Miracle-dz/UniFAR-FTUs huggingface dataset:
Digest: Indirect genetic effects of males on female reproductive traits in the wild *

The indirect genetic effects of fathers on the expression and evolution of female reproductive traits in the wild is not well understood. In a wild population of great tits (Parus major), Evans et al. estimated the genetic and nongenetic effects of male mates on two female reproductive traits, lay date and clutch size. The estimated heritability of lay date (but not of clutch size) was increased by 1.5 times after accounting for male indirect genetic effects. This finding illustrates the importance of considering the effects of social partners in classic quantitative genetic models.
Motion Correction in Multimodal Intraoperative Imaging

Thermographic imaging accompanied with time-resolved analysis is a promising technique for intraoperative imaging in neurosurgery. However, motion due to breathing and pulse of the patient introduces large inaccuracies to the demarcation of normal and pathological brain tissue. Since movements and physiological processes are both manifested as temperature variations, we employ co-registered visual-light images to unambiguously detect motion. In this article, we propose a feature-based approach which is selected from four best-known methods after thorough performance comparison. Complementing our previous work, we evaluate the performance of our methods by applying a frequency analysis and similarity measurements. Our approach enables an accurate motion correction without affecting physiological temperature shifts. Furthermore, real-time performance of the implementation is enabled by serial acceleration and parallelization methods.
Ubiquitination of MHC Class II Is Required for Development of Regulatory but Not Conventional CD4+ T Cells

Key Points MHC II ubiquitination is dispensable for maintenance of conventional CD4+ T cells. MHC II ubiquitination is required for thymic Treg development. Lack of MHC II ubiquitination does not provoke autoimmunity. Visual Abstract MHC class II (MHC II) displays peptides at the cell surface, a process critical for CD4+ T cell development and priming. Ubiquitination is a mechanism that dictates surface MHC II with the attachment of a polyubiquitin chain to peptide-loaded MHC II, promoting its traffic away from the plasma membrane. In this study, we have examined how MHC II ubiquitination impacts the composition and function of both conventional CD4+ T cell and regulatory T cell (Treg) compartments. Responses were examined in two models of altered MHC II ubiquitination: MHCIIKRKI/KI mice that express a mutant MHC II unable to be ubiquitinated or mice that lack membrane-associated RING-CH 8 (MARCH8), the E3 ubiquitin ligase responsible for MHC II ubiquitination specifically in thymic epithelial cells. Conventional CD4+ T cell populations in thymus, blood, and spleen of MHCIIKRKI/KI and March8−/− mice were largely unaltered. In MLRs, March8−/−, but not MHCIIKRKI/KI, CD4+ T cells had reduced reactivity to both self– and allogeneic MHC II. Thymic Treg were significantly reduced in MHCIIKRKI/KI mice, but not March8−/− mice, whereas splenic Treg were unaffected. Neither scenario provoked autoimmunity, with no evidence of immunohistopathology and normal levels of autoantibody. In summary, MHC II ubiquitination in specific APC types does not have a major impact on the conventional CD4+ T cell compartment but is important for Treg development.
Physically Motivated Feature Development for Machine Learning Applications

Physically Motivated Feature Development for Machine Learning Applications by Nicholas Czarnek Department of Electrical and Computer Engineering Duke University Date:_______________________ Approved: ___________________________ Leslie Collins, Supervisor ___________________________ Maciej Mazurowski ___________________________ Stacy Tantum ___________________________ Galen Reeves ___________________________ Kyle Bradbury An abstract of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Electrical and Computer Engineering in the Graduate School of Duke University
RNA-tethering assay and eIF4G:eIF4A obligate dimer design uncovers multiple eIF4F functional complexes

