Miracle-dz/UniFAR-FTUs huggingface dataset:
Is the “end‐of‐study guess” a valid measure of sham blinding during transcranial direct current stimulation?

Studies using transcranial direct current stimulation (tDCS) typically incorporate a fade-in, short-stimulation, fade-out sham (placebo) protocol, which is assumed to be indistinct from a 10-30min active protocol on the scalp. However, many studies report that participants can dissociate active stimulation from sham, even during low-intensity 1mA currents. We recently identified differences in the perception of an active (10min of 1mA) and a sham (20s of 1mA) protocol that lasted for 5 mins after the cessation of sham. In the present study we assessed whether delivery of a higher-intensity 2mA current would exacerbate these differences. Two protocols were delivered to 32 adults in a double-blinded, within-subjects design (active: 10min of 2mA, and sham: 20s of 2mA), with the anode over the left primary motor cortex and the cathode on the right forehead. Participants were asked “Is the stimulation on? ” and “How sure are you? ” at 30s intervals during and after stimulation. The differences between active and sham were more consistent and sustained during 2mA than during 1mA. We then quantified how well participants were able to track the presence and absence of stimulation (i.e. their sensitivity) during the experiment using cross-correlations. Current strength was a good classifier of sensitivity during active tDCS, but exhibited only moderate specificity during sham. The accuracy of the end-of-study guess was no better than chance at predicting sensitivity. Our results indicate that the traditional end-of-study guess poorly reflects the sensitivity of participants to stimulation, and may not be a valid method of assessing sham blinding.
Variation of architecture with size in the multiple-bank retina of a deep-sea teleost, Chauliodus sloani

The pure rod retina of mature Chauliodus sloani contains up to five banks of rods, but that of small specimens contains only one bank. New banks are added progressively as the fish grows. The size of the retinal cells remains approximately constant throughout the range, but, as the retinal thickness increases with growth and new banks are added, the density of nuclei in the outer nuclear layer increases. The density of total rods increases as new banks are added, but that of the vitread bank remains constant or falls slightly. The density of ganglion cells falls with growth, the estimated total in the retina rising to a maximum by about 100 mm standard length. Estimates of convergence ratio of total rods to total ganglion cells increase from about 7:1 in the smallest to about 200:1 in the largest specimens. Implications of the findings for the development and function of the multiple-bank retina are discussed.
GrgA controls Chlamydia trachomatis growth and development by regulating expression of transcription factors Euo and HrcA

The obligate intracellular bacterium Chlamydia trachomatis is an important human pathogen whose biphasic developmental cycle consists of an infectious elementary body and a replicative reticulate body. Whereas σ66, the primary sigma factor, is necessary for transcription of most chlamydial genes throughout the developmental cycle, σ28 is required for expression of some late genes. We previously showed that the Chlamydia-specific transcription factor GrgA physically interacts with both of these sigma factors and activates transcription from σ66- and σ28-dependent promoters in vitro. Here, we investigate the organismal functions of GrgA. We show that GrgA overexpression decreased RB proliferation via time-dependent transcriptomic changes. Significantly, σ66-dependent genes that code for two important transcription repressors are among the direct targets of GrgA. One of these repressors is Euo, which prevents the expression of late genes during early phases. The other is HrcA, which regulates gene expression in response to heat shock. The direct regulon of GrgA also includes a σ28-dependent gene that codes for the putative virulence factor PmpI. Conditional overexpression of Euo and HrcA also inhibited chlamydial growth and affected GrgA expression. Transcriptomic studies suggest that GrgA, Euo, and HrcA have distinct but overlapping indirect regulons. Furthermore, overexpression of either GrgA leads to decreased expression of numerous tRNAs. These findings indicate that a GrgA-mediated transcriptional regulatory network controls C. trachomatis growth and development. IMPORTANCE Chlamydia trachomatis is the most prevalent sexually transmitted bacterial pathogen worldwide and is a leading cause of preventable blindness in under-developed areas as well as developed countries. Previous studies showed that the novel transcription factor GrgA activated chlamydial gene transcription in vitro, but did not addressed the organismal function of GrgA. Here, we demonstrate growth inhibition in C. trachomatis engineered to conditionally overexpress GrgA. GrgA overexpression immediately increases the expression of two other critical transcription factors (Euo and HrcA) and a candidate virulence factor (PmpI), among several other genes. We also reveal chlamydial growth reduction and transcriptomic changes including decreased GrgA mRNA levels in response to either Euo or HrcA overexpression. Thus, the transcription network controlled by GrgA likely plays a crucial role in chlamydial growth and pathogenesis.
Costs and benefits of toxin production in a dinoflagellate

