New Unity for Labor?

From the “Editor’s Introduction”: Within today’s AFL-CIO, a different set of frustrations with the bureaucratic structure and leadership is simmering. The relative lack of new organizing and the continuous toll of jurisdictional rivalries have produced a call for radical restructuring, or “New Unity Partnership” (NUP). As articulated by the leaders of some of the most powerful and dynamic of federation affiliates, including the Service Employees International Union’s president Andrew L. Stern, the promise (or threat, depending on one’s point of view) of the NUP deserves full scrutiny. To that end, we are pleased to present a forum organized by Ruth Milkman and Kim Voss of the University of California’s Institute for Labor and Employment, focused on the core concepts of the NUP proposal. The edited discussion features four labor policy experts: Stephen Lerner, director of the SEIU’s Building Services Division and a leading NUP draftsman; Kate Bronfenbrenner of the Cornell School of Industrial and Labor Relations; Dan Clawson, a sociologist at the University of Massachusetts, Amherst; and Jane Slaughter, of Labor Notes

만성 천식 마우스모델에서 대식세포 조절을 통한 중간엽줄기세포의 항천식 효과 연구

학위논문 (석사) -- 서울대학교 대학원 : 의과대학 의학과, 2020. 8. 강혜련.국문초록 만성 천식 마우스모델에서 대식세포 조절을 통한 중간엽줄기세포의 항천식 효과 연구 천식은 호흡 곤란, 기도 개형 및 기도 과민성의 증가 그리고 점액의 과다 분비를 특징으로 하는 기도내 만성 염증 질환이다. 천식의 병인 기전은 많은 노력에도 불구하고 아직까지 명확히 알려지지 않았으며, 현재까지 진행된 연구들은 주로 천식을 Th2 도움세포의 관점으로만 설명하고 있다는 한계점이 존재한다. 따라서 천식의 병인기전을 완벽하게 파악하기 위해서는TH2 도움세포를 제외한 또 다른 세포와 천식 간의 상관관계를 확인하는 연구가 필요한 상황이다. 줄기세포를 이용한 세포치료제 개발은 현재 전 세계적으로 주목을 받고 있다. 다양한 조직에서 줄기세포의 재생효과가 검증되었으며, 그 효과는 프라이밍 기법을 통하여 더욱 향상된다고 알려져 있다. 그 중에서도 무한 증식이 가능하며 다양한 계열의 세포로 분화할 수 있는 장점을 가진 중간엽줄기세포(MSC)는 천식과 같은 난치성 질병의 연구에 많이 이용되고 있다. 지금까지 다양한 MSC의 항천식 효과는 보고된 바 있다. 하지만 이를 입증한 연구는 대부분 정맥 내로 MSC를 투여하는 방법을 사용하고 있으며 기도 투여 방법이나 프라이밍된 중간엽 줄기세포를 이용한 연구는 아직 많이 수행되지 않았다. 본 연구에서는 프라이밍 된 MSC를 기도투여 하였을 때의 항천식 효과를 확인하고 그 기전을 TH2도움세포가 아닌 대식세포의 관점에서 설명하고자 하였다. 먼저, 인터루킨-13 (IL-13)을 폐 특이적으로 과발현 시킨 만성 천식 마우스 모델을 이용하여, ferroptosis 억제제로 알려진 Liproxstatin-1으로 프라이밍한 인간 탯줄유래 중간엽줄기세포(UC-MSC)를 기도투여 하였을 때의 항천식 효과를 확인하였다. 다음으로, 천식환경에서 대식세포의 변화를 관찰함으로써 대식세포의 조절이 천식에 미치는 영향을 규명하고 MSC가 가지는 항천식 효과의 기전을 설명하였다. 또한, 대식세포가 가지는 천식 치료의 새로운 타겟 세포로서의 가능성을 확인하였다. 만성 천식을 구현한 IL-13과발현 마우스에서 호산구 증가를 중심으로 전체적인 기도와 폐의 염증이 증가하고, 점액의 분비량이 많아지며, 기도개형이 일어나는 것이 확인되었다. 또한, T 세포와 선천성 림프구 세포의 변화는 관찰되지 않았으나 뚜렷한 대식세포의 성격 변화가 확인되었는데, CD11bintF4/80hgih 대식세포의 감소와 더불어 CD11bhighF4/80int 대식세포의 증가가 대표적이었다. 유입된 대식세포 중에서는 대식세포의 아형 중 하나인M2의 증가가 확인되었는데, M2 대식세포 중에서도 염증반응을 유도한다고 알려져 있는 Ly6C가 높게 발현된 세포가 증가하였음을 알 수 있었다. 뿐만 아니라, 호산구와 높은 상관관계를 보이는 CD11c+CD11b+ 대식세포의 증가도 만성 천식 마우스에서 두드러지게 관찰되었다. 만성 천식 마우스에 Liproxstatin-1으로 프라이밍 된 hUC-MSC를 기도 투여하였을 때, 기도폐포세척액 내 대식세포, 호산구, 호중구, 림프구를 포함한 전체 세포 수가 감소하였으며, 폐 조직 내의 염증세포 군집이 확연하게 감소한 것을 확인하였다. 점액 생성 및 만성 천식에서 나타나는 폐 조직의 섬유화 정도도 유의미하게 감소하였다. 간질조직으로 유입된 대식세포 수의 감소와 더불어서 Ly6C를 높게 발현하는 M2 대식세포의 수 또한 유의미하게 감소하였으며, CD11c와 CD11b를 모두 발현하는 대식세포의 수가 크게 감소하였다. 그 중에서도 Ly6C를 발현하는 CD11b+CD11c+ 대식세포의 감소가 가장 두드러졌다. 야생형 마우스에서 CD11c와 CD11b를 모두 발현하는 대식세포는 SiglecF를 높게 발현하고 있지만 만성 천식 마우스에서는 SiglecF가 낮게 발현된다는 특징이 관찰되었다. Liproxstatin-1으로 프라이밍 된 UC-MSC를 투여한 만성 천식 마우스에서는 SiglecF를 높게 발현하는 대식세포와 그렇지 않은 대식세포가 모두 존재함에 따라 야생형과 천식 모델의 특징이 공존한다는 것이 확인되었다. CD11b+CD11c+ 대식세포 중 각각 M1과 M2의 성격을 띄는 대식세포의 비율은 모두 MSC를 투여하지 않은 천식모델보다 MSC를 투여한 천식모델에서 낮게 나타났다. 본 실험 결과를 통해, Liproxstatin-1으로 프라이밍 된 hUC-MSC는 기도로 투여하였을 때도 항천식 효과를 나타내는 것을 입증하였다. 또한, MSC는 대식세포를 조절하여 항천식 효과를 나타낼 수 있으며, 대식세포는 천식의 새로운 치료 표적으로서의 가능성이 있음을 확인하였다. 키워드: 천식, 중간엽줄기세포, 세포치료제, IL-13, 대식세포ABSTRACT Asthma is a chronic airway inflammatory disease characterized by shortness of breath, airway hyperresponsiveness, and excessive mucus production. Despite the numerous attempts to reveal the pathogenesis of asthma, the current studies are limited to correlating asthma only with changes in TH2 cells and TH2 cytokines. Therefore, the interrelation between asthma and other cell types need to be elaborated to unveil the complete mechanisms in the pathogenesis of asthma. Stem cell therapy using mesenchymal stem cell (MSC)s has recently emerged as a potential therapeutic approach for diseases with no known cure, such as severe asthma. MSCs can proliferate and differentiate into various cell types to repair damaged tissues or suppress inflammation, and their therapeutic effects can be further enhanced through priming. However, though numerous studies have successfully