Abstract Eukaryotic cellular mRNAs possess a 5′ cap structure (m7GpppN) which plays a critical role in translation initiation mediated by eukaryotic initiation factor (eIF) 4F. The heterotrimeric eIF4F complex possesses several activities imparted by its subunits that include cap recognition (by eIF4E), RNA unwinding (eIF4A), and factor/ribosome recruitment (eIF4G). Mammalian cells have paralogs of all three eIF4F subunits and it remains an open question as to whether these all can participate in the process of ribosome recruitment. To query the activities of the eIF4F subunits in translation initiation, we adopted an RNA-tethering assay in which select subunits are recruited to a specific address on a reporter mRNA template. We find that all eIF4F subunits can participate in the initiation process. Based on eIF4G:eIF4A structural information, we also designed obligate dimer pairs to probe the activity of all combinations of eIF4G and eIF4A paralogs. We demonstrate that both eIF4GI and eIF4GII can associate with either eIF4A1 or eIF4A2 to recruit ribosomes to mRNA templates. In combination with eIF4E and eIF4E3, our results indicate the presence of up to eight eIF4F complexes that can operate in translation initiation.
ICRP recommendations on radon

The International Commission on Radiological Protection (ICRP) publishes guidance on protection from radon in homes and workplaces, and dose coefficients for use in assessments of exposure for protection purposes. ICRP Publication 126 recommends an upper reference level for exposures in homes and workplaces of 300 Bq m−3. In general, protection can be optimised using measurements of air concentrations directly, without considering radiation doses. However, dose estimates are required for workers when radon is considered as an occupational exposure (e.g. in mines), and for higher exposures in other workplaces (e.g. offices) when the reference level is exceeded persistently. ICRP Publication 137 recommends a dose coefficient of 3 mSv per mJ h m−3 (approximately 10 mSv per working level month) for most circumstances of exposure in workplaces, equivalent to 6.7 nSv per Bq h m−3 using an equilibrium factor of 0.4. Using this dose coefficient, annual exposure of workers to 300 Bq m−3 corresponds to 4 mSv. For comparison, using the same coefficient for exposures in homes, 300 Bq m−3 corresponds to 14 mSv. If circumstances of occupational exposure warrant more detailed consideration and reliable alternative data are available, site-specific doses can be assessed using methodology provided in ICRP Publication 137.
Attenuation of epigenetic regulator SMARCA4 and ERK‐ETS signaling suppresses aging‐related dopaminergic degeneration

How complex interactions of genetic, environmental factors and aging jointly contribute to dopaminergic degeneration in Parkinson's disease (PD) is largely unclear. Here, we applied frequent gene co‐expression analysis on human patient substantia nigra‐specific microarray datasets to identify potential novel disease‐related genes. In vivo Drosophila studies validated two of 32 candidate genes, a chromatin‐remodeling factor SMARCA4 and a biliverdin reductase BLVRA. Inhibition of SMARCA4 was able to prevent aging‐dependent dopaminergic degeneration not only caused by overexpression of BLVRA but also in four most common Drosophila PD models. Furthermore, down‐regulation of SMARCA4 specifically in the dopaminergic neurons prevented shortening of life span caused by α‐synuclein and LRRK2. Mechanistically, aberrant SMARCA4 and BLVRA converged on elevated ERK‐ETS activity, attenuation of which by either genetic or pharmacological manipulation effectively suppressed dopaminergic degeneration in Drosophila in vivo. Down‐regulation of SMARCA4 or drug inhibition of MEK/ERK also mitigated mitochondrial defects in PINK1 (a PD‐associated gene)‐deficient human cells. Our findings underscore the important role of epigenetic regulators and implicate a common signaling axis for therapeutic intervention in normal aging and a broad range of age‐related disorders including PD.
A multimodal study of the effects of tDCS on dorsolateral prefrontal and temporo‐parietal areas during dichotic listening

