[2] The sustained virologic response (SVR) rate of genotype 1 using this new therapy is expected to increase from 55% to more than 70%.[3] However, there has also been an increase in side effects by RBV in the triple therapy, including several severe side effects, such as skin rash by telaprevir, ageusia by boceprevir, and advanced anemia by telaprevir/boceprevir.[3, 4] The main hurdle to resolving the side-effect profile is that the anti-HCV mechanism of RBV is not well understood, although several possible mechanisms have been proposed.[5, 6] To date, there has been no cell-culture system enabling

analysis of the anti-HCV mechanism of RBV at clinically achievable concentrations (5-14 µM), because the human hepatoma cell line, HuH-7, which has been the only cell line available for robust HCV replication, is not sensitive to RBV.[5, 7, 8] Indeed, we also observed that RNA Synthesis inhibitor the 50% effective concentration (EC50) of RBV against HCV RNA replication in our developed HuH-7-derived assay system (OR6), in BKM120 which the genome-length HCV RNA (O strain of genotype 1b) encoding renilla luciferase (RL) replicates efficiently, was more than 100 µM, and 50% cytotoxic concentration (CC50)

was also more than 100 µM.[9, 10] On the other hand, we recently found that a new human hepatoma cell line, Li23, whose gene expression profile was distinct from that of HuH-7, enabling efficient HCV RNA replication and persistent HCV production, was sensitive to RBV.[10-12] Indeed, the EC50 value of RBV against HCV RNA replication in

our developed Li23-derived assay system (ORL8), which is comparable to the OR6 assay system, was 8.7 µM, and the CC50 value was more than 100 µM.[10] It was noteworthy that this EC50 value was equivalent to the clinically achievable concentrations of RBV. Therefore, this finding led us to analyze the anti-HCV mechanism of RBV, and, consequently, we found that the anti-HCV activity of RBV was mediated by the inhibition of inosine monophosphate dehydrogenase (IMPDH), and that IMPDH was required for HCV RNA replication.[10] From these findings, we anticipated that the comparative analysis of RBV-sensitive ORL8 cells and RBV-resistant OR6 cells would lead to the identification of host factor(s) determining the anti-HCV activity of RBV. Here, we report the finding that adenosine kinase 上海皓元医药股份有限公司 (ADK) is an essential determinant of the anti-HCV activity of RBV. HuH-7- and Li23-derived cells and PH5CH8 cells were maintained as described previously.[11] HT17 cells were cultured in Dulbecco’s modified Eagle’s medium supplemented with 10% fetal bovine serum. Primary human hepatocytes (PHHs; PhoenixBio, Higashihiroshima, Japan) were also maintained in the medium for the Li23-derived cells. RBV was kindly provided by Yamasa (Chiba, Japan). Inosine-5′-monophosphate (IMP) and nucleoside triphosphates (cytidine triphosphate, uridine triphosphate, adenosine triphosphate, and guanosine triphosphate [GTP]) were also purchased from Yamasa.

Physical maturity was reached at between 14 and 17 yr of age, apparently a few years after attainment of sexual maturity. Maximum lengths and weights of about 268 cm and Stem Cells antagonist 240 kg were attained. Females appear to lose all their spots by 30 yr, although males may retain some spotting throughout life. Calving occurred throughout the year, with a broad peak from March to June. Of 60 females monitored at sea for >14 yr of the study, none were documented to have more than three calves, suggestive of low reproductive output or low calf survival. “
“The gray whale (Eschrichtius robustus) is a coastal species whose nearshore summer foraging grounds off the coast of British Columbia

offer an opportunity to study the fine

scale foraging response of baleen whales. We explore the relationship between prey density and gray whale foraging starting with regional scale (10 km) assessments of whale density (per square kilometer) and foraging effort as a response to regional mysid density (per cubic meter), between 2006 and 2007. In addition we measure prey density at a local scale (100 m), while following foraging whales during focal surveys. We found regional mysid density had a significant positive relationship with both gray whale density and foraging effort. We identify a threshold response to regional mysid density for both whale density and foraging effort. In 2008 the lowest average local prey density measured beside a foraging whale was 2,300 mysids/m3. This level was maintained even when regional prey AG-014699 mouse density was found to be substantially lower. Similar to other baleen whales, the foraging behavior of gray whales suggests a threshold response to prey density and a complex appreciation of prey availability across fine scales. “
“The conditioning of dolphins to human-interaction behaviors has been documented in several areas worldwide. However, the metrics used to report human-interaction behaviors vary among studies, making comparison across study areas difficult. The purpose of this study was to develop standard metrics for reporting human-interaction 上海皓元 behaviors and utilize these metrics

