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The increasing demand for continuous, comprehensive physiological information captured by skin-interfaced wireless sensors is hindered by their relatively high-power consumption and the associated patient discomfort that can follow from the use of high capacity batteries. This paper presents an adaptive electronics platform and a tri-modal energy harvesting approach to reduce the need for battery power. Specifically, the schemes focus on sensors that involve light in their operation, through use of (i) photometric methods, where ambient light contributes directly to the measurement process, (ii) multijunction photovoltaic cells, where ambient light powers operation and/or charges an integrated battery, and (iii) photoluminescent packaging, where ambient light activates light-emitting species to enhance the first two schemes. Additional features of interest are in (i) in-sensor computational approaches that decrease the bandwidth and thus the energy consumption in wireless data communication and (ii) radio frequency power transfer for battery charging. These ideas have utility across broad other classes of wearable devices as well as small, portable electronic gadgetry. Wearable sensors typically require innovative methods of energy harvesting for low-power electronics. Here, the authors present an adaptive power management system with a trimodal energy harvesting approach.

In neonatal mice, susceptibility to infection is due to an enriched subset of arginase-2-expressing CD71 + erythroid cells, which suppresses the systemic activation of immune cells, thereby protecting neonates against aberrant inflammation triggered by colonization with commensal microbes. Explaining newborns' vulnerability to infection During the first few weeks after birth, infants are highly susceptible to disseminated infection. This vulnerability is commonly attributed to intrinsic defects of the neonates' immune cells, but this study presents evidence that host defences are in fact compromised by active immune suppression within the neonatal environment. Sing Sing Way and colleagues show that in neonate mice, an arginase-2-expressing CD71 + erythrocyte subset suppresses systemic immune cell activation, thereby protecting against harmful inflammation that might be triggered by colonization with the commensal microbes to which the newborn is suddenly exposed. This same suppression has the unfortunate consequence that resistance to infection is also reduced. Newborn infants are highly susceptible to infection. This defect in host defence has generally been ascribed to the immaturity of neonatal immune cells; however, the degree of hyporesponsiveness is highly variable and depends on the stimulation conditions 1 , 2 , 3 , 4 , 5 , 6 , 7 . These discordant responses illustrate the need for a more unified explanation for why immunity is compromised in neonates. Here we show that physiologically enriched CD71 + erythroid cells in neonatal mice and human cord blood have distinctive immunosuppressive properties. The production of innate immune protective cytokines by adult cells is diminished after transfer to neonatal mice or after co-culture with neonatal splenocytes. Neonatal CD71 + cells express the enzyme arginase-2, and arginase activity is essential for the immunosuppressive properties of these cells because molecular inhibition of this enzyme or supplementation with l -arginine overrides immunosuppression. In addition, the ablation of CD71 + cells in neonatal mice, or the decline in number of these cells as postnatal development progresses parallels the loss of suppression, and restored resistance to the perinatal pathogens Listeria monocytogenes and Escherichia coli 8 , 9 . However, CD71 + cell-mediated susceptibility to infection is counterbalanced by CD71 + cell-mediated protection against aberrant immune cell activation in the intestine, where colonization with commensal microorganisms occurs swiftly after parturition 10 , 11 . Conversely, circumventing such colonization by using antimicrobials or gnotobiotic germ-free mice overrides these protective benefits. Thus, CD71 + cells quench the excessive inflammation induced by abrupt colonization with commensal microorganisms after parturition. This finding challenges the idea that the susceptibility of neonates to infection reflects immune-cell-intrinsic defects and instead highlights processes that are developmentally more essential and inadvertently mitigate innate immune protection. We anticipate that these results will spark renewed investigation into the need for immunosuppression in neonates, as well as improved strategies for augmenting host defence in this vulnerable population.

