Effects of glutamine supplementation on gut barrier,glutathione content and acute phase response in malnourished rats during inflammatory shock

AIM: To evaluate the effect of glutamine on intestinal mucosa integrity,glutathione stores and acute phase response in protein-depleted rats during an inflammatory shock. METHODS: Plasma acute phase proteins (APP),jejunal APP mRNA levels,liver and jejunal glutathione concentrations were measured before and one,three and seven days after turpentine injection in 4 groups of control,protein-restricted,protein-restricted rats supplemented with glutamine or protein powder. Bacterial translocation in mesenteric lymph nodes and intestinal morphology were also assessed. RESULTS: Protein deprivation and turpentine injection significantly reduced jejunal villus height,and crypt depths. Mucosal glutathione concentration significantly decreased in protein-restricted rats. Before turpentine oil,glutamine supplementation restored villus heights and glutathione concentration (3.24 ± 1.05 vs 1.72 ± 0.46 μmol/g tissue,P < 0.05) in the jejunum,whereas in the liver glutathione remained low. Glutamine markedly increased jejunal α1-acid glycoprotein mRNA level after turpentine oil but did not affect its plasma concentration. Bacterial translocation in protein-restricted rats was not prevented by glutamine or protein powder supplementation. CONCLUSION: Glutamine restored gut glutathione stores and villus heights in malnourished rats but had no preventive effect on bacterial translocation in our model.

Anti-CD163-dexamethasone conjugate inhibits the acute phase response to lipopolysaccharide in rats

AIM: To study the effect of a new anti-CD163-dexamethasone conjugate targeting activated macrophages on the hepatic acute phase response in rats. METHODS: Wistar rats were injected intravenous with either the CD163 targeted dexamethasone-conjugate(0.02 mg/kg) or free dexamethasone(0.02 or 1 mg/kg) 24 h prior to lipopolysaccharide(LPS)(2.5 mg/kg intraperitoneal). We measured plasma concentrations of tumour necrosis factor-a(TNF-a) and interleukin 6(IL-6) 2 h post-LPS and liver m RNAs and serum concentrations of the rat acute phase protein a-2-macroglobulin(a-2-M) 24 h after LPS. Also, plasma concentrations of alanine aminotransferase and bilirubin were measured at termination of the study. Spleen weight served as an indicator of systemic steroid effects.RESULTS: The conjugate halved the a-2-M liver m RNA(3.3 ± 0.6 vs 6.8 ± 1.1, P < 0.01) and serum protein(201 ± 48 μg/mL vs 389 ± 67 μg/mL, P = 0.04) after LPS compared to low dose dexamethasone treated animals, while none of the free dexamethasone doses had an effect on liver m RNA or serum levels of a-2-M. Also, the conjugate reduced TNF-a(7208 ± 1977 pg/mL vs 21583 ± 7117 pg/mL, P = 0.03) and IL-6(15685 ± 3779 pg/mL vs 25715 ± 4036 pg/mL, P = 0.03) compared to the low dose dexamethasone. The high dose dexamethasone dose decreased the spleen weight(421 ± 11 mg vs 465 ± 12 mg, P < 0.05) compared to controls, an effect not seen in any other group.CONCLUSION: Low-dose anti-CD163-dexamethasone conjugate effectively decreased the hepatic acute phase response to LPS. This indicates an anti-inflammatory potential of the conjugate in vivo.

Acute Phase Response of Rabbit to HgCl_2 and CdCl_2

A variety of changes occur in the rabbit under metal stress which include the appearance of the acute phase protein, C-reactive protein in the serum and significant reduction in the serum litres of albumin and acetylcholinesterase. The phospholipid profile is positively correlated with the higher degree of tissue necrosis encountered in mercury treated rabbit. Cadmium and mercury treatments evoke a similar response pattern in rabbit differing only in the degree of change.

Inflammation: Complexity and significance of cellular and molecular responses

Inflammation is a multifaceted cellular and molecular response triggered by injury,infection,or various pathological conditions.Serving as a protective defense mechanism,the inflammatory response involves clinical signs like redness,swelling,pain,and increased body temperature.Immune cells,notably neutrophils and macrophages,play key roles in orchestrating this response.The delicate balance between proinflammatory and anti-inflammatory mediators,including cytokines and chemokines,regulates the inflammatory cascade.While acute inflammation is crucial for tissue repair,chronic inflammation may indicate an imbalance,contributing to conditions like autoimmune diseases.Understanding these mechanisms is vital for developing therapeutic strategies and managing chronic diseases.

