Miracle-dz/UniFAR-FTUs huggingface dataset:
The Involvement of the McsB Arginine Kinase in Clp-Dependent Degradation of the MgsR Regulator in Bacillus subtilis

Regulated ATP-dependent proteolysis is a common feature of developmental processes and plays also a crucial role during environmental perturbations such as stress and starvation. The Bacillus subtilis MgsR regulator controls a subregulon within the stress- and stationary phase σB regulon. After ethanol exposition and a short time-window of activity, MgsR is ClpXP-dependently degraded with a half-life of approximately 6 min. Surprisingly, a protein interaction analysis with MgsR revealed an association with the McsB arginine kinase and an in vivo degradation assay confirmed a strong impact of McsB on MgsR degradation. In vitro phosphorylation experiments with arginine (R) by lysine (K) substitutions in McsB and its activator McsA unraveled all R residues, which are essentially needed for the arginine kinase reaction. Subsequently, site directed mutagenesis of the MgsR substrate was used to substitute all arginine residues with glutamate (R-E) to mimic arginine phosphorylation and to test their influence on MgsR degradation in vivo. It turned out, that especially the R33E and R94/95E residues (RRPI motif), the latter are adjacently located to the two redox-sensitive cysteines in a 3D model, have the potential to accelerate MgsR degradation. These results imply that selective arginine phosphorylation may have favorable effects for Clp dependent degradation of short-living regulatory proteins. We speculate that in addition to its kinase activity and adaptor function for the ClpC ATPase, McsB might also serve as a proteolytic adaptor for the ClpX ATPase in the degradation mechanism of MgsR.
Balance Training in Older Adults Using Exergames: Game Speed and Cognitive Elements Affect How Seniors Play

Falls in older adults are a serious threat to their health and independence, and a prominent reason for institutionalization. Incorrect weight shifts and poor executive functioning have been identified as important causes for falling. Exergames are increasingly used to train both balance and executive functions in older adults, but it is unknown how game characteristics affect the movements of older adults during exergaming. The aim of this study was to investigate how two key game elements, game speed, and the presence of obstacles, influence movement characteristics in older adults playing a balance training exergame. Fifteen older adults (74 ± 4.4 years) played a step-based balance training exergame, designed specifically for seniors to elicit weight shifts and arm stretches. The task consisted of moving sideways to catch falling grapes and avoid obstacles (falling branches), and of raising the arms to catch stationary chickens that appeared above the avatar. No steps in anterior-posterior direction were required in the game. Participants played the game for eight 2 min trials in total, at two speed settings and with or without obstacles, in a counterbalanced order across participants. A 3D motion capture system was used to capture position data of 22 markers fixed to upper and lower body. Calculated variables included step size, step frequency, single leg support, arm lift frequency, and horizontal trunk displacement. Increased game speed resulted in a decrease in mean single support time, step size, and arm lift frequency, and an increase in cadence, game score, and number of error messages. The presence of obstacles resulted in a decrease in single support ratio, step size, cadence, frequency of arm lifts, and game score. In addition, step size increased from the first to the second trial repetition. These results show that both game speed and the presence of obstacles influence players' movement characteristics, but only some of these effects are considered beneficial for balance training whereas others are detrimental. These findings underscore that an informed approach is necessary when designing exergames so that game settings contribute to rather than hinder eliciting the required movements for effective balance training.
Recent development and applications of nanomaterials for cancer immunotherapy

Abstract Immunotherapy, which utilizes the patient’s own immune system to fight against cancer, further results in durable antitumor responses and reduces metastasis and recurrence, has become one of the most effective and important cancer therapies along with surgery, radiotherapy, and chemotherapy. Nanomaterials with the advantages of large specific surface, delivery function, and controllable surface chemistry are used to deliver antigens or adjuvants, or both, help to boost immune responses with the imaging function or just act as adjuvants themselves and modulate tumor microenvironment (TME). In this review, recent development and applications of nanomaterials for cancer immunotherapy including delivery systems based on nanomaterials, uniting imaging, self-adjuvants, targeting functions, artificial antigen presenting cells, and TME modulation are focused and discussed.
Characterization of cytochrome P450 enzymes and P‐glycoprotein involved in the metabolism and transport of a new anti‐angiogenic agent KR‐31831