Exencephaly/anencephaly is one of the leading causes of neonatal mortality and the most extreme open neural tube defect with no current treatments and limited mechanistic understanding. We hypothesized that exencephaly leads to a local neurodegenerative process in the brain exposed to the amniotic fluid as well as diffuse degeneration in other encephalic areas and the spinal cord. To evaluate the consequences of in utero neural tissue exposure, brain and spinal cord samples from E17 exencephalic murine fetuses (maternal intraperitoneal administration of valproic acid at E8) were analyzed and compared to controls and saline-injected shams ( n  = 11/group). Expression of apoptosis and senescence genes (p53, p21, p16, Rbl2, Casp3, Casp9) was determined by qRT-PCR and protein expression analyzed by western blot. Apoptosis was measured by TUNEL assay and PI/AV flow cytometry. Valproic acid at E8 induced exencephaly in 22% of fetuses. At E17 the fetuses exhibited the characteristic absence of cranial bones. The brain structures from exencephalic fetuses demonstrated a loss of layers in cortical regions and a complete loss of structural organization in the olfactory bulb, hippocampus, dental gyrus and septal cortex. E17 fetuses had reduced expression of NeuN, GFAP and Oligodendrocytes in the brain with primed microglia. Intrinsic apoptotic activation (p53, Caspase9 and 3) was upregulated and active Caspase3 localized to the layer of brain exposed to the amniotic fluid. Senescence via p21-Rbl2 was increased in the brain and in the spinal cord at the lamina I-II of the somatosensory dorsal horn. The current study characterizes CNS alterations in murine exencephaly and demonstrates that degeneration due to intrinsic apoptosis and senescence occurs in the directly exposed brain but also remotely in the spinal cord.

Purpose of Review In utero hematopoietic cellular transplantation (IUHCT) is a promising intervention for the non-toxic treatment of congenital disease that hinges on the assumption of fetal immunologic immaturity and an inability to reject a hematopoietic allograft. However, clinical IUCHT has failed except in cases where the fetus is severely immunocompromised. The current review examines recent studies of engraftment barriers stemming from either the fetal or maternal immune system. Recent Findings New reports have illuminated roles for maternal humoral and cellular immunity and fetal innate cellular immunity in the resistance to allogeneic IUHCT. These experimental findings have inspired new approaches to overcome these barriers. Despite these advances, postulates regarding a maternal immune barrier to IUHCT provide an inadequate explanation for the well-documented clinical success only in the treatment of fetal immunodeficiency with normal maternal immunity. Summary Characterization of the maternal and fetal immune response to allogeneic IUHCT provides new insight into the complexity of prenatal tolerance. Future work in this area should aim to provide a unifying explanation for the observed patterns of success and failure with clinical IUHCT.

The primary benefits of in utero hematopoietic cellular transplantation (IUHCT) arise from transplanting curative cells prior to the immunologic maturation of the fetus. However, this approach has been routinely successful only in the treatment of congenital immunodeficiency diseases that include an inherent NK cell deficiency despite the existence of normal maternal immunity in either setting. These observations raise the possibility that fetal NK cells function as an early barrier to allogeneic IUHCT. Herein, we summarize the findings of previous studies of prenatal NK cell allospecific tolerance in mice and in humans. Cumulatively, this new information reveals the complexity of the fetal immune response in the setting of rejection or tolerance and illustrates the role for fetal NK cells in the final endorsement of allospecific prenatal tolerance.

Invariant NKT (iNKT) cells are critical to the maintenance of tolerance toward alloantigens encountered during postnatal life pointing to the existence of a process for self-education. However, the impact of developmentally encountered alloantigens in shaping the phenotype and function of iNKT cells has not been described. To better understand this process, the current report examined naïve iNKT cells as they matured in an allogeneic environment. Following the prenatal transfer of fetal hematopoietic cells between age-matched allogeneic murine fetuses, cell-extrinsic signals appeared to dictate allospecific patterns of Ly49 receptor expression and lineage diversity in developing iNKT cells. Regulation for this process arose from cells of hematopoietic origin requiring only rare exposure to facilitate broad changes in developing iNKT cells. These findings highlight surprisingly asymmetric allospecific alterations in iNKT cells as they develop and mature in an allogeneic environment and establish a new paradigm for study of the self-education of iNKT cells.

