Impact of Imaging-Guided Localization on Performance of Tailored Axillary Surgery in Patients with Clinically Node-Positive Breast Cancer: Prospective Cohort Study Within TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

BACKGROUND: Tailored axillary surgery (TAS) is a novel surgical concept for clinical node-positive breast cancer. It consists of the removal of the sentinel lymph nodes (LNs), as well as palpably suspicious nodes. The TAS technique can be utilized in both the upfront and neoadjuvant chemotherapy (NACT) setting. This study assessed whether/how imaging-guided localization (IGL) influenced TAS. PATIENTS AND METHODS: This was a prospective observational cohort study preplanned in the randomized phase-III OPBC-03/TAXIS trial. IGL was performed at the surgeon's discretion for targeted removal of LNs during TAS. Immediate back-up axillary lymph node dissection (ALND) followed TAS according to TAXIS randomization. RESULTS: Five-hundred patients were included from 44 breast centers in six countries, 151 (30.2%) of whom underwent NACT. IGL was performed in 84.4% of all patients, with significant variation by country (77.6-100%, p < 0.001). No difference in the median number of removed (5 vs. 4, p = 0.3) and positive (2 vs. 2, p = 0.6) LNs by use of IGL was noted. The number of LNs removed during TAS with IGL remained stable over time (p = 0.8), but decreased significantly without IGL, from six (IQR 4-6) in 2019 to four (IQR 3-4) in 2022 (p = 0.015). An ALND was performed in 249 patients, removing another 12 (IQR 9-17) LNs, in which a median number of 1 (IQR 0-4) was positive. There was no significant difference in residual nodal disease after TAS with or without IGL (68.0% vs. 57.6%, p = 0.2). CONCLUSIONS: IGL did not significantly change either the performance of TAS or the volume of residual nodal tumor burden. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03513614.

Trends in use of neoadjuvant systemic therapy in patients with clinically node-positive breast cancer in Europe: prospective TAXIS study (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

PURPOSE: The aim of this study was to evaluate clinical practice heterogeneity in use of neoadjuvant systemic therapy (NST) for patients with clinically node-positive breast cancer in Europe. METHODS: The study was preplanned in the international multicenter phase-III OPBC-03/TAXIS trial (ClinicalTrials.gov Identifier: NCT03513614) to include the first 500 randomized patients with confirmed nodal disease at the time of surgery. The TAXIS study's pragmatic design allowed both the neoadjuvant and adjuvant setting according to the preferences of the local investigators who were encouraged to register eligible patients consecutively. RESULTS: A total of 500 patients were included at 44 breast centers in six European countries from August 2018 to June 2022, 165 (33%) of whom underwent NST. Median age was 57 years (interquartile range [IQR], 48-69). Most patients were postmenopausal (68.4%) with grade 2 and 3 hormonal receptor-positive and human epidermal growth factor receptor 2-negative breast cancer with a median tumor size of 28 mm (IQR 20-40). The use of NST varied significantly across the countries (p < 0.001). Austria (55.2%) and Switzerland (35.8%) had the highest percentage of patients undergoing NST and Hungary (18.2%) the lowest. The administration of NST increased significantly over the years (OR 1.42; p < 0.001) and more than doubled from 20 to 46.7% between 2018 and 2022. CONCLUSION: Substantial heterogeneity in the use of NST with HR+/HER2-breast cancer exists in Europe. While stringent guidelines are available for its use in triple-negative and HER2+ breast cancer, there is a need for the development of and adherence to well-defined recommendations for HR+/HER2-breast cancer.

A partially sex-reversed giant kelp sheds light into the mechanisms of sexual differentiation in a UV sexual system.

