Arabidopsis BECLIN1-induced autophagy mediates reprogramming in tapetal programmed cell death by altering the gross cellular homeostasis.

In flowering plants, the tapetum degeneration in post-meiotic anther occurs through developmental programmed cell death (dPCD), which is one of the most critical and sensitive steps for the proper development of male gametophytes and fertility. Yet the pathways of dPCD, its regulation, and its interaction with autophagy remain elusive. Here, we report that high-level expression of Arabidopsis autophagy-related gene BECLIN1 (BECN1 or AtATG6) in the tobacco tapetum prior to their dPCD resulted in developmental defects.

Tertiary lymphoid structures as local perpetuators of organ-specific immune injury: implication for lupus nephritis.

In response to inflammatory stimuli in conditions such as autoimmune disorders, infections and cancers, immune cells organize in nonlymphoid tissues, which resemble secondary lymphoid organs. Such immune cell clusters are called tertiary lymphoid structures (TLS). Here, we describe the potential role of TLS in the pathogenesis of autoimmune disease, focusing on lupus nephritis, a condition that incurs major morbidity and mortality.

Steady decrease in systemic sclerosis mortality rates at younger ages over the past five decades.

Objective: We aimed to assess SSc mortality by age in the general population over the past five decades.

Methods: This is a population-based study using a national mortality database and the census data for all US residents. We calculated the proportions of deaths for SSc and for all other causes (non-SSc) by age, and calculated age-standardized mortality rates (ASMRs) for SSc and non-SSc, and the ratio of SSc-ASMR to non-SSc-ASMR by age groups for each year from 1968 through 2015.

Worsening premature death burden gap from systemic sclerosis in men and black persons: A US nationwide population-based study.

Objective: Male sex and black race incur poor prognosis in systemic sclerosis (SSc). There is no nationwide population-based assessment of premature SSc death burden by sex and race.

Methods: This is a population-based study comprising all recorded SSc deaths across the United States.

Diverse Roles of NETosis in the Pathogenesis of Lupus.

NETosis is a form of neutrophil cell death during which extracellular fibrillary structures composed of cytosolic and granule proteins assembled on scaffolds of decondensed chromatin, called neutrophil extracellular traps (NETs), are released. NETs normally contribute to host immune defense. Accumulating evidence implicates aberrant NET production and/or reduced NET clearance, along with alterations of molecules involved in NETosis pathway, in humans and animals with lupus.

Anti-vinculin antibodies in scleroderma (SSc): a potential link between autoimmunity and gastrointestinal system involvement in two SSc cohorts.

Background: Systemic sclerosis (SSc) is an autoimmune disorder and commonly presents with vascular system involvement and motility disorders in the gastrointestinal (GI) tract. Vinculin is a cytoskeletal protein that plays major roles in cell-cell adhesion and is expressed in the neuromuscular apparatus of the gut. Antibodies to vinculin have been identified as a biomarker of irritable bowel syndrome (IBS).

Trends in Systemic Sclerosis Mortality Over Forty-Eight Years, 1968-2015: A US Population-Based Study.

Objective: To identify secular trends associated with systemic sclerosis (SSc) mortality over a 48-year period.

Methods: Using national mortality data compiled by the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research, and population data from the US Census Bureau, we calculated an age-standardized mortality rate (ASMR) for SSc and non-SSc (all other causes), and we also calculated the ratio of the SSc ASMR to the non-SSc ASMR for each year from 1968 to 2015. We then used a joinpoint regression model to evaluate mortality trends overall and by sex and race.

Potential utility of anti-TNF drugs in synovial chondromatosis associated with ankylosing spondylitis.

We describe a previously unreported association of ankylosing spondylitis with synovial chondromatosis, and briefly review previously reported cases and treatment of synovial chondromatosis in patients with other immune-mediated inflammatory arthritides. A 20-year-old man with ankylosing spondylitis whose axial disease was in remission with nonsteroidal anti-inflammatory drugs and oral disease-modifying anti-rheumatic drugs developed recurrent right knee pain and swelling. Magnetic resonance imaging of his right knee revealed calcified loose bodies, suggestive of synovial chondromatosis.

