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Distant metastasis, the leading cause of cancer death, is efficiently kept in check by immune surveillance. Studies have uncovered peripheral natural killer (NK) cells as key antimetastatic effectors and their dysregulation during metastasis. However, the molecular mechanism governing NK cell dysfunction links to metastasis remains elusive. Herein, MAP4K1 encoding HPK1 is aberrantly overexpressed in dysfunctional NK cells in the periphery and the metastatic site. Conditional HPK1 overexpression in NK cells suffices to exacerbate melanoma lung metastasis but not primary tumor growth. Conversely, MAP4K1‐deficient mice are resistant to metastasis and further protected by combined immune‐checkpoint inhibitors. Mechanistically, HPK1 restrains NK cell cytotoxicity and expansion via activating receptors. Likewise, HPK1 limits human NK cell activation and associates with melanoma NK cell dysfunction couples to TGF‐β1 and patient response to immune checkpoint therapy. Thus, HPK1 is an intracellular checkpoint controlling NK‐target cell responses, which is dysregulated and hijacked by tumors during metastatic progression. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic inflammation is a hallmark of refractory chronic rhinosinusitis (CRS) and considered a major therapeutic target. Autophagy deficiency in myeloid cells plays a causal role in eosinophilic CRS (ECRS) via macrophage IL‐1β overproduction, thereby suggesting autophagy regulation as a potential therapeutic modality. Trehalose is a disaccharide sugar with known pro‐autophagy activity and effective in alleviating diverse inflammatory diseases. We sought to investigate the therapeutic potential of autophagy‐enhancing agent, trehalose, or related sugar compounds, and the underlying mechanism focusing on macrophage IL‐1β production in ECRS pathogenesis. Methods: We investigated the therapeutic effects of trehalose and saccharin on macrophage IL‐1β production and eosinophilia in the mouse model of ECRS with myeloid cell‐specific autophagy‐related gene 7 (Atg7) deletion. The mechanisms underlying their anti‐inflammatory effects were assessed using specific inhibitor, genetic knockdown or knockout, and overexpression of cognate receptors. Results: Unexpectedly, trehalose significantly attenuated eosinophilia and disease pathogenesis in ECRS mice caused by autophagy deficiency in myeloid cells. This autophagy‐independent effect was associated with reduced macrophage IL‐1β expression. Various sugars recapitulated the anti‐inflammatory effect of trehalose, and saccharin was particularly effective amongst other sugars. The mechanistic study revealed an involvement of sweet taste receptor (STR), especially T1R3, in alleviating macrophage IL‐1β production and eosinophilia in CRS, which was supported by genetic depletion of T1R3 or overexpression of T1R2/T1R3 in macrophages and treatment with the T1R3 antagonist gurmarin. Conclusion: Our results revealed a previously unappreciated anti‐inflammatory effect of STR agonists, particularly trehalose and saccharin, and may provide an alternative strategy to autophagy modulation in the ECRS treatment. [ABSTRACT FROM AUTHOR]

SUMMARY: In flowering plants, double fertilization between male and female gametophytes, which are separated by distance, largely depends on the unique pattern of the male gametophyte (pollen): two non‐motile sperm cells suspended within a tube‐producing vegetative cell. A morphological screen to elucidate the genetic control governing the strategic patterning of pollen has led to the isolation of a sticky generative cell (sgc) mutant that dehisces abnormal pollen with the generative cell immobilized at the pollen wall. Analyses revealed that the sgc mutation is specifically detrimental to pollen development, causing ectopic callose deposition that impedes the timely internalization and differentiation of the generative cell. We found that the SGC gene encodes the highly conserved domain of unknown function 707 (DUF707) gene that is broadly expressed but is germline specific during pollen development. Additionally, transgenic plants co‐expressing fluorescently fused SGC protein and known organelle markers showed that SGC localizes in the endoplasmic reticulum, Golgi apparatus and vacuoles in pollen. A yeast two‐hybrid screen with an SGC bait identified a thaumatin‐like protein that we named GCTLP1, some homologs of which bind and/or digest β‐1,3‐glucans, the main constituent of callose. GCTLP1 is expressed in a germline‐specific manner and colocalizes with SGC during pollen development, indicating that GCTLP1 is a putative SGC interactor. Collectively, our results show that SGC suppresses callose deposition in the nascent generative cell, thereby allowing the generative cell to fully internalize into the vegetative cell and correctly differentiate as the germline progenitor, with the potential involvement of the GCTLP1 protein, during pollen development in Arabidopsis. Significance Statement: Unlike animals, which set aside their germline cells soon after embryogenesis, flowering plants differentiate their germlines inside multicellular gametophytes produced late during the short haploid phase of their life cycle; callose, a β‐1,3‐glucan polymer with some β‐1,6‐branches, plays a transient but critical role in the production of functional male gametophytes. Our study on Arabidopsis sticky generative cell mutants revealed that the male generative cell suppresses callose deposition for timely internalization and correct differentiation. [ABSTRACT FROM AUTHOR]

