Epitope-Specific Anti-C1q Autoantibodies in Systemic Lupus Erythematosus

OBJECTIVE: In patients with systemic lupus erythematosus (SLE) complement C1q is frequently targeted by autoantibodies (anti-C1q), that correlate best with active renal disease. Anti-C1q bind to largely unknown epitopes on the collagen-like region (CLR) of this highly functional molecule. Here we aimed at exploring the role of epitope-specific anti-C1q in SLE patients. METHODS: First, 22 sera of SLE patients, healthy controls and anti-C1q positive patients without SLE were screened for anti-C1q epitopes by a PEPperMAP(®) microarray, expressing CLR of C1q derived peptides with one amino acid (AA) shift in different lengths and conformations. Afterwards, samples of 378 SLE patients and 100 healthy blood donors were analyzed for antibodies against the identified epitopes by peptide-based ELISA. Relationships between peptide-specific autoantibodies and SLE disease manifestations were explored by logistic regression models. RESULTS: The epitope mapping showed increased IgG binding to three peptides of the C1q A- and three of the C1q B-chain. In subsequent peptide-based ELISAs, SLE sera showed significantly higher binding to two N-terminally located C1q A-chain peptides than controls (p < 0.0001), but not to the other peptides. While anti-C1q were associated with a broad spectrum of disease manifestations, some of the peptide-antibodies were associated with selected disease manifestations, and antibodies against the N-terminal C1q A-chain showed a stronger discrimination between SLE and controls than conventional anti-C1q. CONCLUSION: In this large explorative study anti-C1q correlate with SLE overall disease activity. In contrast, peptide-antibodies are associated with specific aspects of the disease suggesting epitope-specific effects of anti-C1q in patients with SLE

Electrical coupling of neuro-ommatidial photoreceptor cells in the blowfly

A new method of microstimulation of the blowfly eye using corneal neutralization was applied to the 6 peripheral photoreceptor cells (R1-R6) connected to one neuro-ommatidium (and thus looking into the same direction), whilst the receptor potential of a dark-adapted photoreceptor cell was recorded by means of an intracellular microelectrode. Stimulation of the photoreceptor cells not impaled elicited responses in the recorded cell of about 20% of the response elicited when stimulating the recorded cell. This is probably caused by gap junctions recently found between the axon terminals of these cells. Stimulation of all 6 cells together yielded responses that were larger and longer than those obtained with stimulation of just the recorded cell, and intensity-response curves that deviated more strongly from linearity. Evidence is presented that the resistance of the axon terminal of the photoreceptor cells quickly drops in response to a light flash, depending on the light intensity. Incorporating the cable properties of the cell body and the axon, the resistance of the gap junctions, and the (adapting) terminal resistance, a theoretical model is presented that explains the measurements well. Finally, it is argued that the gap junctions between the photoreceptor cells may effectively uncouple the synaptic responses of the cells by counteracting the influence of field potentials.

Sarcoidosis - a multisystem disease.

Sarcoidosis is a systemic inflammatory disease, characterised by granuloma formation upon an unknown trigger in genetically predisposed individuals. The inflammation is characterised by an activation of both the innate immune system, with macrophages differentiating into epitheloid cells and dendritic cells, and the adaptive immune system, particularly T helper (Th) 1 and Th17 cells. Since all organs can be affected to varying extents, clinical presentation is often diverse. Most commonly, the lungs, lymph nodes, skin and eyes are involved, whereas cardiac, renal and neurological manifestations are less common but associated with higher morbidity. Depending on the clinical symptoms, a detailed evaluation including thorough clinical examination, imaging and laboratory tests should explore all possible organ involvements. In some patients, fatigue manifests as a para-sarcoidosis symptom impacting quality of life, even if sarcoidosis is in remission. Some acute syndromic presentations, such as Löfgren's syndrome, have a good prognosis and are commonly self-limiting. If possible, a topical treatment, for example for cutaneous sarcoidosis or bronchial involvement, should be applied. Treatment of severe cases with persisting disease activity necessitates long-term immunosuppressive drugs, with glucocorticoids as the first-line option. Steroid-sparing and second-line drugs include methotrexate, azathioprine, mycophenolate mofetil and immunomodulators such hydroxychloroquine, with the latter being first-line therapy in cutaneous sarcoidosis. Tumour necrosis factor-alpha inhibitors (particularly adalimumab and infliximab) are used as third-line agents but are administered earlier in cases of persistent disease activity, severe organ-involvement or intolerance to conventional drugs. Treatment decisions should be based on a multidisciplinary approach, depending on organ involvement and treatment tolerability. Para-sarcoidosis manifestations, particularly fatigue, should also be carefully addressed, where the patient could also be enrolled in multidimensional rehabilitation programmes. With various organ involvement and different phenotypes, larger studies including real-world data from registries are necessary to evaluate different sarcoidosis endotypes and preferential treatment pathways

Sexual dysfunction and fertility-related distress in young adults with cancer over 5 years following diagnosis: study protocol of the Fex-Can Cohort study