The underlying neural mechanisms of transcranial direct current stimulation (tDCS), especially beyond the primary motor cortex, remain unclear. Several studies examined tDCS effects on either functional activity, neurotransmitters or behavior but few investigated those aspects together to reveal how the brain responds to tDCS. The objective is to elucidate the underlying mechanisms of tDCS using a multimodal approach that extends from behavioral to neurotransmitter levels of explanation. Thirty‐two healthy participants performed an auditory dichotic listening task at two visits, one session with sham and one session with real tDCS (2 mA) while simultaneously undergoing functional magnetic resonance imaging (fMRI). The anode and cathode were placed over the left temporo‐parietal cortex (TPC) and dorsolateral prefrontal cortex, respectively. Before and after simultaneous dichotic listening/fMRI/tDCS, combined glutamate and glutamine (Glx) and myo‐inositol levels were assessed in the stimulated areas. While fMRI and dichotic listening showed expected functional activity and behavioral effects, neither method demonstrated differences between real and sham stimulation. Glx only showed a statistical trend towards higher levels after real tDCS in both stimulated brain areas. There were no significant correlations between behavior and Glx. Despite a reasonable sample size, electrical field strength, and replication of behavioral and functional activity results, tDCS had little to no effect on dichotic listening, Glx, and functional activity. The study emphasizes that findings about the underlying neural mechanisms of the primary motor cortex cannot simply be generalized to other brain areas. Particularly, the TPC might be less sensitive to tDCS. Moreover, the study demonstrates the general feasibility of multimodal approaches.
Retinal Degeneration Reduces Consistency of Network-Mediated Responses Arising in Ganglion Cells to Electric Stimulation

Retinal prostheses use periodic repetition of electrical stimuli to form artificial vision. To enhance the reliability of evoked visual percepts, repeating stimuli need to evoke consistent spiking activity in individual retinal ganglion cells (RGCs). However, it is not well known whether outer retinal degeneration alters the consistency of RGC responses. Hence, here we systematically investigated the trial-to-trial variability in network-mediated responses as a function of the degeneration level. We patch-clamp recorded spikes in ON and OFF types of alpha RGCs from r d10 mice at four different postnatal days (P15, P19, P31, and P60), representing distinct stages of degeneration. To assess the consistency of responses, we analyzed variances in spike count and timing across repeats of the same stimulus delivered multiple times. We found the trial-to-trial variability of network-mediated responses increased considerably as the disease progressed. Compared to responses taken before degeneration onset, those of degenerate retinas showed up to ~70% higher variability (Fano Factor) in spike counts (p < 0.001) and ~95% lower correlation level in spike timing (p < 0.001). These results indicate consistency weakens significantly in electrically-evoked network-mediated responses and therefore raise concerns about the ability of microelectronic retinal implants to elicit consistent visual percepts at advanced stages of retinal degeneration.
A gene expression‐based single sample predictor of lung adenocarcinoma molecular subtype and prognosis

Disease recurrence in surgically treated lung adenocarcinoma (AC) remains high. New approaches for risk stratification beyond tumor stage are needed. Gene expression‐based AC subtypes such as the Cancer Genome Atlas Network (TCGA) terminal‐respiratory unit (TRU), proximal‐inflammatory (PI) and proximal‐proliferative (PP) subtypes have been associated with prognosis, but show methodological limitations for robust clinical use. We aimed to derive a platform independent single sample predictor (SSP) for molecular subtype assignment and risk stratification that could function in a clinical setting. Two‐class (TRU/nonTRU=SSP2) and three‐class (TRU/PP/PI=SSP3) SSPs using the AIMS algorithm were trained in 1655 ACs (n = 9659 genes) from public repositories vs TCGA centroid subtypes. Validation and survival analysis were performed in 977 patients using overall survival (OS) and distant metastasis‐free survival (DMFS) as endpoints. In the validation cohort, SSP2 and SSP3 showed accuracies of 0.85 and 0.81, respectively. SSPs captured relevant biology previously associated with the TCGA subtypes and were associated with prognosis. In survival analysis, OS and DMFS for cases discordantly classified between TCGA and SSP2 favored the SSP2 classification. In resected Stage I patients, SSP2 identified TRU‐cases with better OS (hazard ratio [HR] = 0.30; 95% confidence interval [CI] = 0.18‐0.49) and DMFS (TRU HR = 0.52; 95% CI = 0.33‐0.83) independent of age, Stage IA/IB and gender. SSP2 was transformed into a NanoString nCounter assay and tested in 44 Stage I patients using RNA from formalin‐fixed tissue, providing prognostic stratification (relapse‐free interval, HR = 3.2; 95% CI = 1.2‐8.8). In conclusion, gene expression‐based SSPs can provide molecular subtype and independent prognostic information in early‐stage lung ACs. SSPs may overcome critical limitations in the applicability of gene signatures in lung cancer.
Distribution of chemo‐ and mechanoreceptors on the tarsi and ovipositor of female European grapevine moth, Lobesia botrana

