Tissue Determinants of Human NK Cell Development, Function, and Residence.

Immune responses in diverse tissue sites are critical for protective immunity and homeostasis. Here, we investigate how tissue localization regulates the development and function of human natural killer (NK) cells, innate lymphocytes important for anti-viral and tumor immunity. Integrating high-dimensional analysis of NK cells from blood, lymphoid organs, and mucosal tissue sites from 60 individuals, we identify tissue-specific patterns of NK cell subset distribution, maturation, and function maintained across age and between individuals. Mature and terminally differentiated NK cells with enhanced effector function predominate in blood, bone marrow, spleen, and lungs and exhibit shared transcriptional programs across sites. By contrast, precursor and immature NK cells with reduced effector capacity populate lymph nodes and intestines and exhibit tissue-resident signatures and site-specific adaptations. Together, our results reveal anatomic control of NK cell development and maintenance as tissue-resident populations, whereas mature, terminally differentiated subsets mediate immunosurveillance through diverse peripheral sites. VIDEO ABSTRACT

Randomized Crossover Study Showing Nurse-Led Same Day Review Replacing Next Day Review in Uneventful Phacoemulsification to Be Safe and Efficacious

Purpose. To study whether nurse led same-day review (SDR) after uneventful phacoemulsification can replace next-day review (NDR) in terms of safety and efficacy. Setting. Patients are recruited from an ophthalmology outpatient clinic in Hong Kong. Design. A prospective, randomized crossover study conducted from November 2012 to 2014. Methods. Inclusion criteria include cataract surgery naïve patients undergoing phacoemulsification under local anaesthesia. All patients were seen by our ophthalmic nurse 2 hours after surgery. Before undergoing phacoemulsification of the first eye, patients were randomized to be reviewed on day 1 or 7 after surgery. Surgeons and reviewing doctors were blinded to patient allocation. For the patients’ second eye surgery, group allocation will cross over. Primary outcome measures include visual improvement and patient satisfaction questionnaire. Other measures include cataract characteristics, surgical details, and complications. Statistical tests include paired t-test, Wilcoxon signed rank test, and Chi-square test. Results. 164 eyes from 82 patients were available. Visual improvement, satisfaction, and complications were comparable between both groups. Conclusions. A nurse led SDR can replace NDR in uneventful phacoemulsification in terms of safety and efficacy. Patient satisfaction is also comparable in the setting of Asian culture and when transportation is not a major concern

Synthesis and analysis of the anticancer activity of platinum(ii) complexes incorporating dipyridoquinoxaline variants

Eight platinum(ii) complexes with anticancer potential have been synthesised and characterised. These complexes are of the type [Pt(I)(A)], where I is either dipyrido[3,2-f:2′,3′-h]quinoxaline (dpq) or 2,3-dimethyl-dpq (23Medpq) and A is one of the R,R or S,S isomers of either 1,2-diaminocyclohexane (SS-dach or RR-dach) or 1,2-diaminocyclopentane (SS-dacp or RR-dacp). The CT-DNA binding of these complexes and a series of other complexes were assessed using fluorescent intercalator displacement assays, resulting in unexpected trends in DNA binding affinity. The cytotoxicity of the eight synthesised compounds was determined in the L1210 cell line; the most cytotoxic of these were [Pt(dpq)(SS-dach)]Cl and [Pt(dpq)(RR-dach)]Cl, with IC values of 0.19 and 0.80 μM, respectively. The X-ray crystal structure of the complex [Pt(dpq)(SS-dach)](ClO)·1.75HO is also reported. This journal i

Self-assembly of an imidazolate-bridged FeIII/CuII heterometallic cage

A rare, discrete, mixed-valent, heterometallic Fe(III)/Cu(II) cage, [CuFeL](ClO)χ solvent (HL = tris{[2-{(imidazole-4-yl)methylidene}amino]ethyl} amine), was designed and synthesized via metal-ion-directed self-assembly with neutral tripodal metalloligands. The formation of this coordination cage was demonstrated by X-ray crystallography, ESI mass spectrometry, FT-IR, and UV-vis-NIR spectroscopy

