Extending the clinical phenotype of SPTAN1: From DEE5 to migraine, epilepsy, and subependymal heterotopias without intellectual disability.

Mutations in SPTAN1 gene, encoding the nonerythrocyte αII-spectrin, are responsible for a severe developmental and epileptic encephalopathy (DEE5) and a wide spectrum of neurodevelopmental disorders, as epilepsy with or without intellectual disability (ID) or ID with cerebellar syndrome. A certain genotype-phenotype correlation has been proposed according to the type and location of the mutation. Herein, we report three novel cases with de novo SPTAN1 mutations, one of them associated to a mild phenotype not previously described. They range from (1) severe developmental encephalopathy with ataxia and a mild cerebellar atrophy, without epilepsy; (2) moderate intellectual disability, severe language delay, ataxia and tremor; (3) normal intelligence, chronic migraine, and generalized tonic-clonic seizures. Remarkably, all these patients showed brain MRI abnormalities, being of special interest the subependymal heterotopias detected in the latter patient. Thus we extend the SPTAN1-related phenotypic spectrum, both in its radiological and clinical involvement. Furthermore, after systematic analysis of all the patients so far reported, we noted an excess of male versus female patients (20:9, p = 0.04), more pronounced among the milder phenotypes. Consequently, some protection factor might be suspected among female carriers, which if confirmed should be considered when establishing the pathogenicity of milder genetic variants in this gene.

Health care contact prior to suicide attempts in older adults. A field study in Galicia, Spain.

INTRODUCTION: Older people have the highest suicide rates in the world. In turn, they have the lowest rates of suicide attempts. Many studies have found greater health contact, especially with general practitioner, prior to suicidal behaviour in this age group. Less information is availbale about prior contact with other health services. OBJECTIVE: The objective of the study is to know the characteristics of contact with all levels of health services, prior to a suicide attempt in people over 65 years of age in a defined population. MATERIAL AND METHODS: Along the period January 2015 to December 2017, all persons over 65 years of age admitted by suicide attempt to emergency room in the health area of Santiago de Compostela were interviewed. The interview included a psychiatric evaluation and the collrection of relevant clinical and sociodemographic variables, in particular, data on prior contact with health services. RESULTS: 80 suicide attempts were recorded, which represents an incidence of 35.3 / 100,000. The average age of our sample was 74.85 ± 7 years, the ratio between male: female was 2: 3. 61.3% had visited their general practitioner the month prior to the attempt, 72.5% had visited a health centre. On the other hand, 41.3% were not under the follow up of Mental Health services. CONCLUSIONS: The facts hat two out of three people over 65 years who commit suicide attempt in our area visit their general practitioner the previous month and 90% visit a health service along the previous three months, raise the question of wheter preventive measures of suicide could take place beyond the scope of Primary Care.

Snails prefer it sweet: A multifactorial test of the metal defence hypothesis.

Metal defence against insect herbivory in hyperaccumulator plants is well documented. However, there are contradictory results regarding protection against snails. According to the joint effects hypothesis, inorganic and organic defences cooperate in plant protection. To test this hypothesis, we explored the relationships between snail (Cantareus aspersus) feeding and multiple inorganic and organic leaf components in the Cd hyperaccumulator plant Noccaea praecox. Plants grouped by rosette size growing in nutrient solution supplemented or not with 50 µM Cd were offered to the snails. After 3 days of snail feeding, the plants and snails were analysed. In addition to Cd concentrations, we analysed leaves for nutritional factors (sugar and protein), defence-related compounds (glucosinolates, phenolics, tannins, salicylic acid and jasmonate) and essential mineral nutrients. Cadmium concentrations in the snails and in snail excrements were also analysed. Snails preferentially fed on plants grown without Cd. Medium-sized plants exposed to Cd were the least consumed. Snail excrements from this trial weighed less and had higher Cd concentrations than those from other treatments. Cadmium increased salicylate and jasmonate production. A positive relationship between jasmonate levels and the number of attacked leaves was found. Principal component analysis revealed that leaf sugar concentration was the main factor positively affecting snails' leaf consumption, while leaf Cd had a negative but weaker influence. In conclusion, leaf sugar concentration mainly governs snails' feeding preferences. High leaf Cd concentrations do not deter herbivores from attacking leaves, but they do reduce leaf consumption. Our results clearly support the joint effects hypothesis.

How Plants Handle Trivalent (+3) Elements.

