sensitivity was probed by overexpression or knockdown of specific Nav subtypes, which have distinct sensitivities to isoflurane and are differentially expressed between glutamatergic and GABAergic neurons. We found that the sensitivity of exocytosis to isoflurane was determined by the relative expression of Nav1.1 (associated with lower sensitivity) and Nav1.6 (associated with higher sensitivity). Thus the selective effects of isoflurane on synaptic vesicle exocytosis from hippocampal interneuron subtypes is determined by synaptic diversity in the relative expression of Nav1.1 and Nav1.6. Significance statement The volatile anesthetic isoflurane inhibits hippocampal GABAergic interneuron synaptic vesicle exocytosis with differences in potency between interneuron subtypes. This neuron subtype-specific pharmacology derives in part from synaptic diversity in the expression of presynaptic voltage-gated sodium channels that have different sensitivities to anesthetic modulation of channel function. GABAergic interneurons are generally more resistant to the presynaptic effects of isoflurane owing to predominant Nav1.1 expression, whereas glutamatergic neurons are more sensitive owing to predominant Nav1.6 expression, which supports heterogenous pharmacologic effects on specific neural circuits.
In-depth analysis of proteomic and genomic fluctuations during the time course of human embryonic stem cells directed differentiation into beta cells

Pluripotent stem cells (PSC) endocrine differentiation at a large scale allows sampling of transcriptome and proteome with phosphoproteome (proteoform) at specific time points. We describe the dynamic time course of changes in cells undergoing directed beta-cell differentiation and show target proteins or previously unknown phosphorylation of critical proteins in pancreas development, NKX6-1, and Chromogranin A (CHGA). We describe fluctuations in the correlation between gene expression, its protein abundance, and phosphorylation, which follow differentiation protocol perturbations of cell fates at all stages to identify proteoform profiles. Our computational modeling recognizes outliers on a phenomic landscape of endocrine differentiation, and we outline several new biological pathways involved. We also suggest that non-correlating proteins abundances or new phosphorylation motifs of NKX6.1 and CHGA point to new signaling pathways that may play an essential role in beta-cell development. We present our findings for the research community’s use for the improvement of endocrine differentiation protocols and developmental studies.
An Environmental Data Collection for COVID-19 Pandemic Research

The COVID-19 viral disease surfaced at the end of 2019 and quickly spread across the globe. To rapidly respond to this pandemic and offer data support for various communities (e.g., decision-makers in health departments and governments, researchers in academia, public citizens), the National Science Foundation (NSF) spatiotemporal innovation center constructed a spatiotemporal platform with various task forces including international researchers and implementation strategies. Compared to similar platforms that only offer viral and health data, this platform views virus-related environmental data collection (EDC) an important component for the geospatial analysis of the pandemic. The EDC contains environmental factors either proven or with potential to influence the spread of COVID-19 and virulence or influence the impact of the pandemic on human health (e.g., temperature, humidity, precipitation, air quality index and pollutants, nighttime light (NTL)). In this platform/framework, environmental data are processed and organized across multiple spatiotemporal scales for a variety of applications (e.g., global mapping of daily temperature, humidity, precipitation, correlation of the pandemic to the mean values of climate and weather factors by city). This paper introduces the raw input data, construction and metadata of reprocessed data, and data storage, as well as the sharing and quality control methodologies of the COVID-19 related environmental data collection.
Steam Decontamination of Whole and Cut-Up Raw Chicken

Abstract Short (20 sec) exposure to steam of 170 samples of whole and cut-up chicken in a chamber at 180 to 200 C reduced the aerobic plate counts by 1 to 3 log10 units and Salmonella contamination by 50% when compared to die indigenous flora in matched controls. The incidence of Salmonella contamination in chicken legs declined from 26% (untreated) to 6% (treated), whereas no marked decreases were observed with whole carcasses (15 to 20%) and chicken wings (40 to 30%). These results suggest that short steam treatments could be used to increase the shelf-life of whole and cut-up chicken and to decrease the incidence of salmonellae in chicken legs.
Presencia de los virus de la enfermedad de Marek y anemia infecciosa aviar en aves de levante del norte y oriente del Departamento de Antioquia

Tanto el virus de la enfermedad de Marek (MDV) y virus de la anemia infecciosa aviar (CIAV) son patogenos inmunosupresores que causan el sindrome de mortalidad temprana y bajas en la produccion cuando se da una coinfeccion. Aunque la industria avicola colombiana ha aumentado casi al doble en la ultima decada, no hay informacion sobre algunos agentes infecciosos que circulan en el pais. Es poco probable que ocurran casos clinicos de MVD debido a los programas de vacunacion generalizada con MVD serotipo I y III; sin embargo, las perdidas por infeccion subclinica son comunes debido a la inmunosupresion por MVD y CIAV. Este estudio utilizo PCR y RT-PCR en muestras de DNA extraidas de la sangre y de la pulpa de la pluma para detectar la presencia de Gallid herpesvirus 2, Gallid herpesvirus 3, Meleagrid herpesvirus 1 y CIAV en 4 granjas de postura comercial. El patotipo de MDV fue determinado por PCR, seguido por la alineacion de aminoacidos de la proteina Meq y analisis filogenetico. El intento de aislamiento del virus se realizo en cultivos primarios con confirmacion por PCR. Los organos del sistema inmune se evaluaron por histopatologia para verificar lesiones asociadas con ambos virus. Encontramos que los dos virus estan presentes en todas las granjas evaluadas, lo que podria estar asociado a fallas en la vacunacion. Los resultados de este trabajo demuestran por primera vez la identificacion molecular de MVD y CIAV y la presencia de coinfeccion en aves de Colombia.