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Organization involving waking up cortisol amounts and also aerobic functionality in sugarcane outlying personnel.
However, imprinting divergence most often correlated with local DNA methylation epimutations (9 of 17 assessable loci), which were largely stable within subspecies. Small insertion/deletion events and transposable element insertions accompanied 4 of the 9 locally epimutated loci and associated with imprinting divergence at another 4 of the remaining 8 loci. Correlating epigenetic and genetic variation occurred at key regulatory regions-the promoter and transcription start site of maternally biased genes, and the promoter and gene body of paternally biased genes. Our results reinforce models for the role of maternal-specific DNA hypomethylation in imprinting of both maternally and paternally biased genes, and highlight the role of transposition and epimutation in rice imprinting evolution.In the ocean, most hosts acquire their symbionts from the environment. Due to the immense spatial scales involved, our understanding of the biogeography of hosts and symbionts in marine systems is patchy, although this knowledge is essential for understanding fundamental aspects of symbiosis such as host-symbiont specificity and evolution. Lucinidae is the most species-rich and widely distributed family of marine bivalves hosting autotrophic bacterial endosymbionts. Previous molecular surveys identified location-specific symbiont types that "promiscuously" form associations with multiple divergent cooccurring host species. This flexibility of host-microbe pairings is thought to underpin their global success, as it allows hosts to form associations with locally adapted symbionts. We used metagenomics to investigate the biodiversity, functional variability, and genetic exchange among the endosymbionts of 12 lucinid host species from across the globe. We report a cosmopolitan symbiont species, Candidatus Thiodiazotropha taylori, associated with multiple lucinid host species. Ca. T. taylori has achieved more success at dispersal and establishing symbioses with lucinids than any other symbiont described thus far. This discovery challenges our understanding of symbiont dispersal and location-specific colonization and suggests both symbiont and host flexibility underpin the ecological and evolutionary success of the lucinid symbiosis.Programmed cell death protein-1 (PD-1) expressed on activated T cells inhibits T cell function and proliferation to prevent an excessive immune response, and disease can result if this delicate balance is shifted in either direction. Tumor cells often take advantage of this pathway by overexpressing the PD-1 ligand PD-L1 to evade destruction by the immune system. Alternatively, if there is a decrease in function of the PD-1 pathway, unchecked activation of the immune system and autoimmunity can result. Using a combination of computation and experiment, we designed a hyperstable 40-residue miniprotein, PD-MP1, that specifically binds murine and human PD-1 at the PD-L1 interface with a Kd of ∼100 nM. The apo crystal structure shows that the binder folds as designed with a backbone RMSD of 1.3 Å to the design model. Trimerization of PD-MP1 resulted in a PD-1 agonist that strongly inhibits murine T cell activation. This small, hyperstable PD-1 binding protein was computationally designed with an all-beta interface, and the trimeric agonist could contribute to treatments for autoimmune and inflammatory diseases.As collective cell migration is essential in biological processes spanning development, healing, and cancer progression, methods to externally program cell migration are of great value. However, problems can arise if the external commands compete with strong, preexisting collective behaviors in the tissue or system. We investigate this problem by applying a potent external migratory cue-electrical stimulation and electrotaxis-to primary mouse skin monolayers where we can tune cell-cell adhesion strength to modulate endogenous collectivity. U0126 research buy Monolayers with high cell-cell adhesion showed strong natural coordination and resisted electrotactic control, with this conflict actively damaging the leading edge of the tissue. However, reducing preexisting coordination in the tissue by specifically inhibiting E-cadherin-dependent cell-cell adhesion, either by disrupting the formation of cell-cell junctions with E-cadherin-specific antibodies or rapidly dismantling E-cadherin junctions with calcium chelators, significantly improved controllability. Finally, we applied this paradigm of weakening existing coordination to improve control and demonstrate accelerated wound closure in vitro. These results are in keeping with those from diverse, noncellular systems and confirm that endogenous collectivity should be considered as a key quantitative design variable when optimizing external control of collective migration.Aromatic carotenoid-derived hydrocarbon biomarkers are ubiquitous in ancient sediments and oils and are typically attributed to anoxygenic phototrophic green sulfur bacteria (GSB) and purple sulfur bacteria (PSB). These biomarkers serve as proxies for the environmental growth requirements of PSB and GSB, namely euxinic waters extending into the photic zone. Until now, prevailing models for environments supporting anoxygenic phototrophs include microbial mats, restricted basins and fjords with deep chemoclines, and meromictic lakes with shallow chemoclines. However, carotenoids have been reported in ancient open marine settings for which there currently are no known modern analogs that host GSB and PSB. The Benguela Upwelling System offshore Namibia, known for