The in vitro metabolism and the transport of a novel anti‐angiogenic agent KR‐31831, (2R,3R,4S)‐6‐amino‐4‐[N‐(4‐chlorophenyl)‐N‐(1H‐imidazol‐2‐ylmethyl)amino]‐3‐hydroxy‐2‐dimethyoxymethyl‐3,4‐dihydro‐2‐methyl‐2H‐1‐benzopyran were investigated. Liquid chromatography‐mass spectrometry and tandem mass spectrometry were used for qualitative and quantitative analysis. The bidirectional transport studies of KR‐31831 using Caco‐2 cell monolayers showed the efflux to be significantly higher than influx (29.1 × 10−6 compared to 11.5 × 10−6 cm/s). P‐glycoprotein inhibitors significantly increased the influx of KR‐31831 and decreased the efflux of KR‐31831. These data indicate that KR‐313831 is a substrate for an efflux pump, P‐glycoprotein. The incubations of KR‐31831 with human liver microsomes produced three metabolites, M1, M2, and M3. M1 and M2 were identified as N‐(4‐chlorophenyl)‐N‐(1H‐imidazol‐2‐ylmethyl)amine and (2R,3R,4S)‐6‐amino‐4‐[N‐(4‐chlorophenyl)‐N‐(1H‐imidazol‐2‐ylmethyl)amino]‐3‐hydroxy‐2‐hydroxymethyl‐3,4‐dihydro‐2‐methyl‐2H‐1‐benzopyran by comparison with the authentic standards. M3 was tentatively characterized as hydroxy‐KR‐31831. CYP3A4 was identified as the major enzyme responsible for KR‐31831 metabolism to a major metabolite M1 using the combination of correlation analysis, immuno‐inhibition, chemical inhibition in human liver microsomes, and metabolism by cDNA expressed CYP enzymes. There is the possibility of drug–drug interactions when prescribing KR‐31831 concomitantly with known inhibitors or inducers of CYP3A4 and P‐glycoprotein. KR‐31831 was found to inhibit potently the metabolism of CYP2D6 substrate, suggesting that coadministration of KR‐31831 with CYP2D6 substrates may have significant effects on the pharmacokinetics of CYP2D6 substrates. Drug Dev. Res. 66:40–49. 2006. © 2006 Wiley‐Liss, Inc.
Foraging Behavior and Physiological Adaptation for Diving in Thick‐Billed Murres

Foraging behavior and physiological adaptations for diving were studied in Thick-billed Murres, Uria lomvia, in the field and laboratory. Electronic, light-emitting diode, and capillary recording devices were used to measure foraging behavior. Individual dives were a flattened U shape in profile, and occurred in bouts lasting 15 min. Dive patterns were nocturnal; most dives occurred between 2000 and 0400. Murres probably concentrate their foraging effort at times when prey is most available as it migrates closer to the surface in the evening as part of the deep scattering layer. Although dives averaged 18 m in depth and 55 s in duration, most time-at-depth was spent between 21 and 40 m. Thus, murres made a large number of shallow, short-duration dives. Maximum dive depth was 210 m, while maximum dive duration was 224 s. Descent and ascent rates averaged 0.94 and 0.85 m/s, respectively. Hematocrit, hemoglobin, blood volume, and pectoralis myoglobin levels were measured in the laboratory as 52.8%, 18.0 g/100 mL, 12.3% body mass, and 1.9 g/100 g, respectively. Total useable oxygen store was calculated as 44.8 mL/kg, giving an estimated aerobic dive limit (ADL) of 47 s. Murres exceeded the calculated ADL in 48% of their dives. Long-duration diving is probably a more efficient foraging strategy for murres given their relatively small size and limited oxygen storage capabilities. The observed dive depths raised questions of potential problems with decompression sickness (bends) and lung collapse.
DNA : DNA hybridization studies of Rhizobium japonicum and related Rhizobiaceae

