Notes

[Andrey Zotikov (Several.A dozen.1959-23.2009.2021)].
There is robust evidence that early poverty is associated with poor developmental outcomes, including impaired emotion regulation and depression. However, the specific mechanisms that mediate this risk are less clear. Here we test the hypothesis that one pathway involves hormone mechanisms (testosterone and DHEA) that contribute to disruption of hippocampal brain development, which in turn contributes to perturbed emotion regulation and subsequent risk for depression. To do so, we used data from 167 children participating in the Preschool Depression Study, a longitudinal study that followed children from preschool (ages 3 to 5 y) to late adolescence, and which includes prospective assessments of poverty in preschool, measures of testosterone, DHEA, and hippocampal volume across school age and adolescence, and measures of emotion regulation and depression in adolescence. Using multilevel modeling and linear regression, we found that early poverty predicted shallower increases of testosterone, but not DHEA, across development, which in turn predicted shallower trajectories of hippocampal development. Further, we found that early poverty predicted both impaired emotion regulation and depression. The relationship between early poverty and self-reported depression in adolescence was explained by serial mediation through testosterone to hippocampus to emotion dysregulation. There were no significant interactions with sex. These results provide evidence about a hormonal pathway by which early poverty may contribute to disrupted brain development and risk for mental health problems later in life. Identification of such pathways provide evidence for potential points of intervention that might help mitigate the impact of early adversity on brain development.To create new enzymes and biosensors from scratch, precise control over the structure of small-molecule binding sites is of paramount importance, but systematically designing arbitrary protein pocket shapes and sizes remains an outstanding challenge. Using the NTF2-like structural superfamily as a model system, we developed an enumerative algorithm for creating a virtually unlimited number of de novo proteins supporting diverse pocket structures. The enumerative algorithm was tested and refined through feedback from two rounds of large-scale experimental testing, involving in total the assembly of synthetic genes encoding 7,896 designs and assessment of their stability on yeast cell surface, detailed biophysical characterization of 64 designs, and crystal structures of 5 designs. The refined algorithm generates proteins that remain folded at high temperatures and exhibit more pocket diversity than naturally occurring NTF2-like proteins. CC-99677 We expect this approach to transform the design of small-molecule sensors and enzymes by enabling the creation of binding and active site geometries much more optimal for specific design challenges than is accessible by repurposing the limited number of naturally occurring NTF2-like proteins.Diet provides critical information about the ecology and environment of herbivores. Hence, understanding the dietary strategies of fossil herbivores and the associated temporal changes is one aspect of inferring paleoenvironmental conditions. Here, we present carbon isotope data from more than 1,050 fossil teeth that record the dietary patterns of nine herbivore families in the late Pliocene and early Pleistocene (3.6 to 1.05 Ma) from the Shungura Formation, a hominin-bearing site in southwestern Ethiopia. An increasing trend toward C4 herbivory has been observed with attendant reductions in the proportions of browsers and mixed feeders through time. A high proportion of mixed feeders has been observed prior to 2.9 Ma followed by a decrease in the proportion of mixed feeders and an increase in grazers between 2.7 and 1.9 Ma, and a further increase in the proportion of grazers after 1.9 Ma. The collective herbivore fauna shows two major change points in carbon isotope values at ∼2.7 and ∼2.0 Ma. While hominin fossils from the sequence older than 2.7 Ma are attributed to Australopithecus, the shift at ∼2.7 Ma indicating the expansion of C4 grasses on the landscape was concurrent with the first appearance of Paranthropus The link between the increased C4 herbivory and more open landscapes suggests that Australopithecus lived in more wooded landscapes compared to later hominins such as Paranthropus and Homo, and has implications for key morphological and behavioral adaptations in our lineage.Hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopic imaging (MRSI) is a noninvasive metabolic-imaging modality that probes carbon flux in tissues and infers the state of metabolic reprograming in tumors. Prevailing models attribute elevated hyperpolarized [1-13C]pyruvate-to-[1-13C]lactate conversion rates in aggressive tumors to enhanced glycolytic flux and lactate dehydrogenase A (LDHA) activity (Warburg effect). By contrast, we find by cross-sectional analysis using genetic and pharmacological tools in mechanistic studies applied to well-defined genetically engineered cell lines and tumors that initial hyperpolarized [1-13C]pyruvate-to-[1-13C]lactate conversion rates as well as global conversion were highly dependent on and critically rate-limited by the transmembrane influx of [1-13C]pyruvate mediated predominately by monocarboxylate transporter-1 (MCT1). Specifically, in a cell-encapsulated alginate bead model, induced short hairpin (shRNA) knockdown or overexpression of MCT1 quantitatively inatient populations.Visual motion detection is one of the most important computations performed by visual circuits. Yet, we perceive vivid illusory motion in stationary, periodic luminance gradients that contain no true motion. This illusion is shared by diverse vertebrate species, but theories proposed to explain this illusion have remained difficult to test. Here, we demonstrate that in the fruit fly Drosophila, the illusory motion percept is generated by unbalanced contributions of direction-selective neurons' responses to stationary edges. First, we found that flies, like humans, perceive sustained motion in the stationary gradients. The percept was abolished when the elementary motion detector neurons T4 and T5 were silenced. In vivo calcium imaging revealed that T4 and T5 neurons encode the location and polarity of stationary edges. Furthermore, our proposed mechanistic model allowed us to predictably manipulate both the magnitude and direction of the fly's illusory percept by selectively silencing either T4 or T5 neurons.
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