How Does Escherichia coli Allocate Proteome?

Microorganisms are shown to actively partition their intracellular resources, such as proteins, for growth optimization. Recent experiments have begun to reveal molecular components unpinning the partition; however, quantitatively, it remains unclear how individual parts orchestrate to yield precise resource allocation that is both robust and dynamic. Here, we developed a coarse-grained mathematical framework that centers on guanosine pentaphosphate (ppGpp)-mediated regulation and used it to systematically uncover the design principles of proteome allocation in Escherichia coli. Our results showed that the cellular ability of resource partition lies in an ultrasensitive, negative feedback-controlling topology with the ultrasensitivity arising from zero-order amino acid kinetics and the negative feedback from ppGpp-controlled ribosome synthesis. In addition, together with the time-scale separation between slow ribosome kinetics and fast turnovers of ppGpp and amino acids, the network topology confers the organism an optimization mechanism that mimics sliding mode control, a nonlinear optimization strategy that is widely used in man-made systems. We further showed that such a controlling mechanism is robust against parameter variations and molecular fluctuations and is also efficient for biomass production over time. This work elucidates the fundamental controlling mechanism of E. coli proteome allocation, thereby providing insights into quantitative microbial physiology as well as the design of synthetic gene networks.

mTORC1 phosphorylates and stabilizes LST2 to negatively regulate EGFR.

TORC1 (target of rapamycin complex 1) is a highly conserved protein kinase that plays a central role in regulating cell growth. Given the role of mammalian TORC1 (mTORC1) in metabolism and disease, understanding mTORC1 downstream signaling and feedback loops is important. mTORC1 recognizes some of its substrates via a five amino acid binding sequence called the TOR signaling (TOS) motif. mTORC1 binding to a TOS motif facilitates phosphorylation of a distinct, distal site. Here, we show that LST2, also known as ZFYVE28, contains a TOS motif (amino acids 401 to 405) and is directly phosphorylated by mTORC1 at serine 670 (S670). mTORC1-mediated S670 phosphorylation promotes LST2 monoubiquitination on lysine 87 (K87). Monoubiquitinated LST2 is stable and displays a broad reticular distribution. When mTORC1 is inactive, unphosphorylated LST2 is degraded by the proteasome. The absence of LST2 enhances EGFR (epidermal growth factor receptor) signaling. We propose that mTORC1 negatively feeds back on its upstream receptor EGFR via LST2.

Understanding negative feedback: Changes in high-molecular-weight adrenocorticotropic hormone in adrenocorticotropic hormone-independent Cushing's syndrome.

Cushing's syndrome is characterized by chronic glucocorticoid oversecretion and diverse clinical manifestations. Distinguishing between adrenocorticotropic hormone (ACTH)-independent and ACTH-dependent forms is crucial for determining treatment options. Plasma ACTH levels aid in the differential diagnosis, with undetectable or low levels suggesting ACTH-independent hypercortisolemia. ACTH is derived from pro-opiomelanocortin, and its processing involves prohormone convertase 1/3. High-molecular-weight ACTH is generally found in ACTH-producing pituitary tumors and ectopic ACTH syndrome. The mechanism of negative feedback and the process of high-molecular-weight ACTH alternation during ACTH-independent Cushing's syndrome remain unclear. A 40-year-old woman with hypertension and multiple fractures developed symptoms suggestive of Cushing's syndrome. Computed tomography revealed a left adrenocortical tumor along with atrophy of the right adrenal gland. ACTH levels were undetectable at the previous clinic, indicating ACTH-independent Cushing's syndrome. However, subsequent measurements at our hospital revealed non-suppressed ACTH (18.1 pg/mL), prompting further investigation. Gel exclusion chromatography confirmed the presence of high-molecular-weight ACTH. Metyrapone treatment decreased the cortisol levels. In this situation, in which ACTH levels should be elevated, a decrease in high-molecular-weight ACTH levels was observed. Histological findings revealed cortisol-producing adenoma without ACTH expression. This case highlights the importance of assay differences in evaluating ACTH concentrations and introduces a novel finding of circulating high-molecular-weight ACTH. The observed decline in high-molecular-weight ACTH levels suggests a potential time lag in the negative feedback within the hypothalamic-pituitary-adrenal axis exhibited by glucocorticoids. This temporal aspect of the regulation of ACTH-related molecules warrants further exploration to enhance our understanding of the hypothalamic-pituitary-adrenal axis feedback mechanism.

