Many procedures in modern clinical medicine rely on the use of electronic implants in treating conditions that range from acute coronary events to traumatic injury. However, standard permanent electronic hardware acts as a nidus for infection: bacteria form biofilms along percutaneous wires, or seed haematogenously, with the potential to migrate within the body and to provoke immune-mediated pathological tissue reactions. The associated surgical retrieval procedures, meanwhile, subject patients to the distress associated with re-operation and expose them to additional complications. Here, we report materials, device architectures, integration strategies, and in vivo demonstrations in rats of implantable, multifunctional silicon sensors for the brain, for which all of the constituent materials naturally resorb via hydrolysis and/or metabolic action, eliminating the need for extraction. Continuous monitoring of intracranial pressure and temperature illustrates functionality essential to the treatment of traumatic brain injury; the measurement performance of our resorbable devices compares favourably with that of non-resorbable clinical standards. In our experiments, insulated percutaneous wires connect to an externally mounted, miniaturized wireless potentiostat for data transmission. In a separate set-up, we connect a sensor to an implanted (but only partially resorbable) data-communication system, proving the principle that there is no need for any percutaneous wiring. The devices can be adapted to sense fluid flow, motion, pH or thermal characteristics, in formats that are compatible with the body's abdomen and extremities, as well as the deep brain, suggesting that the sensors might meet many needs in clinical medicine.

Existing vital sign monitoring systems in the neonatal intensive care unit (NICU) require multiple wires connected to rigid sensors with strongly adherent interfaces to the skin. We introduce a pair of ultrathin, soft, skin-like electronic devices whose coordinated, wireless operation reproduces the functionality of these traditional technologies but bypasses their intrinsic limitations. The enabling advances in engineering science include designs that support wireless, battery-free operation; real-time, in-sensor data analytics; time-synchronized, continuous data streaming; soft mechanics and gentle adhesive interfaces to the skin; and compatibility with visual inspection and with medical imaging techniques used in the NICU. Preliminary studies on neonates admitted to operating NICUs demonstrate performance comparable to the most advanced clinical-standard monitoring systems.

Summary In vivo optogenetics provides unique, powerful capabilities in the dissection of neural circuits implicated in neuropsychiatric disorders. Conventional hardware for such studies, however, physically tethers the experimental animal to an external light source limiting the range of possible experiments. Emerging wireless options offer important capabilities that avoid some of these limitations, but the current size, bulk, weight, and wireless area of coverage is often disadvantageous. Here, we present a simple but powerful setup based on wireless, near-field power transfer and miniaturized, thin flexible optoelectronic implants, for complete optical control in a variety of behavioral paradigms. The devices combine subdermal magnetic coil antennas connected to microscale, injectable LEDs, with the ability to operate at wavelengths ranging from ultraviolet to blue, green/yellow, and red. An external loop antenna allows robust, straightforward application in a multitude of behavioral apparatuses. The result is a readily mass-producible, user-friendly technology with broad potential for optogenetics applications.

Thanks to their portability and the non‐equilibrium character of the discharges, microplasmas are finding application in many scientific disciplines. Although microplasma research has traditionally been application driven, microplasmas represent a new realm in plasma physics that still is not fully understood. This paper reviews existing microplasma sources and discusses charged particle kinetics in various microdischarges. The non‐equilibrium character highlighted in this manuscript raises concerns about the accuracy of fluid models and should trigger further kinetic studies of high‐pressure microdischarges. Finally, an outlook is presented on the biomedical application of microplasmas.

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Pluripotency of embryonic stem cells (ESCs) is defined by their ability to differentiate into three germ layers and derivative cell types1-3 and is established by an interactive network of proteins including OCT4 (also known as POU5F1; ref. 4), NANOG (refs 5,6), SOX2 (ref. 7) and their binding partners. The forkhead box O (FoxO) transcription factors are evolutionarily conserved regulators of longevity and stress response whose function is inhibited by AKT protein kinase. FoxO proteins are required for the maintenance of somatic and cancer stem cells8-13; however, their function in ESCs is unknown. We show that FOXO1 is essential for the maintenance of human ESC pluripotency, and that an orthologue of FOXO1 (Foxo1) exerts a similar function in mouse ESCs. This function is probably mediated through direct control by FOXO1 of OCT4 and SOX2 gene expression through occupation and activation of their respective promoters. Finally, AKT is not the predominant regulator of FOXO1 in human ESCs. Together these results indicate that FOXO1 is a component of the circuitry of human ESC pluripotency. These findings have critical implications for stem cell biology, development, longevity and reprogramming, with potentially important ramifications for therapy.

Megakaryoblastic leukemia 1 (MKL1) is a myocardin-related coactivator of the serum response factor (SRF) transcription factor, which has an integral role in differentiation, migration, and proliferation. Serum induces RhoA-dependent translocation of MKL1 from the cytoplasm to the nucleus and also causes a rapid increase in MKL1 phosphorylation. We have mapped a serum-inducible phosphorylation site and found, surprisingly, that its mutation causes constitutive localization to the nucleus, suggesting that phosphorylation of MKL1 inhibits its serum-induced nuclear localization. The key site, serine 454, resembles a mitogen-activated protein kinase phosphorylation site, and its modification was blocked by the MEK1 inhibitor U0126, implying that extracellular signal-regulated kinase 1/2 (ERK1/2) is the serum-inducible kinase that phosphorylates MKL1. Previous results indicated that G-actin binding to MKL1 promotes its nuclear export, and we found that MKL1 phosphorylation is required for its binding to actin, explaining its effect on localization. We propose a model in which serum induction initially stimulates MKL1 nuclear localization due to a decrease in G-actin levels, but MKL1 is then downregulated by nuclear export due to ERK1/2 phosphorylation.Megakaryoblastic leukemia 1/2 proteins (MKL1/2, MRTF-A/B, MAL, BSAC), along with the related protein myocardin, are transcriptional coactivators of serum response factor (SRF) (7). SRF is a transcription factor that belongs to the MADS box family and binds to serum response elements (SRE) in the promoters of various immediate-early and muscle-specific genes (32,33,38). The core sequence of the SRE has the consensus sequence CC(AT) 6 GG and is called a CArG box (13,17). Serum and growth factors stimulate SRF activity via two seemingly independent pathways, one that is dependent on the phosphorylation of ternary complex factors (TCFs) by a mitogen-activated protein kinase (MAPK) cascade and the other that is dependent on Rho signaling and actin dynamics (12, 40). The TCF proteins Elk-1, SAP-1, and Net make sequence-specific DNA contacts with Ets motifs adjoining the CArG boxes of some immediate-early genes, and phosphorylation of their transcriptional activation domains potentiates their ability to activate transcription (29). The second pathway that activates SRF involves the small GTPase RhoA, since the inhibition of RhoA blocks serum induction of TCF-independent SRE reporter genes and some SRF target genes, while activated RhoA can stimulate SRE reporter genes (12). RhoA activation causes stress fiber formation and the reduction of monomeric G-actin. The use of actin mutants and drugs that interfere with actin treadmilling suggests that SRE activation is controlled by the G-actin pool (21, 31).Myocardin was originally identified as a strong coactivator for SRF in heart and smooth muscle cells (35). We and others have identified two myocardin-related SRF-specific coactivators, MKL1 and MKL2, that are expressed in a wide range of embryonic and adult tissues and that stron...

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