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Summary: Two main lineages of T cells develop in the thymus: those that express the αβ T‐cell receptor (TCR) and those that express the γδ TCR. Whereas the development, selection, and peripheral localization of newly differentiated αβ T cells are understood in some detail, these processes are less well characterized in γδ T cells. This review describes research carried out in this laboratory and others, which addresses several key aspects of γδ T‐cell development, including the decision of precursor cells to differentiate into the γδ versus αβ lineage, the ordered differentiation over the course of ontogeny of functional γδ T‐cell subsets expressing distinct TCR structures, programming of ordered Vγ gene rearrangement in the thymus, including a molecular switch that ensures appropriate Vγ rearrangements at the appropriate stage of development, positive selection in the thymus of γδ T cells destined for the epidermis, and the acquisition by developing γδ T cells of cues that determine their correct localization in the periphery. This research suggests a coordination of molecularly programmed events and cellular selection, which enables specialization of the thymus for production of distinct T‐cell subsets at different stages of development.
Abstract A mathematical model of the lactose ( lac ) operon was developed to study diauxic growth on glucose and lactose. The model includes catabolite repression, inducer exclusion, lactose hydrolysis to glucose and galactose, and synthesis and degradation of allolactose. Two models for catabolite repression were tested: (i) cyclic AMP (cAMP) synthesis inversely correlated with the external glucose concentration and (ii) synthesis inversely correlated with the glucose transport rate. No significant differences in the two models were observed. In addition to synthesis, degradation and secretion of cAMP were also included in the model. Two models for the phosphorylation of the glucose produced from lactose hydrolysis were also tested: (i) phosphorylation by intracellular hexokinase and (ii) secretion of glucose and subsequent phosphorylation upon transport back into the cell. The latter model resulted in weak catabolite repression when the glucose produced from lactose was transported out of the cell, whereas the former model showed no catabolite repression during growth on lactose. Parameter sensitivity analysis indicates the importance of key parameters to lac operon expression and cell growth: the lactose and allolactose transformation rates by β‐galactosidase and the glucose concentrations that affect catabolite repression and inducer exclusion. Large values of the allolactose hydrolysis rate resulted in low concentrations of allolactose, low‐level expression of the lac operon, and slow growth due to limited import and metabolism of lactose; small values resulted in a high concentration of allolactose, high‐level expression of the lac operon, and slow growth due to a limiting concentration of glucose 6‐phosphate formed from allolactose. Changes in the rates of all β‐galactosidase‐catalyzed reactions showed similar behavior, but had more drastic effects on the growth rate. Changes in the glucose concentration that inhibited lactose transport could extend or contract the diauxic growth period during growth in the presence of glucose and lactose. Moreover, changes in the glucose concentration that affected catabolite repression affected the cAMP levels and lac operon expression, but had a lesser effect on the growth rate.
Abstract Brain-wide communication supporting flexible behavior requires coordination between sensory and associative regions but how brain networks route sensory information at fast timescales to guide action remains unclear. Using human intracranial electrophysiology and spiking neural networks during spatial attention tasks, where participants detected targets at cued locations, we show that high-frequency activity bursts (HFAb) mark temporal windows of elevated population firing that enable fast, long-range communications. HFAbs were evoked by sensory cues and targets, dynamically coupled to low-frequency rhythms. Notably, both the strength of cue-evoked HFAbs and their decoupling from slow rhythms predicted behavioral accuracy. HFAbs synchronized across the brain, revealing distinct cue- and target-activated subnetworks. These subnetworks exhibited lead-lag dynamics following target onset, with cue-activated subnetworks preceding target-activated subnetworks when cues were informative. Computational modeling suggested that HFAbs reflect transitions to population spiking, denoting temporal windows for network communications supporting attentional performance. These findings establish HFAbs as signatures of population state transitions, supporting information routing across distributed brain networks.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Body-centered Ge<sub>9</sub> parallelepiped building blocks form the basis of the structure of [Ge<sub>9</sub> O<sub>18</sub> (OH)<sub>4</sub> ]⋅2 (H<sub>2</sub> ppz)⋅0.5 (H<sub>2</sub> O) (ASU-14, ppz=piperazine). In this new structure type for an open-framework germanate (see picture for a section of the structure) the building blocks are linked together at each of their eight vertices to give the rare polycubane topology with an intersecting channel system of ten- and eight-membered rings (pore sizes 5×6 and 4×4 Å<sup>2</sup> , respectively) in which the piperazinium cations and water molecules reside.
The COVID-19 pandemic increased remote working, online shopping, and telehealth, with important differences across socioeconomic groups in their ability to use such new technologies. Orkun Saka, Barry Eichengreen, and Cevat Giray Aksoy investigate past epidemics and find that they significantly increase the likelihood that individuals do their banking using the internet, mobile banks, and automated teller machines (ATMs). But inequality plays a role. Individuals who already have internet coverage are more likely to shift toward online banking during an epidemic.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