Direct observation correlates NFκB cRel in B cells with activating and terminating their proliferative program.

Antibody responses require the proliferative expansion of B cells controlled by affinity-dependent signals. Yet, proliferative bursts are heterogeneous, varying between 0 and 8 divisions in response to the same stimulus. NFκB cRel is activated in response to immune stimulation in B cells and is genetically required for proliferation. Here, we asked whether proliferative heterogeneity is controlled by natural variations in cRel abundance. We developed a fluorescent reporter mTFP1-cRel for the direct observation of cRel in live proliferating B cells. We found that cRel is heterogeneously distributed among naïve B cells, which are enriched for high expressors in a heavy-tailed distribution. We found that high cRel expressors show faster activation of the proliferative program, but do not sustain it well, with population expansion decaying earlier. With a mathematical model of the molecular network, we showed that cRel heterogeneity arises from balancing positive feedback by autoregulation and negative feedback by its inhibitor IκBε, confirmed by mouse knockouts. Using live-cell fluorescence microscopy, we showed that increased cRel primes B cells for early proliferation via higher basal expression of the cell cycle driver cMyc. However, peak cMyc induction amplitude is constrained by incoherent feedforward regulation, decoding the fold change of cRel activity to terminate the proliferative burst. This results in a complex nonlinear, nonmonotonic relationship between cRel expression and the extent of proliferation. These findings emphasize the importance of direct observational studies to complement gene knockout results and to learn about quantitative relationships between biological processes and their key regulators in the context of natural variations.

Strong delayed negative feedback.

In this paper, we analyze the strong feedback limit of two negative feedback schemes which have proven to be efficient for many biological processes (protein synthesis, immune responses, breathing disorders). In this limit, the nonlinear delayed feedback function can be reduced to a function with a threshold nonlinearity. This will considerably help analytical and numerical studies of networks exhibiting different topologies. Mathematically, we compare the bifurcation diagrams for both the delayed and non-delayed feedback functions and show that Hopf classical theory needs to be revisited in the strong feedback limit.

A double-negative feedback loop mediated by non-coding RNAs contributes to tooth morphogenesis.

Tooth morphogenesis is a critically ordered process manipulated by a range of signaling factors. Particularly, the involvement of fine-tuned signaling mediated by non-coding RNAs has been of longstanding interest. Here, we revealed a double-negative feedback loop acted by a long non-coding RNA (LOC102159588) and a microRNA (miR-133b) that modulated tooth morphogenesis of miniature swine. Mechanistically, miR-133b repressed the transcription of LOC102159588 through downstream target Sp1. Conversely, LOC102159588 not only inhibited the transport of pre-miR-133b from the nucleus to the cytoplasm by regulating exportin-5 but also served as a sponge in the cytoplasm, suppressing functional miR-133b. Together, the double-negative feedback loop maintained normal tooth morphogenesis by modulating endogenous apoptosis. Related disruptions would lead to an arrest of tooth development and may result in tooth malformations.

Negative feedback systems for modelling NF-κB transcription factor oscillatory activity.