Plant development and fitness largely depend on the adequate availability of mineral elements in the soil. Most essential nutrients are available and can be membrane transported either as mono or divalent cations or as mono- or divalent anions. Trivalent cations are highly toxic to membranes, and plants have evolved different mechanisms to handle +3 elements in a safe way. The essential functional role of a few metal ions, with the possibility to gain a trivalent state, mainly resides in the ion's redox activity; examples are iron (Fe) and manganese. Among the required nutrients, the only element with +3 as a unique oxidation state is the non-metal, boron. However, plants also can take up non-essential trivalent elements that occur in biologically relevant concentrations in soils. Examples are, among others, aluminum (Al), chromium (Cr), arsenic (As), and antimony (Sb). Plants have evolved different mechanisms to take up and tolerate these potentially toxic elements. This review considers recent studies describing the transporters, and specific and unspecific channels in different cell compartments and tissues, thereby providing a global vision of trivalent element homeostasis in plants.

Transport and Use of Bicarbonate in Plants: Current Knowledge and Challenges Ahead.

Bicarbonate plays a fundamental role in the cell pH status in all organisms. In autotrophs, HCO3− may further contribute to carbon concentration mechanisms (CCM). This is especially relevant in the CO2-poor habitats of cyanobacteria, aquatic microalgae, and macrophytes. Photosynthesis of terrestrial plants can also benefit from CCM as evidenced by the evolution of C4 and Crassulacean Acid Metabolism (CAM). The presence of HCO3− in all organisms leads to more questions regarding the mechanisms of uptake and membrane transport in these different biological systems. This review aims to provide an overview of the transport and metabolic processes related to HCO3− in microalgae, macroalgae, seagrasses, and terrestrial plants. HCO3− transport in cyanobacteria and human cells is much better documented and is included for comparison. We further comment on the metabolic roles of HCO3− in plants by focusing on the diversity and functions of carbonic anhydrases and PEP carboxylases as well as on the signaling role of CO2/HCO3− in stomatal guard cells. Plant responses to excess soil HCO3− is briefly addressed. In conclusion, there are still considerable gaps in our knowledge of HCO3− uptake and transport in plants that hamper the development of breeding strategies for both more efficient CCM and better HCO3− tolerance in crop plants.

Zinc hyperaccumulation substitutes for defense failures beyond salicylate and jasmonate signaling pathways of Alternaria brassicicola attack in Noccaea caerulescens.

The hypothesis of metal defense as a substitute for a defective biotic stress signaling system in metal hyperaccumulators was tested using the pathosystem Alternaria brassicicola-Noccaea caerulescens under low (2 µM), medium (12 µM) and high (102 µM) Zn supply. Regardless the Zn supply, N. caerulescens responded to fungal attack with the activation of both HMA4 coding for a Zn transporter, and biotic stress signaling pathways. Salicylate, jasmonate, abscisic acid and indoleacetic acid concentrations, as well as biotic stress marker genes (PDF1.2, CHIB, LOX2, PR1 and BGL2) were activated 24 h upon inoculation. Based on the activation of defense genes 24 h after the inoculation an incompatible fungal-plant interaction could be predicted. Nonetheless, in the longer term (7 days) no effective protection against A. brassicicola was achieved in plants exposed to low and medium Zn supply. After 1 week the biotic stress markers were even further increased in these plants, and this compatible interaction was apparently not caused by a failure in the signaling of the fungal attack, but due to the lack of specificity in the type of the activated defense mechanisms. Only plants receiving high Zn exhibited an incompatible fungal interaction. High Zn accumulation in these plants, possibly in cooperation with high glucosinolate concentrations, substituted for the ineffective defense system and the interaction turned into incompatible. In a threshold-type response, these joint effects efficiently hampered fungal spread and, consequently decreased the biotic stress signaling.

Membrane transporters mediating root signalling and adaptive responses to oxygen deprivation and soil flooding.

This review provides a comprehensive assessment of a previously unexplored topic: elucidating the role that plasma- and organelle-based membrane transporters play in plant-adaptive responses to flooding. We show that energy availability and metabolic shifts under hypoxia and anoxia are critical in regulating membrane-transport activity. We illustrate the high tissue and time dependence of this regulation, reveal the molecular identity of transporters involved and discuss the modes of their regulation. We show that both reduced oxygen availability and accumulation of transition metals in flooded roots result in a reduction in the cytosolic K(+) pool, ultimately determining the cell's fate and transition to programmed cell death (PCD). This process can be strongly affected by hypoxia-induced changes in the amino acid pool profile and, specifically, ϒ-amino butyric acid (GABA) accumulation. It is suggested that GABA plays an important regulatory role, allowing plants to proceed with H2 O2 signalling to activate a cascade of genes that mediate plant adaptation to flooding while at the same time, preventing the cell from entering a 'suicide program'. We conclude that progress in crop breeding for flooding tolerance can only be achieved by pyramiding the numerous physiological traits that confer efficient energy maintenance, cytosolic ion homeostasis, and reactive oxygen species (ROS) control and detoxification.

