Miracle-dz/UniFAR-FTUs huggingface dataset:
Glycine Rich Segments Adopt Polyproline II Helices Which May Contribute to Biomolecular Condensate Formation

Many intrinsically disordered proteins contain Gly-rich regions which are generally assumed to be disordered. Such regions often form biomolecular condensates which play essential roles in organizing cellular processes. However, the bases of their formation and stability are still not completely understood. Considering NMR studies of the Gly-rich H. harveyi “snow flea” antifreeze protein, we recently proposed that Gly-rich sequences, such as the third “RGG” region of Fused in Sarcoma (FUS) protein, may adopt polyproline II helices whose association might stabilize condensates. Here, this hypothesis is tested with a polypeptide corresponding to the third RGG region of FUS. NMR spectroscopy and molecular dynamics simulations suggest that significant populations of polyproline II helix are present. These findings are corroborated in a model peptide Ac-RGGYGGRGGWGGRGGY-NH2, where a peak characteristic of polyproline II helix is observed using CD spectroscopy. Its intensity suggests a polyproline II population of 40%. This result is supported by data from FTIR and NMR spectroscopies. In the latter, NOE correlations are observed between the Tyr and Arg, and Arg and Trp side chain hydrogens, confirming that side chains spaced three residues apart are close in space. Taken together, the data are consistent with a polyproline II helix, which is bent to optimize interactions between guanidinium and aromatic moieties, in equilibrium with a statistical coil ensemble. In cells, the polyproline II population of these peptides could be augmented by binding profilin protein or SH3, WW or OCRE domains, association with RNA or assembly into polyproline II helical bundles. These results lend credence to the hypothesis that Gly-rich segments of disordered proteins may form polyproline II helices which help stabilize biomolecular condensates.
Genetic structure of the Coconut Rhinoceros Beetle (Oryctes rhinoceros) population and the incidence of its biocontrol agent (Oryctes rhinoceros nudivirus) in the South Pacific Islands

Incursions of the Coconut rhinoceros beetle (CRB), Oryctes rhinoceros, have been detected in several countries of the south west Pacific in recent years, resulting in an expansion of the pest’s geographic range. It has been suggested that this resurgence is related to an O. rhinoceros mitochondrial lineage (previously referred to as the CRB-G “biotype”) that is reported to show reduced susceptibility to the well-established classical biocontrol agent, Oryctes rhinoceros nudivirus (OrNV). We investigated O. rhinoceros population genetics and the OrNV status of adult specimens collected in the Philippines and seven different South Pacific island countries (Fiji, New Caledonia, Papua New Guinea (PNG), Samoa, Solomon Islands, Tonga, and Vanuatu). Based on the presence of single nucleotide polymorphisms (snps) in the mitochondrial Cytochrome C Oxidase subunit I (CoxI) gene, we found three major mitochondrial lineages (CRB-G, a PNG lineage (CRB-PNG) and the South Pacific lineage (CRB-S)) across the region. Haplotype diversity varied considerably between and within countries. The O. rhinoceros population in most countries was monotypic and all individuals tested belonged to a single mitochondrial lineage (Fiji, CRB-S; Tonga, CRB-S; Vanuatu, CRB-PNG; PNG (Kimbe), CRB-PNG; New Caledonia CRB-G; Philippines, CRB-G). However, in Samoa we detected CRB-S and CRB-PNG and in Solomon Islands we detected all three haplotype groups. Genotyping-by-Sequencing (GBS) methods were used to genotype 10,000 snps from 230 insects across the Pacific and showed genetic differentiation in the O. rhinoceros nuclear genome among different geographical populations. The GBS data also provided evidence for gene flow and admixture between different haplotypes in Solomon Islands. Therefore, contrary to earlier reports, CRB-G is not solely responsible for damage to the coconut palms reported since the pest was first recorded in Solomon Islands in 2015. We also PCR-screened a fragment of OrNV from 260 insects and detected an extremely high prevalence of viral infection in all three haplotypes in the region. We conclude that the haplotype groups CRB-G, CRB-S, and PNG, do not represent biotypes, subspecies, or cryptic species, but simply represent different invasions of O. rhinoceros across the Pacific. This has important implications for management, especially biological control, of Coconut rhinoceros beetle in the region.
Weighting features by the value displacement rebound