Low-dimensional negative feedback systems (NFSs) were developed within a signal flow model to describe the oscillatory activities of NF-κB caused by interactions with its inhibitor IκBα. The NFSs were established as 3rd- and 4th-order linear systems containing unperturbed and perturbed negative feedback (NF) loops with constant or time-varying NF strengths and a feed-forward loop. NF-related analytical solutions to the NFSs representing the time courses of NF-κB and IκBα were determined and their exact mathematical relationship was found. The NFS's parameters were determined to fit the experimental time courses of NF-κB in TNF-α-stimulated embryonic fibroblasts, rela-/- embryonic fibroblasts reconstituted with RelA, C9L cells, GFP-p65 knock-in embryonic fibroblasts and embryogenic fibroblasts lacking Iκß and IκBε, LPS-stimulated IC-21 macrophages treated or not with DCPA, and anti-IgM-stimulated DT40 B-lymphocytes. The unperturbed and perturbed NFSs describing the above biosystems generated isochronous and non-isochronous solutions, depending on a constant or time-varying NF strength, respectively. The oscillation period of the NF-coupled solutions, the phase difference between them and the time delays in the appearance of cytoplasmic IκBα after stimulation of NF-κB were determined. A significant divergence between the IκBα solutions to the NFSs and the IκBα experimental courses led to a rejection of the NF coupling between NF-κB and IκBα in the above biosystems. It was shown that neither the linearity nor the low dimensionality of the NFSs altered the NF relationship and the divergence between the IκBα solutions to the NFS and IκBα experimental time courses. Although the NF relationship between IκBα and NF-κB was not confirmed in all the experimental data analyzed, delayed negative feedback was found in some cases.

OsPRMT6a-mediated arginine methylation of OsJAZ1 regulates jasmonate signaling and spikelet development in rice.

Although both protein arginine methylation (PRMT) and jasmonate (JA) signaling are crucial for regulating plant development, the relationship between these processes in the control of spikelet development remains unclear. In this study, we used the CRISPR/Cas9 technology to generate two OsPRMT6a loss-of-function mutants that exhibit various abnormal spikelet structures. Interestingly, we found that OsPRMT6a can methylate arginine residues in JA signal repressors OsJAZ1 and OsJAZ7. We showed that arginine methylation of OsJAZ1 enhances the binding affinity of OsJAZ1 with the JA receptors OsCOI1a and OsCOI1b in the presence of JAs, thereby promoting the ubiquitination of OsJAZ1 by the SCFOsCOI1a/OsCOI1b complex and degradation via the 26S proteasome. This process ultimately releases OsMYC2, a core transcriptional regulator in the JA signaling pathway, to activate or repress JA-responsive genes, thereby maintaining normal plant (spikelet) development. However, in the osprmt6a-1 mutant, reduced arginine methylation of OsJAZ1 impaires the interaction between OsJAZ1 and OsCOI1a/OsCOI1b in the presence of JAs. As a result, OsJAZ1 proteins become more stable, repressing JA responses, thus causing the formation of abnormal spikelet structures. Moreover, we discovered that JA signaling reduces the OsPRMT6a mRNA level in an OsMYC2-dependent manner, thereby establishing a negative feedback loop to balance JA signaling. We further found that OsPRMT6a-mediated arginine methylation of OsJAZ1 likely serves as a switch to tune JA signaling to maintain normal spikelet development under harsh environmental conditions such as high temperatures. Collectively, our study establishes a direct molecular link between arginine methylation and JA signaling in rice.

ESR2-HDA6 complex negatively regulates auxin biosynthesis to delay callus initiation in Arabidopsis leaf explants during tissue culture.