The symbiotic nitrogen-fixing bacteria associated with soybeans (Glycine max) have been classified routinely as Rhizobium japonicum. DNA:DNA hybridization studies were conducted to estimate the genetic relationships of strains labelled as R. japonicum to clarify their taxonomic status. Reassociation reactions were carried out using DNA from various Rhizobium and Agrobacterium species. Relationships of DNA sequences were also estimated by comparing the thermal stability of heterologous DNA duplexes with that of the homologous DNA duplex. The results indicated that strains labelled as R. japonicum can be separated into at least three DNA homology groups. Reference strains of other Rhizobium species, with the exception of R. lupini, were not closely related to these homology groups.
“A Proteogenomic workflow reveals distinct molecular phenotypes related to breast cancer appearance”

Proteogenomics approaches have enabled the generation of extensive information levels when compared to single omics technology studies, although burdened by massive experimental efforts. Here, we developed four improvements of a data independent acquisition mass spectrometry proteogenomics workflow to reveal distinct molecular phenotypes related to breast cancer appearance. We confirm mutational processes detectable at the protein level and highlight quantitation and pathway complementarity between RNA and protein data. Our analyses also validated previously established enrichments of estrogen receptor-dependent molecular features relating to transcription factor expression, and provided evidence for molecular differences related to the presence of mammographic appearances in spiculated tumors. In addition, several transcript-protein pairs displayed radically different abundance correlations depending on the overall clinical and pathological properties of the tumor. These results demonstrate that there are differentially regulated protein networks in clinically relevant sample groups, and that these protein networks influence both cancer biology as well as the abundance of potential biomarkers and drug targets.
Total phenolic content, antiradical and antioxidant activities of wild and cultivated Rumex acetosella L. extracts

Edible greens, especially wild greens, play an important role in traditional diets and are rich in phenols and other compounds. The purpose of this study was to investigate total phenolic content (TPC) and antioxidant activities of ethanolic extracts from wild and cultivated Rumex acetosella L. The wild sheep sorrel extract inhibited lipid peroxidation and 1,1-diphenyl-2-picrylhydrazyl radical with EC50 values of 0.02 and 3.67 mg ml− 1; however, the EC50 values for cultivated sheep sorrel extract were 0.76 and 21.94 mg ml− 1. In the reducing power assay, the values of measured absorbance were 0.723 and 0.430 for wild and cultivated extracts, respectively, at 1 mg ml− 1 concentration. The chelating of ferrous ions by the wild and cultivated sheep sorrel was determined as 59.4% and 56.2%, respectively, at 1 mg ml− 1 concentration. TPC of wild and cultivated sheep sorrel was found to be 69.21 ± 8.5 and 57.57 ± 1.8 mg gallic acid equiv. g− 1 extract, respectively. There is a positive correlation between phenolic content and antioxidant assays. The results obtained in this study indicate that wild R. acetosella could be an important dietary source because of its good antioxidant properties.
Effect of Hairy Vetch Incorporated as Green Manure on Growth and N Uptake of Sorghum Crop

Abstract Hairy vetch (Vicia villosa Roth) has the potentials for preventing soil erosion and suppressing weed growth as a winter cover crop. We evaluated the additional N supplied by this crop harvested at different growing stages to the succeeding sorghum in pot experiments. Hairy vetch was grown in 1/5000a Wagner pot, and shoots (S) and roots (R) were mixed separately or together (S+R) into the soil on 30 March, 18 April and 2 May. After incorporation of the plants, seeds of sorghum were sown in the pots. Dry weight and N content of hairy vetch increased throughout the growing period. The value of nitrogenase activity in root nodules peaked on 18 April and then drastically declined. When hairy vetch was harvested on 30 March, N content of sorghum in the S pots was definitely less than that in the R and S+R pots. When hairy vetch harvested on 2 May, however, the N content in the S pots was similar to that in the S+R pots, and it was significantly higher than that in the R pots. Although N input from hairy vetch was higher in the S pots than in the R pots, N uptake by sorghum was not reflected in those values. The belowground parts of hairy vetch may have a considerable effect on N uptake of sorghum when using this plant species as green manures.
CheckV: assessing the quality of metagenome-assembled viral genomes