We describe the number, distribution, and function of sensilla located on different organs of Lobesia botrana (Lepidoptera: Tortricidae) females using scanning electron microscopy, selective staining, and contact electrophysiology. The tarsi of the prothoracic legs bear contact chemo‐mechanoreceptor sensilla chaetica (5–13 per tarsomere), arranged in rings mainly concentrated on ventral surfaces, and different mechanosensory structures (sensilla chaetica, sensilla squamiformia, sensilla campaniformia, and spines). A single contact chemo‐mechanoreceptor sensillum chaeticum is present between the claws on the pretarsus. The ventral surface of the ovipositor lobes is covered with numerous mechanosensory sensilla chaetica of different types, out of which 10 have a contact chemosensory function. Putative contact chemo‐mechanoreceptor sensilla were also observed on the proboscis and antenna. Longitudinal rows of alternated sensilla styloconica and basiconica are present on the distal part of the proboscis, and rings of sensilla chaetica are present at the antennal tip. The sensilla on these body parts may play different roles in the selection of an oviposition site.
Investigation into the origins of an ancient BRCA1 founder mutation identified among Chinese families in Singapore

Identification of ancestry‐specific pathogenic variants is imperative for diagnostic, treatment, management and prevention strategies, and to understand penetrance/modifiers on risk. Our study aimed to determine the clinical significance of a recurrent BRCA1 c.442‐22_442‐13del variant of unknown significance identified among 13 carriers from six Chinese families, all with a significant history of breast and/or ovarian cancer. We further aimed to establish whether this was due to a founder effect and explore its origins. Haplotype analysis, using nine microsatellite markers encompassing 2.5 megabase pairs around the BRCA1 locus, identified a common haploblock specific to the variant carriers, confirming a founder effect. Variant age was estimated to date back 77.9 generations to 69 bc using the Gamma approach. On principal component analysis using single nucleotide polymorphisms merged with 1000 Genomes dataset, variant carriers were observed to overlap predominantly with the southern Han Chinese population. To determine pathogenicity of the variant, we assessed the functional effect on RAD51 foci formation as well as replication fork stability upon induction of DNA damage and observed an impaired DNA repair response associated with the variant. In summary, we identified an ancient Chinese founder mutation dating back 77.9 generations, possibly common among individuals of southern Han Chinese descent. Using evidence from phenotypic/family history studies, segregation analysis and functional characterization, the BRCA1 variant was reclassified from uncertain significance to pathogenic.
Organoarsenic Compounds with In Vitro Activity against the Malaria Parasite Plasmodium falciparum

The rapid development of parasite drug resistance as well as the lack of medications targeting both the asexual and the sexual blood stages of the malaria parasite necessitate the search for novel antimalarial compounds. Eleven organoarsenic compounds were synthesized and tested for their effect on the asexual blood stages and sexual transmission stages of the malaria parasite Plasmodium falciparum using in vitro assays. The inhibitory potential of the compounds on blood stage viability was tested on the chloroquine (CQ)-sensitive 3D7 and the CQ-resistant Dd2 strain using the Malstat assay. The most effective compounds were subsequently investigated for their effect on impairing gametocyte development and gametogenesis, using the gametocyte-producing NF54 strain in respective cell-based assays. Their potential toxicity was investigated on leukemia cell line Nalm-6 and non-infected erythrocytes. Five out of the 11 compounds showed antiplasmodial activities against 3D7, with half-maximal inhibitory concentration (IC50) values ranging between 1.52 and 8.64 µM. Three of the compounds also acted against Dd2, with the most active compound As-8 exhibiting an IC50 of 0.35 µM. The five compounds also showed significant inhibitory effects on the parasite sexual stages at both IC50 and IC90 concentrations with As-8 displaying the best gametocytocidal activity. No hemolytic and cytotoxic effect was observed for any of the compounds. The organoarsenic compound As-8 may represent a good lead for the design of novel organoarsenic drugs with combined antimalarial and transmission blocking activities.
Do Multisensory Stimuli Benefit the Virtual Reality Experience? A Systematic Review

