Reciprocal Balance Research Articles

The difference in the relationship of spinal sagittal alignment between individuals with flat lumbar and normal lordosis posture based on global and regional angles.

According to previous studies, the relationship between lumbar lordosis and thoracic kyphosis or that between pelvic parameters and thoracic kyphosis have been inconsistent. The purpose of this study was to investigate spinal sagittal alignment and its relationship to global and regional lumbar and thoracic angles, pelvic and sway angles, and C7-S1 distance measurements, followed by a detailed subgroup analysis using an inertial measurement unit system. A total of 51 asymptomatic volunteers stood in a comfortable posture with inertial measurement units attached to the T1, T7, T12, L3, and S2 vertebrae. T1, T7, T12, L3, and S2 sagittal angles were acquired during standing posture using the Eulerian angle coordinate system. All angles are reported as the mean of three 5-s measurements. Following the measurement of lumbar lordosis angles (T12 relative S2), participants were divided into the flat lumbar and normal lordosis groups. There were different correlation patterns between groups because of spinal sagittal imbalance, which was greater in the flat lumbar group than in the normal lordosis group. In addition, sacral inclination proved the ideal parameter to evaluate reciprocal balance in lumbar lordosis, showing a stronger correlation with lower than with upper lumbar lordosis. T1 was the key element in assessing thoracic kyphosis, which showed a stronger correlation with upper than with lower thoracic kyphosis. We suggest that when assessing posture, it is necessary to identify the global and regional angles and it is useful to classify spinal sagittal alignment into subgroups according to lumbar lordosis and evaluate the groups separately.

Reciprocal regulatory balance within the CLEC16A–RNF41 mitophagy complex depends on an intrinsically disordered protein region

CLEC16A is an E3 ubiquitin ligase that regulates mitochondrial quality control through mitophagy and is associated with over 20 human diseases. CLEC16A forms a complex with another E3 ligase, RNF41, and a ubiquitin-specific peptidase, USP8; however, regions that regulate CLEC16A activity or the assembly of the tripartite mitophagy regulatory complex are unknown. Here, we report that CLEC16A contains an internal intrinsically disordered protein region (IDPR) that is crucial for CLEC16A function and turnover. IDPRs lack a fixed secondary structure and possess emerging yet still equivocal roles in protein stability, interactions, and enzymatic activity. We find that the internal IDPR of CLEC16A is crucial for its degradation. CLEC16A turnover was promoted by RNF41, which binds and acts upon the internal IDPR to destabilize CLEC16A. Loss of this internal IDPR also destabilized the ubiquitin-dependent tripartite CLEC16A-RNF41-USP8 complex. Finally, the presence of an internal IDPR within CLEC16A was confirmed using NMR and CD spectroscopy. Together, our studies reveal that an IDPR is essential to control the reciprocal regulatory balance between CLEC16A and RNF41, which could be targeted to improve mitochondrial health in disease.

Theory Instruments as Tangible Ways of Knowing

While ethnographers and the data they produce already play a role in affecting industry practices, there is potential to integrate anthropological ways of seeing and knowing into a shared transdisciplinary design praxis. In a series of design research experiments, we have taken a pragmatic and playful approach to physicalizing theory. The result is a set of ‘Theory Instruments’ that transform theory into tangible interaction. Theory Instruments scaffold knowledge production by encouraging new ways of seeing organizations, products, users, and the relations between them. We present two of these instruments, Actor‐Network Rings and Reciprocity Balance, through a case study with a design team at a health product company that wished to generate new design concepts from field material. Theory Instruments helped bridge the gap between the epistemic modes of knowing employed by ethnography practitioners and the technical and tacit modes of knowing familiar to design practitioners. This new mode of collaboration helped them to cross worlds, cultivating a more resilient, transdisciplinary praxis.