Plants exhibit an astonishing ability to regulate organ regeneration upon wounding. Excision of leaf explants promotes the biosynthesis of indole-3-acetic acid (IAA), which is polar-transported to excised regions, where cell fate transition leads to root founder cell specification to induce de novo root regeneration. The regeneration capacity of plants has been utilized to develop in vitro tissue culture technologies. Here, we report that IAA accumulation near the wounded site of leaf explants is essential for callus formation on 2,4-dichlorophenoxyacetic acid (2,4-D)-rich callus-inducing medium (CIM). Notably, a high concentration of 2,4-D does not compensate for the action of IAA because of its limited efflux; rather, it lowers IAA biosynthesis via a negative feedback mechanism at an early stage of in vitro tissue culture, delaying callus initiation. The auxin negative feedback loop in CIM-cultured leaf explants is mediated by an auxin-inducible APETALA2 transcription factor, ENHANCER OF SHOOT REGENERATION 2 (ESR2), along with its interacting partner HISTONE DEACETYLASE 6 (HDA6). The ESR2-HDA6 complex binds directly to, and removes the H3ac mark from, the YUCCA1 (YUC1), YUC7, and YUC9 loci, consequently repressing auxin biosynthesis and inhibiting cell fate transition on 2,4-D-rich CIM. These findings indicate that negative feedback regulation of auxin biosynthesis by ESR2 and HDA6 interferes with proper cell fate transition and callus initiation.

Reciprocal negative feedback between Prrx1 and miR-140-3p regulates rapid chondrogenesis in the regenerating antler.

During growth phase, antlers exhibit a very rapid rate of chondrogenesis. The antler is formed from its growth center reserve mesenchyme (RM) cells, which have been found to be the derivatives of paired related homeobox 1 (Prrx1)-positive periosteal cells. However, the underlying mechanism that drives rapid chondrogenesis is not known. Herein, the miRNA expression profiles and chromatin states of three tissue layers (RM, precartilage, and cartilage) at different stages of differentiation within the antler growth center were analyzed by RNA-sequencing and ATAC-sequencing. We found that miR-140-3p was the miRNA that exhibited the greatest degree of upregulation in the rapidly growing antler, increasing from the RM to the cartilage layer. We also showed that Prrx1 was a key upstream regulator of miR-140-3p, which firmly confirmed by Prrx1 CUT&Tag sequencing of RM cells. Through multiple approaches (three-dimensional chondrogenic culture and xenogeneic antler model), we demonstrated that Prrx1 and miR-140-3p functioned as reciprocal negative feedback in the antler growth center, and downregulating PRRX1/upregulating miR-140-3p promoted rapid chondrogenesis of RM cells and xenogeneic antler. Thus, we conclude that the reciprocal negative feedback between Prrx1 and miR-140-3p is essential for balancing mesenchymal proliferation and chondrogenic differentiation in the regenerating antler. We further propose that the mechanism underlying chondrogenesis in the regenerating antler would provide a reference for helping understand the regulation of human cartilage regeneration and repair.

A unique circ_0067716/EIF4A3 double-negative feedback loop impacts malignant transformation of human bronchial epithelial cells induced by benzo(a)pyrene.

Benzo(a)pyrene as a pervasive environmental contaminant is characterized by its substantial genotoxicity, and epidemiological investigations have established a correlation between benzo(a)pyrene exposure and the susceptibility to human lung cancer. Notably, much research has focused on the link between epigenetic alterations and lung cancer induced by chemicals, although circRNAs are also emerging as relevant contributors to the carcinogenic process of benzo(a)pyrene. In this study, we identified circ_0067716 as being significantly upregulated in response to stress injury and downregulated during malignant transformation induced by benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE) in human bronchial epithelial cells. The observed differential expression of circ_0067716 in cells treated with BPDE for varying durations suggests a strong correlation between this circRNA and BPDE exposure. The tissue samples of lung cancer patients also suggest that a lower circ_0067716 expression is associated with BPDE-DNA adduct levels. Remarkably, we demonstrate that EIF4A3, located in the nucleus, interacts with the flanking sequences of circ_0067716 and inhibits its biogenesis. Conversely, circ_0067716 is capable of sequestering EIF4A3 in the cytoplasm, thereby preventing its translocation into the nucleus. EIF4A3 and circ_0067716 can form a double-negative feedback loop that could be affected by BPDE. During the initial phase of BPDE exposure, the expression of circ_0067716 was increased in response to stress injury, resulting in cell apoptosis through the involvement of miR-324-5p/DRAM1/BAX axis. Subsequently, as cellular adaptation progressed, long-term induction due to BPDE exposure led to an elevated EIF4A3 and a reduced circ_0067716 expression, which facilitated the proliferation of cells by stabilizing the PI3K/AKT pathway. Thus, our current study describes the effects of circ_0067716 on the genotoxicity and carcinogenesis induced by benzo(a)pyrene and puts forwards to the possible regulatory mechanism on the occurrence of smoking-related lung cancer, providing a unique insight based on epigenetics.