The majority of virtual reality (VR) applications rely on audiovisual stimuli and do not exploit the addition of other sensory cues that could increase the potential of VR. This systematic review surveys the existing literature on multisensory VR and the impact of haptic, olfactory, and taste cues over audiovisual VR. The goal is to identify the extent to which multisensory stimuli affect the VR experience, which stimuli are used in multisensory VR, the type of VR setups used, and the application fields covered. An analysis of the 105 studies that met the eligibility criteria revealed that 84.8 percent of the studies show a positive impact of multisensory VR experiences. Haptics is the most commonly used stimulus in multisensory VR systems (86.6 percent). Non-immersive and immersive VR setups are preferred over semi-immersive setups. Regarding the application fields, a considerable part was adopted by health professionals and science and engineering professionals. We further conclude that smell and taste are still underexplored, and they can bring significant value to VR applications. More research is recommended on how to synthesize and deliver these stimuli, which still require complex and costly apparatus be integrated into the VR experience in a controlled and straightforward manner.
Disentangling the role of edaphic variability, flooding regime and topography of Amazonian white‐sand vegetation

Question: How much variation in plant community structure and composition can be predicted using soil, flooding and topography in white-sand vegetation of northern Amazonia? Location: Brazil, northern Amazon, Roraima State, ViruaNational Park (01°46' 34" N, 61°02'06" W). Methods: Data from 17, 1-ha permanent plots distributed across a 25 km 2 landscape within the ViruaNational Park, northern Amazonia, was used to assess the soil, flooding and topography effects on tree species composition, diversity and structure. Our analyses were based on 16 599 trees (DBH 1 cm) belonging to 303 species. Principal components analysis (PCA) was used to reduce the dimensionality of soil variables, whereas dimensionality of floristic composition assemblage was reduced using non-metric multidimen- sional scaling (NMDS). Multiple regression analysis was used to test combined effects of soil, flooding and topography on floristic composition, diversity, basal area and tree density. Results: Depending on the diameter class or the type of data (qualitative or quantitative), NMDS axis 1 explained 45-84% of total variation in species composition among plots. The first and second axes from PCA explained, respectively, 54.8% and 15.1% of the variation related to soil gradients. Soil tex- ture and fertility (PCA axis 1) were the most important predictors of the variation in tree composition, diversity and structure for the three different size classes analysed (DBH 1c m, 1 cm DBH 9.9 cm and DBH 10 cm). Overall, plots on more fertile clayey soils showed higher tree diversity and basal area than those on well-drained sandy soils. Although flooding had little effect on the tree community, the water level was higher in high-stature forests established on more clayey and fertile soils.
On the function of the two types of myotomal muscle fibre in elasmobranch fish

There are two main types of muscle fibre in the dogfish myotome. Slow fibres make upabout 18 % of the mass of the myotome, the remainder consisting of fastfibres. The slow and fast fibres have a different pattern of innervation, and differ in such respects as their fat and glycogen contents, and in abundance of mitochondria. The two typesof fibre show different responses to depolarizing agents. Extracellular recordings from the myotomal muscle taken during the swimming of spinal fish show that only slow muscle fibres are active when the fish swims slowly, whereas during vigorous movements, the fast fibres are active. Although both types of fibre contain glycogen, the fast fibres contain only about 50–60 % ofthe amount found in the slow fibres. After a period of vigorous movement, the glycogen levels in the fast fibres fall markedly, whilst those in the slow fibres donot change. The slow fibres contain around 4–5 times the amount of fat found in thefast fibres; after long periods of sustained slow swimming, the fat levels inthe slow fibres fall, and there also may be a slight decrease in the glycogen levels in the slow fibres. Long periods of slow swimming do not alter the glycogen levels found in the fast fibres.