In UV sexual systems, sex is determined during the haploid phase of the life cycle and males have a V chromosome whereas females have a U chromosome. Previous work in the brown alga Ectocarpus revealed that the V chromosome has a dominant role in male sex determination and suggested that the female developmental programme may occur by 'default'. Here, we describe the identification of a genetically male giant kelp strain presenting phenotypic features typical of a female, despite lacking the U-specific region. The conversion to the female developmental programme is however incomplete, because gametes of this feminized male are unable to produce the sperm-attracting pheromone lamoxirene. We identify the transcriptomic patterns underlying the male and female specific developmental programmes, and show that the phenotypic feminization is associated with both feminization and de-masculinization of gene expression patterns. Importantly, the feminization phenotype was associated with dramatic downregulation of two V-specific genes including a candidate male-determining gene. Our results reveal the transcriptional changes associated with sexual differentiation in a UV system, and contribute to disentangling the role of sex-linked and autosomal gene expression in the initiation of sex-specific developmental programmes. Overall, the data presented here imply that the U-specific region is not required to initiate the female developmental programme, but is critical to produce fully functional eggs, arguing against the idea that female is the 'default' sex in this species.

Host and pathogen autophagy are central to the inducible local defences and systemic response of the giant kelp Macrocystis pyrifera against the oomycete pathogen Anisolpidium ectocarpii.

Kelps are key primary producers of cold and temperate marine coastal ecosystems and exhibit systemic defences against pathogens. Yet, the cellular mechanisms underpinning their immunity remain to be elucidated. We investigated the time course of infection of the kelp Macrocystis pyrifera by the oomycete Anisolpidium ectocarpii using TEM, in vivo autophagy markers and autophagy inhibitors. Over several infection cycles, A. ectocarpii undergoes sequential physiological shifts sensitive to autophagy inhibitors. Initially lipid-rich, pathogen thalli become increasingly lipid-depleted; they subsequently tend to become entirely abortive, irrespective of their lipid content. Moreover, infected algal cells mount local defences and can directly eliminate the pathogen by xenophagy. Finally, autophagy-dependent plastid recycling is induced in uninfected host cells. We demonstrate the existence of local, inducible autophagic processes both in the pathogen and infected host cells, which result in the restriction of pathogen propagation. We also show the existence of a systemic algal response mediated by autophagy. We propose a working model accounting for all our observations, whereby the outcome of the algal-pathogen interaction (i.e. completion or not of the pathogen life cycle) is dictated by the induction, and possibly the mutual hijacking, of the host and pathogen autophagy machineries.

The Pioneering and Unknown Stereotactic Approach of Roeder and Orthner from Göttingen. Part II: Long-Term Outcome and Postmortem Analysis of Bilateral Pallidotomy in the Pre-Levodopa Era.

Before the advent of levodopa, pallidotomy was initially the most effective treatment for Parkinson disease, but it was soon superseded by thalamotomy. It is widely unknown that, similar to Leksell, 2 neurologists from Göttingen, Orthner and Roeder, perpetuated pallidotomy against the mainstream of their time. Postmortem studies demonstrated that true posterior and ventral pallidoansotomy sparing the overwhelming mass of the pallidum was accomplished. This was due to a unique and individually tailored stereotactic technique even allowing bilateral staged pallidotomies. In 1962, the long-term effects (3-year follow-up on average) of the first 18 out of 36 patients with staged bilateral pallidotomies were reported in great detail. Meticulous descriptions of each case indicate long-term improvements in parkinsonian rigidity and associated pain, as well as posture, gait, and akinesia (e.g., improved repetitive movements and arm swinging). Alleviation of tremor was found to require larger lesions than needed for suppression of rigidity. No improvement in speech, drooling, or seborrhea was observed. By 1962, the team had operated 13 patients with postencephalitic oculogyric crises with remarkable results (mean follow-up: 5 years). They also described alleviation of nonparkinsonian hyperkinetic disorders (e.g., hemiballism and chorea) with pallidotomy. The reported rates for surgical mortality and other complications had been remarkably low, even if compared to those reported after the revival of pallidotomy by Laitinen in the post-levodopa era. This applies also to bilateral pallidotomy performed with a positive risk-benefit ratio that has remained unparalleled to date. The intricate history of pallidotomy for movement disorders is incomplete without an appreciation of the achievements of the Göttingen group.

