Arsenic Accumulation and Biotransformation Affected by Nutrients (N and P) in Common Blooming-Forming Microcystis wesenbergii (Komárek) Komárek ex Komárek (Cyanobacteria)

Arsenic accumulation and biotransformation in algae was mostly carried out in a medium that contained far higher nutrient concentrations than that in natural freshwaters. The obtained results might have limited environmental validity and result in a failure to describe authentic arsenic biogeochemical cycles in natural freshwater systems. To validate the assumption, arsenic accumulation, and biotransformation in common bloom forming Microcystis wesenbergii was performed under a high nutrient concentration in BG11 medium (N = 250 mg/L, P = 7.13 mg/L), and adjusted low nutrients that mimicked values in natural freshwaters (N = 1.5 mg/L, P = 0.3 mg/L). The growth rate and maximum M. wesenbergii cell density were much lower in the high nutrient set, but more inhibition was shown with increasing ambient iAs(V) concentrations both in the high and low nutrient sets. The proportion of intracellular contents in total arsenicals decreased with increasing iAs(V) concentrations in both high and low nutrient sets but increased with incubation time. Intracellular iAs(III) was not found in the high nutrient set, while it formed high concentrations that could be comparable to that of an extracellular level in the low nutrient set. M. wesenbergii could methylate arsenic, and a higher proportion of organoarsenicals was formed in the low nutrient set. Lower intracellular MMA(V) and DMA(V) concentrations were found in the high nutrient set; contrarily, they presented a higher concentration that could be comparable to the extracellular ones in the low nutrient set. The results demonstrated that different nutrient regimes could affect arsenic accumulation and biotransformation in M. wesenbergii, and low nutrient concentrations could inhibit the excretion of iAs(III), MMA(V) and DMA(V) out of cells. Further investigations should be based on natural freshwater systems to obtain an authentic arsenic accumulation and biotransformation in cyanobacteria.

In Search of a Role for Extracellular Purine Enzymes in Bone Function

Bone is one of the major tissues that undergoes continuous remodeling throughout life, thus ensuring both organic body growth during development and protection of internal organs as well as repair of trauma during adulthood. Many endogenous substances contribute to bone homeostasis, including purines. Their role has increasingly emerged in recent decades as compounds which, by interacting with specific receptors, can help determine adequate responses of bone cells to physiological or pathological stimuli. Equally, it is recognized that the activity of purines is closely dependent on their interconversion or metabolic degradation ensured by a series of enzymes present at extracellular level as predominantly bound to the cell membrane or, also, as soluble isoforms. While the effects of purines mediated by their receptor interactions have sufficiently, even though not entirely, been characterized in many tissues including bone, those promoted by the extracellular enzymes providing for purine metabolism have not been. In this review, we will try to circumstantiate the presence and the role of these enzymes in bone to define their close relationship with purine activities in maintaining bone homeostasis in normal or pathological conditions.

The Link between Electrical Properties of COVID-19 and Electromagnetic Radiation

The ability of a new vaccine design based on control the intracellular physiological consequences of both the electrical properties and the electromagnetic radiation interactions between a virus and a host cell, which is a method to strengthen immune system develop protection against COVID-19 and new strains. The capacity of COVID-19 to bind to angiotensin-converting enzyme 2 (ACE2) and immune evasion mechanisms are only one of the properties required to stimulate a preventative immune response. In this chapter, a multidimensional new strategy is used to exemplify the empowerment function intracellular and extracellular level information can play in the support of immunogen against COVID-19 pathogens. Besides during this chapter, the nature of electromagnetic radiation is described as a vibrating string based on a string-theory and unification of electromagnetic radiation and gravitational waves by supporting with multiple cites strong evidence. Overall, we demonstrate a new approach to understand the important role of the physiological consequences of the interplay between the immune system and COVID-19 and designing vaccine strategy immunogens that take advantage of that information against COVID-19 and new strains.

The HSP GRP94 interacts with macrophage intracellular complement C3 and impacts M2 profile during ER stress

The role of GRP94, an endoplasmic reticulum (ER) stress protein with both pro- and anti-inflammatory functions, has not been investigated in macrophages during ER stress, whereas ER stress has been reported in many diseases involving macrophages. In this work, we studied GRP94 in M1/LPS + IFNγ and M2/IL-4 primary macrophages derived from human monocytes (isolated from buffy coats), in basal and ER stress conditions induced by thapsigargin (Tg), an inducer of ER calcium depletion and tunicamycin (Tm), an inhibitor of N-glycosylation. We found that GRP94 was expressed on the membrane of M2 but not M1 macrophages. In M2, Tg, but not Tm, while decreased GRP94 content in the membrane, it induced its secretion. This correlated with the induction of a pro-inflammatory profile, which was dependent on the UPR IRE1α arm activation and on a functional GRP94. As we previously reported that GRP94 associated with complement C3 at the extracellular level, we analyzed C3 and confirmed GRP94-C3 interaction in our experimental model. Further, Tg increased this interaction and, in these conditions, C3b and cathepsin L were detected in the extracellular medium where GRP94 co-immunoprecipitated with C3 and C3b. Finally, we showed that the C3b inactivated fragment, iC3b, only present on non-stressed M2, depended on functional GRP94, making both GRP94 and iC3b potential markers of M2 cells. In conclusion, our results show that GRP94 is co-secreted with C3 under ER stress conditions which may facilitate its cleavage by cathepsin L, thus contributing to the pro-inflammatory profile observed in stressed M2 macrophages.