to quantify the prevalence of human-interaction behaviors by common bottlenose dolphins (Tursiops truncatus) near Savannah, Georgia. The four metrics used were percentage of days with human-interaction behaviors, percentage of sightings with human-interaction behaviors, percentage of the catalog that interacted with humans, and spatial extent of human-interaction behaviors. Human-interaction behaviors were observed on 69.6% of days and 23.5% of sightings near Savannah. In addition, 20.1% of the animals in the catalog were observed interacting with humans. These rates are much higher than those found in other areas with known issues with human-interaction behaviors. These behaviors were observed across an area of 272.6 km2, which is larger than other reported areas.

In particular, the breakage of chromosomes 1, 5, 6, 7, and 12 may represent an early event during hepatocarcinogenesis, while the deletions of chromosomes 4, 12, 14, and X appear during HCC progression.12 Of note, the breakpoints described on c-myc/TGF-α chromosomes 1, 4, 7, and 12 correspond to human 1q, 1p, 11p, and 14q that are also rearranged in human HCC.4, 13 In human liver specimens, loss of heterozygosity (LOH) was found to be uncommon in cirrhosis, focal nodular hyperplasia, and hepatocellular 3-MA in vivo adenomas, but detectable

in high-grade dysplastic nodules (DN), which are putative precancerous lesions.13 Importantly, the frequency and pattern of genetic alterations detected in DNs highly resembled those in HCCs. Gains of DNA were found to cluster in chromosome arms 1p, 1q, 7q, 15q, 16p, 17q, and 20q and losses of DNA at 3p, 4q, 9p, and 11q in both lesion types. Also, chromosomal alterations responsible for HCC progression and metastasis were found to be located on chromosome arms 4q, 6q,

8p, 13q, 16q, and 17p.14 Thus, the data from transgenic mice and human HCC together with those obtained by Aleksic et al. strongly support the hypothesis of the need of specific genomic alterations “dictating,” more than simply accompanying, the histopathological and molecular changes along hepatocarcinogenesis. The authors’ findings also have important clinical implications. Indeed, the data from Aleksic et al. further substantiate the unfavorable prognostic role of genomic instability in HCC. In this regard, it is worthwhile noting that gene expression patterns from DEN-initiated/PB-fed selleck inhibitor mice and

c-Myc/TGF-α transgenic mice, both exhibiting elevated genomic instability,5, 7, 12 were highly similar to those of human HCCs characterized by a short survival of the patients.15 The latter human HCC subgroup also displays elevated genomic instability, thus linking a specific gene signature to genomic instability and poor prognosis. A medchemexpress chromosomal instability gene signature predicting the patient’s outcome has been previously described in a vast collection of lung, breast, and brain tumors.16 Noticeably, among the genes that were positively correlated with genomic instability was the forkhead box M1b (FoxM1b) transcription factor and its target genes CYCLIN B1 and B2, CDC2, NEK2, KIF20A, TOP2A, CDC25B, AURORA KINASE A, and AURORA KINASE B.16 Given that FoxM1b is overexpressed in HCC and directly correlates with patient survival,17 it would be significant to determine whether the same chromosomal instability gene signature predicts the prognosis of HCC patients as well. Also, since preliminary data show that FoxM1b can be inhibited pharmacologically,18 it would be of high importance to assess whether HCC with elevated genomic instability would benefit from therapies aimed at suppressing FoxM1b expression. Aleksic et al.

pylori could this website be avoided by determining the presence of antibodies to CagA (using Western Blot, Helico Blot 2.1; Genelabs Diagnostics, Singapore) as these antibodies persist longer in patients [60]. The presence of

CagA in this high-risk European population was associated with an increased risk of gastric cancer (OR = 11.32) [60]. In contrast, Guducuoglu et al. found that in a Turkish population, there was no statistically significant difference between gastric carcinoma and control groups in terms of CagA, heat shock protein (HSP), and flagellin antibodies, but urease-A, urease-B, and OMP-67 were significant (p <.01) [61]. To facilitate the detection of CagA antibodies by EIA rather than the time-consuming Western Blotting, Klimovich et al. assessed a panel of monoclonal antibodies recognizing four different linear epitopes on the CagA molecule, three are localized in conservative parts of VacA and one in the variable

region of CagA; two were used in their final assay which they reported to have high sensitivity and specificity [62]. Serum Beta-2 microglobulin has been shown not to be a marker of gastritis severity [63]. The basis of the urinary 8-hydroxydeoxyguanosine test is that in inflammatory-mediated carcinogenesis, reactive oxygen species derived from infiltrating neutrophils in the gastric mucosa cause cell injury and damage to the deoxyribonucleic acid (DNA). This DNA damage leads to the production of 8-hydroxydeoxyguanosine (8-OHdG), which can be used as a marker find more of the oxidative DNA damage in intestinal metaplasia. The concentration of 8-OHdG in a fasting morning urine sample was determined by Albayrak et al.[64] using the 8-OHdG Check, a competitive ELISA kit (Japan Institute for the Control of Aging, Shizuoka, Japan). There were significant correlations between the concentrations of urinary 8-OHdG and both the atrophy score (r = .441, p = .0001) and the intestinal metaplasia score (r = .436, p = .0001), so the test could be used to identify those at higher risk of gastric atrophy and intestinal metaplasia

[64]. However, there are other causes of raised urinary 8-OHdG, and therefore, this test will not 上海皓元 be specific for H. pylori-related oxidative DNA damage. All these studies demonstrate the complexity of H. pylori virulence and disease progression to gastric cancer and that there is unlikely to be a single marker of gastric cancer risk in all populations. Saliva has been used with limited success to detect H. pylori antibodies as its accuracy is not as high as blood-based serology [65]. However, saliva or dental plaque may prove useful when molecular techniques become cheaper and more common place, as they are easier to collect than blood or stool specimens. In a small study in 18 patients in whom H. pylori was cultured from gastric biopsy specimens, all were positive for H. pylori 16S rDNA gene (Applied Biosystem, Monza, Italy) in their saliva specimens [66].

“
“As an innovative researcher, dedicated teacher, astute clinician, and capable leader, J. Gregory Fitz, “Greg” (Fig. 1), has made significant contributions to the science and practice of hepatology Dactolisib and now continues to advance the mission of the AASLD as president of the organization. Greg was born in Lakeland, Florida, although shortly after his birth the family moved to Hickory, North Carolina. Greg’s father was a cardiologist, the first in Hickory, and a prominent member of the community who soon became a member of the North Carolina Medical Board. Hickory is a small town located near the mountains of western North Carolina. Known for

its handmade furniture and textile industry, its proximity to the Appalachian Mountains provides a myriad of outdoor opportunities; growing up in this beautiful area of the country, it is easy to understand Greg’s lifelong passion for the outdoors. Shortly after arriving in Hickory, Greg was enrolled in the local kindergarten where he met his wife-to-be, Linda. In fact, he and Linda would go on to attend elementary school, high school, and even college together. Linda states that, as a child, “Greg was involved in everything”; an active member of the student body, president of the student council, wrestler,

and high school football player. After high school he and Linda attended the University of North Carolina at Chapel Hill (UNC) see more 上海皓元 where Greg majored in Chemistry and Linda in Special Education. Greg graduated from UNC summa cum laude as a Morehead scholar and, as a crowning achievement to his early successes, he and Linda were married. Greg’s father

was a significant influence in his decision to become a physician, as well as his decision to attend Duke University for medical school. The Fitz’s had a strong history at Duke University, his father was also a Duke graduate and his mother previously worked for Dr. Eugene Stead, the Chair of Internal Medicine and a renowned medical educator, researcher, and founder of the Physician Assistant profession. Greg did not follow in his father’s footsteps to become a cardiologist, however. In fact, Greg’s early interest during medical school was in neurology and he worked in the laboratory of Dr. McNamara, performing research in experimental models of epilepsy. The young, aspiring researcher received the “Best Research Award” from the Epilepsy Foundation of America for this work. While it did not inspire a career as a neuroscientist, it nonetheless formed the foundation for his lifelong interest in ion channels and electrophysiology—the focus of his research activities for years to come.

