The genera Melanothamnus Bornet & Falkenberg and Vertebrata S.F. Gray constitute well-defined clades of the red algal tribe Polysiphonieae (Rhodomelaceae, Ceramiales).

Polysiphonia is the largest genus of red algae, and several schemes subdividing it into smaller taxa have been proposed since its original description. Most of these proposals were not generally accepted, and currently the tribe Polysiphonieae consists of the large genus Polysiphonia (190 species), the segregate genus Neosiphonia (43 species), and 13 smaller genera (< 10 species each). In this paper, phylogenetic relationships of the tribe Polysiphonieae are analysed, with particular emphasis on the genera Carradoriella, Fernandosiphonia, Melanothamnus, Neosiphonia, Polysiphonia sensu stricto, Streblocladia and Vertebrata. We evaluated the consistency of 14 selected morphological characters in the identified clades. Based on molecular phylogenetic (rbcL and 18S genes) and morphological evidence, two speciose genera are recognized: Vertebrata (including the type species of the genera Ctenosiphonia, Enelittosiphonia, Boergeseniella and Brongniartella) and Melanothamnus (including the type species of the genera Fernandosiphonia and Neosiphonia). Both genera are distinguished from other members of the Polysiphonieae by synapomorphic characters, the emergence of which could have provided evolutionarily selective advantages for these two lineages. In Vertebrata trichoblast cells are multinucleate, possibly associated with the development of extraordinarily long, photoprotective, trichoblasts. Melanothamnus has 3-celled carpogonial branches and plastids lying exclusively on radial walls of the pericentral cells, which similarly may improve resistance to damage caused by excessive light. Other relevant characters that are constant in each genus are also shared with other clades. The evolutionary origin of the genera Melanothamnus and Vertebrata is estimated as 75.7-95.78 and 90.7-138.66 Ma, respectively. Despite arising in the Cretaceous, before the closure of the Tethys Seaway, Melanothamnus is a predominantly Indo-Pacific genus and its near-absence from the northeastern Atlantic is enigmatic. The nomenclatural implications of this work are that 46 species are here transferred to Melanothamnus, six species are transferred to Vertebrata and 13 names are resurrected for Vertebrata

Psychosocial Stress at Work Doubles the Risk of Type 2 Diabetes in Middle-Aged Women: Evidence from the Whitehall II Study

OBJECTIVE - To investigate the effect of psychosocial stress at work on risk of type 2 diabetes, adjusting for conventional risk factors, among a sample of British, white-collar, middleaged men and women. RESEARCH DESIGN AND METHODS - This was a prospective analysis (1991-2004) from the Whitehall II cohort study. The current sample consists of 5,895 Caucasian middle-aged civil servants free from diabetes at baseline. Type 2 diabetes was ascertained by an oral glucose tolerance test supplemented by self-reports at baseline and four consecutive waves of data collection including two screening phases. The job strain and iso-strain models were used to assess psychosocial work stress. RESULTS- Iso-strain in the workplace was associated with a twofold higher risk of type 2 diabetes in age-adjusted analysis in women but not in men (hazard ratio 1.94 [95% CI 1.17-3.21). This effect remained robust to adjustment for socioeconomic position and outside work stressors and was only attenuated by 20% after adjustment for health behaviors, obesity, and other type 2 diabetes risk factors. CONCLUSIONS - Psychosocial work stress was an independent predictor of type 2 diabetes among women after a 15-year follow-up. This association was not explained by potential confounding and mediating factors. More evidence from prospective studies using the same work stress models is needed to support the current findings and provide further information on sex differences. © 2009 by the American Diabetes Association

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets. FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. FUNDING: Bill & Melinda Gates Foundation

HLA Genes, Islet Autoantibodies and Residual C-Peptide at the Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years Later

HLA genes, islet autoantibodies and residual C-peptide were studied to determine the independent association of each exposure with diabetic retinopathy (DR), 15 years after the clinical onset of type 1 diabetes in 15-34 year old individuals.The cohort was identified in 1992 and 1993 by the Diabetes Incidence Study in Sweden (DISS), which investigates incident cases of diabetes for patients between 15 and 34 years of age. Blood samples at diagnosis were analyzed to determine HLA genotype, islet autoantibodies and serum C-peptide. In 2009, fundus photographs were obtained from patient records. Study measures were supplemented with data from the Swedish National Diabetes Registry.The prevalence of DR was 60.2% (148/246). Autoantibodies against the 65 kD isoform of glutamate decarboxylase (GADA) at the onset of clinical diabetes increased the risk of DR 15 years later, relative risk 1.12 for each 100 WHO units/ml, [95% CI 1.02 to 1.23]. This equates to risk estimates of 1.27, [95% CI 1.04 to 1.62] and 1.43, [95% CI 1.06 to 1.94] for participants in the highest 25(th) (GADA>233 WHO units/ml) and 5(th) percentile (GADA>319 WHO units/ml) of GADA, respectively. These were adjusted for duration of diabetes, HbA(1c), treated hypertension, sex, age at diagnosis, HLA and C-peptide. Islet cell autoantibodies, insulinoma-antigen 2 autoantibodies, residual C-peptide and the type 1 diabetes associated haplotypes DQ2, DQ8 and DQ6 were not associated with DR.Increased levels of GADA at the onset of type 1 diabetes were associated with DR 15 years later. These results, if confirmed, could provide additional insights into the pathogenesis of the most common microvascular complication of diabetes and lead to better risk stratification for both patient screenings and DR treatment trials

Association between LTA, TNF and AGER Polymorphisms and Late Diabetic Complications

