Dynamics of intracellular mannan and cell wall folding in the drought responses of succulent <i>Aloe</i> species

Plants have evolved a multitude of adaptations to survive extreme conditions. Succulent plants have the capacity to tolerate periodically dry environments, due to their ability to retain water in a specialized tissue, termed hydrenchyma. Cell wall polysaccharides are important components of water storage in hydrenchyma cells. However, the role of the cell wall and its polysaccharide composition in relation to drought resistance of succulent plants are unknown. We investigate the drought response of leaf-succulent Aloe (Asphodelaceae) species using a combination of histological microscopy, quantification of water content, and comprehensive microarray polymer profiling. We observed a previously unreported mode of polysaccharide and cell wall structural dynamics triggered by water shortage. Microscopical analysis of the hydrenchyma cell walls revealed highly regular folding patterns indicative of predetermined cell wall mechanics in the remobilization of stored water and the possible role of homogalacturonan in this process. The in situ distribution of mannans in distinct intracellular compartments during drought, for storage, and apparent upregulation of pectins, imparting flexibility to the cell wall, facilitate elaborate cell wall folding during drought stress. We conclude that cell wall polysaccharide composition plays an important role in water storage and drought response in Aloe

Impact‐based forecasting for pluvial floods

Pluvial floods in urban areas are caused by local, fast storm events with very high rainfall rates, which lead to inundation of streets and buildings before the storm water reaches a watercourse. An increase in frequency and intensity of heavy rainfall events and an ongoing urbanization may further increase the risk of pluvial flooding in many urban areas. Currently, warnings for pluvial floods are mostly limited to information on rainfall intensities and durations over larger areas, which is often not detailed enough to effectively protect people and goods. We present a proof-of-concept for an impact-based forecasting system for pluvial floods. Using a model chain consisting of a rainfall forecast, an inundation, a contaminant transport and a damage model, we are able to provide predictions for the expected rainfall, the inundated areas, spreading of potential contamination and the expected damage to residential buildings. We use a neural network-based inundation model, which significantly reduces the computation time of the model chain. To demonstrate the feasibility, we perform a hindcast of a recent pluvial flood event in an urban area in Germany. The required spatio-temporal accuracy of rainfall forecasts is still a major challenge, but our results show that reliable impact-based warnings can be forecasts are available up to 5 min before the peak of an extreme rainfall event. Based on our results, we discuss how the outputs of the impact-based forecast could be used to disseminate impact-based early warnings

The crystal structure of human Rogdi provides insight into the causes of Kohlschutter-Tonz Syndrome

Kohlschutter-T&amp;ouml;nz syndrome (KTS) is a rare autosomal-recessive disorder of childhood onset characterized by global developmental delay, spasticity, epilepsy, and amelogenesis imperfecta. Rogdi, an essential protein, is highly conserved across metazoans, and mutations in Rogdi are linked to KTS. However, how certain mutations in Rogdi abolish its physiological functions and cause KTS is not known. In this study, we determined the crystal structure of human Rogdi protein at atomic resolution. Rogdi forms a novel elongated curved structure comprising the ?? domain, a leucine-zipper-like four-helix bundle, and a characteristic ??-sheet domain. Within the ?? domain, the N-terminal H1 helix (residues 19-45) pairs with the C-terminal H6 helix (residues 252-287) in an antiparallel manner, indicating that the integrity of the four-helix bundle requires both N- and C-terminal residues. The crystal structure, in conjunction with biochemical data, indicates that the ?? domain might undergo a conformational change and provide a structural platform for protein-protein interactions. Disruption of the four-helix bundle by mutation results in significant destabilization of the structure. This study provides structural insights into how certain mutations in Rogdi affect its structure and cause KTS, which has important implications for the development of pharmaceutical agents against this debilitating neurological disease

Paediatric autoimmune encephalopathies:Clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens

Objective: To report the clinical and investigative features of children with a clinical diagnosis of probable autoimmune encephalopathy, both with and without antibodies to central nervous system antigens. Method: Patients with encephalopathy plus one or more of neuropsychiatric symptoms, seizures, movement disorder or cognitive dysfunction, were identified from 111 paediatric serum samples referred from five tertiary paediatric neurology centres to Oxford for antibody testing in 2007-2010. A blinded clinical review panel identified 48 patients with a diagnosis of probable autoimmune encephalitis whose features are described. All samples were tested/retested for antibodies to N-methyl-D-aspartate receptor (NMDAR), VGKC-complex, LGI1, CASPR2 and contactin-2, GlyR, D1R, D2R, AMPAR, GABA(B)R and glutamic acid decarboxylase. Results Seizures (83%), behavioural change (63%), confusion (50%), movement disorder (38%) and hallucinations (25%) were common. 52% required intensive care support for seizure control or profound encephalopathy. An acute infective organism (15%) or abnormal cerebrospinal fluid (32%), EEG (70%) or MRI (37%) abnormalities were found. One 14-year-old girl had an ovarian teratoma. Serum antibodies were detected in 21/48 (44%) patients: NMDAR 13/48 (27%), VGKC-complex 7/48(15%) and GlyR 1/48(2%). Antibody negative patients shared similar clinical features to those who had specific antibodies detected. 18/34 patients (52%) who received immunotherapy made a complete recovery compared to 4/14 (28%) who were not treated; reductions in modified Rankin Scale for children scores were more common following immunotherapies. Antibody status did not appear to in fluence the treatment effect. Conclusions: Our study outlines the common clinical and paraclinical features of children and adolescents with probable autoimmune encephalopathies. These patients, irrespective of positivity for the known antibody targets, appeared to benefit from immunotherapies and further antibody targets may be defined in the future