Microheterogeneity of acute phase proteins in patients with uIterative colitis

AIM： TO estimate the serum α1-antichymotrypsin （ACT）, α1-acid glycoprotein （AGP） and transferrin （Tf） concentrations and to evaluate the microheterogeneity of these acute phase proteins in patients with ulcerative colitis. METHODS： Twenty-seven patients with ulcerative colitis （UC） and 17 healthy control subjects were studied. The patients were categorised as severe （n = 9）, moderate （n = 10） and mild groups （n = 8） using Truelove and Witts＇ classification of ulcerative colitis. Microheterogeneity of ACT, AGP and Tf was analysed by crossed immunoaffinity electrophoresis （CIAE） with concanavalin A. In all serum samples standard electrophoresis of serum proteins was performed, iron （Fe） concentration, total iron binding capacity （TIBC） and C-reactive protein （CRP） were also measured. RESULTS： Our patients suffering from ulcerative colitis had significantly higher serum ACT and AGP concentrations and lower serum transferrin concentration in comparison to healthy subjects. Changes in concentrations of acute phase proteins were dependent on the activity of the inflammatory process. The glycosylation patterns of transferrin were related to the inflammation status. We also observed the correlation between ACT and AGP concentrations, patterns of transferrin glycosylation and changes in standard protein electrophoresis or blood cell count. CONCLUSION： The glycosylation patterns of transferrin obtained from patients suffering from ulcerative colitis are highly branched and sialylated compared with those obtained from healthy subjects. In contrast, the glycosylation patterns of transferrin do not differ according to the activity index of ulcerative colitis. The microheterogeneity patterns of AGP and ACT are similar in ulcerative colitis patients and healthy subjects.

Breed and adaptive response modulate bovine peripheral blood cells＇ transcriptome

Background： Adaptive response includes a variety of physiological modifications to face changes in external or internal conditions and adapt to a new situation. The acute phase proteins（APPs） are reactants synthesized against environmental stimuli like stress, infection, inflammation.Methods： To delineate the differences in molecular constituents of adaptive response to the environment we performed the whole-blood transcriptome analysis in Italian Holstein（IH） and Italian Simmental（IS） breeds. For this, 663 IH and IS cows from six commercial farms were clustered according to the blood level of APPs. Ten extreme individuals（five APP＋ and APP-variants） from each farm were selected for the RNA-seq using the Illumina sequencing technology. Differentially expressed（DE） genes were analyzed using dynamic impact approach（DIA）and DAVID annotation clustering. Milk production data were statistically elaborated to assess the association of APP＋ and APP-gene expression patterns with variations in milk parameters.Results： The overall de novo assembly of cDNA sequence data generated 13,665 genes expressed in bovine blood cells. Comparative genomic analysis revealed 1,152 DE genes in the comparison of all APP＋ vs. all APP-variants; 531 and 217 DE genes specific for IH and IS comparison respectively. In all comparisons overexpressed genes were more represented than underexpressed ones. DAVID analysis revealed 369 DE genes across breeds, 173 and 73 DE genes in IH and IS comparison respectively. Among the most impacted pathways for both breeds were vitamin B6 metabolism, folate biosynthesis, nitrogen metabolism and linoleic acid metabolism.Conclusions： Both DIA and DAVID approaches produced a high number of significantly impacted genes and pathways with a narrow connection to adaptive response in cows with high level of blood APPs. A similar variation in gene expression and impacted pathways between APP＋ and APP-variants was found between two studied breeds. Such similarity was also confirmed by annotation clustering of the DE genes. However, IH breed showed higher and more differentiated impacts compared to IS breed and such particular features in the IH adaptive response could be explained by its higher metabolic activity. Variations of milk production data were significantly associated with APP＋ and APP-gene expression patterns.