Educational Lecture 1 - Role of Innate and Adaptive Immunity in Endometriosis

Endometriosis is a multifactorial disease that mainly affects women of reproductive age and is associated with chronic pelvic pain and infertility. The exact pathogenesis of this disease is still debatable. In 2010, we established “bacterial contamination hypothesis”, a new concept in endometriosis. As a component of innate immunity, the role of bacterial endotoxin (lipopolysaccharide, LPS) and Toll-like receptor 4 (TLR4) in endometriosis was investigated and the possible source of endotoxin in uterine and pelvic environment was examined. We found that LPS regulates the pro-inflammatory response in pelvis and growth of endometriosis via LPS/TLR4 cascade. The highly contaminated menstrual blood with Escherichia coli was associated with significantly higher levels of endotoxin in the menstrual fluid and peritoneal fluid collected from women with endometriosis than that in control women. Most recently we examined the hypothesis that antibiotic treatment with or without GnRHa may decrease IUMC with reduction of inflammation and cell growth in women with endometriosis. We will report our current findings on this issue. The innate immunity and adaptive immunity are integral part of immune system. As a component of adaptive immunity, regulatory T (Treg) cells and T-helper-17 (Th17) cells may be involved in endometriosis. A reciprocal balance between Treg and Th17 cells may promote or retard the growth of endometriosis. Our knowledge on the changes in the percentages of Treg and Th-17 cells in the peripheral blood and in the peritoneal fluid of women with early and advanced endometriosis in unclear. We will report our current findings on this issue.

P53/NF-kB Balance in SARS-CoV-2 Infection: From OMICs, Genomics and Pharmacogenomics Insights to Tailored Therapeutic Perspectives (COVIDomics).

SARS-CoV-2 infection affects different organs and tissues, including the upper and lower airways, the lung, the gut, the olfactory system and the eye, which may represent one of the gates to the central nervous system. Key transcriptional factors, such as p53 and NF-kB and their reciprocal balance, are altered upon SARS-CoV-2 infection, as well as other key molecules such as the virus host cell entry mediator ACE2, member of the RAS-pathway. These changes are thought to play a central role in the impaired immune response, as well as in the massive cytokine release, the so-called cytokine storm that represents a hallmark of the most severe form of SARS-CoV-2 infection. Host genetics susceptibility is an additional key side to consider in a complex disease as COVID-19 characterized by such a wide range of clinical phenotypes. In this review, we underline some molecular mechanisms by which SARS-CoV-2 modulates p53 and NF-kB expression and activity in order to maximize viral replication into the host cells. We also face the RAS-pathway unbalance triggered by virus-ACE2 interaction to discuss potential pharmacological and pharmacogenomics approaches aimed at restoring p53/NF-kB and ACE1/ACE2 balance to counteract the most severe forms of SARS-CoV-2 infection.

Protein Kinase CK2 Maintains Reciprocal Balance Between Th17 and Treg Cells in the Pathogenesis of UC.

T helper 17 and regulatory T cells balance have crucial effects on the development of ulcerative colitis (UC). Currently, how to break this balance has not yet been found. Protein kinase CK2 is involved in the pathogenesis of immune-related disorders. However, its effects on the development of UC are obscure. The level of CK2 in the colonic tissues of UC patients was quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and immune-histochemistry. Peripheral blood CD4+ T cells were treated with CK2 inhibitor CX4945 or transfected with Csnk2-interfering lentivirus; the mRNA expression and protein levels of inflammatory cytokines were detected by qRT-PCR, enzyme-linked immunosorbent assay, and flow cytometry. Moreover, CX4945 was administered to trinitrobenzene sulfonic acid (TNBS)-induced colitis mice model for determining the function of CK2 on the regulation of intestinal inflammation. The CK2 level was markedly increased in inflamed mucosa of UC and highly expressed in CD4+ T cells. Blockade of CK2 by CX4945 inhibited Th17 but promoted regulatory T-cell (Treg) immune responses in CD4+ T cells from patients with UC. Moreover, CK2 blockade alleviated TNBS-induced colitis in mice. Inhibition of CK2 suppressed Th17 but promoted Treg differentiation by decreasing the phosphorylation level of signal transducer and activator of transcription (STAT) 3 and increasing the phosphorylation level of STAT5. The RNA-Seq and co-immunoprecipitation analysis further showed that CK2 could interact with Sirtuin 1 (SIRT1) and downregulate SIRT1 expression, which participated in Th17 inhibition but promoted Treg differentiation. Sirtuin 1 upregulation ameliorated TNBS-induced colitis, whereas SIRT1 blockade aggravated TNBS-induced colitis in mice. CK2 have crucial effects on the development of UC by maintaining reciprocal balance between Th17 and Treg cells. Protein kinase CK2 blockade might be considered as a new therapeutic approach for UC treatment.

