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The discovery that certain diseases have specific miRNA signatures which correspond to disease progression opens a new biomarker category. The detection of these small non-coding RNAs is performed routinely using body fluids or tissues with real-time PCR, next-generation sequencing, or amplification-based miRNA assays. Antibody-based detection systems allow an easy onset handling compared to PCR or sequencing and can be considered as alternative methods to support miRNA diagnostic in the future. In this study, we describe the generation of a camelid heavy-chain-only antibody specifically recognizing miRNAs to establish an antibody-based detection method. The generation of nucleic acid-specific binders is a challenge. We selected camelid binders via phage display, expressed them as VHH as well as full-length antibodies, and characterized the binding to several miRNAs from a signature specific for dilated cardiomyopathy. The described workflow can be used to create miRNA-specific binders and establish antibody-based detection methods to provide an additional way to analyze disease-specific miRNA signatures.
Importance Alcohol consumption (AC) leads to death and disability worldwide. Ongoing discussions on potential negative effects of the COVID-19 pandemic on AC need to be informed by real-world evidence.
Objective To examine whether lockdown measures are associated with AC and consumption-related temporal and psychological within-person mechanisms.
Design, Setting, and Participants This quantitative, intensive, longitudinal cohort study recruited 1743 participants from 3 sites from February 20, 2020, to February 28, 2021. Data were provided before and within the second lockdown of the COVID-19 pandemic in Germany: before lockdown (October 2 to November 1, 2020); light lockdown (November 2 to December 15, 2020); and hard lockdown (December 16, 2020, to February 28, 2021).
Main Outcomes and Measures Daily ratings of AC (main outcome) captured during 3 lockdown phases (main variable) and temporal (weekends and holidays) and psychological (social isolation and drinking intention) correlates.
Results Of the 1743 screened participants, 189 (119 [63.0%] male; median [IQR] age, 37 [27.5-52.0] years) with at least 2 alcohol use disorder (AUD) criteria according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) yet without the need for medically supervised alcohol withdrawal were included. These individuals provided 14 694 smartphone ratings from October 2020 through February 2021. Multilevel modeling revealed significantly higher AC (grams of alcohol per day) on weekend days vs weekdays (β = 11.39; 95% CI, 10.00-12.77; P < .001). Alcohol consumption was above the overall average on Christmas (β = 26.82; 95% CI, 21.87-31.77; P < .001) and New Year’s Eve (β = 66.88; 95% CI, 59.22-74.54; P < .001). During the hard lockdown, perceived social isolation was significantly higher (β = 0.12; 95% CI, 0.06-0.15; P < .001), but AC was significantly lower (β = −5.45; 95% CI, −8.00 to −2.90; P = .001). Independent of lockdown, intention to drink less alcohol was associated with lower AC (β = −11.10; 95% CI, −13.63 to −8.58; P < .001). Notably, differences in AC between weekend and weekdays decreased both during the hard lockdown (β = −6.14; 95% CI, −9.96 to −2.31; P = .002) and in participants with severe AUD (β = −6.26; 95% CI, −10.18 to −2.34; P = .002).
Conclusions and Relevance This 5-month cohort study found no immediate negative associations of lockdown measures with overall AC. Rather, weekend-weekday and holiday AC patterns exceeded lockdown effects. Differences in AC between weekend days and weekdays evinced that weekend drinking cycles decreased as a function of AUD severity and lockdown measures, indicating a potential mechanism of losing and regaining control. This finding suggests that temporal patterns and drinking intention constitute promising targets for prevention and intervention, even in high-risk individuals.
Objective: A role for microRNAs is implicated in several biological and pathological processes. We investigated the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on molecular markers of diabetic cardiomyopathy in rats.
Methods: Eighteen male Wistar rats (260 ± 10 g; aged 8 weeks) with streptozotocin (STZ)-induced type 1 diabetes mellitus (55 mg/kg, IP) were randomly allocated to three groups: control, MICT, and HIIT. The two different training protocols were performed 5 days each week for 5 weeks. Cardiac performance (end-systolic and end-diastolic dimensions, ejection fraction), the expression of miR-206, HSP60, and markers of apoptosis (cleaved PARP and cytochrome C) were determined at the end of the exercise interventions.