Summary: Sexual reproduction in flowering plants relies on the production of haploid gametophytes that consist of germline and supporting cells. During male gametophyte development, the asymmetric mitotic division of an undetermined unicellular microspore segregates these two cell lineages. To explore genetic regulation underlying this process, we screened for pollen cell patterning mutants and isolated the heterozygous myb81‐1 mutant that sheds ~50% abnormal pollen. Typically, myb81‐1 microspores fail to undergo pollen mitosis I (PMI) and arrest at polarized stage with a single central vacuole. Although most myb81‐1 microspores degenerate without division, a small fraction divides at later stages and fails to acquire correct cell fates. The myb81‐1 allele is transmitted normally through the female, but rarely through pollen. We show that myb81‐1 phenotypes result from impaired function of the GAMYB transcription factor MYB81. The MYB81 promoter shows microspore‐specific activity and a MYB81–RFP fusion protein is only expressed in a narrow window prior to PMI. Ectopic expression of MYB81 driven by various promoters can severely impair vegetative or reproductive development, reflecting the strict microspore‐specific control of MYB81. Our data demonstrate that MYB81 has a key role in the developmental progression of microspores, enabling formation of the two male cell lineages that are essential for sexual reproduction in Arabidopsis. Significance Statement: Sexual reproduction in flowering plants relies on the production of haploid gametophytes that consist of germline and supporting cells. During male gametophyte development, the asymmetric pollen mitosis I (PMI) of an undetermined unicellular microspore segregates these two cell lineages. In this study, we show that the microspore‐specific GAMYB transcription factor MYB81 promotes PMI and therefore has a key role in the formation of the two cell lineages essential for pollen development and plant fertility. [ABSTRACT FROM AUTHOR]

Abstract: Under endoplasmic reticulum (ER)‐stress conditions, the unfolded protein response (UPR) generates a defense mechanism in mammalian cells. The regulation of UPR signaling is important in oocyte maturation, embryo development, and female reproduction of pigs. Recent studies have shown that melatonin plays an important role as an antioxidant to improve pig oocyte maturation. However, there is no report on the role of melatonin in the regulation of UPR signaling and ER‐stress during in vitro maturation (IVM) of porcine oocytes. Therefore, the objective of this study was to investigate the antioxidative effects of melatonin on porcine oocyte maturation through the regulation of ER‐stress and UPR signaling. We investigated the changes in the mRNA/protein expression levels of three UPR signal genes (Bip/Grp78, ATF4, P90/50ATF6, sXbp1, and CHOP) on oocytes, cumulus cells, and cumulus‐oocyte complexes (COCs) during IVM (metaphase I; 22 hours and metaphase II; 44 hours) by Western blot and reverse transcription‐polymerase chain reaction analysis. Treatment with the ER‐stress inducer, tunicamycin (Tm), significantly increased expression of UPR markers. Additionally, cumulus cell expansion and meiotic maturation of oocytes were reduced in COCs of Tm‐treated groups (1, 5, and 10 μg/mL). We confirmed the reducing effects of melatonin (0.1 μmol/L) on ER‐stress after pretreatment with Tm (5 μg/mL; 22 hours) in maturing COCs. Addition of melatonin (0.1 μmol/L) to Tm‐pretreated COCs recovered meiotic maturation rates and expression of most UPR markers. In conclusion, we confirmed a role for melatonin in the modulation of UPR signal pathways and reducing ER‐stress during IVM of porcine oocytes. [ABSTRACT FROM AUTHOR]