Reduced dose of PTCy followed by adjuvant \u03b1-galactosylceramide enhances GVL effect without sacrificing GVHD suppression

Posttransplantation cyclophosphamide (PTCy) has become a popular option for haploidentical hematopoietic stem cell transplantation (HSCT). However, personalized methods to adjust immune intensity after PTCy for each patient’s condition have not been well studied. Here, we investigated the effects of reducing the dose of PTCy followed by α-galactosylceramide (α-GC), a ligand of iNKT cells, on the reciprocal balance between graft-versus-host disease (GVHD) and the graft-versus-leukemia (GVL) effect. In a murine haploidentical HSCT model, insufficient GVHD prevention after reduced-dose PTCy was efficiently compensated for by multiple administrations of α-GC. The ligand treatment maintained the enhanced GVL effect after reduced-dose PTCy. Phenotypic analyses revealed that donor-derived B cells presented the ligand and induced preferential skewing to the NKT2 phenotype rather than the NKT1 phenotype, which was followed by the early recovery of all T cell subsets, especially CD4+Foxp3+ regulatory T cells. These studies indicate that α-GC administration soon after reduced-dose PTCy restores GVHD-preventing activity and maintains the GVL effect, which is enhanced by reducing the dose of PTCy. Our results provide important information for the development of a novel strategy to optimize PTCy-based transplantation, particularly in patients with a potential relapse risk.

Mesenchymal Stem Cells Attenuates TGF-β1-Induced EMT by Increasing HGF Expression in HK-2 Cells.

Background:Mesenchymal stem cells (MSCs) have recently shown promise for the treatment of various types of chronic kidney disease models. However, the mechanism of this effect is still not well understood. Our study is aimed to investigate the effect of MSCs on transforming growth factor beta 1 (TGF-β1)-induced epithelial mesenchymal transition (EMT) in renal tubular epithelial cells (HK-2 cells) and the underlying mechanism related to the reciprocal balance between hepatocyte growth factor (HGF) and TGF-β1.Methods:Our study was performed at Ningbo University, Ningbo, Zhejiang, China between Mar 2017 and Jun 2018. HK-2 cells were initially treated with TGF-β1, then co-cultured with MSCs. The induced EMT was assessed by cellular morphology and the expressions of alpha-smooth muscle actin (α-SMA) and EMT-related proteins. MTS assay and flow cytometry were employed to detect the effect of TGF-β1 and MSCs on HK-2 cell proliferation and apoptosis. SiRNA against hepatocyte growth factor (siHGF) was transfected to decrease the expression of HGF to identify the role of HGF in MSCs inhibiting HK-2 cells EMT.Results:Overexpressing TGF-β1 decreased HGF expression, induced EMT, suppressed proliferation and promoted apoptosis in HK-2 cells; but when co-cultured with MSCs all the outcomes were reversed. However, after treated with siHGF, all the benefits taken from MSCs vanished.Conclusion:TGF-β1 was a motivating factor of kidney cell EMT and it suppressed the HGF expression. However, MSCs provided protection against EMT by increasing HGF level and decreasing TGF-β1 level. Our results also demonstrated HGF is one of the critical factor in MSCs anti- fibrosis.

GRIM19 Impedes Obesity by Regulating Inflammatory White Fat Browning and Promoting Th17/Treg Balance.

Obesity, a condition characterized by excessive accumulation of body fat, is a metabolic disorder related to an increased risk of chronic inflammation. Obesity is mediated by signal transducer and activator of transcription (STAT) 3, which is regulated by genes associated with retinoid-interferon-induced mortality (GRIM) 19, a protein ubiquitously expressed in various human tissues. In this study, we investigated the role of GRIM19 in diet-induced obese C57BL/6 mice via intravenous or intramuscular administration of a plasmid encoding GRIM19. Splenocytes from wild-type and GRIM19-overexpressing mice were compared using enzyme-linked immunoassay, real-time polymerase chain reaction, Western blotting, flow cytometry, and histological analyses. GRIM19 attenuated the progression of obesity by regulating STAT3 activity and enhancing brown adipose tissue (BAT) differentiation. GRIM19 regulated the differentiation of mouse-derived 3T3-L1 preadipocytes into adipocytes, while modulating gene expression in white adipose tissue (WAT) and BAT. GRIM19 overexpression reduced diet-induced obesity and enhanced glucose and lipid metabolism in the liver. Moreover, GRIM19 overexpression reduced WAT differentiation and induced BAT differentiation in obese mice. GRIM19-transgenic mice exhibited reduced mitochondrial superoxide levels and a reciprocal balance between Th17 and Treg cells. These results suggest that GRIM19 attenuates the progression of obesity by controlling adipocyte differentiation.