Evaluation of presumably disease causing SCN1A variants in a cohort of common epilepsy syndromes

Objective: The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. Methods: We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. Results and Interpretation: We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%). Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP-001159435.1) are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 7 10-4; OR = 0.32, fishers exact test), previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions

Antibody-associated epilepsies: Clinical features, evidence for immunotherapies and future research questions.

PURPOSE: The growing recognition of epilepsies and encephalopathies associated with autoantibodies against surface neuronal proteins (LGI1, NMDAR, CASPR2, GABABR, and AMPAR) means that epileptologists are increasingly asking questions about mechanisms of antibody-mediated epileptogenesis, and about the use of immunotherapies. This review summarizes clinical and paraclinical observations related to autoimmune epilepsies, examines the current evidence for the effectiveness of immunotherapy, and makes epilepsy-specific recommendations for future research. METHOD: Systematic literature search with summary and review of the identified publications. Studies describing the clinical characteristics of autoantibody-associated epilepsies and treatments are detailed in tables. RESULTS: Literature describing the clinical manifestations and treatment of autoimmune epilepsies associated with neuronal cell-surface autoantibodies (NSAbs) is largely limited to retrospective case series. We systematically summarize the features of particular interest to epileptologists dividing patients into those with acute or subacute encephalopathies associated with epilepsy, and those with chronic epilepsy without encephalopathy. Available observational studies suggest that immunotherapies are effective in some clinical circumstances but outcome data collection methods require greater standardization. CONCLUSIONS: The clinical experience captured suggests that clusters of clinical features associate well with specific NSAbs. Intensive and early immunotherapy is indicated when patients present with autoantibody-associated encephalopathies. It remains unclear how patients with chronic epilepsy and the same autoantibodies should be assessed and treated. Tables in this paper provide a comprehensive resource for systematic descriptions of both clinical features and treatments, and highlight limitations of current studies

Evaluation of presumably disease causing SCN1A variants in a cohort of common epilepsy syndromes

Objective: The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. Methods: We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. Results and Interpretation: We identified 8 known missense mutations, previously reported as path

APETALA2 control of barley internode elongation

Many plants dramatically elongate their stems during flowering, yet how this response is coordinated with the reproductive phase is unclear. We demonstrate that microRNA (miRNA) control of APETALA2 (AP2) is required for rapid, complete elongation of stem internodes in barley, especially of the final 'peduncle' internode directly underneath the inflorescence. Disrupted miR172 targeting of AP2 in the Zeo1.b barley mutant caused lower mitotic activity, delayed growth dynamics and premature lignification in the peduncle leading to fewer and shorter cells. Stage- and tissue-specific comparative transcriptomics between Zeo1.b and its parent cultivar showed reduced expression of proliferation-associated genes, ectopic expression of maturation-related genes and persistent, elevated expression of genes associated with jasmonate and stress responses. We further show that applying methyl jasmonate (MeJA) phenocopied the stem elongation of Zeo1.b, and that Zeo1.b itself was hypersensitive to inhibition by MeJA but less responsive to promotion by gibberellin. Taken together, we propose that miR172-mediated restriction of AP2 may modulate the jasmonate pathway to facilitate gibberellin-promoted stem growth during flowering

Plant cell culture technology in the cosmetics and food industries : current state and future trends

The production of drugs, cosmetics, and food which are derived from plant cell and tissue cultures has a long tradition. The emerging trend of manufacturing cosmetics and food products in a natural and sustainable manner has brought a new wave in plant cell culture technology over the past 10 years. More than 50 products based on extracts from plant cell cultures have made their way into the cosmetics industry during this time, whereby the majority is produced with plant cell suspension cultures. In addition, the first plant cell culture-based food supplement ingredients, such as Echigena Plus and Teoside 10, are now produced at production scale. In this mini review, we discuss the reasons for and the characteristics as well as the challenges of plant cell culture-based productions for the cosmetics and food industries. It focuses on the current state of the art in this field. In addition, two examples of the latest developments in plant cell culture-based food production are presented, that is, superfood which boosts health and food that can be produced in the lab or at home

16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65 046 European population controls (5/393 cases versus 32/65 046 controls; Fisher's exact test P = 2.83 × 10−6, odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10−4). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical R