Foraging animals optimize feeding decisions by adjusting both common and rare behavioral patterns. Here, we characterize the relationship between an animal's arousal state and a rare decision to ...leave a patch of bacterial food. Using long-term tracking and behavioral state classification, we find that food leaving decisions in
are coupled to arousal states across multiple timescales. Leaving emerges probabilistically over minutes from the high arousal roaming state, but is suppressed during the low arousal dwelling state. Immediately before leaving, animals have a brief acceleration in speed that appears as a characteristic signature of this behavioral motif. Neuromodulatory mutants and optogenetic manipulations that increase roaming have a coupled increase in leaving rates, and similarly acute manipulations that inhibit feeding induce both roaming and leaving. By contrast, inactivating a set of chemosensory neurons that depend on the cGMP-gated transduction channel TAX-4 uncouples roaming and leaving dynamics. In addition,
expressing sensory neurons promote lawn-leaving behaviors that are elicited by feeding inhibition. Our results indicate that sensory neurons responsive to both internal and external cues play an integrative role in arousal and foraging decisions.
Imprinted gene expression occurs during seed development in plants and is associated with differential DNA methylation of parental alleles, particularly at proximal transposable elements (TEs). ...Imprinting variability could contribute to observed parent-of-origin effects on seed development. We investigated intraspecific variation in imprinting, coupled with analysis of DNA methylation and small RNAs, among three Arabidopsis strains with diverse seed phenotypes. The majority of imprinted genes were parentally biased in the same manner among all strains. However, we identified several examples of allele-specific imprinting correlated with intraspecific epigenetic variation at a TE. We successfully predicted imprinting in additional strains based on methylation variability. We conclude that there is standing variation in imprinting even in recently diverged genotypes due to intraspecific epiallelic variation. Our data demonstrate that epiallelic variation and genomic imprinting intersect to produce novel gene expression patterns in seeds.
Foraging animals optimize feeding decisions by adjusting both common and rare behavioral patterns. Here, we characterize the relationship between an animal’s arousal state and a rare decision to ...leave a patch of bacterial food. Using long-term tracking and behavioral state classification, we find that food leaving decisions in
Caenorhabditis elegans
are coupled to arousal states across multiple timescales. Leaving emerges probabilistically over minutes from the high arousal roaming state, but is suppressed during the low arousal dwelling state. Immediately before leaving, animals have a brief acceleration in speed that appears as a characteristic signature of this behavioral motif. Neuromodulatory mutants and optogenetic manipulations that increase roaming have a coupled increase in leaving rates, and similarly acute manipulations that inhibit feeding induce both roaming and leaving. By contrast, inactivating a set of chemosensory neurons that depend on the cGMP-gated transduction channel TAX-4 uncouples roaming and leaving dynamics. In addition,
tax-4-
expressing sensory neurons promote lawn-leaving behaviors that are elicited by feeding inhibition. Our results indicate that sensory neurons responsive to both internal and external cues play an integrative role in arousal and foraging decisions.
When animals forage for food, they show distinct behavioral patterns in their movement. For instance, the nematode worm
Caenorhabditis elegans
shows two long-term behavioral states when exploring a patch of food: dwelling, when it moves slowly in a small area, and roaming, when it makes quick and wide-ranging movements. The worms will also occasionally suddenly decide to leave a piece of food and go explore the rest of their environment.
Scientists know that the likelihood of the worms either roaming or dwelling is regulated by neurons passing molecules, such as serotonin and dopamine, to one another. However, it is not known how these two long-term behavioral states impact the momentary decision to leave a piece of food, and which mechanisms may regulate this coupling.
To investigate, Scheer and Bargmann tracked the movement of genetically modified
C. elegans
and characterized their behavior. This revealed that the decision to leave food is not random but a distinct choice that primarily happens when worms are roaming. A characteristic signature of this response was that worms briefly accelerate immediately before leaving.
Following this discovery, Scheer and Bargmann identified sensory neurons that are involved in this process. As well as detecting external sensory cues, these neurons also integrate internal signals, like whether the animal can eat, to specify how often a worm will leave food.
The implications of this research extend beyond the realm of tiny nematodes. This study provides a new framework to examine the relationship between long-term behavior and momentary decision making. Such insights are crucial in understanding brain function across different organisms, including humans. It paves the way for further research into how behavior is regulated on multiple timescales in the brain.