Results: Both exercise interventions (HIIT and MICT) decreased blood glucose levels and improved cardiac performance, with greater changes in the HIIT group (p < 0.001, η2: 0.909). While the expressions of miR-206 and apoptotic markers decreased in both training protocols (p < 0.001, η2: 0.967), HIIT caused greater reductions in apoptotic markers and produced a 20% greater reduction in miR-206 compared with the MICT protocol (p < 0.001). Furthermore, both training protocols enhanced the expression of HSP60 (p < 0.001, η2: 0.976), with a nearly 50% greater increase in the HIIT group compared with MICT.
Conclusions: Our results indicate that both exercise protocols, HIIT and MICT, have the potential to reduce diabetic cardiomyopathy by modifying the expression of miR-206 and its downstream targets of apoptosis. It seems however that HIIT is even more effective than MICT to modulate these molecular markers.
Aims: High intensity interval training (HIIT) improves mitochondrial characteristics. This study compared the impact of two workload-matched high intensity interval training (HIIT) protocols with different work:recovery ratios on regulatory factors related to mitochondrial biogenesis in the soleus muscle of diabetic rats.
Materials and methods: Twenty-four Wistar rats were randomly divided into four equal-sized groups: non-diabetic control, diabetic control (DC), diabetic with long recovery exercise [4–5 × 2-min running at 80%–90% of the maximum speed reached with 2-min of recovery at 40% of the maximum speed reached (DHIIT1:1)], and diabetic with short recovery exercise (5–6 × 2-min running at 80%–90% of the maximum speed reached with 1-min of recovery at 30% of the maximum speed reached [DHIIT2:1]). Both HIIT protocols were completed five times/week for 4 weeks while maintaining equal running distances in each session.
Results: Gene and protein expressions of PGC-1α, p53, and citrate synthase of the muscles increased significantly following DHIIT1:1 and DHIIT2:1 compared to DC (p ˂ 0.05). Most parameters, except for PGC-1α protein (p = 0.597), were significantly higher in DHIIT2:1 than in DHIIT1:1 (p ˂ 0.05). Both DHIIT groups showed significant increases in maximum speed with larger increases in DHIIT2:1 compared with DHIIT1:1.
Conclusion: Our findings indicate that both HIIT protocols can potently up-regulate gene and protein expression of PGC-1α, p53, and CS. However, DHIIT2:1 has superior effects compared with DHIIT1:1 in improving mitochondrial adaptive responses in diabetic rats.
The Role of the Precuneus in Human Spatial Updating in a Real Environment Setting—A cTBS Study
(2022)
As we move through an environment, we update positions of our body relative to other objects, even when some objects temporarily or permanently leave our field of view—this ability is termed egocentric spatial updating and plays an important role in everyday life. Still, our knowledge about its representation in the brain is still scarce, with previous studies using virtual movements in virtual environments or patients with brain lesions suggesting that the precuneus might play an important role. However, whether this assumption is also true when healthy humans move in real environments where full body-based cues are available in addition to the visual cues typically used in many VR studies is unclear. Therefore, in this study we investigated the role of the precuneus in egocentric spatial updating in a real environment setting in 20 healthy young participants who underwent two conditions in a cross-over design: (a) stimulation, achieved through applying continuous theta-burst stimulation (cTBS) to inhibit the precuneus and (b) sham condition (activated coil turned upside down). In both conditions, participants had to walk back with blindfolded eyes to objects they had previously memorized while walking with open eyes. Simplified trials (without spatial updating) were used as control condition, to make sure the participants were not affected by factors such as walking blindfolded, vestibular or working memory deficits. A significant interaction was found, with participants performing better in the sham condition compared to real stimulation, showing smaller errors both in distance and angle. The results of our study reveal evidence of an important role of the precuneus in a real-environment egocentric spatial updating; studies on larger samples are necessary to confirm and further investigate this finding.