exceptionally high primary productivity, is prone to recurrent toxic gas eruptions whereupon hydrogen sulfide emanates from sediments into the overlying water column. These events, visible in satellite imagery as water masses clouded with elemental sulfur, suggest that the Benguela Upwelling System may be capable of supporting GSB and PSB. Here, we compare distributions of biomarkers in the free and sulfur-bound organic matter of Namibian shelf sediments. Numerous compounds-including acyclic isoprenoids, steranes, triterpanes, and carotenoids-were released from the polar lipid fractions upon Raney nickel desulfurization. The prevalence of isorenieratane and β-isorenieratane in sampling stations along the shelf verified anoxygenic photosynthesis by low-light-adapted, brown-colored GSB in this open marine setting. Renierapurpurane was also present in the sulfur-bound carotenoids and was typically accompanied by lower abundances of renieratane and β-renierapurpurane, thereby identifying cyanobacteria as an additional aromatic carotenoid source.The posteromedial cortex (PMC) is known to be a core node of the default mode network. Given its anatomical location and blood supply pattern, the effects of targeted disruption of this part of the brain are largely unknown. Here, we report a rare case of a patient (S19_137) with confirmed seizures originating within the PMC. Intracranial recordings confirmed the onset of seizures in the right dorsal posterior cingulate cortex, adjacent to the marginal sulcus, likely corresponding to Brodmann area 31. Upon the onset of seizures, the patient reported a reproducible sense of self-dissociation-a condition he described as a distorted awareness of the position of his body in space and feeling as if he had temporarily become an outside observer to his own thoughts, his "me" having become a separate entity that was listening to different parts of his brain speak to each other. Importantly, 50-Hz electrical stimulation of the seizure zone and a homotopical region within the contralateral PMC induced a subjectively similar state, reproducibly. We supplement our clinical findings with the definition of the patient's network anatomy at sites of interest using cortico-cortical-evoked potentials, experimental and resting-state electrophysiological connectivity, and individual-level functional imaging. This rare case of patient S19_137 highlights the potential causal importance of the PMC for integrating self-referential information and provides clues for future mechanistic studies of self-dissociation in neuropsychiatric populations.Most high-dimensional datasets are thought to be inherently low-dimensional-that is, data points are constrained to lie on a low-dimensional manifold embedded in a high-dimensional ambient space. Here, we study the viability of two approaches from differential geometry to estimate the Riemannian curvature of these low-dimensional manifolds. The intrinsic approach relates curvature to the Laplace-Beltrami operator using the heat-trace expansion and is agnostic to how a manifold is embedded in a high-dimensional space. The extrinsic approach relates the ambient coordinates of a manifold's embedding to its curvature using the Second Fundamental Form and the Gauss-Codazzi equation. We found that the intrinsic approach fails to accurately estimate the curvature of even a two-dimensional constant-curvature manifold, whereas the extrinsic approach was able to handle more complex toy models, even when confounded by practical constraints like small sample sizes and measurement noise. To test the applicability of the extrinsic approach to real-world data, we computed the curvature of a well-studied manifold of image patches and recapitulated its topological classification as a Klein bottle. Lastly, we applied the extrinsic approach to study single-cell transcriptomic sequencing (scRNAseq) datasets of blood, gastrulation, and brain cells to quantify the Riemannian curvature of scRNAseq manifolds.Rhythm perception is fundamental to speech and music. Humans readily recognize a rhythmic pattern, such as that of a familiar song, independently of the tempo at which it occurs. This shows that our perception of auditory rhythms is flexible, relying on global relational patterns more than on the absolute durations of specific time intervals. Given that auditory rhythm perception in humans engages a complex auditory-motor cortical network even in the absence of movement and that the evolution of vocal learning is accompanied by strengthening of forebrain auditory-motor pathways, we hypothesize that vocal learning species share our perceptual facility for relational rhythm processing. We test this by asking whether the best-studied animal model for vocal learning, the zebra finch, can recognize a fundamental rhythmic pattern-equal timing between event onsets (isochrony)-based on temporal relations between intervals rather than on absolute durations. Prior work suggests that vocal nonlearners (pigeons and rats) are quite limited in this regard and are biased to attend to absolute durations when listening to rhythmic sequences. In contrast, using naturalistic sounds at multiple stimulus rates, we show that male zebra finches robustly recognize isochrony independent of absolute time intervals, even at rates distant from those used in training. Our findings highlight the importance of comparative studies of rhythmic processing and suggest that vocal learning species are promising animal models for key aspects of human rhythm perception. Such models are needed to understand the neural mechanisms behind the positive effect of rhythm on certain speech and movement disorders.
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