Many phytoplankton respond to chemical cues from grazers by upregulating defensive capabilities. Inducible defences like these are often assumed to come at a cost to the organism, but these trade-offs have not been experimentally established. A reason for this may be that costs only become evident under resource limiting conditions. Here, we exposed the toxin-producing dinoflagellate Alexandrium minutum to chemical cues from copepods under different levels of nitrogen limitation. Induced cells had higher cellular toxin content and a larger fraction of the cells were rejected by a copepod, demonstrating the clear benefits of toxin production. Induced cells also had a higher carbon and nitrogen content, despite an up to 25% reduction in cell size. Unexpectedly, induced cells seemed to grow faster than controls, likely owing to a higher nutrient affinity due to reduced size. We thus found no clear trade-offs, rather the opposite. However, we argue that indirect ecological costs that do not manifest under laboratory conditions are important and that the induction of toxins specific to particular defences prevents the cells from constantly synthesizing the large array of secondary metabolites that they are capable of producing.
Anxiety makes time pass quicker: neural correlates

Anxiety can be an adaptive process that promotes harm avoidance. It is accompanied by shifts in cognitive processing, but the precise nature of these changes and the neural mechanisms that underlie them are not fully understood. One theory is that anxiety impairs concurrent (non-harm related) cognitive processing by commandeering finite neurocognitive resources. For example, we have previously shown that anxiety reliably ‘speeds up time’, promoting temporal underestimation, possibly due to loss of temporal information. Whether this is due anxiety ‘overloading’ neurocognitive processing of time is unknown. We therefore set out to understand the neural correlates of this effect, examining whether anxiety and time processing overlap, particularly in regions of the cingulate cortex. Across two studies (an exploratory Study 1, N=13, followed by a pre-registered Study 2, N=29) we combined a well-established anxiety manipulation (threat of shock) with a temporal bisection task while participants were scanned using functional magnetic resonance imaging. Consistent with our previous work, time was perceived to pass more quickly under induced anxiety. Anxiety induction led to widespread activation in cingulate cortex, while the perception of longer intervals was associated with more circumscribed activation in a mid-cingulate area. Importantly, conjunction analysis identified convergence between anxiety and time processing in the insula and mid-cingulate cortex. These results provide tentative support for the hypothesis that anxiety impacts cognitive processing by overloading already-in-use neural resources. In particular, overloading mid-cingulate cortex capacity may drive emotion-related changes in temporal perception, consistent with the hypothesised role of this region in mediating cognitive affective and behavioural responses to anxiety.
Metabolic interactions involving sulphate‐reducing and methanogenic bacteria in the human large intestine