demonstrated the anti-asthmatic effects of MSCs in vivo models, none has been successfully introduced to human. Therefore, MSCs-based cell therapies with better efficiency are needed to be established for human application. This study aimed to evaluate the therapeutic effects of intratracheally administered primed MSCs, and to explain their action mechanisms with lung macrophages in addition to TH2 cells. First, the anti-asthmatic abilities of umbilical cord (UC)-derived MSCs primed with Liproxstatin-1, a ferroptosis inhibitor, were examined using a murine chronic asthma model. Then, the macrophage modulation in asthmatic conditions were investigated in attempt to explain the mechanism of the observed anti-asthmatic effects of the MSCs. Moreover, the study sought to evaluate the potential of macrophages as a new therapeutic target for asthma. Genetically modified transgenic (TG) mice constitutively overexpressing interleukin (IL)-13 in lung were used to represent chronic persistent asthma for the study. IL-13 TG mice showed excessive eosinophilic infiltration in the airways, mucus metaplasia, and airway remodeling. No change in TH2 or innate lymphoid cell populations were noted, but prominent differences in macrophage populations were observed; CD11bintF4/80high macrophages were greatly diminished while CD11bhighF4/80int macrophages increased. Among the CD11bhigh F4/80int macrophages recruited to the lung interstitium in response to the inflammatory cues, IL-13 TG mice showed an upregulation of alternatively activated (M2) macrophages. The M2 macrophages of IL-13 TG mice showed high expression levels of Ly6C, a conceivable pro-inflammatory marker. Additionally, total CD11c+CD11b+ macrophages, that are also known to be pro-inflammatory, were also increased in numbers in IL-13 mice. Among the CD11c+CD11b+ macrophages, upregulation of Ly6C-expressing populations was noted in the IL-13 TG mice. Upon intratracheal administration of Liproxstatin-1-primed human UC-MSCs (hUC-MSCs), a significant reduction in the total number of inflammatory cells, eosinophils, neutrophils, and lymphocytes in bronchoalveolar lavage fluid was observed. In the lung tissues, a decrease in inflammatory cell recruitments around the airways, mucus production, and collagen deposition were seen. In addition, a reduction in the total number of CD11bhighF4/80int macrophages and Ly6C+M2 macrophages, as well as CD11c+CD11b+ macrophages were observed. Among the CD11c+CD11b+ macrophages, the reduction in CD11c+CD11b+ Ly6C+ populations were conspicuous. In contrast to the CD11c+CD11b+ macrophages of healthy WT mice that showed high expressions of SiglecF, those of the IL-13 TG mice showed low expressions. In the IL-13 mice that received the hUC-MSC, both SiglecF- and siglecF+ CD11b+CD11c+ macrophages were discovered. Moreover, both CD11c+CD11b+ classically activated (M1) and alternatively activated (M2) macrophages were decreased in the IL-TG mice treated with MSCs compared to those that did not receive the treatment. This study confirmed that intratracheally administered Liproxstatin-1-primed hUC-MSCs have effective anti-asthmatic abilities. In addition, the study revealed that the observed anti-asthmatic effects of the MSCs were exerted through modulation of macrophage phenotypes and therefore validated the potential of macrophages as a new therapeutic target molecule for asthma. Keywords: asthma, mesenchymal stem cells, cell therapy, interleukin-13, macrophage Student ID Number: 2018-28440INTRODUCTION 1 MATERIALS AND METHODS 6 RESULTS 14 - Liproxstatin-1-primed MSCs exerted greater anti-asthmatic effects than naïve MSCs do 14 - Liproxstatin-1-primed hUC-MSCs reduced inflammatory cell infiltrations and mucus production in the airway of murine chronic asthma model 18 - Liproxstatin-1-primed hUC-MSCs suppressed airway remodeling in chronic asthma model 23 - Liproxstatin-1-primed hUC-MSCs led to alterations in the lung macrophage populations 26 - Liproxstatin-1-primed hUC-MSCs reduced the number of Ly6C+ M2 macrophages 31 - Liproxstatin-1-primed hUC-MSCs caused a reduction in the numbers of CD11b+ CD11c+ pro-inflammatory macrophages 35 - The characteristics of CD11c+ CD11b+ macrophages were altered in asthmatic conditions, and Liproxstatin-1-primed hUC-MSCs revert their characteristics to those in healthy conditions 39 DISCUSSION 42 REFERENCES 55 ABSTRACT IN KOREAN 72Maste