Interaction function of coupled bursting neurons

The interaction functions of electrically coupled Hindmarsh–Rose（HR） neurons for different firing patterns are investigated in this paper.By applying the phase reduction technique,the phase response curve（PRC） of the spiking neuron and burst phase response curve（BPRC） of the bursting neuron are derived.Then the interaction function of two coupled neurons can be calculated numerically according to the PRC（or BPRC） and the voltage time course of the neurons.Results show that the BPRC is more and more complicated with the increase of the spike number within a burst,and the curve of the interaction function oscillates more and more frequently with it.However,two certain things are unchanged：Φ = 0,which corresponds to the in-phase synchronization state,is always the stable equilibrium,while the anti-phase synchronization state with Φ = 0.5 is an unstable equilibrium.

Phase-response synchronization in neuronal population

In this study,we have formulated the phase description of the neuronal oscillator with non-instantaneous synaptic inputs and external periodic stimulus by using the phase sensitivity function.By numerical simulation,we have found that the phase of a neuronal oscillator undergoes periodic evolution or locked state,which is determined by the synaptic time constant.The synaptic time constant is also an important condition under which the global network is synchronized.When the synaptic time constant is relatively small,perfectly synchronized behavior quickly occurs in the neuronal population.As the synaptic time constant becomes slightly larger,periodic synchronization emerges in the neuronal population.However,synchronized activity in the neuronal population is lost for larger synaptic time constant.The external periodic stimulus can change the synchronization patterns in the neuronal population.With a weak low-frequency stimulus,the neuronal populations quick synchronized bursting;whereas a high-frequency stimulus can produce synchronized overlapping bursting.We have also found that neuronal oscillators with type-II phase response curves are more susceptible to synchronization than those with type-I phase response curves.

Entrainment mechanism of the cyanobacterial circadian clock induced by oxidized quinone

The circadian clock is a self-sustained biological oscillator which can be entrained by environmental signals.The cyanobacteria circadian clock is the simplest one,which is composed of the proteins KaiA,KaiB and KaiC.The phosphorylation/dephosphorylation state of KaiC exhibits a circadian oscillator.KaiA and KaiB activate KaiC phosphorylation and dephosphorylation respectively.CikA competing with KaiA for the same binding site on KaiB affects the phosphorylation state of KaiC.Quinone is a signaling molecule for entraining the cyanobacterial circadian clock which is oxidized at the onset of darkness and reduced at the onset of light,reflecting the environmental light-dark cycle.KaiA and CikA can sense external signals by detecting the oxidation state of quinone.However,the entrainment mechanism is far from clear.We develop an enhanced mathematical model including oxidized quinone sensed by KaiA and CikA,with which we present a detailed study on the entrainment of the cyanobacteria circadian clock induced by quinone signals.We find that KaiA and CikA sensing oxidized quinone pulse are related to phase advance and delay,respectively.The time of oxidized quinone pulse addition plays a key role in the phase shifts.The combination of KaiA and CikA is beneficial to the generation of entrainment,and the increase of signal intensity reduces the entrainment phase.This study provides a theoretical reference for biological research and helps us understand the dynamical mechanisms of cyanobacteria circadian clock.

SYNTHESIS AND PROPERTIES OF A NEW AZOBENZENE SIDE-CHAIN POLYMER CONTAINING A TEMPO RADICAL

To allow anisotropies of optical properties in a magnetic field, nitroxide radical is introduced into the ortho-position of the phenylene ring in the side chain. A new azobenzene side-chain polymer (TEMPO-PAZ) containing TEMPO radical was synthesized. The polymer has a good solubility in organic solvents. The ESR spectrum of the polymer indicated three absorption lines characteristic of TEMPO radical. The optical phase conjugated responses (I-4) of the polymer films were investigated by degenerate four-wave mixing (DFWM). The experimental results showed that optical phase conjugated response of the TEMPO-PAZ could be easily controlled by choosing the appropriate direction of magnetic field presumably due to the nitroxide radical in the TEMPO-PAZ molecular structure. For the polymer investigated here, the nitroxide radical was introduced to increase optical phase conjugated response intensity in a magnetic field, aiming originally at searching for a new photo-active organic magnetic multifunctional materials.