Mesenchymal stem cells are multipotent cells that can be isolated from adult bone marrow and can be induced in vitro and in vivo to differentiate into a variety of mesenchymal tissues, including bone, cartilage, tendon, fat, bone marrow stroma, and muscle 1 , 2 . Despite their potential clinical utility for cellular and gene therapy, the fate of mesenchymal stem cells after systemic administration is mostly unknown. To address this, we transplanted a well-characterized human mesenchymal stem cell population 3 into fetal sheep early in gestation, before and after the expected development of immunologic competence. In this xenogeneic system, human mesenchymal stem cells engrafted and persisted in multiple tissues for as long as 13 months after transplantation. Transplanted human cells underwent site-specific differentiation into chondrocytes, adipocytes, myocytes and cardiomyocytes, bone marrow stromal cells and thymic stroma. Unexpectedly, there was long-term engraftment even when cells were transplanted after the expected development of immunocompetence. Thus, mesenchymal stem cells maintain their multipotential capacity after transplantation, and seem to have unique immunologic characteristics that allow persistence in a xenogeneic environment. Our data support the possibility of the transplantability of mesenchymal stem cells and their potential utility in tissue engineering, and cellular and gene therapy applications.

Newborn infants are highly susceptible to infection. This defect in host defence has generally been ascribed to the immaturity of neonatal immune cells; however, the degree of hyporesponsiveness is highly variable and depends on the stimulation conditions (1-7). These discordant responses illustrate the need for a more unified explanation for why immunity is compromised in neonates. Here we show that physiologically enriched [CD71.sup.+] erythroid cells in neonatal mice and human cord blood have distinctive immunosuppressive properties. The production of innate immune protective cytokines by adult cells is diminished after transfer to neonatal mice or after co-culture with neonatal splenocytes. Neonatal [CD71.sup.+] cells express the enzyme arginase-2, and arginase activity is essential for the immunosuppressive properties of these cells because molecular inhibition of this enzyme or supplementation with L-arginine overrides immunosuppression. In addition, the ablation of [CD71.sup.+] cells in neonatal mice, or the decline in number of these cells as postnatal development progresses parallels the loss of suppression, and restored resistance to the perinatal pathogens Listeria monocytogenes and Escherichia coli (8,9). However, [CD71.sup.+] cell-mediated susceptibility to infection is counterbalanced by [CD71.sup.+] cell-mediated protection against aberrant immune cell activation in the intestine, where colonization with commensal microorganisms occurs swiftly after parturition (10,11). Conversely, circumventing such colonization by using antimicrobials or gnotobiotic germ-free mice overrides these protective benefits. Thus, [CD71.sup.+] cells quench the excessive inflammation induced by abrupt colonization with commensal microorganisms after parturition. This finding challenges the idea that the susceptibility of neonates to infection reflects immune-cell-intrinsic defects and instead highlights AA processes that are developmentally more essential and inadvertently mitigate innate immune protection. We anticipate that these results will spark renewed investigation into the need for immunosuppression in neonates, as well as improved strategies for augmenting host defence in this vulnerable population.

The treatment of congenital hematologic disorders before birth by in utero hematopoietic stem cell transplantation remains a challenging goal. Although success has been achieved in X-linked severe combined immunodeficiency, the approach has failed in all other disorders attempted thus far. In this review, we examine relevant experimental data from the perspective of an analysis of why failure has occurred. We will also attempt to pose the important questions that will need to be answered prior to further clinical attempts to treat most target disorders by this approach.

Given these somewhat surprising results, the activation of adult cells within neonates was inves- tigated. Because differences in susceptibility between neonatal and adult mice become apparent within 48 h of infection (Fig. lb), we focused on essential innate immune protective cytokines such as tumour-necrosis factor-a (TNF-a)14\"16. By contrast, the depletion of immune lineage cells not only retained but also exaggerated the suppression by the remaining CD71+ cells (Fig. 2d). [...]the depletion of CD71 + cells in mouse splenocyte or human cord blood cell populations unleashed more robust cytokine production by the remaining immune lineage cells, indicating that CD71+ cells also impair neonatal immune cell activation (Fig. 2e, f and Extended Data Figs 5b and 6).