Learning from examples draws on similarity, a concept which formalisation leads to the notion of instance space. Continuous spaces are easier to embrace since, unlike discrete, they often can be seen as hyper-constructs of 3D. Unsurprisingly, the instance-based learning methods are more developed for continuous domains than for discrete ones. The value difference metric (VDM) is one of the few examples of metrics for discrete spaces. Mixed reports about utility of VDM exist. In this paper VDM is compared with another approach where data features are weighted by the Information Gain. Some vulnerabilities of VDM are identified. A weighting method, nothing like VDM, although inspired by the former, is proposed. The results are in favour of the new weighting scheme with illustration of utility for health diagnostics.
A Prospective Analysis of Lesion-Symptom Relationships in Acute Vestibular and Ocular Motor Stroke

Background: Diagnosing stroke as a cause of acute vertigo, dizziness, or double vision remains a challenge, because symptom characteristics can be variable. The purpose of this study was to prospectively investigate lesion-symptom relationships in patients with acute vestibular or ocular motor stroke. Methods: Three hundred and fifty one patients with acute and isolated vestibular or ocular motor symptoms of unclear etiology were enrolled in the EMVERT lesion trial. Symptom quality was assessed by the chief complaint (vertigo, dizziness, double vision), symptom intensity by the visual analog scale, functional impairment by EQ-5D-5L, and symptom duration by daily rating. Acute vestibular and ocular motor signs were registered by videooculography. A standardized MRI (DWI-/FLAIR-/T2-/T2*-/3D-T1-weighted sequences) was recorded within 7 days of symptom onset. MRIs with DWI lesions were further processed for voxel-based lesion-symptom mapping (VLSM). Results: In 47 patients, MRI depicted an acute unilateral stroke (13.4%). The chief complaints were dizziness (42.5%), vertigo (40.4%) and double vision (17.0%). Lesions in patients with vertigo or dizziness showed a large overlap in the cerebellar hemisphere. VLSM indicated that strokes in the medial cerebellar layers 7b, 8, 9 were associated with vertigo, strokes in the lateral cerebellar layer 8, crus 1, 2 with dizziness, and pontomesencephalic strokes with double vision. Symptom intensity and duration varied largely between patients. Higher symptom intensity and longer duration were associated with medial cerebellar lesions. Hemispheric lesions of the cortex were rare and presented with milder symptoms of shorter duration. Conclusions: Prospective evaluation of patients with acute vestibular or ocular motor stroke revealed that symptom quality, intensity and duration were not suited to differentiating peripheral from central etiologies. Lesions in the lateral cerebellum, thalamus, or cortex presented with unspecific, mild and transient symptoms prone to being misdiagnosed.
Design, Synthesis, and Biological Evaluation of Novel Thiazolidinone-Containing Quinoxaline-1,4-di-N-oxides as Antimycobacterial and Antifungal Agents

Tuberculosis and fungal infections can pose serious threats to human health. In order to find novel antimicrobial agents, 26 novel quinoxaline-1,4-di-N-oxides containing a thiazolidinone moiety were designed and synthesized, and their antimycobacterial activities were evaluated. Among them, compounds 2t, 2u, 2y, and 2z displayed the most potent antimycobacterial activity against Mycobacterium tuberculosis strain H37Rv (minimal inhibitory concentration [MIC] = 1.56 μg/mL). The antifungal activity of all the compounds was also evaluated against Candida albicans, Candida tropicalis, Aspergillus fumigatus, and Cryptococcus neoformans. Compounds 2t, 2u, 2y, and 2z exhibited potential antifungal activities, with an MIC between 2 and 4 μg/mL. Comparative molecular field analysis (CoMFA: q2 = 0.914, r2 = 0.967) and comparative molecular similarity index analysis (CoMSIA: q2 = 0.918, r2 = 0.968) models were established to investigate the structure and antimycobacterial activity relationship. The results of contour maps revealed that electronegative and sterically bulky substituents play an important role in the antimycobacterial activity. Electronegative and sterically bulky substituents are preferred at the C7 position of the quinoxaline ring and the C4 position of the phenyl group to increase the antimycobacterial activity. Additionally, more hydrogen bond donor substituents should be considered at the C2 side chain of the quinoxaline ring to improve the activity.
Developmentally Regulated Rebound Depolarization Enhances Spike Timing Precision in Auditory Midbrain Neurons