Response to lipopolysaccharide in Octodon degus pups produces age-related sickness behavior but does not have effects in juveniles

During vertebrate development,the immune function is inefficient and is mainly controlled by innate defense.While there have been detailed studies of various aspects of innate immune function,the effects of this func­tion in the growth of vertebrates is still not well known.Similarly,there is little information regarding how ear­ly endotoxin exposure would affect juvenile phenotypes,specifically in a non-model mammal like a precocial rodent.We evaluated the response to an antigen and its cost in offspring of the rodent Octodon degus.We in­oculated pups at 4 different ages(8,15,22 and 30 days after birth)with an antigen to determine the ontogeny and costs of the response to an endotoxin.We assessed changes in body mass,body temperature,sickness be­havior and the levels of a key mediator of the inflammatory response,the cytokine interleukin-1β.We also de­termined the effects of early endotoxin exposure on the resting metabolic rate of juvenile animals(i.e.90 days after birth).The cytokine levels,body mass and body temperature were unaffected by time of inoculation and treatment.However,pups subjected to inoculation at 22 days after birth with the antigen showed reduced loco­motion.Juvenile resting metabolic rate was not affected by early endotoxin exposure.These results suggest that the magnitude of O.degus responses would not change with age.We discuss whether the lack of effect of the response on body mass or body condition is caused by environmental variables or by the precocial characteris­tics of O.degus.

New Phase of Phase

Year 2021 is special.It sees the renaissance of concept of phase and the birth of a phase theory for matters much beyond complex numbers and single-input single-output(SISO)linear timeinvariant(LTI)systems while we celebrate the 60 th birthday of Lei Guo,an exemplary research leader of our times.Here we give a short tutorial of the newly developed phase theory,as a birthday present.

Hepatic cecum:a key integrator of immunity in amphioxus

The vertebrate liver is regarded as an organ essential to the regulation of immunity and inflammation as well as being central to the metabolism of nutrients.Here,we discuss the functions that the hepatic cecum of amphioxus plays in the regulation of immunity and inflammation,and the molecular basis of this.It is apparent that the hepatic cecum performs important roles in the immunity of amphioxus including immune surveillance,clearance of pathogens and acute phase response.Therefore,the hepatic cecum,like the vertebrate liver,is an organ functioning as a key integrator of immunity in amphioxus.

Disaster Risk Governance as Assemblage: The Chilean Framework of the 1985 San Antonio Earthquake

The purpose of this article is to analyze disaster risk governance through assemblage theory, identifying how-during the altered political context of a military regime with a centralized disaster risk management as in the case of Chile in 1985-new actors emerge during the disaster response phase as a de/reterritorialization effect that is influenced by their agencies and relationships, disfiguring the edges of the assemblage. Based on this conceptualization, it is possible to investigate the interactions between the different actors, their power relations, and their reconfigurations in the governance exercise. For this purpose, we reviewed the response phase of the 1985 San Antonio earthquake that affected the central zone of Chile, where strategic functions, institutions, and forms of power are concentrated.To describe and visualize the actors during the response phase in the disaster risk governance framework, a map of actors was developed that identifies the existing relationships and their different weights. The central scale proved to be dominant and occupied a political space that was transfigured by its overrepresentation-enforced by allies such as the banking system and business associations-enhancing a neoliberal agenda. The leaps in scale from the central scale to the local scale cancel agency of the last, destabilizing its capacity to deal with the effects of the earthquake and isolating it from the decision-making processes. Consequently,delays in providing aid demonstrate that authoritarian governments do not provide better management in the disaster response phase.

A current-mode DC-DC buck converter with adaptive zero compensation

To achieve fast transient response for a DC-DC buck converter,an adaptive zero compensation circuit is presented.The compensation resistance is dynamically adjusted according to the different output load conditions, and achieves an adequate system phase margin under the different conditions.An improved capacitor multiplier circuit is adopted to realize the minimized compensation capacitance size.In addition,analysis of the small-signal model shows the correctness of the mechanism of the proposed adaptive zero compensation technique.A currentmode DC-DC buck converter with the proposed structure has been implemented in a 0.35μm CMOS process,and the die size is only 800×1040μm;.The experimental results show that the transient undershoot/overshoot voltage and the recovery times do not exceed 40 mV and 30μs for a load current variation from 100 mA to 1 A.