Daytime temperature is sensed by phytochrome B in Arabidopsis through a transcriptional activator HEMERA.

Ambient temperature sensing by phytochrome B (PHYB) in Arabidopsis is thought to operate mainly at night. Here we show that PHYB plays an equally critical role in temperature sensing during the daytime. In daytime thermosensing, PHYB signals primarily through the temperature-responsive transcriptional regulator PIF4, which requires the transcriptional activator HEMERA (HMR). HMR does not regulate PIF4 transcription, instead, it interacts directly with PIF4, to activate the thermoresponsive growth-relevant genes and promote warm-temperature-dependent PIF4 accumulation. A missense allele hmr-22, which carries a loss-of-function D516N mutation in HMR's transcriptional activation domain, fails to induce the thermoresponsive genes and PIF4 accumulation. Both defects of hmr-22 could be rescued by expressing a HMR22 mutant protein fused with the transcriptional activation domain of VP16, suggesting a causal relationship between HMR-mediated activation of PIF4 target-genes and PIF4 accumulation. Together, this study reveals a daytime PHYB-mediated thermosensing mechanism, in which HMR acts as a necessary activator for PIF4-dependent induction of temperature-responsive genes and PIF4 accumulation

Immigration Legislation and Issues in the 111th Congress

[Excerpt] The Speaker of the House and the Senate Majority Leader have pledged to take up comprehensive immigration reform legislation at some point in the 111th Congress. Efforts to enact broad immigration reform in the 109th and 110th Congresses were unsuccessful. It is unclear what the components of any immigration reform proposals that the 111th Congress may consider will be. In the past, comprehensive bills have addressed border security, enforcement of immigration laws within the United States (interior enforcement), employment eligibility verification, temporary worker programs, permanent admissions and, most controversially, unauthorized aliens in the United States. The 111th Congress has considered various immigration issues and has enacted a number of targeted immigration provisions. It has passed legislation (P.L. 111-8, P.L. 111-9, P.L. 111-68) to extend the life of several immigration programs—the E-Verify electronic employment eligibility verification system, the Immigrant Investor Regional Center Program, the Conrad State J-1 Waiver Program, and the special immigrant visa for religious workers—all of which are currently authorized until October 31, 2009. With respect to these programs, the House-passed and Senate-passed versions of the Department of Homeland Security Appropriations Act, 2010 (H.R. 2892), include different provisions to further extend E-Verify. The Senate-passed bill also would extend the other three programs. Among the other subjects of legislation enacted by this Congress are refugees (P.L. 111-8) and border security (P.L. 111-5, P.L. 111-32). This report discusses these and other immigration-related issues that have seen legislative action or are of significant congressional interest. Department of Homeland Security (DHS) appropriations are addressed in CRS Report R40642, Homeland Security Department: FY2010 Appropriations, and, for the most part, are not covered here. This report will be updated as legislative developments occur