Distinct BOLD variability changes in the default mode and salience networks in Alzheimer\u2019s disease spectrum and associations with cognitive decline

Optimal levels of intrinsic Blood-Oxygenation-Level-Dependent (BOLD) signal variability (variability hereafter) are important for normative brain functioning. However, it remains largely unknown how network-specific and frequency-specific variability changes along the Alzheimer’s disease (AD) spectrum and relates to cognitive decline. We hypothesized that cognitive impairment was related to distinct BOLD variability alterations in two brain networks with reciprocal relationship, i.e., the AD-specific default mode network (DMN) and the salience network (SN). We examined variability of resting-state fMRI data at two characteristic slow frequency-bands of slow4 (0.027–0.073 Hz) and slow5 (0.01–0.027 Hz) in 96 AD, 98 amnestic mild cognitive impairment (aMCI), and 48 age-matched healthy controls (HC) using two commonly used pre-processing pipelines. Cognition was measured with a neuropsychological assessment battery. Using both global signal regression (GSR) and independent component analysis (ICA), results generally showed a reciprocal DMN-SN variability balance in aMCI (vs. AD and/or HC), although there were distinct frequency-specific variability patterns in association with different pre-processing approaches. Importantly, lower slow4 posterior-DMN variability correlated with poorer baseline cognition/smaller hippocampus and predicted faster cognitive decline in all patients using both GSR and ICA. Altogether, our findings suggest that reciprocal DMN-SN variability balance in aMCI might represent an early signature in neurodegeneration and cognitive decline along the AD spectrum.

The role of cortical areas hMT/V5+ and TPJ on the magnitude of representational momentum and representational gravity: a transcranial magnetic stimulation study.

The perceived vanishing location of a moving target is systematically displaced forward, in the direction of motion-representational momentum-, and downward, in the direction of gravity-representational gravity. Despite a wealth of research on the factors that modulate these phenomena, little is known regarding their neurophysiological substrates. The present experiment aims to explore which role is played by cortical areas hMT/V5+, linked to the processing of visual motion, and TPJ, thought to support the functioning of an internal model of gravity, in modulating both effects. Participants were required to perform a standard spatial localization task while the activity of the right hMT/V5+ or TPJ sites was selectively disrupted with an offline continuous theta-burst stimulation (cTBS) protocol, interspersed with control blocks with no stimulation. Eye movements were recorded during all spatial localizations. Results revealed an increase in representational gravity contingent on the disruption of the activity of hMT/V5+ and, conversely, some evidence suggested a bigger representational momentum when TPJ was stimulated. Furthermore, stimulation of hMT/V5+ led to a decreased ocular overshoot and to a time-dependent downward drift of gaze location. These outcomes suggest that a reciprocal balance between perceived kinematics and anticipated dynamics might modulate these spatial localization responses, compatible with a push-pull mechanism.

Lower resting cardiac autonomic balance in young adults with current major depression.

Research on cardiac autonomic function in major depressive disorder (MDD) has predominantly examined cardiac vagal control and adopted a model of reciprocal autonomic balance. A proposed bivariate autonomic continuum uses cardiac autonomic balance (CAB) and cardiac autonomic regulation (CAR) models, derived from normalized values of respiratory sinus arrhythmia and pre-ejection period, to more adequately index patterns of autonomic control. The purpose of this study was to assess resting levels of CAB and CAR among young adults with and without a current diagnosis of major depression. One hundred forty-two young adults (n=65 MDD, n=77 healthy controls; 20.8±2.6 years) completed a structured diagnostic interview, cardiovascular assessment, and a maximal aerobic fitness test. The findings revealed that CAB, but not CAR, significantly predicted current MDD status (OR=0.70, 95% CI [0.53, 0.93]), an effect that remained after controlling for aerobic fitness and body mass index. Although CAB was found to be a significant predictor of current MDD status among a sample of young adults, there remained substantial variation in autonomic control that was not captured by the traditional model of reciprocal autonomic balance.