BACKGROUND: Several candidate genes on the short arm of chromosome 6 including the HLA locus, TNF, LTA and AGER could be associated with late diabetic complications. The aim of our study was therefore to explore whether polymorphisms (TNF -308 G-->A, LTA T60N C-->A and AGER -374 T-->A) in these genes alone or together (as haplotypes) increased the risk for diabetic complications. METHODOLOGY/PRINCIPAL FINDINGS: The studied polymorphisms were genotyped in 742 type 1 and 2957 type 2 diabetic patients as well as in 206 non-diabetic control subjects. The Haploview program was used to analyze putative linkage disequilibrium between studied polymorphisms. The TNF, LTA and AGER polymorphisms were associated with the HLA-DQB1 risk genotypes. The AGER -374 A allele was more common in type 1 diabetic patients with than without diabetic nephropathy (31.2 vs. 28.4%, p = 0.007). In a logistic regression analysis, the LTA but not the AGER polymorphism was associated with diabetic nephropathy (OR 2.55[1.11-5.86], p = 0.03). The AGER -374 A allele was associated with increased risk of sight threatening retinopathy in type 2 diabetic patients (1.65[1.11-2.45], p = 0.01) and also with increased risk for macrovascular disease in type 1 diabetic patients (OR 2.05[1.19-3.54], p = 0.01), but with decreased risk for macrovascular disease in type 2 diabetic patients (OR 0.66[0.49-0.90], p = 0.009). The TNF A allele was associated with increased risk for macrovascular complications in type 2 (OR 1.53 [1.04-2.25], p = 0.03, but not in type 1 diabetic patients. CONCLUSIONS/SIGNIFICANCE: The association between diabetic complications and LTA, TNF and AGER polymorphisms is complex, with partly different alleles conferring susceptibility in type 1 and type 2 diabetic patients. We can not exclude the possibility that the genes are part of a large haplotype block that also includes HLA-DQB1 risk genotypes

THE GENUS HYPOGLOSSUM KÜTZING (DELESSERIACEAE, RHODOPHYTA) IN THE TROPICAL WESTERN ATLANTIC, INCLUDING H. ANOMALUM SP. NOV. 1

Observations are made on the occurrence and distribution of the red algal genus Hypoglossum KÜtzing (Delesseriaceae, Ceramiales) in the tropical western Atlantic. In addition to the type of the genus, H. hypoglossoides (Stackh.) Coll. & Herv., three other species are reported: H. anomalum sp. nov., H. involvens (Harv.) J. Ag., and H. tenuifolium (Harv.) J. Ag. A key is presented to distinguish these four species. The newly described species, H. anomalum, is like other species in the genus in that its branches arise endogenously from the primary axial row but it is unique in that the branches emerge from the parent blade at some point between the midline and the margin of the blade. The new species is reported from Puerto Rico and Florida.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65648/1/j.1529-8817.1986.tb04162.x.pd

A gene-centric approach to biomarker discovery identifies transglutaminase 1 as an epidermal autoantigen

Publisher Copyright: © 2021 National Academy of Sciences. All rights reserved.Autoantigen discovery is a critical challenge for the understanding and diagnosis of autoimmune diseases. While autoantibody markers in current clinical use have been identified through studies focused on individual disorders, we postulated that a reverse approach starting with a putative autoantigen to explore multiple disorders might hold promise. We here targeted the epidermal protein transglutaminase 1 (TGM1) as a member of a protein family prone to autoimmune attack. By screening sera from patients with various acquired skin disorders, we identified seropositive subjects with the blistering mucocutaneous disease paraneoplastic pemphigus. Validation in further subjects confirmed TGM1 autoantibodies as a 55% sensitive and 100% specific marker for paraneoplastic pemphigus. This gene-centric approach leverages the wealth of data available for human genes and may prove generally applicable for biomarker discovery in autoimmune diseases.Peer reviewe

Identification of Non-HLA Genes Associated with Celiac Disease and Country-Specific Differences in a Large, International Pediatric Cohort

In conclusion, using a genetic analysis of a large international cohort of children, we associated celiac disease development with 5 non-HLA regions previously associated with the disease and 8 regions not previously associated with celiac disease. We identified 5 regions associated with development of tTGA. Two loci associated with celiac disease progression reached a genome-wide association threshold in subjects from Sweden.</p

Long-Lasting Immune Responses 4 Years after GAD-Alum Treatment in Children with Type 1 Diabetes

A phase II clinical trial with glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) has shown efficacy in preserving residual insulin secretion in children and adolescents with recent-onset type 1 diabetes (T1D). We have performed a 4-year follow-up study of 59 of the original 70 patients to investigate long-term cellular and humoral immune responses after GAD-alum-treatment. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with GAD65. Frequencies of naïve, central and effector memory CD4+ and CD8+ T cells were measured, together with cytokine secretion, proliferation, gene expression and serum GAD65 autoantibody (GADA) levels. We here show that GAD-alum-treated patients display increased memory T-cell frequencies and prompt T-cell activation upon in vitro stimulation with GAD65, but not with control antigens, compared with placebo subjects. GAD65-induced T-cell activation was accompanied by secretion of T helper (Th) 1, Th2 and T regulatory cytokines and by induction of T-cell inhibitory pathways. Moreover, post-treatment serum GADA titres remained persistently increased in the GAD-alum arm, but did not inhibit GAD65 enzymatic activity. In conclusion, memory T- and B-cell responses persist 4 years after GAD-alum-treatment. In parallel to a GAD65-induced T-cell activation, our results show induction of T-cell inhibitory pathways important for regulating the GAD65 immunity

Lectotypification of Sebdenia flabellata (J. Agardh) Parkinson (Gigartinales, Rhodophyta)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149746/1/tax01178.pd