...because of the transposition, some p-values in Figure 1—source data 5 were calculated incorrectly (a side-by-side comparison is shown in Supplementary file 1, file held on figshare under ...http://dx.doi.org/10.6084/m9.figshare.1409445). The correction does not change any of the conclusions that we drew from these data, which were ‘Imprinting calls based on whole-genome mRNA-seq were validated by sequencing or performing CAPs digestion on RT-PCR amplicons of 29 genes from independently isolated embryo and endosperm RNA samples (Figure 1—figure supplement 2, Figure 1—source data 5); results were mostly consistent with the mRNA-seq data’.
Throughout the animal kingdom, internal states generate long-lasting and self-perpetuating chains of behavior. In Drosophila, males instinctively pursue females with a lengthy and elaborate courtship ...ritual triggered by activation of sexually dimorphic P1 interneurons. Gustatory pheromones are thought to activate P1 neurons but the circuit mechanisms that dictate their sensory responses to gate entry into courtship remain unknown. Here, we use circuit mapping and in vivo functional imaging techniques to trace gustatory and olfactory pheromone circuits to their point of convergence onto P1 neurons and reveal how their combined input underlies selective tuning to appropriate sexual partners. We identify inhibition, even in response to courtship-promoting pheromones, as a key circuit element that tunes and tempers P1 neuron activity. Our results suggest a circuit mechanism in which balanced excitation and inhibition underlie discrimination of prospective mates and stringently regulate the transition to courtship in Drosophila.
•P1 neurons are functionally tuned toward appropriate potential mates•Gustatory and olfactory pheromone circuits converge on P1 neurons•Pheromone signals are carried by parallel excitatory and inhibitory branches•This neural architecture allows stringent and flexible control of courtship behavior
Gustatory and olfactory pheromone afferents converge on courtship-promoting P1 neurons in the male Drosophila brain. Integration of these positive and negative chemosensory signals tunes P1 neural responses to generate selective courtship to appropriate mates.
Abstract Gastric cancer is the second most common cancer and a leading cause of cancer-related death worldwide. The Kruppel-like factor 6 ( KLF6 ) tumour suppressor gene had been previously shown to ...be inactivated in a number of human cancers through loss of heterozygosity (LOH), somatic mutation, decreased expression and increased alternative splicing into a dominant negative oncogenic splice variant, KLF6 -SV1. In the present study, 37 gastric cancer samples were analysed for the presence of loss of heterozygosity (LOH) of the KLF6 locus and somatic mutation. In total, 18 of 34 (53%) of the gastric cancer samples analysed demonstrated KLF6 locus specific loss. Four missense mutations, such as T179I, R198G, R71Q and S180L, were detected. Interestingly, two of these mutations R71Q and S180L have been identified independently by several groups in various malignancies including prostate, colorectal and gastric cancers. In addition, decreased wild-type KLF6 (wtKLF6) expression was associated with loss of the KLF6 locus and was present in 48% of primary gastric tumour samples analysed. Functional studies confirmed that wtKLF6 suppressed proliferation of gastric cancer cells via transcriptional regulation of the cyclin-dependent kinase inhibitor p21 and the oncogene c-myc. Functional characterisation of the common tumour-derived mutants demonstrated that the mutant proteins fail to suppress proliferation and function as dominant negative regulators of wtKLF6 function. Furthermore, stable overexpression of the R71Q and S180L tumour-derived mutants in the gastric cancer cell line, Hs746T, resulted in an increased tumourigenicity in vivo . Combined, these findings suggest an important role for the KLF6 tumour suppressor gene in gastric cancer development and progression and identify several highly cancer-relevant signalling pathways regulated by the KLF6 tumour suppressor gene.
It is well known that weather and pacing have an influence on elite marathon performance. However, there is limited knowledge about the effect of weather on running speed in elite marathoners. The ...aim of the present cross-sectional study was to investigate potential associations between running speed and weather variables in elite runners competing in the 'New York City Marathon' between 1999 and 2019. Data from all official female and male finishers with name, sex, age, calendar year, split times at 5 km, 10 km, 15 km, 20 km, 25 km, 30 km, 35 km, 40 km and finish and hourly values for temperature (°Celsius), barometric pressure (hPa), humidity (%) and sunshine duration (min) between 09:00 a.m. and 04:00 p.m. were obtained from official websites. A total of 560,731 marathon runners' records were available for analysis (342,799 men and 217,932 women). Pearson and Spearman correlation analyses were performed between the average running speed and the weather variables (temperature, pressure, humidity and sunshine). Ordinary Least Squares (OLS) regressions were also performed. The runner´s records were classified into four performance groups (all runners, top 100, top 10 and top 3) for comparison. Differences in running speed between the four performance groups were statistically significant (p < 0.05) for both men and women. Pearson (linear) correlation indicated a weak and positive association with humidity in the top 10 (r = 0.16) and top 3 (r = 0.13) performance groups that the running speed of the elite runners was positively correlated with humidity. Regarding sunshine duration, there was a weak and positive correlation with the running speed of the elite groups (r = 0.16 in the top 10 and r = 0.2 in the top 3). Spearman correlation (non-linear) identified a weak but negative correlation coefficient with temperature in all runners' groups. Also, non-linear positive correlation coefficients with humidity and sunshine can be observed in the Spearman matrixes. A Multivariate Ordinary Least Squares (OLS) regression analysis showed no predictive power of weather factors. For elite runners competing in the 'New York City Marathon' between 1999 and 2019, the main findings were that elite runners became faster with increasing humidity and sunshine duration while overall runners became slower with increasing temperature, increasing humidity and sunshine duration. Weather factors affected running speed and results but did not provide a significant predictive influence on performance.
: The COVID-19 outbreak has become a major health and economic crisis. The World Health Organization declared it a pandemic in March 2020, and many sporting events were canceled.
: We examined the ...effects of the COVID-19 pandemic on endurance and ultra-endurance running (UER) and analyzed finishes and events during the COVID-19 pandemic (observation period March 2020-October 2020) to the same time period pre-COVID-19 outbreak (March 2019-October 2019).
Endurance finishes decreased during the pandemic (459,029 to 42,656 (male: 277,493 to 25,582; female 181,536 to 17,074; all
< 0.001). Similarly, the numbers of endurance events decreased (213 vs. 61 events;
< 0.001). Average marathon finishing times decreased during the pandemic in men (5:18:03 ± 0:16:34 vs. 4:43:08 ± 0:25:08 h:min:s (
= 0.006)) and women (5:39:32 ± 0:19:29 vs. 5:14:29 ± 0:26:36 h:min:s (
= 0.02)). In UER, finishes decreased significantly (580,289 to 110,055;
< 0.001) as did events (5839 to 1791;
< 0.001). Popular event locations in United States, France, UK, and Germany decreased significantly (
< 0.05). All distance and time-limited UER events saw significant decreases (
< 0.05).
: The COVID-19 pandemic has had a significant effect on endurance and UER, and it is unlikely that running activities return to pre-pandemic levels any time soon. Mitigation strategies and safety protocols should be established.
The purposes of this study were (i) to describe differences in participation in 100-mile ultra-marathons by continent; (ii) to investigate differences in performance between continents; and (iii) to ...identify the fastest runners by continent and country. Data from 148,169 athletes (119,408 men), aged 18-81 years, and finishers in a 100-miles ultra-marathon during 1870-2020 were investigated. Information about age, gender, origin, performance level (top three, top 10, top 100) was obtained. Kruskal-Wallis tests and linear regressions were performed. Athletes were mostly from America and Europe. A macro-analysis showed that the fastest men runners were from Africa, while the fastest women runners were from Europe and Africa. Women from Sweden, Hungary and Russia presented the best performances in the top three, top 10 and top 100. Men from Brazil, Russia and Lithuania were the fastest. The lowest performance and participation were observed for runners from Asia. In summary, in 100-miles ultra-marathon running, the majority of athletes were from America, but for both sexes and performance levels, the fastest runners were from Africa. On a country level, the fastest women were from Sweden, Hungary and Russia, while the fastest men were from Brazil, Russia and Lithuania.
The 50-km ultra-marathon is a popular race distance, slightly longer than the classic marathon distance. However, little is known about the country of affiliation and age of the fastest 50-km ...ultra-marathon runners and where the fastest races are typically held. Therefore, this study aimed to investigate a large dataset of race records for the 50-km distance race to identify the country of affiliation and the age of the fastest runners as well as the locations of the fastest races. A total of 1,398,845 50-km race records (men, n = 1,026,546; women, n = 372,299) were analyzed using both descriptive statistics and advanced regression techniques. This study revealed significant trends in the performance of 50-km ultra-marathoners. The fastest 50-km runners came from African countries, while the fastest races were found to occur in Europe and the Middle East. Runners from Ethiopia, Lesotho, Malawi, and Kenya were the fastest in this race distance. The fastest 50-km racecourses, providing ideal conditions for faster race times, are in Europe (Luxembourg, Belarus, and Lithuania) and the Middle East (Qatar and Jordan). Surprisingly, the fastest ultra-marathoners in the 50-km distance were found to fall into the age group of 20-24 years, challenging the conventional belief that peak ultra-marathon performance comes in older age groups. These findings contribute to a better understanding of the performance models in 50-km ultra-marathons and can serve as valuable insights for runners, coaches, and race organizers in optimizing training strategies and racecourse selection.
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