Fitness, risk taking, and spatial behavior covary with boldness in experimental vole populations
(2022)
Individuals of a population may vary along a pace-of-life syndrome from highly fecund, short-lived, bold, dispersive “fast” types at one end of the spectrum to less fecund, long-lived, shy, plastic “slow” types at the other end. Risk-taking behavior might mediate the underlying life history trade-off, but empirical evidence supporting this hypothesis is still ambiguous. Using experimentally created populations of common voles (Microtus arvalis)—a species with distinct seasonal life history trajectories—we aimed to test whether individual differences in boldness behavior covary with risk taking, space use, and fitness. We quantified risk taking, space use (via automated tracking), survival, and reproductive success (via genetic parentage analysis) in 8 to 14 experimental, mixed-sex populations of 113 common voles of known boldness type in large grassland enclosures over a significant part of their adult life span and two reproductive events. Populations were assorted to contain extreme boldness types (bold or shy) of both sexes. Bolder individuals took more risks than shyer ones, which did not affect survival. Bolder males but not females produced more offspring than shy conspecifics. Daily home range and core area sizes, based on 95% and 50% Kernel density estimates (20 ± 10 per individual, n = 54 individuals), were highly repeatable over time. Individual space use unfolded differently for sex-boldness type combinations over the course of the experiment. While day ranges decreased for shy females, they increased for bold females and all males. Space use trajectories may, hence, indicate differences in coping styles when confronted with a novel social and physical environment. Thus, interindividual differences in boldness predict risk taking under near-natural conditions and have consequences for fitness in males, which have a higher reproductive potential than females. Given extreme inter- and intra-annual fluctuations in population density in the study species and its short life span, density-dependent fluctuating selection operating differently on the sexes might maintain (co)variation in boldness, risk taking, and pace-of-life.
Biological invasions may result from multiple introductions, which might compensate for reduced gene pools caused by bottleneck events, but could also dilute adaptive processes. A previous common-garden experiment showed heritable latitudinal clines in fitness-related traits in the invasive goldenrod Solidago canadensis in Central Europe. These latitudinal clines remained stable even in plants chemically treated with zebularine to reduce epigenetic variation. However, despite the heritability of traits investigated, genetic isolation-by-distance was non-significant. Utilizing the same specimens, we applied a molecular analysis of (epi)genetic differentiation with standard and methylation-sensitive (MSAP) AFLPs. We tested whether this variation was spatially structured among populations and whether zebularine had altered epigenetic variation. Additionally, we used genome scans to mine for putative outlier loci susceptible to selection processes in the invaded range. Despite the absence of isolation-by-distance, we found spatial genetic neighborhoods among populations and two AFLP clusters differentiating northern and southern Solidago populations. Genetic and epigenetic diversity were significantly correlated, but not linked to phenotypic variation. Hence, no spatial epigenetic patterns were detected along the latitudinal gradient sampled. Applying genome-scan approaches (BAYESCAN, BAYESCENV, RDA, and LFMM), we found 51 genetic and epigenetic loci putatively responding to selection. One of these genetic loci was significantly more frequent in populations at the northern range. Also, one epigenetic locus was more frequent in populations in the southern range, but this pattern was lost under zebularine treatment. Our results point to some genetic, but not epigenetic adaptation processes along a large-scale latitudinal gradient of S. canadensis in its invasive range.
Intelligence, as well as working memory and attention, affect the acquisition of mathematical competencies. This paper aimed to examine the influence of working memory and attention when taking different mathematical skills into account as a function of children’s intellectual ability. Overall, intelligence, working memory, attention and numerical skills were assessed twice in 1868 German pre-school children (t1, t2) and again at 2nd grade (t3). We defined three intellectual ability groups based on the results of intellectual assessment at t1 and t2. Group comparisons revealed significant differences between the three intellectual ability groups. Over time, children with low intellectual ability showed the lowest achievement in domain-general and numerical and mathematical skills compared to children of average intellectual ability. The highest achievement on the aforementioned variables was found for children of high intellectual ability. Additionally, path modelling revealed that, depending on the intellectual ability, different models of varying complexity could be generated. These models differed with regard to the relevance of the predictors (t2) and the future mathematical skills (t3). Causes and conclusions of these findings are discussed.
