ER Stress Responses: An Emerging Modulator for Innate Immunity.

The endoplasmic reticulum (ER) is a critical organelle, storing the majority of calcium and governing protein translation. Thus, it is crucial to keep the homeostasis in all ER components and machineries. The ER stress sensor pathways, including IRE1/sXBP1, PERK/EIf2 and ATF6, orchestrate the major regulatory circuits to ensure ER homeostasis. The embryonic or postnatal lethality that occurs upon genetic depletion of these sensors reveals the essential role of the ER stress pathway in cell biology. In contrast, the impairment or excessive activation of ER stress has been reported to cause or aggravate several diseases such as atherosclerosis, diabetes, NAFDL/NASH, obesity and cancer. Being part of innate immunity, myeloid cells are the first immune cells entering the inflammation site. Upon entry into a metabolically stressed disease environment, activation of ER stress occurs within the myeloid compartment, leading to the modulation of their phenotype and functions. In this review, we discuss causes and consequences of ER stress activation in the myeloid compartment with a special focus on the crosstalk between ER, innate signaling and metabolic environments

Mitochondrial Control and Guidance of Cellular Activities of T Cells.

Immune cells protect us against infection and cancer cells, as well as functioning during healing processes to support tissue repairing and regeneration. These behaviors require that upon stimulation from immune activation the appropriate subsets of immune cells are generated. In addition to activation-induced signaling cascades, metabolic reprogramming (profound changes in metabolic pathways) also provides a novel form of regulation to control the formation of desirable immune responses. Immune cells encounter various nutrient compositions by circulating in bloodstream and infiltrating into peripheral tissues; therefore, proper engagement of metabolic pathways is critical to fulfill the metabolic demands of immune cells. Metabolic pathways are tightly regulated mainly via mitochondrial dynamics and the activities of the tricarboxylic acid cycle and the electron transport chain. In this review, we will discuss how metabolic reprogramming influences activation, effector functions, and lineage polarization in T cells, with a particular focus on mitochondria-regulated metabolic checkpoints. Additionally, we will further explore how in various diseases deregulation and manipulation of mitochondrial regulation can occur and be exploited. Furthermore, we will discuss how this knowledge can facilitate the design of immunotherapies

DCision-making in tumors governs T cell anti-tumor immunity.

The exploitation of T cell-based immunotherapies and immune checkpoint blockade for cancer treatment has dramatically shifted oncological treatment paradigms and broadened the horizons of cancer immunology. Dendritic cells have emerged as the critical tailors of T cell immune responses, which initiate and coordinate anti-tumor immunity. Importantly, genetic alterations in cancer cells, cytokines and chemokines produced by cancer and stromal cells, and the process of tumor microenvironmental regulation can compromise dendritic cell-T cell cross-talk, thereby disrupting anti-tumor T cell responses. This review summarizes how T cell activation is controlled by dendritic cells and how the tumor microenvironment alters dendritic cell properties in the context of the anti-tumor immune cycle. Furthermore, we will highlight therapeutic options for tailoring dendritic cell-mediated decision-making in T cells for cancer treatment

Precise measurements of radio-frequency magnetic susceptibility in (anti)ferromagnetic materials

Dynamic magnetic susceptibility, $\chi$, was studied in several intermetallic materials exhibiting ferromagnetic, antiferromagnetic and metamagnetic transitions. Precise measurements by using a 14 MHz tunnel diode oscillator (TDO) allow detailed insight into the field and temperature dependence of $\chi$. In particular, local moment ferromagnets show a sharp peak in $\chi(T)$ near the Curie temperature, $T_c$. The peak amplitude decreases and shifts to higher temperatures with very small applied dc fields. Anisotropic measurements of CeVSb$_3$ show that this peak is present provided the magnetic easy axis is aligned with the excitation field. In a striking contrast, small moment, itinerant ferromagnets (i.e., ZrZn$_2$) show a broad maximum in $\chi(T)$ that responds differently to applied field. We believe that TDO measurements provide a very sensitive way to distinguish between local and itinerant moment magnetic orders. Local moment antiferromagnets do not show a peak at the N\'eel temperature, $T_N$, but only a sharp decrease of $\chi$ below $T_N$ due to the loss of spin-disorder scattering changing the penetration depth of the ac excitation field. Furthermore, we show that the TDO is capable of detecting changes in spin order as well as metamagnetic transitions. Finally, critical scaling of $\chi(T,H)$ in the vicinity of $T_C$ is discussed in CeVSb$_3$ and CeAgSb$_2$

CD40 signal rewires fatty acid and glutamine metabolism for stimulating macrophage anti-tumorigenic functions.

Exposure of lipopolysaccharide triggers macrophage pro-inflammatory polarization accompanied by metabolic reprogramming, characterized by elevated aerobic glycolysis and a broken tricarboxylic acid cycle. However, in contrast to lipopolysaccharide, CD40 signal is able to drive pro-inflammatory and anti-tumorigenic polarization by some yet undefined metabolic programming. Here we show that CD40 activation triggers fatty acid oxidation (FAO) and glutamine metabolism to promote ATP citrate lyase-dependent epigenetic reprogramming of pro-inflammatory genes and anti-tumorigenic phenotypes in macrophages. Mechanistically, glutamine usage reinforces FAO-induced pro-inflammatory and anti-tumorigenic activation by fine-tuning the NAD <sup>+</sup> /NADH ratio via glutamine-to-lactate conversion. Genetic ablation of important metabolic enzymes involved in CD40-mediated metabolic reprogramming abolishes agonistic anti-CD40-induced antitumor responses and reeducation of tumor-associated macrophages. Together these data show that metabolic reprogramming, which includes FAO and glutamine metabolism, controls the activation of pro-inflammatory and anti-tumorigenic polarization, and highlight a therapeutic potential of metabolic preconditioning of tumor-associated macrophages before agonistic anti-CD40 treatments

Ursolic acid inhibits the initiation, progression of prostate cancer and prolongs the survival of TRAMP mice by modulating pro-inflammatory pathways

10.1371/journal.pone.0032476PLoS ONE73

A novel method to create a vortex in a Bose-Einstein condensate

It has been shown that a vortex in a BEC with spin degrees of freedom can be created by manipulating with external magnetic fields. In the previous work, an optical plug along the vortex axis has been introduced to avoid Majorana flips, which take place when the external magnetic field vanishes along the vortex axis while it is created. In the present work, in contrast, we study the same scenario without introducing the optical plug. The magnetic field vanishes only in the center of the vortex at a certain moment of the evolution and hence we expect that the system will lose only a fraction of the atoms by Majorana flips even in the absence of an optical plug. Our conjecture is justified by numerically solving the Gross-Pitaevskii equation, where the full spinor degrees of freedom of the order parameter are properly taken into account. A significant simplification of the experimental realization of the scenario is attained by the omission of the optical plug.Comment: 8 pages, 11 figure

Rapid Noninvasive Skin Monitoring by Surface Mass Recording and Data Learning.

Skin problems are often overlooked due to a lack of robust and patient-friendly monitoring tools. Herein, we report a rapid, noninvasive, and high-throughput analytical chemical methodology, aiming at real-time monitoring of skin conditions and early detection of skin disorders. Within this methodology, adhesive sampling and laser desorption ionization mass spectrometry are coordinated to record skin surface molecular mass in minutes. Automated result interpretation is achieved by data learning, using similarity scoring and machine learning algorithms. Feasibility of the methodology has been demonstrated after testing a total of 117 healthy, benign-disordered, or malignant-disordered skins. Remarkably, skin malignancy, using melanoma as a proof of concept, was detected with 100% accuracy already at early stages when the lesions were submillimeter-sized, far beyond the detection limit of most existing noninvasive diagnosis tools. Moreover, the malignancy development over time has also been monitored successfully, showing the potential to predict skin disorder progression. Capable of detecting skin alterations at the molecular level in a nonsurgical and time-saving manner, this analytical chemistry platform is promising to build personalized skin care