Signal cross talk in Arabidopsis exposed to cadmium, silicon, and Botrytis cinerea.

The role of defence gene expression triggered by Cd toxicity in the plant's response to Botrytis cinerea was investigated in Arabidopsis thaliana Columbia 0. Silicon (0 or 1.5 mM) and Cd (0, 1 or 10 µM) were supplied to 3-month-old solution-cultured plants. After 3 days, half of the plants of each treatment were inoculated with Botrytis. Supplied Cd concentrations were below the toxicity threshold and did not cause shoot growth inhibition or evidence of oxidative stress, while Botrytis infection severely decreased plant growth in all treatments. The expression of marker genes PR1 and BGL2 for the salicylic acid (SA) and the PDF1.2 for the jasmonic acid-ethylene (JA-ET) signalling pathways was enhanced in 10 µM Cd-treated non-infected plants. Twenty hours after inoculation, PDF1.2 expression showed a strong increase in all treatments, while enhanced PR1, BGL2, and CHIB expression was only found 7 days after infection. A great synergistic effect of Cd and Botrytis on PDF1.2 expression was found in 10 µM Cd-treated plants. Silicon decreased PR1, BGL2, and CHIB, while increasing PDF1.2 expression, which indicates its role as a modulator of the signalling pathways involved in the plant's response to fungal infection. Botrytis growth decreased in 10 µM Cd-treated plants, which could be due to the combined effects of Cd and Botrytis activating the SA and JA-ET-mediated signalling pathways. Taken together, our results provide support for the view that Cd concentrations close to the toxicity threshold induce defence signalling pathways which potentiate the plant's response against fungal infection.

Variant in CACNA1G as a Possible Genetic Modifier of Neonatal Epilepsy in an Infant with a De Novo SCN2A Mutation.

Mutations in SCN2A genes have been described in patients with epilepsy, finding a large phenotypic variability, from benign familial epilepsy to epileptic encephalopathy. To explain this variability, it was proposed the existence of dominant modifier alleles at one or more loci that contribute to determine the severity of the epilepsy phenotype. One example of modifier factor may be the CACNA1G gene, as proved in animal models. We present a 6-day-old male newborn with recurrent seizures in which a mutation in the SCN2A gene is observed, in addition to a variant in CACNA1G gene. Our patient suffered in the first days of life myoclonic seizures, with pathologic intercritical electroencephalogram pattern, requiring multiple drugs to achieve adequate control of them. During the next weeks, the patient progressively improved until complete remission at the second month of life, being possible to withdraw the antiepileptic treatment. We propose that the variant in CACNA1G gene could have acted as a modifier of the epilepsy syndrome produced by the mutation in SCN2A gene in our patient.

Vascular psychosis in the elderly: response to clozapine.

Cerebrovascular disease is a cause of late-onset psychosis in the elderly more frequent, accompanied or not, multi-infarct dementia. In many cases the patient has adequate preservation of cognitive functions or in any case, no criteria for dementia. In those that do, is in vascular dementia where psychotic symptoms are more frequent, occurring in over half cases, compared to one third of patients with Alzheimer disease. A case of a 92 year-old woman with no somatic background -except for a bilateral progressive hearing loss-, who debuted at this age with psychotic delusions structured injury and auditory hallucinations. The CT scan showed signs of cortico-subcortical atrophy. Neuropsychological examinations showed some cognitive impairment but no clinical criteria for dementia. Was refractory to first-line atypical antipsychotics, remitting symptoms after administration of low doses of clozapine. We discuss the clinical features of this psychosis, as well as its therapeutic approach.

Exploring the role of ecology and social organisation in agropastoral societies: A Bayesian network approach.

The present contribution focuses on investigating the interaction of people and environment in small-scale farming societies. Our study is centred on the particular way settlement location constraints economic strategy when technology is limited, and social division of work is not fully developed. Our intention is to investigate prehistoric socioeconomic organisation when farming began in the Old World along the Levant shores of Iberian Peninsula, the Neolithic phenomenon. We approach this subject extracting relevant information from a big set of ethnographic and ethnoarchaeological cases using Machine Learning methods. This paper explores the use of Bayesian networks as explanatory models of the independent variables-the environment- and dependent variables-social decisions-, and also as predictive models. The study highlights how subsistence strategies are modified by ecological and topographical variables of the settlement location and their relationship with social organisation. It also establishes the role of Bayesian networks as a suitable supervised Machine Learning methodology for investigating socio-ecological systems, introducing their use to build useful data-driven models to address relevant archaeological and anthropological questions.