BACKGROUND: There is a lack of firm knowledge regarding sexual problems and fertility-related distress in young adults following a diagnosis with cancer. Establishing such understanding is essential to identify patients in need of specific support and to develop cancer care accordingly. This study protocol describes the Fex-Can Cohort study, a population-based prospective cohort study investigating sexual dysfunction and fertility-related distress in young adults diagnosed with cancer in Sweden. The primary objective of the study is to determine the prevalence and predictors of sexual dysfunction and fertility-related distress following a cancer diagnosis in young adulthood compared to prevalence rates for the general population. Further aims are to investigate the trajectories of these issues over time, the co-existence between sexual dysfunction and fertility-related distress, and the relation between these issues and body image, anxiety and depression, health-related quality of life, self-efficacy related to sexuality and fertility, and fertility-related knowledge. METHODS: Participants in the Fex-Can Cohort will be identified via the Swedish National Quality Registries for Brain Tumors, Breast Cancer, Gynecological Oncology, Lymphoma, and Testicular Cancer. All patients diagnosed at the ages of 18-39, during a period of 18 months, will be invited to participate. Established instruments will be used to measure sexual function (PROMIS SexFS), fertility-related distress (RCAC), body image (BIS), anxiety and depression (HADS), and health-related quality of life (QLQ-C30); Self-efficacy and fertility-related knowledge will be assessed by study-specific measures. The survey will be administered to participants at baseline (approximately 1.5 year after diagnosis) and at 3 and 5 years post-diagnosis. Registry data will be used to collect clinical variables. A comparison group of 2000 young adults will be drawn from the Swedish population register (SPAR) and subsequently approached with the same measures as the cancer group. DISCUSSION: The study will determine the prevalence and predictors of sexual dysfunction and fertility-related distress in young men and women with cancer. The findings will form a basis for developing interventions to alleviate sexual problems and fertility-related distress in young adults with cancer in the short and long term. TRIAL REGISTRATION: This is an observational cohort study and clinical trial registration was therefore not obtained

Micro-computed tomography and histology to explore internal morphology in decapod larvae

Traditionally, the internal morphology of crustacean larvae has been studied using destructive techniques such as dissection and microscopy. The present study combines advances in microcomputed tomography (micro-CT) and histology to study the internal morphology of decapod larvae, using the common spider crab (Maja brachydactyla Balss, 1922) as a model and resolving the individual limitations of these techniques. The synergy of micro-CT and histology allows the organs to be easily identified, revealing simultaneously the gross morphology (shape, size, and location) and histological organization (tissue arrangement and cell identification). Micro-CT shows mainly the exoskeleton, musculature, digestive and nervous systems, and secondarily the circulatory and respiratory systems, while histology distinguishes several cell types and confirms the organ identity. Micro-CT resolves a discrepancy in the literature regarding the nervous system of crab larvae. The major changes occur in the metamorphosis to the megalopa stage, specifically the formation of the gastric mill, the shortening of the abdominal nerve cord, the curving of the abdomen beneath the cephalothorax, and the development of functional pereiopods, pleopods, and lamellate gills. The combination of micro-CT and histology provides better results than either one alone.Financial support was provided by the Spanish Ministry of Economy and Competitiveness through the INIA project (grant number RTA2011-00004-00-00) to G.G. and a pre-doctoral fellowship to D.C. (FPI-INIA)

Anatomical study of the female reproductive system and bacteriome of Diaphorina citri Kuwayama, (Insecta: Hemiptera, Liviidae) using micro-computed tomography

Huanglongbing (HLB) (citrus greening disease) is one of the most serious bacterial diseases of citrus. It is caused by (1) Candidatus Liberibacter africanus, transmitted by Trioza erytreae and (2) C.L. asiaticus and C.L. americanus, transmitted by Diaphorina citri. As part of a multidisciplinary project on D. citri (www.citrusgreening.org), we made a detailed study, using micro-computed tomography, of the female abdominal terminalia, reproductive system (ovaries, accessory glands, spermatheca, colleterial (= cement) gland, connecting ducts, and ovipositor) and bacteriome, which we present here. New terms and structures are introduced and described, particularly concerning the spermatheca, ovipositor and bacteriome. The quality of images and bacteriome reconstructions are comparable, or clearer, than those previously published using a synchrotron or fuorescence in situ hybridisation (FISH). This study: reviews knowledge of the female reproductive system and bacteriome organ in D. citri; represents the frst detailed morphological study of D. citri to use micro-CT; and extensively revises existing morphological information relevant to psylloids, hemipterans and insects in general. High quality images and supplementary videos represent a signifcant advance in knowledge of psylloid anatomy and are useful tools for future research and as educational aids.Kansas State University (KSU) S15192.01University of Granada, USDA-NIFA S15192.01 2014-70016-2302

Mechanisms, functions and ecology of colour vision in the honeybee.

notes: PMCID: PMC4035557types: Journal Article© The Author(s) 2014.This is an open access article that is freely available in ORE or from Springerlink.com. Please cite the published version available at: http://link.springer.com/article/10.1007%2Fs00359-014-0915-1Research in the honeybee has laid the foundations for our understanding of insect colour vision. The trichromatic colour vision of honeybees shares fundamental properties with primate and human colour perception, such as colour constancy, colour opponency, segregation of colour and brightness coding. Laborious efforts to reconstruct the colour vision pathway in the honeybee have provided detailed descriptions of neural connectivity and the properties of photoreceptors and interneurons in the optic lobes of the bee brain. The modelling of colour perception advanced with the establishment of colour discrimination models that were based on experimental data, the Colour-Opponent Coding and Receptor Noise-Limited models, which are important tools for the quantitative assessment of bee colour vision and colour-guided behaviours. Major insights into the visual ecology of bees have been gained combining behavioural experiments and quantitative modelling, and asking how bee vision has influenced the evolution of flower colours and patterns. Recently research has focussed on the discrimination and categorisation of coloured patterns, colourful scenes and various other groupings of coloured stimuli, highlighting the bees' behavioural flexibility. The identification of perceptual mechanisms remains of fundamental importance for the interpretation of their learning strategies and performance in diverse experimental tasks.Biotechnology and Biological Sciences Research Council (BBSRC