A comprehensive study involving 87 healthy human volunteers showed that dissimilatory sulphate-reducing bacteria (SRB) occurred in high numbers in faeces of non-methanogenic persons. Three broad population groupings were identified on the basis of SRB carriage rates. Individuals in Group A (n=21) were strongly methanogenic and SRB were never detected in significant numbers in their faeces. In Group B (n=9), methanogenesis occurred, how numbers of faecal SRB (ca. 105 g (wet wt. faeces)−1) were found. Volunteers in Group C (n=57) had high counts of faecal SRB (ca. 109 (g wet wt. faeces)−1) and no methanogenesis. These data were confirmed by CH4 production and SO42− reduction rates in faecal slurries. The principal SRB were identified as lactate and H2 utilizing Desulfovibrio spp. (64–81%), acetate utilizing Desulfobacter spp. (9–16%), propionate and H2 utilizing Desulfobulbus spp. (5–8%), lactate utilizing Desulfomonas spp. (3–10%) and acetate and butyrate utilizing Desulfotomaculum spp. (2%). Measurements of SRB numbers and activities in digesta taken from the proximal and distal colons from 2 individuals who had died suddenly, showed no significant difference in SRB counts or the relative distribution of genera in these regions. However, in the methanogenic person, MB were higher by approximately 3 orders of magnitude in the distal gut. Inhibition experiments with 2-bromoethanesulphonic acid (BES) and sodium molybdate (Mo) showed that H2 production was higher in the distal colon compared to the proximal gut (33% and 263% respectively, in CH4 producing and non-CH4 producing digesta). Inhibition of methanogenesis had little qualitative or quantitative effect on short chain fatty acid (SCFA) formation, but inhibition of SRB resulted in an increase in accumulation of SCFA, together with succinate and lactate. These data demonstrate the greater metabolic diversity and capacity of human colonic SRB compared to MB, and suggest that SRB may play a significant role in the turnover of fatty acids in the colons of some individuals.
Modified Contemporary and Herdmate Comparisons in Sire Summary

Abstract The influence of various factors on differences in sire evaluation from herdmate comparison and modified contemporary comparison methodology was examined. The average Predicted Difference for milk of bulls with 10 or more daughters changed —8, 33, 13, —20, and —8kg in Ayrshires, Brown Swiss, Guernseys, Holsteins, and Jerseys; standard deviations of change ranged from 76 to 118kg. The population from which the bulls were selected (pedigree group means) accounted for 49 to 73% of the change. Genetic average of herdmates' sires accounted for 26 to 39% of the change. For bulls with repeatabilities of over 80%, the genetic average of herd-mates' sires accounted for 41 to 83%. New repeatabilities averaged 1.6 to 1.9 less than those from the old method but were more variable. Correlations of Predicted Difference for milk by modified contemporary comparison with information from daughters added after the October, 1974 summary were from . 04 to . 15 higher than Predicted Differences by herdmate comparison. The Predicted Difference by modified contemporary comparison had the greatest advantage over that from the herdmate comparison when bulls had small numbers of daughters. Correlation of Predicted Difference by modified contemporary comparison with additional daughter information was . 13 higher than that of the herdmate comparison when fewer than 10 daughters were in the summary and was only . 04 higher when more than 100 daughters were in the summary.
Muscle Activation Patterns Are More Constrained and Regular in Treadmill Than in Overground Human Locomotion

The use of motorized treadmills as convenient tools for the study of locomotion has been in vogue for many decades. However, despite the widespread presence of these devices in many scientific and clinical environments, a full consensus on their validity to faithfully substitute free overground locomotion is still missing. Specifically, little information is available on whether and how the neural control of movement is affected when humans walk and run on a treadmill as compared to overground. Here, we made use of linear and nonlinear analysis tools to extract information from electromyographic recordings during walking and running overground, and on an instrumented treadmill. We extracted synergistic activation patterns from the muscles of the lower limb via non-negative matrix factorization. We then investigated how the motor modules (or time-invariant muscle weightings) were used in the two locomotion environments. Subsequently, we examined the timing of motor primitives (or time-dependent coefficients of muscle synergies) by calculating their duration, the time of main activation, and their Hurst exponent, a nonlinear metric derived from fractal analysis. We found that motor modules were not influenced by the locomotion environment, while motor primitives resulted overall more regular in treadmill than in overground locomotion, with the main activity of the primitive for propulsion shifted earlier in time. Our results suggest that the spatial and sensory constraints imposed by the treadmill environment forced the central nervous system to adopt a different neural control strategy than that used for free overground locomotion. A data-driven indication that treadmills induce perturbations to the neural control of locomotion.
Activation of STING due to COPI-deficiency