Background
Maximal isokinetic strength ratios of joint flexors and extensors are important parameters to indicate the level of muscular balance at the joint. Further, in combat sports athletes, upper and lower limb muscle strength is affected by the type of sport. Thus, this study aimed to examine the differences in maximal isokinetic strength of the flexors and extensors and the corresponding flexor–extensor strength ratios of the elbows and knees in combat sports athletes.
Method
Forty male participants (age = 22.3 ± 2.5 years) from four different combat sports (amateur boxing, taekwondo, karate, and judo; n = 10 per sport) were tested for eccentric peak torque of the elbow/knee flexors (EF/KF) and concentric peak torque of the elbow/knee extensors (EE/KE) at three different angular velocities (60, 120, and 180°/s) on the dominant and non-dominant side using an isokinetic device.
Results
Analyses revealed significant, large-sized group × velocity × limb interactions for EF, EE, and EF–EE ratio, KF, KE, and KF–KE ratio (p ≤ 0.03; 0.91 ≤ d ≤ 1.75). Post-hoc analyses indicated that amateur boxers displayed the largest EE strength values on the non-dominant side at ≤ 120°/s and the dominant side at ≥ 120°/s (p < 0.03; 1.21 ≤ d ≤ 1.59). The largest EF–EE strength ratios were observed on amateur boxers’ and judokas’ non-dominant side at ≥ 120°/s (p < 0.04; 1.36 ≤ d ≤ 2.44). Further, we found lower KF–KE strength measures in karate (p < 0.04; 1.12 ≤ d ≤ 6.22) and judo athletes (p ≤ 0.03; 1.60 ≤ d ≤ 5.31) particularly on the non-dominant side.
Conclusions
The present findings indicated combat sport-specific differences in maximal isokinetic strength measures of EF, EE, KF, and KE particularly in favor of amateur boxers on the non-dominant side.
Objective
To improve consumer decision making, the results of risk assessments on food, feed, consumer products or chemicals need to be communicated not only to experts but also to non-expert audiences. The present study draws on evidence from literature reviews and focus groups with diverse stakeholders to identify content to integrate into an existing risk assessment communication (Risk Profile).
Methods
A combination of rapid literature reviews and focus groups with experts (risk assessors (n = 15), risk managers (n = 8)), and non-experts (general public (n = 18)) were used to identify content and strategies for including information about risk assessment results in the “Risk Profile” from the German Federal Institute for Risk Assessment. Feedback from initial focus groups was used to develop communication prototypes that informed subsequent feedback rounds in an iterative process. A final prototype was validated in usability tests with experts.
Results
Focus group feedback and suggestions from risk assessors were largely in line with findings from the literature. Risk managers and lay persons offered similar suggestions on how to improve the existing communication of risk assessment results (e.g., including more explanatory detail, reporting probabilities for individual health impairments, and specifying risks for subgroups in additional sections). Risk managers found information about quality of evidence important to communicate, whereas people from the general public found this information less relevant. Participants from lower educational backgrounds had difficulties understanding the purpose of risk assessments. User tests found that the final prototype was appropriate and feasible to implement by risk assessors.
Conclusion
An iterative and evidence-based process was used to develop content to improve the communication of risk assessments to the general public while being feasible to use by risk assessors. Remaining challenges include how to communicate dose-response relationships and standardise quality of evidence ratings across disciplines.
Symmetric, elegantly entangled structures are a curious mathematical construction that has found their way into the heart of the chemistry lab and the toolbox of constructive geometry. Of particular interest are those structures—knots, links and weavings—which are composed locally of simple twisted strands and are globally symmetric. This paper considers the symmetric tangling of multiple 2-periodic honeycomb networks. We do this using a constructive methodology borrowing elements of graph theory, low-dimensional topology and geometry. The result is a wide-ranging enumeration of symmetric tangled honeycomb networks, providing a foundation for their exploration in both the chemistry lab and the geometers toolbox.
Digitale Musikmedien und -technologien in der Musiklehrer*innenausbildung an der Universität Potsdam
(2022)
Background
The aim of this study was to analyze the shoulder functional profile (rotation range of motion [ROM] and strength), upper and lower body performance, and throwing speed of U13 versus U15 male handball players, and to establish the relationship between these measures of physical fitness and throwing speed.