Intracellular role of IL-6 in mesenchymal stromal cell immunosuppression and proliferation

Interleukin (IL)-6 is a pleiotropic cytokine involved in the regulation of hematological and immune responses. IL-6 is secreted chiefly by stromal cells, but little is known about its precise role in the homeostasis of human mesenchymal stromal cells (hMSCs) and the role it may play in hMSC-mediated immunoregulation. We studied the role of IL-6 in the biology of bone marrow derived hMSC in vitro by silencing its expression using short hairpin RNA targeting. Our results show that IL-6 is involved in immunosuppression triggered by hMSCs. Cells silenced for IL-6 showed a reduced capacity to suppress activated T-cell proliferation. Moreover, silencing of IL-6 significantly blocked the capacity of hMSCs to proliferate. Notably, increasing the intracellular level of IL-6 but not recovering the extracellular level could restore the proliferative impairment observed in IL-6-silenced hMSC. Our data indicate that IL-6 signals in hMSCs by a previously undescribed intracellular mechanism.

Exosomal arrow (Arr)/lipoprotein receptor protein 6 (LRP6) in Drosophila melanogaster increases the extracellular level of Sol narae (Sona) in a Wnt-independent manner

Wg/Wnt as a signaling protein binds to Frizzled (Fz) and Arrow (Arr), two Wg co-receptors essential for Wg signaling for cell proliferation, differentiation, and cell survival. Arr has a long extracellular region, a single transmembrane domain and an intracellular region. Here, we report that a new arrm7 mutant is identified in a genetic screen as a suppressor of lethality induced by overexpression of Sol narae (Sona), a secreted metalloprotease in ADAMTS family involved in Wg signaling. arrm7 allele has a premature stop codon, which encodes Arrm7 protein missing the intracellular region. arrm7 clones show cell death phenotype and overexpression of Arrm7 protein also induces cell death. Levels of extracellular Sona were decreased in both arrm7 and arr2 null clones, demonstrating that Arr increases the level of extracellular Sona. Indeed, Arr but not Arrm7, increased levels of Sona in cytoplasm and exosome fraction by inhibiting the lysosomal degradation pathway. Interestingly, Arr itself was identified in the exosome fraction, demonstrating that Arr is secreted to extracellular space. When Sona-expressing S2 cells were treated with exosomal Arr, the extracellular level of active Sona was increased. These results show that exosomal Arr dictates Sona-expressing cells to increase the level of extracellular Sona. This new function of Arr occurred in the absence of Wg because S2 cells do not express Wg. We propose that Arr plays two distinct roles, one as an exosomal protein to increase the level of extracellular Sona in a Wnt-independent manner and the other as a Wg co-receptor in a Wnt-dependent manner.

TGF-β Signaling

Transforming growth factor-β (TGF-β) represents an evolutionarily conserved family of secreted polypeptide factors that regulate many aspects of physiological embryogenesis and adult tissue homeostasis. The TGF-β family members are also involved in pathophysiological mechanisms that underlie many diseases. Although the family comprises many factors, which exhibit cell type-specific and developmental stage-dependent biological actions, they all signal via conserved signaling pathways. The signaling mechanisms of the TGF-β family are controlled at the extracellular level, where ligand secretion, deposition to the extracellular matrix and activation prior to signaling play important roles. At the plasma membrane level, TGF-βs associate with receptor kinases that mediate phosphorylation-dependent signaling to downstream mediators, mainly the SMAD proteins, and mediate oligomerization-dependent signaling to ubiquitin ligases and intracellular protein kinases. The interplay between SMADs and other signaling proteins mediate regulatory signals that control expression of target genes, RNA processing at multiple levels, mRNA translation and nuclear or cytoplasmic protein regulation. This article emphasizes signaling mechanisms and the importance of biochemical control in executing biological functions by the prototype member of the family, TGF-β.

Vertical nanowire array-based biosensors: device design strategies and biomedical applications

We review the recent progress of vertical nanowire (VNW) array-based biosensors for the effective collection of biomedical information at the molecular level, extracellular level, and intracellular level.