Over the last several years, metagenomics has enabled the assembly of millions of new viral sequences that have vastly expanded our knowledge of Earth’s viral diversity. However, these sequences range from small fragments to complete genomes and no tools currently exist for estimating their quality. To address this problem, we developed CheckV, which is an automated pipeline for estimating the completeness of viral genomes as well as the identification and removal of non-viral regions found on integrated proviruses. After validating the approach on mock datasets, CheckV was applied to large and diverse viral genome collections, including IMG/VR and the Global Ocean Virome, revealing that the majority of viral sequences were small fragments, with just 3.6% classified as high-quality (i.e. > 90% completeness) or complete genomes. Additionally, we found that removal of host contamination significantly improved identification of auxiliary metabolic genes and interpretation of viral-encoded functions. We expect CheckV will be broadly useful for all researchers studying and reporting viral genomes assembled from metagenomes. CheckV is freely available at: http://bitbucket.org/berkeleylab/CheckV.
Allochronic Divergence Driven by Spatial Asynchrony in Precipitation in Neotropical Frogs?

The role of geographic barriers in promoting reproductive isolation across space is well understood. Isolation by the time of breeding, however, may also promote population divergence when populations reproduce asynchronically in space, even in the absence of geographic barriers. Few examples exist of divergence due to breeding allochrony, particularly in vertebrates. We tested whether in Neotropical frogs’ asynchrony in precipitation patterns promotes intraspecific genetic divergence, speciation, and regional accumulation of diversity. We assessed the relationship between spatial asynchrony in precipitation and genetic divergence controlling for ecological connectivity across 48 Neotropical frog species. In addition, we examined whether regions within which precipitation regimes are more asynchronous across space have higher species richness and have experienced greater speciation rates. Beyond a generalized expected effect of ecological connectivity on intraspecific genetic divergence, we found that asynchrony in precipitation is positively associated with genetic differentiation in 31% of the species tested, resulting in a significantly positive cross-species effect of asynchrony in precipitation on genetic divergence in a meta-analysis. However, the effect of asynchrony in precipitation on population divergence seems not to scale to macroevolutionary patterns because spatial asynchrony in precipitation was not associated with geographical patterns of species richness or speciation rates. Our results indicate that genetic divergence can be promoted by asynchronous breeding lag in the absence of geographic barriers in species where breeding is associated with water availability, but such effects may not be stable enough through time to influence macroevolutionary patterns.
ATAC-Seq Identifies Chromatin Landscapes Linked to the Regulation of Oxidative Stress in the Human Fungal Pathogen Candida albicans