COPA syndrome is caused by loss-of-function mutations in the COP-α subunit of coatomer protein complex I (COPI), which participates in retrograde vesicular trafficking of proteins from the Golgi to the endoplasmic reticulum (ER). Disease manifests early in life with arthritis, lung pathology, kidney dysfunction and systemic inflammation associated with NF-κB activation and type I interferon (IFNαβ) production. Here, we generated in vitro models for COPA syndrome and interrogated inflammatory signalling pathways via a range of biochemical and molecular biological techniques. Results were confirmed with cell lines in which mutant COPA was overexpressed and with COPA syndrome patient PBMCs. We identified Stimulator of Interferon Genes (STING), as a driver of inflammation in COPA syndrome. Furthermore, we found that genetic deletion of COPG1, another COPI subunit protein, induced NF-κB and type I IFN pathways similar to COPA-deficiency. Finally, we demonstrate that in vitro, inflammation due to COPA syndrome mutations was ameliorated by treatment with the small molecule STING inhibitor H-151. Therefore, inflammation induced by deletion of COPI subunits in general suggests a link between retrograde trafficking and STING regulation, and this innate immune sensor represents a novel therapeutic target in COPA syndrome.
Winter wheat competition against jointed goatgrass (Aegilops cylindrica) as influenced by wheat plant height, seeding rate, and seed size

Abstract Jointed goatgrass is a troublesome weed in winter wheat with selective control only possible with a herbicide-resistant crop. Even with herbicide-resistant wheat, cultural control is still an important part of jointed goatgrass management. A study was conducted in 1998 and 2000 to determine whether using larger sized seed of a tall wheat variety at an increased seeding rate would reduce the effect of jointed goatgrass on winter wheat. Wheat seed size, seeding rate, and variety height had no effect on jointed goatgrass plant density. Tall (∼130 cm) wheat reduced mature jointed goatgrass biomass 46 and 16% compared with short (∼100 cm) wheat in years 1 and 2 of the experiment, respectively. Spikelet biomass was also reduced approximately 70 and 30% in the same respective years. One thousand–spikelet weight of jointed goatgrass was reduced 37 and 7% in years 1 and 2, respectively, when grown in competition with taller compared with shorter wheat. Moreover, dockage was 80 and 30% less in years 1 and 2, respectively, when grown in competition with taller than shorter wheat. Mature jointed goatgrass height was similar regardless of the competitive wheat height. However, jointed goatgrass was as much as 18% taller than the short wheat and 15% shorter than the tall wheat. Seeding rate had the most consistent effect on wheat yield. Wheat seed yield was about 10% greater with 60 than 40 seed m−1 of row when competing with jointed goatgrass. Results of this study indicate that growers could use a tall winter wheat variety to improve crop competition against jointed goatgrass. Results also indicate that plant breeders should consider plant height because herbicide-resistant varieties are developed for the integrated management of jointed goatgrass. Nomenclature: Jointed goatgrass, Aegilops cylindrica Host. AEGCY; winter wheat, Triticum aestivum L. ‘Nugaines’.
Improvement studies on mutton sheep for Marmara region conditions: I. fertility, lamb survival, and growth traits of lambs

Th e present study was conducted to compare the fertility of ewes, the survival rates, and the growth performance of lambs that were crossbred by mating German Black-Headed Mutton (GBM) rams with Kivircik ewes. Th e average lambing rates of the GBM × K(F 1 ), Bandirma-I and Bandirma-II genotype, and Kivircik ewes were 80.00%, 75.73%, 76.78%, and 83.72%, respectively. Th e diff erences in lambing rates between the genotypes were signifi cant (P < 0.01). Th e genotypes had a signifi cant eff ect on litter size at birth, but not on fecundity. Th e diff erences in lambs' survival rates between the genotypes were signifi cant (P < 0.05). Th e birth weight (BW), weaning weight (WW), and yearling live weight (YLW) of the lambs were 3.77 kg, 34.11 kg, and 43.71 kg for the GBM × K (F 1 ); 3.74 kg, 32.98 kg, and 44.91 kg for the Bandirma-I; 3.73 kg, 33.18 kg, and 45.71 kg for the Bandirma-II; and 3.45 kg, 30.92 kg, and 42.22 kg for the Kivircik lambs. Th e results of this study showed that crossbreeding between the GBM and Kivircik breed did not signifi cantly increase lamb production. However, crossbred lambs did not have signifi cant survival problems when compared to native Kivircik lambs and had higher growth performance than purebred Kivircik lambs.
On the Source of Peptides for Major Histocompatibility Class I Antigen Presentation: A Dissertation