Sacred Trash and Personhood: Living in Daily Waste-Management Infrastructures in the Eastern Himalayas

Different interpretations of what constitutes "trash" can reveal complex interactions between Tibetans and Han Chinese in the Eastern Himalayas. This article adopts the term "trash talk" to illuminate how the Tibetan practice of depositing garments as offerings to sacred mountains has become a center of Tibetan-Han debates about ethnic identity, morality, and personhood. Establishing the contours of waste-management infrastructure in a Tibetan area of Yunnan, China, that has been developed for tourism, this article examines the Tibetan term dreg pa དྲེག་པ(pollution), a morally laden notion of impurity. The author highlights how Tibetans seek to avoid dreg pa and achieve a reciprocal balance with "mountain-persons" (mountains as sacred beings) by making offerings of personal garments. The Han Chinese waste-management sector's perception of these garment offerings as litter creates a dispute between Tibetans and Han as to what is sacred and what is trash. Drawing on field research, the author argues that the offered garments should be seen not as trash but as people—active entities that mediate the reciprocal relationship between humans and the environment. Further analysis of the experience of two Tibetan informants reveals how the issue of used garments and dreg pa can even form a basis for personal transformation and the reinvention of personhood. These linkages among the local notion of dreg pa, uncertainties surrounding used garments, and personhood suggest that waste-management policies must take local notions of waste into consideration in order to be both efficient and culturally sensitive, especially in the current troubled trash politics of mass tourism and global environmentalism.

Contributions and Issues of Jacques Dupuis’ Trinitarian Christology in the Context of Religious Pluralism

Pneumatological Christology is one of several currents in contemporary theology which have emerged since the Second Vatican Council. Another notable trend is the increasing attempt to develop Christology in the context of interreligious dialogue and religious pluralism. These two movements occasionally intersect, raising questions about Jesus Christ’s uniqueness and universality which became paramount issues in today’s theological discourse. Accordingly, this paper looks to examine how the Christology of Jacques Dupuis attempts to address this issue in question. At the center of Dupuis’ Christological inquiry is the following question: “How are we to preserve and confess our faith in Jesus Christ as the unique savior of humanity, while acknowledging the universal presence of the Holy Spirit who operates in other religions and cultures?” In addressing this complex issue, Dupuis was able to propound a theological vision relevant to the contemporary contexts of interreligious dialogue and religious pluralism. But in addition to such contribution, his attempts also incited much controversy and hence gave rise to new issues in theology. In this context, the task of presenting an ideal model that harmoniously integrates Logos Christology and pneumatological Christology poses a significant challenge. The key lies in acknowledging the theological tension that may exist between the two while maintaining balance and harmony. Hence, the two models of Christology should not be mutually exclusive, but rather mutually complementary. But, it is not easy to maintain this reciprocal balance when developing pneumatological Christology in the context of interreligious dialogue and religious pluralism. This is because the task of preserving such harmony is ultimately tied to the mystery of Jesus Christ’s uniqueness and universality. Jacques Dupuis’ Christology can be seen as a tentative attempt to interpret this issue in a novel way without overstepping the boundaries of traditional theology.제2차 바티칸 공의회 이후의 현대 신학에서는 그리스도론의 새로운 흐름들이 전개되고 있는데, ‘성령론적 그리스도론’은 이러 한 새로운 흐름들 중의 하나이다. 그리고 ‘종교 간 대화’ 및 ‘종교다원주의’ 맥락에서의 그리스도론 역시 최근 새로이 전개되고 있는 흐름들 중 하나이다. 이 두 가지 흐름은 때로는 상호 교차되어 전개되기도 하는데, 이러한 상황 속에서 예수 그리스도의 ‘유일성’과 ‘보편성’에 관련한 문제가 최고의 신학적 쟁점으로 부상하게 되었다. 본 논문에서는 이 주제와 관련하여, 자크 뒤피 신부의 그리스도론을 살펴본다. 뒤피의 그리스도론적 질문의 핵심 은 바로 다음과 같은 것이었다. “어떻게 우리는 예수 그리스도를 모든 인류의 구원자로 고백하고 선포하는 신앙을 간직하면서도, 동시에 다른 세계 종교들과 여러 문화 안에서 활동하시는 성령의 보편적 현존을 인정할 것인가?” 이처럼 복잡하고도 어려운 주제를 다룸에 있어, 뒤피는 현대의 종교 간 대화 및 종교다원주의 맥락에서 볼 때 매우 의미 있는 신학적 전망을 제시하게 되었다. 하지만 뒤피의 이러한 시도는 동시에 많은 찬반논쟁을 불러일으켰으며, 여러 신학적 쟁점들을 새로이 부상시키게 되었다. 바로 이러한 맥락에서, ‘말씀 그리스도론’과 ‘성령론적 그리스도론’을 조화롭게 통합시키는 과제는 매우 중요한 과제로 부상하게 되었다. 이 두 가지 그리스도론 흐름들 사이에 존재할 수도 있는 그 어떤 긴장을 인식하면서도, 동시에 어떻게 전체적인 균형과 조화를 유지하는가에 그 해결의 열쇠가 있다고 할 수 있다. 그러므로 이 두 가지의 그리스도론적 모델들은 상호 배타적이지 않고 상호 보완적이어야만 한다. 하지만 종교 간 대화 및 종교다원주의 맥락에 마주하여 성령론적 그리스도론을 개진해 나가는 상황에서, 그러한 상호 균형을 유지하는 것은 쉽지 않은 일이다. 이러한 작 업은 결국 예수 그리스도의 유일성과 보편성이란 핵심 주제와 연결되기 때문이다. 자크 뒤피 신부의 그리스도론은, 전통적인 그리스도론의 범위를 벗어나지 않으면서도 이러한 주제를 참신하게 해석하고자 한 시도라고 평가할 수 있을 것이다.