Single microcystin exposure impairs the hypothalamic-pituitary-gonadal axis at different levels in female rats.

Microcystin (MC) is most common cyanobacterial toxin. Few studies have evaluated the MC effects on the hypothalamic-pituitary-gonadal (HPG) axis and metabolic function. In this study, we assessed whether MC exposure results in HPG axis and metabolic changes. Female rats were exposed to a single dose of MC at environmentally relevant levels (5, 20 and 40 µg/kg). After 24 h, we evaluated reproductive and metabolic parameters for 15 days. MC reduced the hypothalamic GnRH protein expression, increased the pituitary protein expression of GnRHr and IL-6. MC reduced LH levels and increased FSH levels. MC reduced the primary follicles, increased the corpora lutea, elevated levels of anti-Müllerian hormone (AMH) and progesterone, and decreased estrogen levels. MC increased ovarian VEGFr, LHr, AMH, ED1, IL-6 and Gp91-phox protein expression. MC increased uterine area and reduced endometrial gland number. A blunted estrogen-negative feedback was observed in MC rats after ovariectomy, with no changes in LH levels compared to intact MC rats. Therefore, these data suggest that a MC leads to abnormal HPG axis function in female rats.

A Wide-Band Magnetoelectric Sensor Based on a Negative-Feedback Compensated Readout Circuit.

Magnetoelectric (ME) sensors cannot effectively detect broadband magnetic field signals due to their narrow bandwidth, and existing readout circuits are unable to vary the bandwidth of the sensors. To expand the bandwidth, this paper introduces a negative-feedback readout circuit, fabricated by introducing a negative-feedback compensation circuit based on the direct readout circuit of the ME sensor. The negative-feedback compensation circuit contains a current amplifier, a feedback resistor, and a feedback coil. For this purpose, a Metglas/PVDF/Metglas ME sensor was prepared. Experimental measurements show that there is a six-fold difference between the maximum and minimum values of the ME voltage coefficients in the 6-39 kHz frequency band for the ME sensor without the negative-feedback compensation circuit when the sensor operates at the optimal bias magnetic field. However, the ME voltage coefficient in this band remains stable, at 900 V/T, after the charge amplification of the direct-reading circuit and the negative-feedback circuit. In addition, experimental results show that this negative-feedback readout circuit does not increase the equivalent magnetic noise of the sensor, with a noise level of 240 pT/√Hz in the frequency band lower than 25 kHz, 63 pT/√Hz around the resonance frequency of 30 kHz, and 620 pT/√Hz at 39 kHz. This paper proposes a negative-feedback readout circuit based on the direct readout circuit, which greatly increases the bandwidth of ME sensors and promotes the widespread application of ME sensors in the fields of broadband weak magnetic signal detection and DBS electrode positioning.

Arginine-assembly as NO nano-donor prevents the negative feedback of macrophage repolarization by mitochondrial dysfunction for cancer immunotherapy.