Although type 1 disease is the most common of the three VWD types [1], little was known about its molecular pathogenesis

until the last decade. Recent multicentre studies have led to enhanced understanding of the disease phenotype and genotype. Accurate measurement C646 mw of FVIII activity is important in several areas including the diagnosis and management of haemophilia A and potency determination for FVIII containing clotting factor concentrates. Two-stage CS methods determine ability of FVIII to potentiate activation of FX by FIXa in the presence of calcium ions and phospholipid. Use of high plasma dilutions enables the CS assay measurements to reflect only tenase activity making utility of the test widely applicable. FVIII

inhibitors MLN0128 ic50 are the most frequently occurring blood coagulation inhibitors with an incidence of up to 30% in severe haemophiliacs [2]. Inhibitors against other coagulations factors including FIX, FXI, FV, FII and Fibrinogen have been described; however, their incidence is low and all occur exclusively after substitution therapy of the respective factor. In contrast, FVIII inhibitors not only occur as a result of substitution therapy in haemophiliacs (allo-antibodies), but may also develop as autologous inhibitors, mostly in elderly people in association with an autoimmune disease or a malignancy, but frequently without an underlying associated disease [3]. Each of these areas will be discussed. Three multicentre studies on type 1 VWD conducted in the European Union (EU), Canada and the UK each recruited index cases (IC), previously diagnosed with type 1 VWD, their affected and unaffected family members (AFM, UFM) plus healthy controls (HC) [4–6]. Recruitment was based on the 1994 VWD classification [7] and included patients considered to fit the criteria (EU), or used upper (≤0.50 IU mL−1, Canada and UK) and lower (0.05 IU mL−1,

Canada) assay limits for plasma VWF. 305 IC were MCE recruited. A previously designed BS tool was further developed for the EU study [8]. Participants were scored on 11 different bleeding symptoms with possible summed scores from −3 to 45. IC with a median BS of 9 had significantly more bleeding than HC (median −1). BS was useful for determining extent and significance of bleeding in an individual and correlated inversely with ristocetin cofactor activity (VWF: RCo). IC bled more than their AFM in many cases suggesting that further factors influence disease severity. BS tools are in routine use by several haemostasis specialists and are being further developed to enhance their utility. Candidate mutations were sought in 305 IC and identified in 65%, leaving a significant proportion with no mutation identified. 75% of mutations were missense alterations; other variants included splice, small deletions and insertions, nonsense and promoter region changes.

Identical analyses of the ribosomal protein genes rpl22 and rps3 were used for further classification

OTX015 clinical trial and revealed affiliation of the phytoplasmas with the rpIC subgroups. This is the first report of naturally occurring clover phyllody phytoplasma in A. graveolens in both the Czech Republic and worldwide. “
“Vine decline of kiwifruit was observed in an orchard in Bartın province of Turkey. Affected vines exhibited poor terminal growth, leaf discoloration and various degrees of dieback, including complete vine death. Symptoms were observed in the field on roots, crowns and stems. Two Phytophthora species were isolated from decayed cortical roots and lower stems of kiwifruits. They were identified as Phytophthora cryptogea and Phytophthora megasperma by their morphological characteristics and the analysis of sequences of the internal transcribed spacer (ITS) region of the rDNA. Pathogenicity of the isolates was tested by stem inoculation on kiwifruit seedlings. After 4 weeks, cankers developed in the plants inoculated with P. cryptogea, while no cankers formed in those inoculated with P. megasperma and in control

plants. This is the first report of P. cryptogea causing root and stem rot of kiwifruit in Turkey. “
“All Phytophthora ramorum EU1 lineage isolates tested are of A1 mating type, except for three rare isolates from 2002 to 2003 from Belgium, which were originally assigned the A2 mating type. In one of these isolates (2338), a switch from A2 to A1 mating type was observed in 2006. This observation initiated a larger study in which all cultures and subcultures of the MK0683 in vivo original three EU1 A2 isolates, maintained in three laboratories under different storage conditions, were checked for mating type change. The A2 to A1 mating type switch was observed in four of seven independently maintained isolates that were derived from isolate 2338 in two laboratories, using

different transfer regimes and storage conditions. Following the mating type switch to A1 in these four derived isolates, no reversion back to A2 mating was observed, even after up to 5 years of additional isolate 上海皓元 maintenance and several more subculturing events. The three other isolates that were derived from isolate 2338 as well as the other EU1 A2 isolates collected in 2002 and 2003 and stored in the same conditions did not display such mating type change. The potential causes of the mating type conversions as well as their epidemiological implications are discussed. Phytophthora ramorum is the causal agent of ‘sudden oak death’ in the US (Rizzo et al. 2002) and ‘sudden larch death’ in the UK (Webber et al. 2010). It also causes twig dieback and leaf necrosis in many ornamental plants in the US and Europe (Werres et al. 2001). P. ramorum is a heterothallic species with two mating types, A1 and A2.