The inferior colliculus (IC) is an auditory midbrain structure involved in processing biologically important temporal features of sounds. The responses of IC neurons to these temporal features reflect an interaction of synaptic inputs and neuronal biophysical properties. One striking biophysical property of IC neurons is the rebound depolarization produced following membrane hyperpolarization. To understand how the rebound depolarization is involved in spike timing, we made whole-cell patch clamp recordings from IC neurons in brain slices of P9–21 rats. We found that the percentage of rebound neurons was developmentally regulated. The precision of the timing of the first spike on the rebound increased when the neuron was repetitively injected with a depolarizing current following membrane hyperpolarization. The average jitter of the first spikes was only 0.5 ms. The selective T-type Ca2+ channel antagonist, mibefradil, significantly increased the jitter of the first spike of neurons in response to repetitive depolarization following membrane hyperpolarization. Furthermore, the rebound was potentiated by one to two preceding rebounds within a few hundred milliseconds. The first spike generated on the potentiated rebound was more precise than that on the non-potentiated rebound. With the addition of a calcium chelator, BAPTA, into the cell, the rebound potentiation no longer occurred, and the precision of the first spike on the rebound was not improved. These results suggest that the postinhibitory rebound mediated by T-type Ca2+ channel promotes spike timing precision in IC neurons. The rebound potentiation and precise spikes may be induced by increases in intracellular calcium levels.
Suicide Attempts Among French and Brazilian Adolescents Admitted to an Emergency Room. A Comparative Study of Risk and Protective Factors

Background Suicide is the second most common cause of preventable mortality among Brazilian and French adolescents. The aim of the current study was to compare the main risk and protective factors associated with a suicide attempt (SA) and to highlight differences based on geographical characteristics. Method We compared a Brazilian sample (N = 45) of adolescents admitted to the emergency room of a public hospital in São Paulo for SA to a French sample (N = 320) of adolescents hospitalized for SA across 5 paediatric departments. Then, we ran several multivariate models to examine how each selected variable was related to geographic origin and to the other selected variables linked to geographic origin. Results The two samples presented no significant differences regarding gender, age or schooling. Both samples had high rates of depressive disorders, anxiety disorders, substance use, disruptive disorders, borderline psychopathology, and lifetime SAs. However, the Brazilian sample presented significantly higher levels of psychopathology and had more insecure attachment relationships (fearful and detached), whereas the French sample had a more secure attachment style. Brazilian adolescents had more recourse to spiritual beliefs and spiritual support, whereas the French adolescents had higher scores on the Reasons for Living Inventory and used more help-seeking strategies from their social network, mainly close friends. Multivariate models showed that two productive coping strategies (seeking spiritual support and social action) and the dependence score were significantly associated with membership in the Brazilian cohort, whereas a secure attachment style and depression severity (evaluated by the Beck Depression Inventory) were significantly associated with membership in the French cohort. Conclusion Despite presenting similar psychopathologies, Brazilian adolescents presented a more insecure attachment style and used the religious kind of coping more commonly than their French counterparts. We hypothesize that religion may compensate for the social vulnerabilities present in a middle-income country such as Brazil. More transcultural studies may help to elucidate this phenomenon.
Functional Predictors of Causative Cis-Regulatory Mutations in Mendelian Disease