Methods
One-hundred and nineteen young male handball players (under (U)-13 (U13) [n = 85]) and U15 [n = 34]) volunteered to participate in this study. The participating athletes had a mean background of sytematic handball training of 5.5 ± 2.8 years and they exercised on average 540 ± 10.1 min per week including sport-specific team handball training and strength and conditioning programs. Players were tested for passive shoulder range-of-motion (ROM) for both internal (IR) and external rotation (ER) and isometric strength (i.e., IR and ER) of the dominant/non-dominant shoulders, overhead medicine ball throw (OMB), hip isometric abductor (ABD) and adductor (ADD) strength, hip ROM, jumps (countermovement jump [CMJ] and triple leg-hop [3H] for distance), linear sprint test, modified 505 change-of-direction (COD) test and handball throwing speed (7 m [HT7] and 9 m [HT9]).
Results
U15 players outperformed U13 in upper (i.e., HT7 and HT9 speed, OMB, absolute IR and ER strength of the dominant and non-dominant sides; Cohen’s d: 0.76–2.13) and lower body (i.e., CMJ, 3H, 20-m sprint and COD, hip ABD and ADD; d: 0.70–2.33) performance measures. Regarding shoulder ROM outcomes, a lower IR ROM was found of the dominant side in the U15 group compared to the U13 and a higher ER ROM on both sides in U15 (d: 0.76–1.04). It seems that primarily anthropometric characteristics (i.e., body height, body mass) and upper body strength/power (OMB distance) are the most important factors that explain the throw speed variance in male handball players, particularly in U13.
Conclusions
Findings from this study imply that regular performance monitoring is important for performance development and for minimizing injury risk of the shoulder in both age categories of young male handball players. Besides measures of physical fitness, anthropometric data should be recorded because handball throwing performance is related to these measures.
The protein fraction, important for coffee cup quality, is modified during post-harvest treatment prior to roasting. Proteins may interact with phenolic compounds, which constitute the major metabolites of coffee, where the processing affects these interactions. This allows the hypothesis that the proteins are denatured and modified via enzymatic and/or redox activation steps. The present study was initiated to encompass changes in the protein fraction. The investigations were limited to major storage protein of green coffee beans. Fourteen Coffea arabica samples from various processing methods and countries were used. Different extraction protocols were compared to maintain the status quo of the protein modification. The extracts contained about 4–8 µg of chlorogenic acid derivatives per mg of extracted protein. High-resolution chromatography with multiple reaction monitoring was used to detect lysine modifications in the coffee protein. Marker peptides were allocated for the storage protein of the coffee beans. Among these, the modified peptides K.FFLANGPQQGGK.E and R.LGGK.T of the α-chain and R.ITTVNSQK.I and K.VFDDEVK.Q of β-chain were detected. Results showed a significant increase (p < 0.05) of modified peptides from wet processed green beans as compared to the dry ones. The present study contributes to a better understanding of the influence of the different processing methods on protein quality and its role in the scope of coffee cup quality and aroma. View Full-Text
Pokhara (ca. 850 m a.s.l.), Nepal's second-largest city, lies at the foot of the Higher Himalayas and has more than tripled its population in the past 3 decades. Construction materials are in high demand in rapidly expanding built-up areas, and several informal settlements cater to unregulated sand and gravel mining in the Pokhara Valley's main river, the Seti Khola. This river is fed by the Sabche glacier below Annapurna III (7555 m a.s.l.), some 35 km upstream of the city, and traverses one of the steepest topographic gradients in the Himalayas. In May 2012 a sudden flood caused >70 fatalities and intense damage along this river and rekindled concerns about flood risk management. We estimate the flow dynamics and inundation depths of flood scenarios using the hydrodynamic model HEC-RAS (Hydrologic Engineering Center’s River Analysis System). We simulate the potential impacts of peak discharges from 1000 to 10 000 m3 s−1 on land cover based on high-resolution Maxar satellite imagery and OpenStreetMap data (buildings and road network). We also trace the dynamics of two informal settlements near Kaseri and Yamdi with high potential flood impact from RapidEye, PlanetScope, and Google Earth imagery of the past 2 decades. Our hydrodynamic simulations highlight several sites of potential hydraulic ponding that would largely affect these informal settlements and sites of sand and gravel mining. These built-up areas grew between 3- and 20-fold, thus likely raising local flood exposure well beyond changes in flood hazard. Besides these drastic local changes, about 1 % of Pokhara's built-up urban area and essential rural road network is in the highest-hazard zones highlighted by our flood simulations. Our results stress the need to adapt early-warning strategies for locally differing hydrological and geomorphic conditions in this rapidly growing urban watershed.