Giant kelp vegetative propagation: Adventitious holdfast elements rejuvenate senescent individuals of the Macrocystis pyrifera "integrifolia" ecomorph.

Recent findings on holdfast development in the giant kelp highlighted its key importance for Macrocystis vegetative propagation. We report here for the first time the development of adventitious holdfasts from Macrocystis stipes. Swellings emerge spontaneously from different areas of the stipes, especially in senescent or creeping individuals. After being manually fastened to solid substrata, these swellings elongated into haptera, which became strongly attached after 1 month. Within 4 months, new thalli increased in size and vitality, and developed reproductive fronds. Our results suggest the usage of these structures for auxiliary attachment techniques. These could act as a backup, when primary holdfasts are weak, and thus improve the survival rate of the giant kelp in natural beds.

Nestin-expressing vascular wall cells drive development of pulmonary hypertension.

Nestin, a well-known marker of neuronal stem cells, was recently suggested to characterise stem cell-like progenitors in non-neuronal structures during development and tissue repair. Integrating novel morphological approaches (CLARITY), we investigate whether nestin expression defines the proliferating cell population that essentially drives vascular remodelling during development of pulmonary hypertension.The role of nestin was investigated in lungs of nestin-GFP (green fluorescent protein) mice, models of pulmonary hypertension (rat: monocrotaline, SU5416/hypoxia; mouse: hypoxia), samples from pulmonary hypertension patients and human pulmonary vascular smooth muscle cells (VSMCs).Nestin was solely found in lung vasculature and localised to proliferating VSMCs, but not bronchial smooth muscle cells. Nestin was shown to affect cell number and was significantly enhanced in lungs early during development of pulmonary hypertension, correlating well with increased VSMC proliferation, expression of phosphorylated (activated) platelet-derived growth factor receptor ß and downregulation of the smooth muscle cell differentiation marker calponin. At later time points when pulmonary hypertension became clinically evident, nestin expression and proliferation returned to control levels. Increase of nestin-positive VSMCs was also found in human pulmonary hypertension, both in vessel media and neointima.Nestin expression seems to be obligatory for VSMC proliferation, and specifies lung vascular wall cells that drive remodelling and (re-)generation. Our data promise novel diagnostic tools and therapeutic targets for pulmonary hypertension.

Nuclear DNA level and life cycle of kelps: Evidence for sex-specific polyteny in Macrocystis (Laminariales, Phaeophyceae).

Giant kelp, Macrocystis pyrifera (Linnaeus) C. Agardh, is the subject of intense breeding studies for marine biomass production and conservation of natural resources. In this context, six gametophyte pairs and a sporophyte offspring of Macrocystis from South America were analyzed by flow cytometry. Minimum relative DNA content per cell (1C) was found in five males. Unexpectedly, nuclei of all female gametophytes contained approximately double the DNA content (2C) of males; the male gametophyte from one locality also contained 2C, likely a spontaneous natural diploid variant. The results illustrate a sex-specific difference in nuclear DNA content among Macrocystis gametophytes, with the chromosomes of the females in a polytenic condition. This correlates with significantly larger cell sizes in female gametophytes compared to males and resource allocation in oogamous reproduction. The results provide key information for the interpretation of DNA measurements in kelp life cycle stages and prompt further research on the regulation of the cell cycle, metabolic activity, sex determination, and sporophyte development.

Adverse Effects of Plant Food Supplements and Plants Consumed as Food: Results from the Poisons Centres-Based PlantLIBRA Study.