Undiagnosed neurodevelopmental disease is significantly associated with rare variants in cis-regulatory elements (CRE) but demonstrating causality is challenging as target gene consequences may differ from a causative variant affecting the coding region. Here, we address this challenge by applying a procedure to discriminate likely diagnostic regulatory variants from those of neutral/low-penetrant effect. We identified six rare CRE variants using targeted and whole genome sequencing in 48 unrelated males with apparent X-linked intellectual disability (XLID) but without detectable coding region variants. These variants segregated appropriately in families and altered conserved bases in predicted CRE targeting known XLID genes. Three were unique and three were rare but too common to be plausibly causative for XLID. We compared the cis-regulatory activity of wild-type and mutant alleles in zebrafish embryos using dual-color fluorescent reporters. Two variants showed striking changes: one plausibly causative (FMR1CRE) and the other likely neutral/low-penetrant (TENM1CRE). These variants were “knocked-in” to mice and both altered embryonic neural expression of their target gene. Only Fmr1CRE mice showed disease-relevant behavioral defects. FMR1CRE is plausibly disease-associated resulting in complex misregulation of Fmr1/FMRP rather than loss-of-function. This is consistent both with absence of Fragile X syndrome in the probands and the observed electrophysiological anomalies in the FMR1CRE mouse brain. Although disruption of in vivo patterns of endogenous gene expression in disease-relevant tissues by CRE variants cannot be used as strong evidence for Mendelian disease association, in conjunction with extreme rarity in human populations and with relevant knock-in mouse phenotypes, such variants can become likely pathogenic.
The incidence and antibiotics susceptibility of Escherichia coli O157:H7 from beef in Ibadan Municipal, Nigeria

The incidence of Escherichia coli 0157: H7 was assessed in meat samples from slaughtered cattle in Ibadan metropolis by culturing on sorbitol MacConkey agar and confirmed using serological agglutination kits. The isolates were tested for susceptibility to seven commonly used antimicrobial agents. Out of the total of the 116 non-sorbitol fermenting (NSF) E. coli isolated from the samples, 71 (comprising of 18.4, 2.0, 3.2 and 4.8% from Bodija abattoir, Bashorun, Apata and Iwo Road slaughter slabs, respectively) were confirmed as E. coli O157:H7 serotype. Antibiotics susceptibility profile showed that all the isolates were resistant to one or multiple antibiotics, resulting in eight different resistance patterns. Tetracycline resistant isolates were the highest with 91.4% incidence. The results are of public health significance confirming cattle as major reservoir of EHEC and antimicrobialresistant organisms. The high level of carcass contamination with microorganisms may be due to unhygienic slaughtering and meat processing engaged in these abattoir and slabs. Indiscriminate and misuse of antimicrobials on livestock in Nigeria could also be responsible for the multiple resistance pattern of the organism. Application of food hygiene practices such as HACCP is recommended for high quality farm to fork wholesome and safe meat for public consumption in Nigeria.
Global RNA sequencing reveals enhanced photosynthetic activity and auxin response in Brassica napus treated with Pseudomonas chlororaphis PA23

Plant growth promoting bacteria (PGPB) are a growing subset of agricultural adjuncts which can be used to increase crop yield and plant productivity. Although substantial research has been conducted on the metabolites and active molecules secreted by PGPBs, relatively little is known about their effects on the global transcriptome of the host plant. The present study was carried out to investigate changes in the gene expression landscape of early vegetative Brassica napus following treatment with Pseudomonas chlororaphis PA23. This PGPB was isolated from the soybean rhizosphere and has been extensively studied as a biocontrol agent. However, little is known about its effects on plant growth and development. Using a combination of RNA-sequencing and physiological analyses, we identified increased abundance of mRNA transcripts associated with photosynthesis and phytohormone response. Phenotypically we observed increased photosynthetic rates and larger root and shoot systems in B. napus following P. chlororaphis PA23 treatment. Lastly, we identified auxin production by P. chlororaphis PA23 which likely contributes to changes in gene expression and the observed phenotypic differences in root and shoot structures. Together, the results of our study suggest that PA23 is a potent plant growth promoting agent with the potential for field applications as an agricultural adjunct.
Neural repetition suppression modulates time perception: evidence from electrophysiology and pupillometry