Human fungal pathogens often encounter fungicidal stress conditions upon host invasion, but they can swiftly adapt by transcriptional reprogramming that enables pathogen survival. Fungal immune evasion is tightly connected to chromatin regulation. Hence, fungal chromatin modifiers pose alternative treatment options to combat fungal infections. Here, we present an ATAC-seq protocol adapted for the opportunistic pathogen Candida albicans to gain further insight into the interplay of chromatin accessibility and gene expression mounted during fungal adaptation to oxidative stress. The ATAC-seq workflow facilitates the robust detection of genomic regions with accessible chromatin, but also allows for the precise modeling of nucleosome positions in C. albcians. Importantly, the data reveal genes with altered chromatin accessibility in upstream regulatory regions, which correlate with transcriptional regulation during the oxidative stress response. Interestingly, many genes show increased chromatin accessibility yet no change in gene expression upon stress exposure. Such chromatin signatures could predict yet unknown regulatory factors under highly dynamic transcriptional control. In addition, de novo motif analysis in genomic regions with increased chromatin accessibility upon hydrogen peroxide treatment shows significant enrichment for Cap1 binding sites, a major factor of oxidative stress responses in C. albicans. Taken together, the ATAC-seq workflow enables the identification of chromatin signatures and uncovers the dynamics of regulatory mechanisms mediating environmental adaptation of C. albicans to host immune surveillance. Importance The opportunistic fungal pathogen Candida albicans colonizes and infects various tissues and organs of the human host. This is due to its rapid environmental adaptation facilitated by changes in gene expression coupled to chromatin alterations. Recent advances in chromatin profiling approaches, such as the development of ATAC-seq, shed light on the dynamic interplay of chromatin accessibility and transcriptional control. The here presented expansion of the ATAC-seq method to C. albicans demonstrates the robustness of ATAC-seq to detect dynamic modulations of chromatin accessibility in response to oxidative stress. This work serves as a basis to further exploit this application to characterize regulatory mechanisms that drive fungal environmental adaptation, such as during host invasion, and thus, will open novel antifungal treatment strategies targeting fungal chromatin regulation.
Shoot and root thermomorphogenesis are linked by a developmental trade-off

Temperature is one of the most impactful environmental factors to which plants adjust their growth and development. While the regulation of temperature signaling has been extensively investigated for the aerial part of plants, much less is known and understood about how roots sense and modulate their growth in response to fluctuating temperatures. Here we found that shoot and root growth responses to high ambient temperature are coordinated during early seedling development. A shoot signaling module that includes HY5, the phytochromes and the PIFs exerts a central function in coupling these growth responses and control auxin levels in the root. In addition to the HY5/PIF-dependent shoot module, a regulatory axis composed of auxin biosynthesis and auxin perception factors controls root responses to high ambient temperature. Together, our findings show that shoot and root developmental responses to temperature are tightly coupled during thermomorphogenesis and suggest that roots integrate energy signals with local hormonal inputs.
DMT alters cortical travelling waves

Psychedelic drugs are potent modulators of conscious states and therefore powerful tools for investigating their neurobiology. N,N, Dimethyltryptamine (DMT) is a particularly interesting serotonergic psychedelic that can rapidly induce an extremely immersive state of consciousness characterized by vivid and elaborate visual imagery. In the present study, we investigated the electrophysiological correlates of the DMT-induced altered state, by recording EEG signals from a pool of participants receiving DMT and (separately) placebo (saline), intravenously, while instructed to keep their eyes closed (i.e. ‘resting state’). Consistent with our prior hypotheses, results revealed a spatio-temporal pattern of cortical activation (i.e., travelling waves) similar to that elicited by visual stimulation. Moreover, the typical top-down alpha-band rhythms of closed-eyes rest (i.e. a backward travelling wave) were significantly decreased, while the bottom-up ‘forward travelling wave’, was significantly increased. These results support a recent model proposing that psychedelics reduce the ‘precision-weighting of priors’, thus altering the balance of top-down versus bottom-up information passing, where properties of backward waves are considered correlates of this precision weighting. The robust hypothesis-confirming nature of the present findings imply the discovery of an important mechanistic principle underpinning psychedelic-induced altered states – i.e. reduced backward and increased forward travelling waves - and lend further support to prior assumptions about the functional significance of cortical travelling waves.
Low dosages of gamma irradiation of seed increase the growth and yield of two cultivars of sunflower

Seeds of cv. Restoler and Noor of sunflower (Helianthus annuus L.) were subjected to 0.5 to 50 krad 60Co gamma radiation (1 rad = 10 mGy) and grown to maturity in a greenhouse. Two low dosages, i.e., 1 krad in cv. Restoler and 3 krad in cv. Noor, caused statistically significant stimulation of vegetative growth and seed yield (both total number and weight). For cv. Noor, 3 krad also significantly stimulated the weight of an individual seed. Significant declines in the yield of mature seeds occurred only at critical dosages of > 10 to 20 krad.