Peptides generated from cellular protein degradation via the ubiquitin-proteasome pathway are presented on MHC class I as a means for the immune system to monitor polypeptides being synthesized by cells. For CD8 + T cells to prevent the spread of an incipient infection, it appears essential they should be able to sense foreign polypeptides being synthesized as soon as possible. A prompt detection of viral proteins is of great importance for the success of an adaptive immune response. Defective ribosomal products (DRiPs) have been postulated as a preferential source which would allow for a rapid presentation of peptides derived from the degradation of all newly synthesized proteins. Although this hypothesis is intellectually appealing there is lack of experimental data supporting a mechanism that would prioritize presentation from DRiPs. In this dissertation I describe a series of experiments that probe the DRiPs hypothesis by assessing the contribution to class I presentation of model epitopes derived from DRiPs or from functional proteins. The results show that even at the early stages after mRNA synthesis DRiPs do not account for a significant fraction of the class I presented peptides. These observations suggest that the currently widespread model whereby a mechanism exists which selectively allows for DRiPs to preferentially contribute to class I antigen presentation, is incorrect. Rather, properly folded functional proteins can significantly contribute to class I antigen presentation as they are normally turned over by the ubiquitin-proteasome pathway.
The molecular architecture of CenH3-deficient holocentromeres in Lepidoptera is dependent on transcriptional and chromatin dynamics

Despite their essentiality for chromosome segregation, centromeres are diverse among eukaryotes and embody two main configurations: mono- and holocentromeres, referring respectively to a localized or unrestricted distribution of centromeric activity. Previous studies revealed that holocentricity in many insects coincides with the loss of the otherwise essential centromere component CenH3 (CENP-A), suggesting a molecular link between the two events. In this study, we leveraged recently-identified centromere components to map and characterize the centromeres of Bombyx mori. This uncovered a robust correlation between centromere profiles and regions of low chromatin dynamics. Transcriptional perturbation experiments showed that low chromatin activity is crucial for centromere formation in B. mori. Our study points to a novel mechanism of centromere formation that occurs in a manner recessive to the chromosome-wide chromatin landscape. Based on similar profiles in additional Lepidoptera, we propose an evolutionarily conserved mechanism that underlies the establishment of holocentromeres through loss of centromere specificity.
Lilikoi V2.0: a deep learning–enabled, personalized pathway-based R package for diagnosis and prognosis predictions using metabolomics data

Previously we developed Lilikoi, a personalized pathway-based method to classify diseases using metabolomics data. Given the new trends of computation in the metabolomics field, here we report the next version of Lilikoi as a significant upgrade. The new Lilikoi v2.0 R package has implemented a deep-learning method for classification, in addition to popular machine learning methods. It also has several new modules, including the most significant addition of prognosis prediction, implemented by Cox-PH model and the deep-learning based Cox-nnet model. Additionally, Lilikoi v2.0 supports data preprocessing, exploratory analysis, pathway visualization and metabolite-pathway regression. In summary, Lilikoi v2.0 is a modern, comprehensive package to enable metabolomics analysis in R programming environment.
Evidence for reduced immune gene diversity and activity during the evolution of termites

The evolution of biological complexity is associated with the emergence of bespoke immune systems that maintain and protect organism integrity. Unlike the well studied immunity at the cell and individual level, little is known about the origins of immunity during the transition to eusociality, a major evolutionary transition comparable to the evolution of multicellular organisms from single-celled ancestors. We tackle this by characterizing the immune gene repertoire of 18 cockroach and termite species, spanning the spectrum of solitary, subsocial and eusocial lifestyles. We identified five significant immune gene family contractions and one immune gene family expansion along the spine of a time-calibrated phylogeny, correlating with key transitions in termite sociality. In cross-species comparisons of immune gene expression, we find that termites appear to have evolved a caste-specific social defense system at the expense of individual immune protection. Our study indicates that a major transition in organismal complexity entailed a fundamental reshaping of the immune system optimized for group over individual defense.