»Plus outre« – immer weiter
(2022)
This paper aims to contribute a different approach to transitional justice, one in which political decisions are rocketed to the forefront of the research. Theory asserts that, after a transition to democracy, it is the constituency who defines the direction a country will take. Therefore, pleasing them should be at the fore of the responses taken by those in power. However, reality distances itself from theory. History provides us with many examples of the contrary, which indicates that the politicization of transitional justice is an ever-present event. The first section will outline current definitions and obstacles faced by transitional justice, focusing on the implicit ties between them and the aforementioned politicization. An original categorization of Transitional Justice as a method of analysis will also be introduced, which I denominate Political Opportunism. The case of Argentina, a country that is usually described as a model to export but that after 35 years is still dealing with the consequences brought by the contradictions of using several methods of justice, will then be reinterpreted through this perspective. At the end of the paper, the inevitable question will be posed: can this new angle be exported and implemented in every transition?
Physical fatigue (PF) negatively affects postural control, resulting in impaired balance performance in young and older adults. Similar effects on postural control can be observed for mental fatigue (MF) mainly in older adults. Controversial results exist for young adults. There is a void in the literature on the effects of fatigue on balance and cortical activity. Therefore, this study aimed to examine the acute effects of PF and MF on postural sway and cortical activity. Fifteen healthy young adults aged 28 ± 3 years participated in this study. MF and PF protocols comprising of an all-out repeated sit-to-stand task and a computer-based attention network test, respectively, were applied in random order. Pre and post fatigue, cortical activity and postural sway (i.e., center of pressure displacements [CoPd], velocity [CoPv], and CoP variability [CV CoPd, CV CoPv]) were tested during a challenging bipedal balance board task. Absolute spectral power was calculated for theta (4–7.5 Hz), alpha-2 (10.5–12.5 Hz), beta-1 (13–18 Hz), and beta-2 (18.5–25 Hz) in frontal, central, and parietal regions of interest (ROI) and baseline-normalized. Inference statistics revealed a significant time-by-fatigue interaction for CoPd (p = 0.009, d = 0.39, Δ 9.2%) and CoPv (p = 0.009, d = 0.36, Δ 9.2%), and a significant main effect of time for CoP variability (CV CoPd: p = 0.001, d = 0.84; CV CoPv: p = 0.05, d = 0.62). Post hoc analyses showed a significant increase in CoPd (p = 0.002, d = 1.03) and CoPv (p = 0.003, d = 1.03) following PF but not MF. For cortical activity, a significant time-by-fatigue interaction was found for relative alpha-2 power in parietal (p < 0.001, d = 0.06) areas. Post hoc tests indicated larger alpha-2 power increases after PF (p < 0.001, d = 1.69, Δ 3.9%) compared to MF (p = 0.001, d = 1.03, Δ 2.5%). In addition, changes in parietal alpha-2 power and measures of postural sway did not correlate significantly, irrespective of the applied fatigue protocol. No significant changes were found for the other frequency bands, irrespective of the fatigue protocol and ROI under investigation. Thus, the applied PF protocol resulted in increased postural sway (CoPd and CoPv) and CoP variability accompanied by enhanced alpha-2 power in the parietal ROI while MF led to increased CoP variability and alpha-2 power in our sample of young adults. Potential underlying cortical mechanisms responsible for the greater increase in parietal alpha-2 power after PF were discussed but could not be clearly identified as cause. Therefore, further future research is needed to decipher alternative interpretations.