Localization of aluminium in tea (Camellia sinensis) leaves using low energy X-ray fluorescence spectro-microscopy.

Information on localization of Al in tea leaf tissues is required in order to better understand Al tolerance mechanism in this Al-accumulating plant species. Here, we have used low-energy X-ray fluorescence spectro-microscopy (LEXRF) to study localization of Al and other low Z-elements, namely C, O, Mg, Si and P, in fully developed leaves of the tea plant [Camellia sinensis (L.) O. Kuntze]. Plants were grown from seeds for 3 months in a hydroponic solution, and then exposed to 200 microM AlCl(3) for 2 weeks. Epidermal-mesophyll and xylem phloem regions of 20 microm thick cryo-fixed freeze-dried tea-leaf cross-sections were raster scanned with 1.7 and 2.2 keV excitation energies to reach the Al-K and P-K absorption edges. Al was mainly localized in the cell walls of the leaf epidermal cells, while almost no Al signal was obtained from the leaf symplast. The results suggest that the retention of Al in epidermal leaf apoplast represent the main tolerance mechanism to Al in tea plants. In addition LEXRF proved to be a powerful tool for localization of Al in plant tissues, which can help in our understanding of the processes of Al uptake, transport and tolerance in plants.

Luxury zinc supply acts as antiaging agent and enhances reproductive fitness in Arabidopsis thaliana.

Developmental senescence in plants is an age dependent process affected by phytohormones, nutrient status, and environmental factors, while the antiaging effects of zinc are recognized in humans. This study explores the possible influence of a high, non-toxic Zn-supply (12 µM) on senescence and reproductive fitness in A. thaliana. Auxin-resistance mutant, axr1-12, and auxin overexpressing YUCCA6 mutant, yuc6-1D, and their corresponding background genotypes were grown until complete rosette senescence to quantify the fruit biomass and seed number. Gene expression of different antioxidant, auxin and senescence-associated markers were analyzed after the onset of senescence. All mutants showed delayed developmental senescence. Luxury Zn delayed senescence in wild type, but not in the mutant genotypes. Excluding axr1-12 mutants, which showed very low expression of the auxin gene marker INDOLE-3-ACETIC ACID INDUCIBLE 2 (IAA2), enhanced expression of the senescence markers SENESCENCE-ASSOCIATED GENE 12 (SAG12) and AUXIN RESPONSE FACTOR 2 (ARF2) coincided with decreased expression of IAA2. Delayed senescence and total number of seeds per plant were related to higher expression of the peroxisomal antioxidant enzymes Cu/Zn superoxide dismutase (SOD3) and catalase (CAT2). These results evidence that high Zn-induced delayed senescence and improved reproductive fitness in Arabidopsis are related to an auxin-independent mechanism that retains antioxidant activity.

Percutaneous closure of an atrial septal defect in a patient with Ebstein anomaly and right-to-left shunt.

Ebstein anomaly is a congenital disease frequently associated with atrial septal defects, which can generate a right-to-left shunt, leading to systemic desaturation and right ventricular failure. We describe the case of a 68-year-old man with central cyanosis due to Ebstein anomaly and a patent foramen ovale. An atrial septal occluder was initially implanted after having performed prolonged test occlusion of the interatrial communication. In this case, device embolization occurred due to high right pressure. Percutaneous closure of atrial septal defects in the presence of a right-to-left shunt can offer a significant clinical improvement in selected cases. In patients with Ebstein anomaly, the implantation of atrial septal defect closure devices may be desirable, due to the larger size of the waist, which may provide better stability in the event of an increase in right pressure.

Contrasting allocation of magnesium, calcium and manganese in leaves of tea (Camellia sinensis (L.) Kuntze) plants may explain their different extraction efficiency into tea.

During tea preparation mineral elements are extracted from the dried leaves of tea (Camellia sinensis (L.) Kuntze) plants into the solution. Micro-particle induced X-ray emission was employed to investigate the spatial distribution of magnesium (Mg), calcium (Ca) and manganese (Mn) in the young and old leaves of tea plants grown in the absence and presence of aluminium (Al) in the substrate. Results revealed that in tea leaves the largest concentrations of Mg occurred in the epidermis, of Ca in oxalate crystals and of Mn in epidermis and oxalate crystals; there was a leaf-age effect on tissue-specific concentrations of Mg, Ca and Mn with all tissues of old leaves containing larger concentrations of Mg, Ca and Mn than young leaves; supplementation of substrate with Al reduced concentrations of Mg, Ca and Mn in the old leaves, and a link between the distribution of Mg, Ca and Mn in the tea leaves with the extraction efficiencies of these elements into the tea was possible. We conclude that old leaves of tea plants cultivated under conditions of low Al availability will have the largest concentrations of Mg, Ca and Mn and may represent most acceptable ingredient for the preparation of tea.