(2011). Extracted genomic DNA was used as template in subsequent PCR reactions. In addition, psbA was amplified FK506 solubility dmso and sequenced from the C. ovata stock culture following the same methods to ensure Esoptrodinium sequence identity by direct and phylogenetic sequence comparison (below). Reportedly dinoflagellate-specific primers bAf1 (5′-GGTCAAGGTTCTTTCTCTGAYGGNATGCC-3′) and bAr1 (5′-GTTGTGAGCGTTACGTTCRTGCATNACYTC-3′; Zhang et al. 2000) were used to amplify 500 bp of a highly conserved region of the psbA gene. PCR was carried out in 0.5 mL PCR tubes containing 45 μL of Platinum® PCR Super Mix (Invitrogen Corp., Carlsbad, CA, USA), 100 ng of each primer, 20 ng of template DNA, and 2.5 μL CP-673451 concentration DMSO with appropriate

(+) and (−) controls. PCR was conducted using a Mastercycler® gradient thermal

block (Eppendorf AG, Hamburg, Germany) and reaction protocol: initial denaturing at 94°C for 2 min, 35 cycles of 94°C for 30 s, 55°C for 30 s, 72°C for 1:00, followed by 72°C for 4 min. PCR products were visualized and size checked by gel electrophoresis, and purified using polyethylene glycol (Thermo Fisher Scientific Inc., Waltham, MA, USA) and ethanol following Bachvaroff et al. (2009). Purified products were sequenced in both directions using Applied Biosystems BigDye Terminator version 3.1 (GENEWIZ, Inc., South Plainfield, NJ, USA). Alignments used to create final psbA phylogenies were performed with Muscle (Edgar 2004) in MEGA5 (Tamura

et al. 2011) using default parameters MCE as suggested by Hall (2011). Nucleotide sequences were converted to amino acid sequences, aligned, and then reverted back to nucleotides before phylogenetic analysis was performed (Hall 2011), and an overall mean P-distance was calculated to ensure the alignment was reliable. The initial 1,095 nucleotide alignment contained 44 taxa plus three outgroups (Mesostigma viride, Nephroselmis olivacea, and Cyanophora paradoxa) based on Zhang et al. (2000) (Table S1 in the Supporting Information). MEGA5 was used to conduct maximum likelihood (ML) and maximum parsimony (MP) analyses to infer evolutionary history from the psbA alignment. The alignment was analyzed beforehand with jModelTest v0.1.1 (Posada 2008) and the general time reversible (GTR) model plus invariable sites with a Gamma distributed rate of variation (GTR+Ι+Γ) achieved the lowest log-likelihood score. A ML phylogenetic tree was constructed using this model with 8 discrete gamma categories and a Nearest-Neighbor-Interchange heuristic method applied. All gaps and missing data were removed, and the 3rd position in each codon was excluded (Hoppenrath and Leander 2010), resulting in 285 nucleotide positions in the final alignment. Bootstrap (BS) support was conducted with 100 replicates. The MP phylogenetic tree was constructed using a Close-Neighbor-Interchange search method from 10 initial trees.

Results: We performed a retrospective study of 41 patients and undergoing 65 endoscopic treatment cases of sigmoid colon volvulus between April 2004 and March 2014. We included a total of 41 patients (men 28, women 13) with a mean age of 78.2 years old. The average session of endoscopic intervention was 1.91 ± 1.55 times. The success rate of endoscopic detortion for sigmoid colon volvulus was 80% (52/65). In 13 unsuccessful endoscopic detortion cases, 4 cases were successful endoscopic detortion (repeated), 6 cases were operated on, 3 cases died. Conclusion: Endoscopic

detortion for sigmoid colon volvulus was effective; however, the principal therapy see more of this condition is surgery. Only occasionally in patients with advanced age, lack of bowel symptoms and multiple co-morbidities might surgical repair not be considered. Key Word(s): 1. colon volvulus Presenting Author: MOTOHIKO HIROSE Additional Authors: HIRANO NAOKI, SATO SHINJI, DOMON KAORU, UMAKOSHI TOMOKO, IGARASHI YOSHINORI Corresponding Selleck Ipatasertib Author: MOTOHIKO HIROSE Affiliations: Toho University Omori Medical Center, Toho University