Plant food supplements (PFS) are products of increasing popularity and wide-spread distribution. Nevertheless, information about their risks is limited. To fill this gap, a poisons centres-based study was performed as part of the EU project PlantLIBRA. Multicentre retrospective review of data from selected European and Brazilian poisons centres, involving human cases of adverse effects due to plants consumed as food or as ingredients of food supplements recorded between 2006 and 2010. Ten poisons centres provided a total of 75 cases. In 57 cases (76%) a PFS was involved; in 18 (24%) a plant was ingested as food. The 10 most frequently reported plants were Valeriana officinalis, Camellia sinensis, Paullinia cupana, Melissa officinalis, Passiflora incarnata, Mentha piperita, Glycyrrhiza glabra, Ilex paraguariensis, Panax ginseng, and Citrus aurantium. The most frequently observed clinical effects were neurotoxicity and gastro-intestinal symptoms. Most cases showed a benign clinical course; however, five cases were severe. PFS-related adverse effects seem to be relatively infrequent issues for poisons centres. Most cases showed mild symptoms. Nevertheless, the occurrence of some severe adverse effects and the increasing popularity of PFS require continuous active surveillance, and further research is warranted. Copyright © 2016 John Wiley & Sons, Ltd.

Comparative transcriptome analysis of Discosporangium mesarthrocarpum (Phaeophyceae), Schizocladia ischiensis (Schizocladiophyceae), and Phaeothamnion confervicola (Phaeothamniophyceae), with special reference to cell wall-related genes.

Within the stramenopile lineage, only brown algae (Phaeophyceae) have evolved complex multicellularity, although some other members of the lineage (e.g., Schizocladia in Schizocladiophyceae; Phaeothamnion in Phaeothamniophyceae) also develop simple multicellular thalli. The development of an adherent extracellular matrix (ECM) is considered to be one of the key steps in the evolution of multicellularity, because ECM is involved in adhesion of cells to each other and in cell-cell communication essential for developmental, reproductive, and sophisticated defense systems. Because there are no unicellular organisms within brown algae, we considered that comparison of other stramenopile taxa closely related to brown algae and having multicellular thalli could yield clues to elucidate the evolution of multicellularity in brown algae. In this study, we investigated transcriptomes involved in cell wall polysaccharide metabolism of three stramenopile species, Discosporangium mesarthrocarpum, which is suggested to be one of the most basal taxa within Phaeophyceae, S. ischiensis, and P. confervicola. We employed 454-FLX high-throughput pyrosequencing to generate expressed sequence tag (EST) databases for these species, and performed comparative analyses between these databases and the genome sequence of the brown alga Ectocarpus siliculosus. Results indicate that cell wall polysaccharide metabolism pathways of D. mesarthrocarpum are similar to E. siliculosus, whereas those of S. ischiensis and P. confervicola are significantly different from E. siliculosus, suggesting that the components of the cell wall in S. ischiensis and P. confervicola are likely to be different from those of E. siliculosus.

Intracellular eukaryotic pathogens in brown macroalgae in the Eastern Mediterranean, including LSU rRNA data for the oomycete Eurychasma dicksonii .

For the Mediterranean Sea, and indeed most of the world's oceans, the biodiversity and biogeography of eukaryotic pathogens infecting marine macroalgae remains poorly known, yet their ecological impact is probably significant. Based on 2 sampling campaigns on the Greek island of Lesvos in 2009 and 1 in northern Greece in 2012, this study provides first records of 3 intracellular eukaryotic pathogens infecting filamentous brown algae at these locations: Eurychasma dicksonii, Anisolpidium sphacellarum, and A. ectocarpii. Field and microscopic observations of the 3 pathogens are complemented by the first E. dicksonii large subunit ribosomal RNA (LSU rRNA) gene sequence analyses of isolates from Lesvos and other parts of the world. The latter highlights the monophyly of E. dicksonii worldwide and confirms the basal position of this pathogen within the oomycete lineage (Peronosporomycotina). The results of this study strongly support the notion that the geographic distribution of the relatively few eukaryotic seaweed pathogens is probably much larger than previously thought and that many of the world's marine bioregions remain seriously undersampled and understudied in this respect.

Ethanol is indispensable for virucidal hand antisepsis: memorandum from the alcohol-based hand rub (ABHR) Task Force, WHO Collaborating Centre on Patient Safety, and the Commission for Hospital Hygiene and Infection Prevention (KRINKO), Robert Koch Institute, Berlin, Germany.

