Nlrp6 promotes recovery after peripheral nerve injury independently of inflammasomes

Background: NOD-like receptors (Nlrs) are key regulators of immune responses during infection and autoimmunity. A subset of Nlrs assembles inflammasomes, molecular platforms that are activated in response to endogenous danger and microbial ligands and that control release of interleukin (IL)-1 beta and IL-18. However, their role in response to injury in the nervous system is less understood. Methods: In this study, we investigated the expression profile of major inflammasome components in the peripheral nervous system (PNS) and explored the physiological role of different Nlrs upon acute nerve injury in mice. Results: While in basal conditions, predominantly members of NOD-like receptor B (Nlrb) subfamily (NLR family, apoptosis inhibitory proteins (NAIPs)) and Nlrc subfamily (ICE-protease activating factor (IPAF)/NOD) are detected in the sciatic nerve, injury causes a shift towards expression of the Nlrp family. Sterile nerve injury also leads to an increase in expression of the Nlrb subfamily, while bacteria trigger expression of the Nlrc subfamily. Interestingly, loss of Nlrp6 led to strongly impaired nerve function upon nerve crush. Loss of the inflammasome adaptor apoptosis-associated speck-like protein containing a CARD (ASC) and effector caspase-1 and caspase-11 did not affect sciatic nerve function, suggesting that Nlrp6 contributed to recovery after peripheral nerve injury independently of inflammasomes. In line with this, we did not detect release of mature IL-1 beta upon acute nerve injury despite potent induction of pro-IL-1 beta and inflammasome components Nlrp3 and Nlrp1. However, Nlrp6 deficiency was associated with increased pro-inflammatory extracellular regulated MAP kinase (ERK) signaling, suggesting that hyperinflammation in the absence of Nlrp6 exacerbated peripheral nerve injury. Conclusions: Together, our observations suggest that Nlrp6 contributes to recovery from peripheral nerve injury by dampening inflammatory responses independently of IL-1 beta and inflammasomes

The Gospel of Peter

Some early editions divided the Gospel of Peter into fourteen chapters following the numbering system created by A. Harnack, while others divided it into sixty verses following the system devised by J.A. Robinson. Scholars have followed the practice of using both, or more recently, use only Robinson’s numbering. In our translation we follow both. The translation below uses the Greek text in Bart D. Ehrman and Zlatko Pleše, The Apocryphal Gospels: Texts and Translations (Oxford University Press, 2011), pp. 378-386

Forge: Thermoelectric Cookstove

Our interdisciplinary team, known as Forge, has built a cookstove that not only can be a portable cookstove, but also includes a port to charge devices such as a phone using thermoelectrics. The product has been designed for developing areas in Nicaragua where power is inaccessible and a multi-purpose cookstove/phone charger could be of use. The cookstove features a cylindrical combustion chamber that can be used for gasification. Gasification is a burning process where smoke from the fire is also burned, creating higher temperatures and a cleaner burn. The combustion chamber is insulated using refractory cement, which will drop the temperature from about 700 Celsius inside the chamber to 200 Celsius outside the chamber. The cookstove outputs heat at a rate of 4.6-6.6 kW. The cookstove has thermoelectric modules attached to the outside, which, by utilizing the Seebeck effect, convert excess heat into electrical energy. Ideally, the energy would be transferred into the phone at 5 volts and 0.5-0.6 amps and some of the electrical energy would be used to power a cooling fan to help the stove function properly. The final temperatures that were recorded ranged from around 400ºC to 700ºC in the combustion chamber and around 500ºC for the cooking surface. Gasification was successfully occurring during this stage, and the smoke was being visibly burned off. The electrical output was less successful, resulting with only around 0.08 V coming out of the thermoelectric generators due to the lack of air flow within the electrical housing and poor electrical connection. The stove does achieve its primary functionality of being more than capable of boiling water, something that presently available cookstoves in Nicaragua cannot do consistently

Profiling peripheral nerve macrophages reveals two macrophage subsets with distinct localization, transcriptome and response to injury

The authors identify two subsets of peripheral nerve macrophages residing in the endoneurium and the epineurium and displaying a distinct transcriptome and response to injury. These cells lack the main microglia identity and have a distinct origin. While CNS microglia have been extensively studied, relatively little is known about macrophages populating the peripheral nervous system. Here we performed ontogenic, transcriptomic and spatial characterization of sciatic nerve macrophages (snMacs). Using multiple fate-mapping systems, we show that snMacs do not derive from the early embryonic precursors colonizing the CNS, but originate primarily from late embryonic precursors and become replaced by bone-marrow-derived macrophages over time. Using single-cell transcriptomics, we identified a tissue-specific core signature of snMacs and two spatially separated snMacs: Relm alpha(+)Mgl1(+) snMacs in the epineurium and Relm alpha(-)Mgl1(-) snMacs in the endoneurium. Globally, snMacs lack most of the core signature genes of microglia, with only the endoneurial subset expressing a restricted number of these genes. In response to nerve injury, the two resident snMac populations respond differently. Moreover, and unlike in the CNS, monocyte-derived macrophages that develop during injury can engraft efficiently in the pool of resident peripheral nervous system macrophages

Hepatic macrophage responses in inflammation, a function of plasticity, heterogeneity or both?

peer-reviewedWith the increasing availability and accessibility of single cell technologies, much attention has been given to delineating the specific populations of cells present in any given tissue. In recent years, hepatic macrophage heterogeneity has also begun to be examined using these strategies. While previously any macrophage in the liver was considered to be a Kupffer cell (KC), several studies have recently revealed the presence of distinct subsets ofhepatic macrophages, including those distinct from KCs both under homeostatic and non-homeostatic conditions. This heterogeneity has brought the concept of macrophage plasticity into question. Are KCs really as plastic as once thought, being capable of responding efficiently and specifically to any given stimuli? Or are the differential responses observed from hepatic macrophages in distinct settings due to the presence of multiple subsets of these cells? With these questions in mind, here we examine what is currently understood regarding hepatic macrophage heterogeneity in mouse and human and examine the role of heterogeneity vs plasticity in regards to hepatic macrophage responses in settings of both pathogen-induced and sterile inflammation