Repolarizing the tumor-associated macrophages (TAMs) towards the antitumoral M1-like phenotype has been a promising approach for cancer immunotherapy. However, the anti-cancer immune response is severely limited mainly by the repolarized M1-like macrophages belatedly returning to the M2-like phenotype (i.e., negative feedback). Inspired by nitric oxide (NO) effectively preventing repolarization of inflammatory macrophages in inflammatory diseases, herein, we develop an arginine assembly, as NO nano-donor for NO generation to prevent the negative feedback of the macrophage repolarization. The strategy is to first apply reversible tagging of hydrophobic terephthalaldehyde to create an arginine nano-assembly, and then load a toll-like receptor 7/8 agonist resiquimod (R848) (R848@Arg). Through this strategy, a high loading efficiency of 40 % for the arginine and repolarization characteristics for TAMs can be achieved. Upon the macrophage repolarization by R848, NO can be intracellularly generated from the released arginine by the upregulated inducible nitric oxide synthase. Mechanistically, NO effectively prevented the negative feedback of the repolarized macrophage by mitochondrial dysfunction via blocking oxidative phosphorylation. Notably, R848@Arg significantly increased the tumor inhibition ratio by 3.13-fold as compared to the free R848 by maintaining the M1-like phenotype infiltrating into tumor. The Arg-assembly as NO nano-donor provides a promising method for effective repolarization of macrophages.

Negative feedback-seeking in depression: The moderating roles of rumination and interpersonal life stress.

OBJECTIVES: Swann's self-verification theory proposes that negative feedback seeking (NFS)-the solicitation of negative feedback from others that confirms one's self-views-works in a negative cycle to maintain and exacerbate depression in the face of interpersonal stress. We propose a cognitive-interpersonal integration account of NFS such that this maladaptive behavior prospectively predicts depression only among those with a trait tendency to ruminate on the causes and consequences of depressed mood and stress. METHOD: Participants included 91 young adults who were over-sampled for a lifetime history of a unipolar depressive disorder (age 17-33; 69% women; 67% lifetime depressive disorder). At baseline, participants completed a structured diagnostic interview and self-report measures of NFS, rumination, and depression symptoms. In addition, participants engaged in an interpersonal rejection task (the Yale Interpersonal Stressor) followed by a behavioral measure of NFS. At a 3-month follow-up, depression symptoms were again assessed by self-report and exposure to stressful interpersonal life events in the intervening period were assessed with a rigorous contextual interview and independent rating system. RESULTS: Controlling for baseline depression severity, greater self-reported, and behaviorally assessed NFS predicted greater follow-up depression severity, but only among those with higher trait tendency to ruminate. For self-reported NFS, this association was further moderated by level of interpersonal, but not noninterpersonal, life events experienced over follow-up. CONCLUSION: These findings suggest that rumination may represent a modifiable intervention target that could break the vicious interpersonal cycle of depression and, thus, mitigate the depressogenic effects of NFS.

An Electrochemically Initiated Self-Limiting Hydrogel Electrolyte for Dendrite-Free Zinc Anode.

The zinc dendrite growth generally relies upon a "positive-feedback" mode, where the fast-grown tips receive higher current densities and ion fluxes. In this study, a self-limiting polyacrylamide (PAM) hydrogel that presents negative feedback to dendrite growth is developed. The monomers are purposefully polymerized at the dendrite tips, then the hydrogel reduces the local current density and ion flux by limiting zinc ion diffusion with abundant functional groups. As a consequence, the accumulation at the dendrite tips is restricted, and the (002) facets-oriented deposition is achieved. Moreover, the refined porous structure of the gel enhances Coulombic Efficiency by reducing water activity. Due to the synergistic effects, the zinc anodes perform an ultralong lifetime of 5100 h at 0.5 mA cm-2 and 1500 h at 5 mA cm-2, which are among the best records for PAM-based gel electrolytes. Further, the hydrogel significantly prolongs the lifespan of zinc-ion batteries and capacitors by dozens of times. The developed in situ hydrogel presents a feasible and cost-effective way to commercialize zinc anodes and provides inspiration for future research on dendrite suppression using the negative-feedback mechanism.

Travelling waves due to negative plant-soil feedbacks in a model including tree life-stages.