In flowering plants, male gametes arise via meiosis of diploid pollen mother cells followed by two rounds of mitotic division. Haploid microspores undergo polar nuclear migration and asymmetric division at pollen mitosis I to segregate the male germline, followed by division of the germ cell to generate a pair of sperm cells. We previously reported two gemini pollen ( gem) mutants that produced twin-celled pollen arising from polarity and cytokinesis defects at pollen mitosis I in Arabidopsis. Here, we report an independent mutant, gem3, with a similar division phenotype and severe genetic transmission defects through pollen. Cytological analyses revealed that gem3 disrupts cell division during male meiosis, at pollen mitosis I and during female gametophyte development. We show that gem3 is a hypomorphic allele ( aug6-1) of AUGMIN subunit 6, encoding a conserved component in the augmin complex, which mediates microtubule ( MT)-dependent MT nucleation in acentrosomal cells. We show that MT arrays are disturbed in gem3/aug6-1 during male meiosis and pollen mitosis I using fluorescent MT-markers. Our results demonstrate a broad role for the augmin complex in MT organization during sexual reproduction, and highlight gem3/aug6-1 mutants as a valuable tool for the investigation of augmin-dependent MT nucleation and dynamics in plant cells. [ABSTRACT FROM AUTHOR]

In this paper, we present novel organic light-emitting diode (OLED) display panel compensation technologies for large-sized ultra-high-definition OLED TVs considering variations of threshold voltage, mobility, channel size, OLED efficiency, and OLED uniformity. Using these technologies, we have successfully launched 55-, 65- and 77-in. ultra-high-definition OLED TVs. [ABSTRACT FROM AUTHOR]

Background Radioactive-iodine remnant ablation is an integral part of the papillary thyroid carcinoma (PTC) treatment. Although a minimum dose is usually recommended, there is controversy as to whether the low-dose (1100 MBq) radioactive-iodine remnant ablation is adequate for selected patients. Methods A retrospective cohort study was conducted on 691 patients. Patients with no remnant thyroid on the follow-up whole body scan and low stimulated thyroglobulin (sTg) level (<2.0 ng/mL) were deemed as successful treatment cases. Results Initial low-dose radioactive-iodine remnant ablation was successful in 431 patients (62.3%). Multivariate analysis demonstrated a negative correlation between successful radioactive-iodine remnant ablation and coexisting Hashimoto thyroiditis based on histopathology diagnosis (odds ratio [OR] = 3.23; p < .001) as well as elevated preablation sTg (OR = 1.24; p < .001). Conclusion Our data suggest that coexisting Hashimoto thyroiditis and elevated sTg are negative predictive factors for successful low-dose radioactive-iodine remnant ablation treatment. An appropriate risk-adjusted approach may improve the efficacy of radioactive-iodine remnant ablation treatment. © 2015 Wiley Periodicals, Inc. Head Neck 38: E730-E735, 2016 [ABSTRACT FROM AUTHOR]

The biological underpinnings linking stress to Alzheimer's disease ( AD) risk are poorly understood. We investigated how corticotrophin releasing factor ( CRF), a critical stress response mediator, influences amyloid-β (Aβ) production. In cells, CRF treatment increases Aβ production and triggers CRF receptor 1 ( CRFR1) and γ-secretase internalization. Co-immunoprecipitation studies establish that γ-secretase associates with CRFR1; this is mediated by β-arrestin binding motifs. Additionally, CRFR1 and γ-secretase co-localize in lipid raft fractions, with increased γ-secretase accumulation upon CRF treatment. CRF treatment also increases γ-secretase activity in vitro, revealing a second, receptor-independent mechanism of action. CRF is the first endogenous neuropeptide that can be shown to directly modulate γ-secretase activity. Unexpectedly, CRFR1 antagonists also increased Aβ. These data collectively link CRF to increased Aβ through γ-secretase and provide mechanistic insight into how stress may increase AD risk. They also suggest that direct targeting of CRF might be necessary to effectively modulate this pathway for therapeutic benefit in AD, as CRFR1 antagonists increase Aβ and in some cases preferentially increase Aβ42 via complex effects on γ-secretase. [ABSTRACT FROM AUTHOR]

BACKGROUND 'Atypia of undetermined significance' (AUS) in the Bethesda System for Reporting Thyroid Cytopathology is a heterogeneous category for cases that cannot be easily classified into benign, suspicious, or malignant. This study evaluated whether cytomorphology-based subcategorization could better predict the malignancy risk in cases designated as AUS, and how the subcategories correlated with BRAF mutation status in thyroid fine-needle aspirates (FNA). METHODS Of 3589 cases of thyroid FNA diagnosed at the authors' institution in Seongnam, Korea, from January 2010 to December 2011, 331 cases of AUS were reviewed and subcategorized based on cytomorphological features, including nuclear atypia (NA), microfollicle formation (MF), Hürthle cell change (HC), and others (O). The malignancy rate of each subcategory was calculated using cases with histologic follow-up. Pyrosequencing was conducted to detect BRAF mutations. RESULTS Malignancy was histologically proven in 23.3% (77 of 331) of cases diagnosed as AUS. In cytomorphology-based subcategories, the rate of malignancy was 30.8% (66 of 214) for AUS-NA, 14.5% (8 of 55) for AUS-O, 4.8% (2 of 42) for AUS-MF, and 5% (1 of 20) for AUS-HC. The BRAF V600E mutation was found in 40% (48 of 120) of AUS-NA, 30.8% (4 of 13) of AUS-HC, 6.7% (1 of 15) of AUS-O, and 2.8% (1 of 35) of AUS-MF. CONCLUSIONS The AUS-NA subcategory was associated with the highest risk of malignancy and the greatest frequency of BRAF V600E (substitution of valine to glutamic acid at position 600) mutation. These findings suggest that subcategorization of AUS by cytomorphology and BRAF V600E mutation status is important for predicting the risk of malignancy. Cancer (Cancer Cytopathol) 2014;122:512-520. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background Atypia or follicular lesions of undetermined significance ( AUS/ FLUS) is a broad cytological category in the Bethesda system for classifying thyroid cytology. This study investigated the diagnostic accuracy of ultrasound ( US) analysis of thyroid nodules with AUS/ FLUS. Patients and Methods Of 5062 subjects with nodules subjected to fine-needle aspiration cytology ( FNACs) at our institution from January 2010 through May 2012, 383 met the Bethesda criteria for AUS/ FLUS. After excluding subjects who had a history of thyroid cancer, who only underwent repeat FNA or who underwent no further examinations, we selected 249 subjects who had subsequently undergone a core-needle biopsy and/or surgery. Of these, 100 were found to have malignant nodules (40·2%), 122 had benign nodules (49%), and 27 had nodules with indeterminate status (10·8%). We compared specific US parameters, including size, location, content, shape, margin, echogenicity, echotexture and calcification across these subject groups. Results Multivariate analysis revealed that malignancy was associated with taller-than-wide shape ( TDW) ( OR = 8·43, P = 0·002), ill-defined margin ( OR = 3·23, P = 0·002) and marked hypoechogenicity. ( OR = 3·61, P = 0·001). The specificity and positive predictive values of TDW were 98% and 90·6%,respectively. The specificity and positive predictive values of ' TDW and marked hypoechogenicity' were both 100%. Conclusion US findings play a complementary role in the diagnosis of thyroid nodules with AUS/ FLUS. In case of highly suspicious US findings such as ' TDW and marked hypoechogenicity', could be very helpful in the diagnosis of malignancy. [ABSTRACT FROM AUTHOR]

Over-activation of microglia cells in the brain contributes to neurodegenerative processes promoted by the production of various neurotoxic factors including pro-inflammatory cytokines and nitric oxide. Recently, accumulating evidence has suggested that mitochondrial dynamics are an important constituent of cellular quality control and function. However, the role of mitochondrial dynamics in microglial activation is still largely unknown. In this study, we determined whether mitochondrial dynamics are associated with the production of pro-inflammatory mediators in lipopolysaccharide ( LPS)-stimulated immortalization of murine microglial cells (BV-2) by a v-raf/v-myc carrying retrovirus (J2). Excessive mitochondrial fission was observed in lentivirus-transfected BV-2 cells stably expressing DsRed2-mito following LPS stimulation. Furthermore, mitochondrial localization of dynamin-related protein 1 (Drp1) (a key regulator of mitochondrial fission) was increased and accompanied by de-phosphorylation of Ser637 in Drp1. Interestingly, inhibition of LPS-induced mitochondrial fission and reactive oxygen species ( ROS) generation by Mdivi-1 and Drp1 knock-down attenuated the production of pro-inflammatory mediators via reduced nuclear factor kappa-light-chain-enhancer of activated B cells ( NF-κB) and mitogen-activated protein kinase ( MAPK) signaling. Our results demonstrated for the first time that mitochondrial fission regulates mitochondrial ROS production in activated microglial cells and influences the expression of pro-inflammatory mediators through the activation of NF-κB and MAPK. We therefore suggest that mitochondrial dynamics may be essential for understanding pro-inflammatory mediator expression in activated microglial cells. This could represent a new therapeutic approach for preventing neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Laser lipolysis has a skin tightening effect by heating the deep dermis, in addition to the removal of fat tissues. The 1444-nm neodymium:yttrium-aluminum-garnet ( Nd: YAG) laser has been expected to be more effective and safe for laser lipolysis, due to higher affinity to fat and water, than 1064-nm and 1320-nm wavelengths. The purpose of this study was to evaluate the skin tightening effect of the 1444-nm Nd: YAG laser through in vivo guinea pig models. The 1444-nm Nd: YAG laser was used to irradiate shaved dorsal skin of the guinea pigs and compared with controls (no power, only tunneling). Immediately, 1 week, 1 month and 3 months after laser administration, full-thickness skins were harvested and to evaluate dermal thickness, collagen organization, fibroblast proliferation, and intensity of elastic fibers and mucopolysaccharides, using hematoxylin-eosin, Masson-trichrome, Verhoeff's stain and Alcian blue stain. Dermal thickness showed an increase with time in all groups. In collagen organization, fibroblast proliferation, and intensity of elastic fibers and mucopolysaccharides, the treatment groups were higher than those of the control group, overall. Our study showed that the 1444-nm Nd: YAG laser appeared to be effective for the skin tightening effect in in vivo guinea pig models. The 1444-nm Nd: YAG laser can be used for skin tightening, as well as reduction of fat tissues. [ABSTRACT FROM AUTHOR]

Despite a long-standing hypothesis that chronic graft-versus-host disease (cGVHD) is an autoimmune disorder, most mouse models of cGVHD have been developed on the assumption that donor T cells are essential for its development. Here we show that cGVHD may be caused by autoreactive host T cells in mice that have been lethally irradiated and grafted with T-cell-depleted allogeneic bone marrow cells. In this chimera, host T cells derived from radioresistant intrathymic T-cell precursors caused dermal fibrosis and periportal inflammation, without the requirement for donor T cells. The lack of host DCs within the thymus after high-dose irradiation allowed autoreactive host T cells to escape thymic negative selection. Moreover, the homeostatic expansion of these T cells may augment their autoreactivity. These findings indicate that host T-cell-mediated cGVHD is an autoimmune process that occurs following the grafting of T-cell-depleted BM cells into hosts with functioning thymuses. We propose, based on the present data, that host T-cell-dependent autoimmunity is a potential mechanism by which cGVHD is induced. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Gore-Tex is known to be a relatively safe material. However, it leads to complications. Although widely used, the reasons complications occur are poorly understood. Thus, this study attempted to investigate histological changes between the Gore-Tex, removed within a certain period of time after rhinoplasty, and its neighboring tissues. Methods: This study involved 122 Gore-Tex samples obtained at the time of reoperation in patients who had undergone augmentation rhinoplasty. The subject group included 31 men and 91 women. The mean patient age was 30.2 years, and the mean Gore-Tex implantation period was 23.2 months (range, 1 week-13 years). We noted the shapes of the Gore-Tex samples, their relationships and extent of adhesion with neighboring tissues, and the changes of thickness. We also observed tissue ingrowth, calcification, inflammation, foreign body reaction, and structural changes using light microscopy and electron microscopy. Results: After the Gore-Tex samples had been in place for an extended period of time, the neighboring tissues grew into the central portions of the samples, which enhanced adhesion between the samples and the tissues. In addition, Gore-Tex samples that had been implanted for longer periods of time were associated with decreased thickness and calcification, foreign body reactions, and increased structural changes. Conclusions: In contrast to previous studies, our study showed that Gore-Tex samples implanted in human bodies for extended periods of time prompted ingrowth of neighboring tissues, calcified tissue degeneration, and inflammation. Foreign body reactions were found in a large number of samples. The Gore-Tex structures were destroyed and transformed. As a result, it is important to follow the stability of Gore-Tex material on a long-term basis. Laryngoscope, 2009 [ABSTRACT FROM AUTHOR]