BACKGROUND: The approval of ethanol by the Biocidal Products Regulation has been under evaluation since 2007. This follows concern over alcohol uptake from ethanol-based hand rubs (EBHR). If ethanol is classified as carcinogenic, mutagenic, or reprotoxic by the European Chemicals Agency (ECHA), then this would affect infection prevention and control practices. AIM: A review was performed to prove that ethanol is toxicological uncritical and indispensable for hand antisepsis because of its unique activity against non-enveloped viruses and thus the resulting lack of alternatives. Therefore, the following main points are analyzed: The effectiveness of ethanol in hand hygiene, the evidence of ethanol at blood/tissue levels through hand hygiene in healthcare, and the evidence of toxicity of different blood/tissue ethanol levels and the non-comparability with alcoholic consumption and industrial exposure. RESULTS: EBHR are essential for preventing infections caused by non-enveloped viruses, especially in healthcare, nursing homes, food industry and other areas. Propanols are effective against enveloped viruses as opposed to non-enveloped viruses but there are no other alternatives for virucidal hand antisepsis. Long-term ingestion of ethanol in the form of alcoholic beverages can cause tumours. However, lifetime exposure to ethanol from occupational exposure < 500 ppm does not significantly contribute to the cancer risk. Mutagenic effects were observed only at doses within the toxic range in animal studies. While reprotoxicity is linked with abuse of alcoholic beverages, there is no epidemiological evidence for this from EBHR use in healthcare facilities or from products containing ethanol in non-healthcare settings. CONCLUSION: The body of evidence shows EBHRs have strong efficacy in killing non-enveloped viruses, whereas 1-propanol and 2-propanol do not kill non-enveloped viruses, that pose significant risk of infection. Ethanol absorbed through the skin during hand hygiene is similar to consumption of beverages with hidden ethanol content (< 0.5% v/v), such as apple juice or kefir. There is no risk of carcinogenicity, mutagenicity or reprotoxicity from repeated use of EBHR. Hence, the WHO Task Force strongly recommend retaining ethanol as an essential constituent in hand rubs for healthcare.

Impact of medication adherence on the efficacy of Baroreflex activation therapy.

Therapy adherence significantly determines the success of antihypertensive therapy, especially in patients with resistant hypertension. Our study investigates the impact of drug adherence on the efficacy of Baroreflex-activation-therapy (BAT). In this retrospective analysis, the authors measured blood pressure (BP) and antihypertensive medication adherence (by gas chromatography-mass spectrometry [GC-MS] urine analysis) before and 6 months after BAT initiation. Adherence was defined as detection of ≥80% intake of prescribed medication at the time of follow-up. Response to BAT was defined as BP drop ≥5 mmHg in systolic 24 h-ambulatory BP (ABP) after 6 months. Overall patients (n = 38) median medication adherence was low, but rose from 60% (IQR 25%-100%) to 75% (IQR 38%-100%; p = .0194). After 6 months of BAT, mean systolic and diastolic office BP (-21 ± 25 mmHg and -9 ± 15 mmHg; p < .0001 and .0004) as well as 24 h-ABP dropped significantly (-9 ± 17 mmHg and -5 ± 12 mmHg; p = .0049 and .0280). After 6 months of BAT, 21 patients (60%) could be classified as responders. There was neither significant difference in mean office systolic (-21 ± 23 mmHg vs. -21 ± 28 mmHg; p = .9581) nor in 24 h-systolic ABP decrease (-11 ± 19 mmHg vs. -7 ± 15 mmHg; p = .4450) comparing adherent and non-adherent patients. Whereas Antihypertensive Therapeutic Index (ATI) was unchanged in non-responders, it significantly decreased in responders (from 50 ± 16 to 46 ± 16; p = .0477). These data are the first to show that BAT-initiation leads to a clear BP reduction independently of patients´ medication adherence. Response to BAT is associated with a significant lowering of ATI, which might contribute to an underestimation of BAT efficacy.