Heparin and aspirin combination therapy restores T-cell phenotype in pregnant patients with antiphospholipid syndrome-related recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) is the most common manifestation of anti-phospholipid syndrome (APS), and activated CD4 T cells are involved in its pathogenesis. Treatment with low-molecular weight heparin (LMWH) and aspirin combination improves pregnancy outcome, however, its mechanism of action is unclear. We investigated the effect of this therapy on Th1/Th2 cells in 89 patients with APS-RPL.

Generalized Cytokine Increase in the Setting of a Multisystem Clinical Disorder and Carcinoid Syndrome Associated with a Novel NLRP12 Variant.

Background: Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are a group of cytoplasmic sensors that survey danger signals released by invading pathogens or damaged tissue. Mutations in the NLRP subfamily affect pro-inflammatory mediators and cause nonspecific systemic symptoms.

Aims: We sought to identify a potential genetic etiology of an inflammatory syndrome in a patient that presented with an atypical multisystem illness with carcinoid syndrome as well as atopic and autoimmune features.

Quantitative Proteomics Using Formalin-fixed, Paraffin-embedded Biopsy Tissues in Inflammatory Disease.

Background: Investigations in human disease pathogenesis have been hampered due to paucity of access to fresh-frozen tissues (FFT) for use in global, data-driven methodologies. As an alternative, formalin-fixed, paraffin-embedded (FFPE) tissues are readily available in pathology banks. However, the use of formalin for fixation can lead to the loss of proteins that appear during inflammation, thus introducing an inherent sample bias.

pDCs in lung and skin fibrosis in a bleomycin-induced model and patients with systemic sclerosis.

Fibrosis is the end result of most inflammatory conditions, but its pathogenesis remains unclear. We demonstrate that, in animals and humans with systemic fibrosis, plasmacytoid DCs (pDCs) are unaffected or are reduced systemically (spleen/peripheral blood), but they increase in the affected organs (lungs/skin/bronchoalveolar lavage). A pivotal role of pDCs was shown by depleting them in vivo, which ameliorated skin and/or lung fibrosis, reduced immune cell infiltration in the affected organs but not in spleen, and reduced the expression of genes and proteins implicated in chemotaxis, inflammation, and fibrosis in the affected organs of animals with bleomycin-induced fibrosis.

Brief Report: Lupus-An Unrecognized Leading Cause of Death in Young Females: A Population-Based Study Using Nationwide Death Certificates, 2000-2015.

Objective: Mortality statistics from the Centers for Disease Control and Prevention (CDC) are used for planning health care policy and allocating resources. The CDC uses these data to compile its annual ranking of leading causes of death based on a selected list of 113 causes. Systemic lupus erythematosus (SLE) is not included on this list.

46-Year Trends in Systemic Lupus Erythematosus Mortality in the United States, 1968 to 2013: A Nationwide Population-Based Study.

Background: No large population-based studies have been done on systemic lupus erythematosus (SLE) mortality trends in the United States.

Objective: To identify secular trends and population characteristics associated with SLE mortality.

Design: Population-based study using a national mortality database and census data.

Effects of Invariant NKT Cells on Parasite Infections and Hygiene Hypothesis.

Invariant natural killer T (iNKT) cells are unique subset of innate-like T cells recognizing glycolipids. iNKT cells can rapidly produce copious amounts of cytokines upon antigen stimulation and exert potent immunomodulatory activities for a wide variety of immune responses and diseases. We have revealed the regulatory effect of iNKT cells on autoimmunity with a serial of publications.

Anti-inflammatory therapies of amyotrophic lateral sclerosis guided by immune pathways.

Sporadic ALS patients display heterogeneous immune pathways in peripheral blood mononuclear cells (PBMCs). We tested nine sALS patients and one unaffected identical twin of an index case by RNA-Seq of PBMCs. The inflammatory patients (n = 3) clustered into a subset with an inflammatory Th1/Th17 signature and the non-inflammatory patients (n = 7) into another subset with a B cell signature.

Production of β-galactosidase from streptococcus thermophilus for galactooligosaccharides synthesis.

Efficiency of different methods for disruption of Streptococcus thermophilus cells, isolated from different dairy products, to release β-galactosidase and synthesis of GOS by extracted enzyme using whey supplemented with different concentrations of lactose as a substrate was studied. Unlike most other studies on GOS synthesis which used only one method of cell disruption and only few microbial strains, we compared five different cell disruption methods and used 30 strains of S. thermophilus in order to find out the most effective method and efficient strain for production of β-galactosidase.