Amelogenin: A Potential Regulator of Cementum‐Associated Genes

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142042/1/jper1423.pd

Dysregulation of glucose metabolism is an early event in sporadic Parkinson's disease

AbstractUnlike most other cell types, neurons preferentially metabolize glucose via the pentose phosphate pathway (PPP) to maintain their antioxidant status. Inhibiting the PPP in neuronal cell models causes cell death. In rodents, inhibition of this pathway causes selective dopaminergic cell death leading to motor deficits resembling parkinsonism. Using postmortem human brain tissue, we characterized glucose metabolism via the PPP in sporadic Parkinson's disease (PD), Alzheimer's disease (AD), and controls. AD brains showed increased nicotinamide adenine dinucleotide phosphate (NADPH) production in areas affected by disease. In PD however, increased NADPH production was only seen in the affected areas of late-stage cases. Quantifying PPP NADPH-producing enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase by enzyme-linked immunosorbent assay, showed a reduction in the putamen of early-stage PD and interestingly in the cerebellum of early and late-stage PD. Importantly, there was no decrease in enzyme levels in the cortex, putamen, or cerebellum of AD. Our results suggest that down-regulation of PPP enzymes and a failure to increase antioxidant reserve is an early event in the pathogenesis of sporadic PD

Validation of a score tool for measurement of histological severity in juvenile dermatomyositis and association with clinical severity of disease.

OBJECTIVES: To study muscle biopsy tissue from patients with juvenile dermatomyositis (JDM) in order to test the reliability of a score tool designed to quantify the severity of histological abnormalities when applied to biceps humeri in addition to quadriceps femoris. Additionally, to evaluate whether elements of the tool correlate with clinical measures of disease severity. METHODS: 55 patients with JDM with muscle biopsy tissue and clinical data available were included. Biopsy samples (33 quadriceps, 22 biceps) were prepared and stained using standardised protocols. A Latin square design was used by the International Juvenile Dermatomyositis Biopsy Consensus Group to score cases using our previously published score tool. Reliability was assessed by intraclass correlation coefficient (ICC) and scorer agreement (α) by assessing variation in scorers' ratings. Scores from the most reliable tool items correlated with clinical measures of disease activity at the time of biopsy. RESULTS: Inter- and intraobserver agreement was good or high for many tool items, including overall assessment of severity using a Visual Analogue Scale. The tool functioned equally well on biceps and quadriceps samples. A modified tool using the most reliable score items showed good correlation with measures of disease activity. CONCLUSIONS: The JDM biopsy score tool has high inter- and intraobserver agreement and can be used on both biceps and quadriceps muscle tissue. Importantly, the modified tool correlates well with clinical measures of disease activity. We propose that standardised assessment of muscle biopsy tissue should be considered in diagnostic investigation and clinical trials in JDM

Plasma kininogen and kininogen fragments are biomarkers of progressive renal decline in type-1 diabetes

The ability of microalbuminuria to predict early progressive renal function decline in type-1 diabetic patients has been questioned. To resolve this, we determined the plasma proteome differences between microalbuminuric patients with type-1 diabetes and stable renal function (controls) and patients at risk for early progressive renal function decline (cases) and asked whether these differences have value as surrogate biomarkers. Mass spectrometry was used to analyze small (less than 3 kDa) plasma peptides isolated from well-matched case and control plasma obtained at the beginning of an 8-12 year follow-up period. Spearman analysis of plasma peptide abundance and the rate of renal function decline during follow-up identified seven masses with a significant negative correlation with early progressive renal function decline. Tandem mass spectrometry identified three fragments of high molecular weight kininogen. Increased plasma high molecular weight kininogen in the cases was confirmed by immunoblot. One peptide, des-Arg9-BK(1-8), induced Erk1/2 phosphorylation when added apically to two proximal tubular cell lines grown on permeable inserts. Thus, we have identified plasma protein fragments, some of which have biological activity with moderate to strong correlation, with early progressive renal function decline in microalbuminuric patients with type-1 diabetes. Other peptides are candidates for validation as candidate biomarkers of diabetes-associated renal dysfunction