Cyclic GMP signaling in rat urinary bladder, prostate, and epididymis: tissue-specific changes with aging and in response to Leydig cell depletion.

Aging of the male reproductive system leads to changes in endocrine signaling and is frequently associated with the emergence of prostate hyperplasia and bladder dysfunctions. Recent reports highlight prostate and bladder as promising targets for therapeutic interventions with inhibitors of the cyclic GMP (cGMP)-degrading phosphodiesterase 5 (PDE5). However, the cGMP signaling system in these organs is as yet poorly characterized, and the possibility of age-related alterations has not been addressed. This study investigates key proteins of cGMP pathways in bladder, prostate, and epididymis of young (3 months) and old (23-24 months) Wistar rats. Local differences in the abundance of PDE5, soluble guanylyl cyclase (sGC) and particulate guanylyl cyclases (GC-A, GC-B), endothelial nitric oxide synthase, and cGMP-dependent protein kinase I (PRKG1 (cGKI)) revealed pronounced tissue-specific peculiarities. Although cGMP-generating enzymes were not affected by age in all organs, we recognized age-related decreases of PDE5 expression in bladder and a selective diminishment of membrane-associated PRKG1 in epididymis. In disagreement with published data, all cGMP pathway proteins including PDE5 are poorly expressed in prostate. However, prostatic PRKG1 expression increases with aging. Androgen withdrawal during temporary Leydig cell elimination induced a massive (>12-fold) upregulation of PRKG1 in prostate but not in other (penis and epididymis) androgen-dependent organs. These findings identify PRKG1 as a key androgen-sensitive signaling protein in prostate of possible importance for growth regulation. The elucidated effects may have significance for age-associated pathologies in the male lower-urinary tract.

Identification of a lectin causing the degeneration of neuronal processes using engineered embryonic stem cells.

Unlike the mechanisms involved in the death of neuronal cell bodies, those causing the elimination of processes are not well understood owing to the lack of suitable experimental systems. As the neurotrophin receptor p75(NTR) is known to restrict the growth of neuronal processes, we engineered mouse embryonic stem (ES) cells to express an Ngfr (p75(NTR)) cDNA under the control of the Mapt locus (the gene encoding tau), which begins to be active when ES cell-derived progenitors start elongating processes. This caused a progressive, synchronous degeneration of all processes, and a prospective proteomic analysis showed increased levels of the sugar-binding protein galectin-1 in the p75(NTR)-engineered cells. Function-blocking galectin-1 antibodies prevented the degeneration of processes, and recombinant galectin-1 caused the processes of wild-type neurons to degenerate first, followed by the cell bodies. In vivo, the application of a glutamate receptor agonist, a maneuver known to upregulate p75(NTR), led to an increase in the amount of galectin-1 and to the degeneration of neurons and their processes in a galectin-1-dependent fashion. Section of the sciatic nerve also rapidly upregulated levels of p75(NTR) and galectin-1 in terminal Schwann cells, and the elimination of nerve endings was delayed at the neuromuscular junction of mice lacking Lgals1 (the gene encoding galectin-1). These results indicate that galectin-1 actively participates in the elimination of neuronal processes after lesion, and that engineered ES cells are a useful tool for studying relevant aspects of neuronal degeneration that have been hitherto difficult to analyze.

Eligibility for Baroreflex Activation Therapy and medication adherence in patients with apparently resistant hypertension.