The emergence and maintenance of tree species diversity in tropical forests is commonly attributed to the Janzen-Connell (JC) hypothesis, which states that growth of seedlings is suppressed in the proximity of conspecific adult trees. As a result, a JC distribution due to a density-dependent negative feedback emerges in the form of a (transient) pattern where conspecific seedling density is highest at intermediate distances away from parent trees. Several studies suggest that the required density-dependent feedbacks behind this pattern could result from interactions between trees and soil-borne pathogens. However, negative plant-soil feedback may involve additional mechanisms, including the accumulation of autotoxic compounds generated through tree litter decomposition. An essential task therefore consists in constructing mathematical models incorporating both effects showing the ability to support the emergence of JC distributions. In this work, we develop and analyse a novel reaction-diffusion-ODE model, describing the interactions within tropical tree species across different life stages (seeds, seedlings, and adults) as driven by negative plant-soil feedback. In particular, we show that under strong negative plant-soil feedback travelling wave solutions exist, creating transient distributions of adult trees and seedlings that are in agreement with the Janzen-Connell hypothesis. Moreover, we show that these travelling wave solutions are pulled fronts and a robust feature as they occur over a broad parameter range. Finally, we calculate their linear spreading speed and show its (in)dependence on relevant nondimensional parameters.

Changes in hypothalamic-pituitary-adrenal axis function, immunity, and glucose during acute Plasmodium relictum infection in house sparrows (Passer domesticus).

Hosts of the same species vary in physiological responses to the same parasite, and some groups of individuals can disproportionately affect disease dynamics; however, the underlying pathophysiology of host-parasite interactions is poorly understood in wildlife. We tested the hypothesis that the hypothalamic-pituitary-adrenal (HPA) axis mediates host resistance and tolerance to avian malaria during the acute phase of infection by evaluating whether individual variation in circulating glucocorticoids predicted resistance to avian malaria in a songbird. We experimentally inoculated wild-caught house sparrows (Passer domesticus) with naturally sourced Plasmodium relictum and quantified baseline and restraint-induced circulating corticosterone, negative feedback ability, cellular and humoral immune function, and baseline and restraint-induced glycemia, prior to and during acute malaria infection. During peak parasitemia, we also evaluated the expression of several liver cytokines that are established pathological hallmarks of malaria in mammals: two pro-inflammatory (IFN-γ and TNF-α) and two anti-inflammatory (IL-10 and TGF-ß). Although most of the host metrics we evaluated were not correlated with host resistance or tolerance to avian malaria, this experiment revealed novel relationships between malarial parasites and the avian immune system that further our understanding of the pathology of malaria infection in birds. Specifically, we found that: (1) TNF-α liver expression was positively correlated with parasitemia; (2) sparrows exhibited an anti-inflammatory profile during malaria infection; and (3) IFN-γ and circulating glucose were associated with several immune parameters, but only in infected sparrows. We also found that, during the acute phase of infection, sparrows increased the strength of corticosterone negative feedback at the level of the pituitary. In the context of our results, we discuss future methodological considerations and aspects of host physiology that may confer resistance to avian malaria, which can help inform conservation and rehabilitation strategies for avifauna at risk.

Temperature-Dependent Electrical Characteristics of Silicon Biristor.

In this study, we investigate the temperature-dependent electrical characteristics of bistable silicon resistors (biristors) at temperatures ranging from 275 to 400 K. The proposed biristor exhibits low latch voltages owing to the surface accumulation layer transistor concept. Moreover, the biristor was abruptly turned on and off by positive and negative feedback phenomena, respectively. As the temperature increased from 275 to 400 K, the latch-up voltage decreased from 2.131 to 1.696 V, while the latch-down voltage increased from 1.486 to 1.637 V. Mechanisms of temperature-dependent change in latch voltage were analyzed using energy band diagrams. This temperature-dependent analysis on silicon biristor can serve as blueprint for the contribution of stable operation.