A novel male sterility-fertility restoration system in plants for hybrid seed production.

Hybrid seeds are used for stimulated crop production, as they harness heterosis. The achievement of complete male-sterility in the female-parent and the restored-fertility in F1-hybrids are the major bottlenecks in the commercial hybrid seed production. Here, we report a male sterility-fertility restoration system by engineering the in most nutritive anther wall layer tapetum of female and male parents.

Langerhans Cells Maintain Local Tissue Tolerance in a Model of Systemic Autoimmune Disease.

Systemic autoimmune diseases such as lupus affect multiple organs, usually in a diverse fashion where only certain organs are affected in individual patients. It is unclear whether the "local" immune cells play a role in regulating tissue specificity in relation to disease heterogeneity in systemic autoimmune diseases. In this study, we used skin as a model to determine the role of tissue-resident dendritic cells (DCs) in local and systemic involvement within a systemic lupus disease model.

Hypoglycaemic effect of galactooligosaccharides in alloxan-induced diabetic rats.

This study was conducted to assess the effect of prebiotic galactooligosaccharides (GOS) on alloxan-induced diabetes in male Sprague-Dawley (SD) rats. Diabetes was induced by administration of alloxan (100 mg/kg) and rats were divided in 4 groups: normal control group (NCG), prebiotic control group (PCG), diabetic control group (DCG) and diabetic prebiotic group (DPG). While PCG and DPG were fed with GOS supplemented (10% w/w) diet, NCG and DCG were administered with basal diet.

Process optimisation for preparation of caseinophosphopeptides from buffalo milk casein and their characterisation.

Caseinophosphopeptides (CPPs) are multifunctional bioactive peptides containing phosphorylated seryl residues in their sequence. In the present study, method for the production of CPPs from buffalo milk casein was optimised and characterised for their sequence, calcium solubilising and calcium binding activities. Response surface methodology was used to optimise the conditions for hydrolysis of buffalo casein by trypsin to obtain maximum yield of CPPs.

Prevalence of subclinical atherosclerosis is increased in systemic sclerosis and is associated with serum proteins: a cross-sectional, controlled study of carotid ultrasound.

Objectives: SSc is associated with an increased prevalence of atherosclerosis (ATS). This study assessed the prevalence of subclinical ATS as measured by carotid US and explored serum proteins to identify potential biomarkers of SSc-ATS.

Methods: Forty-six SSc female patients and 46 age- and ethnicity-matched controls underwent carotid US to assess the presence of plaque and carotid intima media thickness (CIMT).

HRES-1/Rab4-mediated depletion of Drp1 impairs mitochondrial homeostasis and represents a target for treatment in SLE.

Objective: Accumulation of mitochondria underlies T-cell dysfunction in systemic lupus erythematosus (SLE). Mitochondrial turnover involves endosomal traffic regulated by HRES-1/Rab4, a small GTPase that is overexpressed in lupus T cells. Therefore, we investigated whether (1) HRES-1/Rab4 impacts mitochondrial homeostasis and (2) Rab geranylgeranyl transferase inhibitor 3-PEHPC blocks mitochondrial accumulation in T cells, autoimmunity and disease development in lupus-prone mice.

Germline deletion of β2 microglobulin or CD1d reduces anti-phospholipid antibody, but increases autoantibodies against non-phospholipid antigens in the NZB/W F1 model of lupus.

Introduction: β2-microglobulin (β2m) is required for the surface expression of MHC class I and class I-like proteins such as CD1d, Qa1 and neonatal Fc receptor (FcRn), all of which may impact the development of autoimmunity. Since CD1d is known to bind and present phospholipid antigens to T cells, we asked if the deficiency of β2m or CD1d will impact the development of anti-phospholipid antibodies as compared to other aspects of lupus autoimmunity.

Methods: We introgressed the β2m-null genotype onto the NZB and NZW backgrounds for 12 to 14 generations to generate genetically lupus-susceptible (NZB/NZW)F1 (BWF1) mice that are β2m-deficient (β2m°).