A prospective longitudinal study of perceived infant outcomes at 18-24 months: Neural and psychological correlates of parental thoughts and actions assessed during the first month postpartum

The first postpartum months constitute a critical period for parents to establish an emotional bond with their infants. Neural responses to infant-related stimuli have been associated with parental sensitivity. However, the associations among these neural responses, parenting, and later infant outcomes for mothers and fathers are unknown. In the current longitudinal study, we investigated the relationships between parental thoughts/actions and neural activation in mothers and fathers in the neonatal period with infant outcomes at the toddler stage. At the first month postpartum, mothers (n=21) and fathers (n=19) underwent a neuroimaging session during which they listened to their own and unfamiliar baby’s cry. Parenting-related thoughts/behaviors were assessed by interview twice at the first month and 3-4 months postpartum and infants’ socioemotional outcomes were reported by mothers and fathers at 18-24 months postpartum. In mothers, higher levels of anxious thoughts/actions about parenting at the first month postpartum, but not at 3-4 months postpartum, were associated with infant’s low socioemotional competencies at 18-24 months. Anxious thoughts/actions were also associated with heightened responses in the motor cortex and reduced responses in the substantia nigra to own infant cry sounds. On the other hand, in fathers, higher levels of positive perception of being a parent at the first month postpartum, but not at 3-4 months postpartum, were associated with higher infant socioemotional competencies at 18-24 months. Positive thoughts were associated with heightened responses in the auditory cortex and caudate to own infant cry sounds. The current study provides evidence that parental thoughts are related to concurrent neural responses to their infants at the first month postpartum as well as their infant’s future socioemotional outcome at 18-24 months. Parent differences suggest that anxious thoughts in mothers and positive thoughts in fathers may be the targets for parenting-focused interventions very early postpartum

The Kaon B-parameter in Mixed Action Chiral Perturbation Theory

We calculate the kaon B-parameter, B_K, in chiral perturbation theory for a partially quenched, mixed action theory with Ginsparg-Wilson valence quarks and staggered sea quarks. We find that the resulting expression is similar to that in the continuum, and in fact has only two additional unknown parameters. At one-loop order, taste-symmetry violations in the staggered sea sector only contribute to flavor-disconnected diagrams by generating an O(a^2) shift to the masses of taste-singlet sea-sea mesons. Lattice discretization errors also give rise to an analytic term which shifts the tree-level value of B_K by an amount of O(a^2). This term, however, is not strictly due to taste-breaking, and is therefore also present in the expression for B_K for pure G-W lattice fermions. We also present a numerical study of the mixed B_K expression in order to demonstrate that both discretization errors and finite volume effects are small and under control on the MILC improved staggered lattices.Comment: 29 pages, 4 figures; Expanded spurion discussion, other discussions clarified, version to appear in PR

Alterations in serum amino acid concentrations in dogs with protein-losing enteropathy

BackgroundCertain amino acids are decreased in humans with inflammatory bowel disease (IBD) and supplementation with the same amino acids has shown beneficial effects in animal models of IBD. Currently, the amino acid status of dogs with protein-losing enteropathy (PLE) is unknown.Hypothesis/objectiveTo determine if serum amino acid concentrations are abnormal in dogs with PLE and correlated with clinical and laboratory variables and outcome.AnimalsThirty client-owned dogs diagnosed with PLE and 12 apparently healthy dogs seen at Bristol Veterinary School.MethodsRetrospective study using stored residual serum from fasted dogs with PLE, collected at the time of diagnostic investigation and from apparently healthy dogs. Serum was analyzed for 30 amino acids using an automated high-performance liquid chromatography amino acid analyzer.ResultsSerum tryptophan concentrations were significantly decreased in dogs with PLE (median, 22 nmol/mL; range, 1-80 nmol/mL) compared with apparently healthy control dogs (median, 77.5 nmol/mL; range, 42-135 nmol/mL, P < .001). There were no significant differences in the remaining 29 serum amino acids between dogs with PLE and apparently healthy. Serum tryptophan concentrations were also significantly correlated with serum albumin concentrations in dogs with PLE (P = .001, R2 = 0.506).Conclusions and clinical importanceDecreased serum tryptophan concentration might play a role in the pathogenesis of canine PLE or be a consequence of the disease