Uncontrolled hypertension is a main risk factor for cardiovascular morbidity. Baroreflex activation therapy (BAT) is an effective therapy option addressing true resistant hypertension. We evaluated patients' eligibility for BAT in a staged assessment as well as adherence to antihypertensive drug therapy. Therefore, we analyzed files of 345 patients, attending the hypertension clinic at University Medicine Göttingen. Additionally, gas chromatographic-mass spectrometric urine analyses of selected individuals were performed evaluating their adherence. Most common cause for a revoked BAT recommendation was blood pressure (BP) control by drug adjustment (54.2%). Second leading cause was presence of secondary hypertension (31.6%). Patients to whom BAT was recommended (59 (17.1%)) were significantly more often male (67.8% vs. 43.3%, P = .0063), had a higher body mass index (31.8 ± 5.8 vs. 30.0 ± 5.7 kg/m², P = .0436), a higher systolic office (168.7 ± 24.7 vs. 147.7 ± 24.1 mmHg, P < .0001), and 24h ambulatory BP (155.0 ± 14.6 vs. 144.4 ± 16.8 mmHg, P = .0031), took more antihypertensive drugs (5.8 ± 1.3 vs. 4.4 ± 1.4, P < .0001), and suffered more often from numerous concomitant diseases. Eventually, 27 (7.8%) received a BAT system. In the toxicological analysis of 75 patients, mean adherence was 75.1%. 16 patients (21.3%) showed non-adherence. Thus, only a small number of patients eventually received a BAT system, as treatable reasons for apparently resistant hypertension could be identified frequently. This study is-to our knowledge-the first report of a staged assessment of patients' suitability for BAT and underlines the need for a careful examination and indication. Non-adherence was proven to be a relevant issue concerning apparently resistant hypertension and therefore non-eligibility for interventional antihypertensive therapy.

The membrane receptors guanylyl cyclase-A and -B undergo distinctive changes in post-translational modification during brain development.

Temporal carbohydrate expression patterns at cell surfaces are thought to be of crucial regulatory significance during developmental processes. Hitherto, however, data on individual membrane proteins undergoing development-associated changes in glycosylation are sparsely. Here, we show that the two natriuretic peptide receptors, guanylyl cyclase-A (GC-A) and GC-B are subject to pronounced size alterations in the rat brain between postnatal day 1 and adult. Comparable size changes were not detectable for GC-A and GC-B in peripheral tissues and for three other membrane proteins (insulin receptor, insulin-like growth factor-II/mannose-6-phoshate receptor, neutral endopeptidase) in brain, indicating remarkable specificity. As revealed by treatments with carbohydrate-digesting enzymes, both GC-A and GC-B are hyperglycosylated at N-linked glycosylation sites in the developing brain. At postnatal day 1, the vast majority of GC-B (but not GC-A) molecules contain additionally an O-linked carbohydrate modification of about 1 kDa in mass and a further modification of similar size which is resistant to enzymatic removal. The glycoforms exhibited functional activity in membrane GC assays, indicating proper folding and signaling capability. These data link recently reported roles of natriuretic peptides during brain development for the first time with specific glycosylation states of their cyclic GMP-generating receptors.

Secondary zoospores in the algal endoparasite Maullinia ectocarpii (Plasmodiophoromycota).

The present paper deals with the ultrastructure of zoospores produced by the plasmodiophorid Maullinia ectocarpii, living in the marine algal host Ectocarpus siliculosus. The zoospores described here are very similar to secondary zoospores of Polymyxa graminis and Phagomyxa sp. (the latter an algal endoparasite, also). Our results indicate that M. ectocarpii produces two types of plasmodia, and suggest that is a species with a complete life cycle, as it is known for all the Plasmodiophormycota that have been studied. Sporogenic and sporangial plasmodia produce, respectively, primary zoospores with parallel flagella within thick walled resting sporangia, and secondary zoospores with opposite flagella within thin walled sporangia.

Ectocarpus: an evo-devo model for the brown algae.

Ectocarpus is a genus of filamentous, marine brown algae. Brown algae belong to the stramenopiles, a large supergroup of organisms that are only distantly related to animals, land plants and fungi. Brown algae are also one of only a small number of eukaryotic lineages that have evolved complex multicellularity. For many years, little information was available concerning the molecular mechanisms underlying multicellular development in the brown algae, but this situation has changed with the emergence of Ectocarpus as a model brown alga. Here we summarise some of the main questions that are being addressed and areas of study using Ectocarpus as a model organism and discuss how the genomic information, genetic tools and molecular approaches available for this organism are being employed to explore developmental questions in an evolutionary context.