Mesenchymal Stem Cells Attenuate the Renal Tubular Epithelial Cells Epithelial Mesenchymal Transition by Restoring the Reciprocal Balance between Hepatocyte Growth Factor and Transforming Growth Factor-β1

Objective: Mesenchymal stem cells (MSCs) have recently shown promise for the treatment of various types of chronic kidney disease models. However, the mechanism of this effect is still not well understood. Our study is aimed to investigate the effect of MSCs on transforming growth factor-β1 (TGF-β1)-induced EMT in renal tubular epithelial cells (HK-2 cells) and the underlying mechanism related to the reciprocal balance between hepatocyte growth factor (HGF) and TGF-β1.Methods: HK-2 cells were treated with TGF-β1-then co-cultured with MSCs. The induced EMT was assessed by cellular morphology and the expressions of alpha-smooth muscle actin (α-SMA) and EMT-related proteins. MTT assay and flow cytometry were employed to detect the effect of TGF-β1 and MSCs on HK-2 cell proliferation and apoptosis. SiRNA against hepatocyte growth factor (siHGF) was transfected to decrease the expression of HGF to identify the role of HGF in MSCs inhibiting HK-2 EMT.Results: TGF-β1 decreased HGF expression, induced EMT, suppressed proliferation and promoted apoptosis in HK-2 cells; but when co-cultured with MSCs all the outcomes were reversed. However, after treated with siHGF, all the benefits taken from MSCs vanished.Conclusion: TGF-β1 was a motivating factor of renal cell EMT and it suppressed the HGF expression. However, MSCs provided protection against EMT by increasing HGF level and decreasing TGF-β1 level. Our results also demonstrated HGF is one of the critical factor in MSCs anti-fibrosis.

Metformin ameliorates experimental-obesity-associated autoimmune arthritis by inducing FGF21 expression and brown adipocyte differentiation

Rheumatoid arthritis (RA) is a systemic autoimmune disease involving excessive inflammation. Recently, RA associated with a metabolic disorder was revealed to be non-responsive to RA medications. Metformin has been reported to have a therapeutic effect on RA and obesity. The aim of this investigation was to study the therapeutic effect and the underlying mechanism of metformin's action in an experimental model of collagen-induced arthritis (CIA) associated with obesity. Metformin was administered daily for 13 weeks to mice with CIA that had been fed a high-fat diet. Metformin ameliorated the development of CIA in obese mice by reducing autoantibody expression and joint inflammation. Furthermore, metformin decreased the expression levels of pSTAT3 and pmTOR and had a small normalizing effect on the metabolic profile of obese CIA mice. In addition, metformin increased the production of pAMPK and FGF21. Metformin also induced the differentiation of brown adipose tissue (BAT), which led to a reciprocal balance between T helper (Th) 17 and regulatory T (Treg) cells in vitro and in vivo. These results suggest that metformin can dampen the development of CIA in obese mice and reduce metabolic dysfunction by inducing BAT differentiation. Thus, metformin could be a therapeutic candidate for non-responsive RA.