Human time perception is malleable and subject to many biases. For example, it has repeatedly been shown that stimuli that are physically intense or that are unexpected seem to last longer. Two competing hypotheses have been proposed to account for such biases: one states that these temporal illusions are the result of increased levels of arousal which speeds up neural clock dynamics, whereas the alternative ‘magnitude coding’ account states that the magnitude of sensory responses causally modulates perceived durations. Common experimental paradigms used to study temporal biases can not dissociate between these accounts, as arousal and sensory magnitude covary and modulate each other. Here, we present two temporal discrimination experiments where two flashing stimuli demarcated the start and end of a to-be-timed interval. These stimuli could either be in the same or in a different location, which led to different sensory responses due to neural repetition suppression. Crucially, changes and repetitions were fully predictable, which allowed us explore effects of sensory response magnitude without impacting arousal or surprise. Intervals with changing markers were perceived as lasting longer than those with repeating markers. We measured EEG (Experiment 1) and pupil size (Experiment 2), and found that temporal perception was related to changes in event-related potentials (P2) and pupil constriction, both of which have been related to responses in sensory cortex. Conversely, correlates of surprise and arousal (P3 amplitude and pupil dilation) were unaffected by stimulus repetitions and changes. These results demonstrate, for the first time, that sensory magnitude affects time perception even under constant levels of arousal.
Eye Movement Dynamics Differ between Encoding and Recognition of Faces

Facial recognition is widely thought to involve a holistic perceptual process, and optimal recognition performance can be rapidly achieved within two fixations. However, is facial identity encoding likewise holistic and rapid, and how do gaze dynamics during encoding relate to recognition? While having eye movements tracked, participants completed an encoding (“study”) phase and subsequent recognition (“test”) phase, each divided into blocks of one- or five-second stimulus presentation time conditions to distinguish the influences of experimental phase (encoding/recognition) and stimulus presentation time (short/long). Within the first two fixations, several differences between encoding and recognition were evident in the temporal and spatial dynamics of the eye-movements. Most importantly, in behavior, the long study phase presentation time alone caused improved recognition performance (i.e., longer time at recognition did not improve performance), revealing that encoding is not as rapid as recognition, since longer sequences of eye-movements are functionally required to achieve optimal encoding than to achieve optimal recognition. Together, these results are inconsistent with a scan path replay hypothesis. Rather, feature information seems to have been gradually integrated over many fixations during encoding, enabling recognition that could subsequently occur rapidly and holistically within a small number of fixations.
The inhibition of glycogen synthase kinase 3β by a metabotropic glutamate receptor 5 mediated pathway confers neuroprotection to Aβ peptides

Activation of glycogen synthase kinase 3β (Gsk3β) has been shown to be a key component in signaling pathways that underlie neurodegeneration and neurodegenerative disease. Conversely, inactivation of Gsk3β by phosphoinositide 3‐kinase (PI3K)/Akt is an important neuroprotective mechanism. Previous studies have shown that agonist activation of group I metabotropic glutamate receptors (mGluRs) can increase neuronal survival and prevent apoptosis. However, little is known about the signaling pathways that couple mGluR5 to neuroprotection. In this report, we investigated whether activation of the PI3K/Akt/Gsk3β pathway, which has been shown to have an important neuroprotective mechanism, is required for mGluR5 activation mediated neuroprotection against β‐amyloid. We found that brief incubations of mouse hippocampal slices with (R,S)‐3,5‐dihydroxyphenylglycine (DHPG) resulted in increased phosphorylation of Akt and Gsk3β. The PI3K inhibitors, LY294002 and wortmannin, blocked the DHPG‐induced increased phosphorylation of Akt and Gsk3β. Similar results were observed in rat primary hippocampal cultures. Finally, we found that the PI3K inhibitor LY294002 can block (R,S)‐2‐chloro‐5‐hydroxyphenylglycine (CHPG) mediated neuroprotection against β‐amyloid. Thus, these findings suggest that mGluR5 can modulate the PI3K/Akt/Gsk3β pathway in the hippocampus, and that modulation of this signaling pathway can reverse β‐amyloid‐induced neuronal toxicity.