Different effects of aluminum on the actin cytoskeleton and brefeldin A-sensitive vesicle recycling in root apex cells of two maize varieties differing in root elongation rate and aluminum tolerance.

A relationship between aluminum (Al) toxicity, endocytosis, endosomes and vesicle recycling in the root transition zone has recently been demonstrated. Here the importance of filamentous actin (F-actin)-based vesicle trafficking for Al tolerance has been investigating in maize varieties differing in their Al sensitivities. More Al was internalized into root tip cells of the Al-sensitive variety 16x36 than in the Al-tolerant variety Cateto. The actin cytoskeleton and vesicle trafficking were primary targets for Al toxicity in the root tips of the sensitive variety. Visualization of boron-cross-linked rhamnogalacturonan II (RGII)-containing brefeldin A (BFA) compartments revealed that Al inhibited the formation of these compartments, especially in variety 16x36. The time sequence of Al effects on pectin recycling matches the growth effects of Al in this sensitive variety. These results support the hypothesis that Al binding to pectin-rich cell walls can contribute to reversible inhibition of root elongation. Al-induced alterations on F-actin were most evident in the central part of the transition zone of Al-sensitive 16x36, where Al was localized inside the nucleoli. In relation to this observation, a role for symplastic Al in both irreversible growth inhibition and amelioration of BFA-induced inhibition of root elongation is discussed.

Boron-induced amelioration of aluminium toxicity in a monocot and a dicot species.

Previous research has reported inconsistent results from experiments on the influence of boron (B) on plant sensitivity to potentially toxic aluminium (Al) concentrations. Differences in B requirement and cell wall properties among species, especially between Poaceae and dicots, may account for this. This investigation reports amelioration by B of Al-induced inhibition of root elongation in Al-sensitive cucumber (Cucumis sativus), but not in Al-sensitive maize (Zea mays). Vital staining, however, also revealed a positive influence of B supply on Al tolerance in maize. In both species, adequate B supply decreased Al-induced damage of cell integrity. In cucumber, increasing B supply enhanced Al concentrations and haematoxylin staining in root tips. In maize, no differences for root Al among B treatments were observed. These results indicate that the positive effect of B on Al resistance was not due to less Al accumulation in root tips. Enhanced concentrations of reduced glutathione were found in roots of Al-stressed maize plants growing with adequate B. It is concluded that adequate B supply is essential for prevention of Al toxicity in both the dicot and the monocot species. In dicot cucumber, the B-induced amelioration of root elongation, despite higher Al accumulation in root tips, indicates B-induced change in either or both Al speciation and compartmentation in the tips. The protection by an adequate B supply of roots against Al-induced cell death suggests a role for B in the defence against oxidative stress. This is supported by the observation that Al induced enhanced levels of GSH in roots of maize plants growing with adequate B supply but not in those growing with either deficient or excess B concentrations.

A glance into aluminum toxicity and resistance in plants.

Aluminum toxicity is an important stress factor for plants in acidic environments. During the last decade considerable advances have been made in both techniques to assess the potentially toxic Al species in environmental samples, and knowledge about the mechanisms of Al toxicity and resistance in plants. After a short introduction on Al risk assessment, this review aims to give an up-to-date glance into current developments in the field of Al toxicity and resistance in plants, also providing sufficient background information for non-specialists in aluminum research. Special emphasis is paid to root growth and development as primary targets for Al toxicity. Mechanisms of exclusion of Al from sensitive root tips, as well as tolerance of high Al tissue levels are considered.

Can metals defend plants against biotic stress?

Farmers have used metal compounds in phytosanitary treatments for more than a century; however, it has recently been suggested that plants absorb high concentrations of metals from the substrate as a self-defense mechanism against pathogens and herbivores. This metal defense hypothesis is among the most attractive proposals for the 'reason to be' of metal hyperaccumulator species. On a molecular basis, metal defense against biotic stress seems to imply common and/or complementary pathways of signal perception, signal transduction and metabolism. This does not imply a broad band of co-resistance to different stress types but reflects a continuous cross talk during the coevolution of plants, pathogens and herbivores competing in an environment where efficient metal ion acquisition and ion homeostasis are essential for survival.