Omori Medical Center, Toho University Omori Medical Center, Toho University Omori Medical Center, Toho University Omori Medical Center Objective: The volvulus of sigmoid colon is well known as a cause of colorectal obstruction. When the volvulus is not treated, it will result to intestinal strangulations and necrosis, perforation and peritonitis. So it requires emergency treatments. The volvulus is found frequently in patients such as bedridden elderly and neurological patients. Thus, it needs no invasive treatments. It is reported that endoscopic treatments for volvulus and surgical excision are effective. Methods: We studied forty-one patients with sigmoid colon volvulus treated endoscopically from April 2004 to March 2014 in our

hospital. Mean average age was 78.2 ± 11.0, male 28 cases and female 13 cases. Recurrence was 6 cases. Results: Endoscopic treatments for the volvulus of sigmoid colon were 65 times, 52 of all cases were succeessful (80.0%). 13 cases were impossible to endoscopic Monoiodotyrosine release for volvulus and intestinal necrosis was seen in 7 cases. Emergency surgical operation was performed on 4 cases. Two of 6 cases without intestinal necrosis required no emergency surgical operation. Conclusion: Endoscopic treatments for the volvulus were effective for sigmoid colon. When it is impossible to release of volvulus, we recommend surgical operation. Key Word(s): 1. sigmoid colon volvulus Presenting Author: SUNG PYO HONG Additional Authors: KWANG HYUN KO, WON HEE KIM Corresponding Author: SUNG PYO HONG Affiliations: Cha Bundang Medical Center, Cha Bundang Medical Center Objective: Radiation proctitis is a common complication of radiation to lower abdomen and pelvis. Different modalities of treatment are available; however, the efficacy is incomplete.

B7-H1 mRNA levels in liver grafts promptly increased after WT-to-WT LT and peaked at 6 hours (Fig. 1A). When separated hepatocytes and NPCs were analyzed, B7-H1 mRNA up-regulation, though seen in both fractions, was more prominent CHIR-99021 mouse in hepatocytes versus the NPC fraction 3 and 6 hours after LT (Fig. 1B). A subsequent analysis of B7-H1 protein expression by flow cytometry showed that under steady-state conditions (naive mice), B7-H1 was

expressed on CD11c+ DCs and CD31+ sinusoidal endothelial cells (SECs) but not on hepatocytes (Fig. 1C). After hepatic I/R injury in WT-to-WT LT, B7-H1 protein expression was up-regulated in all three types of liver cells (Fig. 1C). In contrast, selleck kinase inhibitor after B7-H1 KO-to-WT LT, we observed a modest up-regulation of B7-H1 only on DCs, most likely because of infiltrating WT recipient DCs (Fig. 1C). To directly examine the role of hepatic graft B7-H1 expression in the pathogenesis of transplant-induced liver I/R injury, we compared the severities of hepatic injury for B7-H1 KO grafts and WT grafts transplanted into WT recipients with 24 hours of cold storage. Serum alanine aminotransferase (ALT) levels were 1.5- to 2-fold higher for KO-to-WT LT versus WT-to-WT LT 6 hours (5759 ± 549 versus 2100 ± 368 IU/L, P < 0.05) and 12 hours (8750 ± 1123 versus 5867 ± 654 IU/L, P < 0.05) after LT; this indicated

that the lack of graft B7-H1 expression augmented hepatic I/R injury (Fig. 2A). A histopathological analysis at 12 hours confirmed increased areas of necrosis in oxyclozanide B7-H1 KO grafts versus WT grafts (Fig. 2B). To explore the mechanisms of increased injury in liver grafts lacking B7-H1 expression, we conducted flow cytometry for hepatic NPCs obtained from WT and KO grafts after 6 hours of reperfusion in WT recipients.

As shown in Fig. 3A, liver CD45+CD31− cells were defined as hepatic NPCs and were analyzed for their phenotypes. During cold I/R injury, there was a dramatic increase in side scatter (SSC)high NPCs in WT-to-WT LT. In contrast, KO grafts showed a notable increase in SSClow lymphoid lineage NPCs. These changes reflected striking percentage increases in CD11b+ cells among hepatic NPCs in WT grafts versus KO grafts (80.7% versus 46.4%; Fig. 3A). Likewise, the increases in SSClow lymphocytes in KO grafts were mostly due to higher frequencies of CD3+ T cells (Fig. 3A). In agreement with the flow cytometry findings, immunofluorescence staining of liver grafts 6 hours after LT showed more CD3+ T cells in KO grafts versus WT grafts (Fig. 3B). Also, according to immunohistochemistry, more CD11b+ cells were detected in WT grafts versus KO grafts (Fig. 3B). Interestingly, CD11b+ cells typically showed focal accumulation in WT grafts (Fig. 3B, lower arrows); however, in KO grafts, they were distributed homogeneously throughout the liver and did not form focal aggregates.