Perceptions of reciprocity in friendship by community dwelling people with mild to moderate dementia.

Positive social interaction is important for people with dementia, providing emotional and psychological benefits. Friendships may retain more reciprocal balance than caregiver relationships, which often become one-sided. This qualitative study investigates the meaning that friendship has for people with dementia, and how reciprocity relates to positive social identity. Individuals experiencing dementia were recruited from programs sponsored by a Midwest chapter of The Alzheimer’s Association. In a face-to-face, one-time interview, participants were asked to share their perceptions about reciprocal friendship. Participants included 10 individuals who were primarily White, averaged 76 years old, with at least some college education. The data were analyzed using a phenomenological approach that revealed five themes of reciprocal friendship: recognizing the importance of longevity in friendship, helping one another is a normal part of friendship, feeling “alive” through the give and take in friendship, knowing somebody is there for them, and seeking security through friendship.

Effects of ability difference and strategy imitation on cooperation network formation: A study with game theoretic modeling and multi-agent simulation

Using game theoretic modeling and multi-agent simulation, this study examines cooperation networks in business ecosystems. Business ecosystems generally involve various stakeholders, which develop complex and interdependent relations. Many related studies qualitatively assess these issues from actual case studies, but it is difficult to clarify the general mechanism that forms an ecosystem. In this study, particularly addressing cooperative behavior between agents in business ecosystems, we construct a game theoretic model of cooperation network formation based on Nowak's model of indirect reciprocity and Heider's balance theory. Multi-agent simulation demonstrates that in case agents have different abilities, a cooperation network is likely to collapse because low-ability agents leave the cooperative network. Furthermore, if the agents are able to imitate strategies, then simulation similarly demonstrates that cooperation is insufficiently constructed because of a delay of increasing evaluation values. However, the surviving cooperation network under the conditions of ability difference and strategy imitation forms strong cooperative relations. This result can be regarded as a strong coupling, whereas loosely coupled relations, as demonstrated by Iansiti and Levien, are desirable in terms of the health of ecosystems. Finally, we present discussion of how to form business ecosystems in terms of ability differences and strategy imitation.

Gain and loss of esteem, direct reciprocity and Heider balance

The effect of gain and loss of esteem is introduced into the equations of time evolution of social relations, hostile or friendly, in a group of actors. The equations allow for asymmetric relations. We prove that in the presence of this asymmetry, the majority of stable solutions are jammed states, i.e. the Heider balance is not attained there. A phase diagram is constructed with three phases: the jammed phase, the balanced phase with two mutually hostile groups, and the phase of so-called paradise, where all relations are friendly.

PTEN ameliorates autoimmune arthritis through down-regulating STAT3 activation with reciprocal balance of Th17 and Tregs.

PTEN is a tyrosine phosphatase with significant function in inhibiting STAT3 activation. Recently, inactivation of STAT3 has been demonstrated as a therapeutic candidate for autoimmune arthritis. The expression of PTEN controlled by p53 regulates autoimmune arthritis through modulating the balance between Th17 and Treg. We hypothesized that PTEN regulated by p53 might reduce CIA severity and inflammatory response via inhibiting STAT3 activation. Our results revealed that PTEN could ameliorate experimental autoimmune arthritis by reducing STAT3 activity and Th17 differentiation. Systemic infusion of PTEN overexpression downregulated CIA severity. In addition, PTEN overexpression decreased the activation of T cells and modulated reciprocal differentiation of Th17 and Treg cells. We observed that PTEN expression downregulated by p53 deficiency induced the activation of STAT3. Loss of p53 exacerbated autoimmune arthritis and dysregulated the population of Th17 and Treg. These data suggest that induction of STAT3-modulatory activity of PTEN may be a therapeutic target for rheumatoid arthritis therapy.