Abstract Background: It has been unclear as to whether the Rome II criteria could be applied to patients in the Asia region with functional gastrointestinal (GI) diseases. The aim of the present study was to determine if symptoms of Asian patients with functional gastrointestinal disorders formed groups which corresponded to the Rome II diagnostic criteria. Methods: A modified English version of Talley's bowel disease questionnaire was developed in collaboration with various research teams in accordance with the Rome II criteria. This instrument was translated into the local languages of the following nine Asian regions: China, Hong Kong, Indonesia, Korea, Malaysia, Singapore, Taiwan, Thailand and Vietnam. From September to December 2001, newly enrolled outpatients attending 14 GI or medical clinics in these regions were invited to complete the questionnaire. From these respondents, patients with functional gastrointestinal disorders fulfilling the ‘12 weeks out of 12 months’ criteria were separated for further analysis. Principal component factor analysis with varimax rotation was used to identify symptom clusters or factors. These factors were compared with the existing classification of functional GI diseases derived from the Rome II criteria. Results: Factor analysis of symptoms from 1012 functional GI patients supported the Rome II classification of the following groups of functional GI disorders: diarrhea-predominant irritable bowel syndrome, functional constipation, functional dyspepsia, functional abdominal pain syndrome, functional heartburn, and functional vomiting. Functional diarrhea was combined with functional anorectal disorders, and globus merged with functional dysphagia into one factor. Some of the functional dyspepsia, abdominal bloating and belching symptoms were loaded into one factor. Conclusions: Factor analysis of symptoms from a sample of Asian patients with functional GI disorders partially supported the use of the Rome II... [ABSTRACT FROM AUTHOR]

Abstract Gastro-oesophageal reflux disease (GORD) occurs more frequently in Europe and North America than in Asia but its prevalence is now increasing in many Asian countries. Many reasons have been given for the lower prevalence of GORD in Asia. Low dietary fat and genetically determined factors, such as body mass index and maximal acid output, may be important. Other dietary factors appear to be less relevant. Increased intake of carbonated drinks or aggravating medicines may influence the increasing rates of GORD in some Asian countries but no strong evidence links other factors, such as the age of the population, smoking or alcohol consumption, to GORD. The management of GORD in Asia is similar to that in Europe and North America but the lower incidence of severe oesophagitis in Asia may alter the approach slightly. Also, because Asians tend to develop stomach cancer at an earlier age, endoscopy is used routinely at an earlier stage of investigation. Gastro-oesophageal reflux disease is essentially a motility disorder, so short-term management of the disease can usually be achieved using prokinetic agents (or histamine (H2)-receptor antagonists). More severe and recurrent GORD may require proton pump inhibitors (PPI) or a combination of prokinetic agents and PPI. The choice of long-term treatment may be influenced by the relative costs of prokinetic agents and PPI. © 2000 Blackwell Science Asia Pty Ltd. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized by the loss of dopaminergic neurons and the formation of eosinophilic intracytoplasmic inclusion bodies known as Lewy bodies. Although alpha-synuclein is known to be a pivotal factor implicated in the pathogenesis of PD, its function remains to be elucidated. We used the pGEX expression system to develop a simple and rapid method for purifying alpha-synuclein proteins in suitable forms for biochemical studies of their functions. The wild-type alpha-synuclein protein was overexpressed in Escherichia coli and purified to approx. 80% purity with relatively high yields. We also used this expression system to investigate the expression pattern of the various domains of alpha-synuclein. With the exception of the alpha-synuclein protein that was truncated at amino acid residue 95, all domain constructs of alpha-synuclein were purified at similar levels with relatively high yields. Unexpectedly, removal of amino acid residues 96-140 in the C-terminal acidic region of alpha-synuclein promotes its conversion to a protease-sensitive form during expression and purification in E. coli. Our study suggests a method for generating useful reagents to investigate the molecular mechanism by which alpha-synuclein regulates the pathogenesis of PD.