Ion channel genes and human neurological disease: Recent progress, prospects, and challenges

What do epilepsy, migraine headache, deafness, episodic ataxia, periodic paralysis, malignant hyperthermia, and generalized myotonia have in common? These human neurological disorders can be caused by mutations in genes for ion channels. Many of the channel diseases are “paroxysmal disorders” whose principal symptoms occur intermittently in individuals who otherwise may be healthy and active. Some of the ion channels that cause human neurological disease are old acquaintances previously cloned and extensively studied by channel specialists. In other cases, however, disease-gene hunts have led the way to the identification of new channel genes. Progress in the study of ion channels has made it possible to analyze the effects of human neurological disease-causing channel mutations at the level of the single channel, the subcellular domain, the neuronal network, and the behaving organism.

Oceanic minerals: Their origin, nature of their environment, and significance

The chemical and isotopic compositions of oceanic biogenic and authigenic minerals contain invaluable information on the evolution of seawater, hence on the history of interaction between tectonics, climate, ocean circulation, and the evolution of life. Important advances and greater understanding of (a) key minor and trace element cycles with various residence times, (b) isotopic sources and sinks and fractionation behaviors, and (c) potential diagenetic problems, as well as developments in high-precision instrumentation, recently have been achieved. These advances provided new compelling evidence that neither gradualism nor uniformitarianism can explain many of the new important discoveries obtained from the chemistry and isotopic compositions of oceanic minerals. Presently, the best-developed geochemical proxies in biogenic carbonates are 18O/16O and Sr/Ca ratios (possibly Mg/Ca) for temperature; 87Sr/86Sr for input sources, Cd/Ca and Ba/Ca ratios for phosphate and alkalinity concentrations, respectively, thus also for ocean circulation; 13C/12C for ocean productivity; B isotopes for seawater pH;, U, Th isotopes, and 14C for dating; and Sr and Mn concentrations for diagenesis. The oceanic authigenic minerals most widely used for chemical paleoceanography are barite, evaporite sulfates, and hydrogenous ferromanganese nodules. Marine barite is an effective alternative monitor of seawater 87Sr/86Sr, especially where carbonates are diagenetically altered or absent. It also provides a high-resolution record of seawater sulfate S isotopes, (evaporite sulfates only carry an episodic record), with new insights on factors affecting the S and C cycles and atmospheric oxygen. High-resolution studies of Sr, Nd, and Pb isotopes of well-dated ferromanganese nodules contain invaluable records on climate driven changes in oceanic circulation.

Brain activity evidence for recognition without recollection after early hippocampal damage

Amnesic patients with early and seemingly isolated hippocampal injury show relatively normal recognition memory scores. The cognitive profile of these patients raises the possibility that this recognition performance is maintained mainly by stimulus familiarity in the absence of recollection of contextual information. Here we report electrophysiological data on the status of recognition memory in one of the patients, Jon. Jon's recognition of studied words lacks the event-related potential (ERP) index of recollection, viz., an increase in the late positive component (500–700 ms), under conditions that elicit it reliably in normal subjects. On the other hand, a decrease of the ERP amplitude between 300 and 500 ms, also reliably found in normal subjects, is well preserved. This so-called N400 effect has been linked to stimulus familiarity in previous ERP studies of recognition memory. In Jon, this link is supported by the finding that his recognized and unrecognized studied words evoked topographically distinct ERP effects in the N400 time window. These data suggest that recollection is more dependent on the hippocampal formation than is familiarity, consistent with the view that the hippocampal formation plays a special role in episodic memory, for which recollection is so critical.

General and specific brain regions involved in encoding and retrieval of events: what, where, and when.

Remembering an event involves not only what happened, but also where and when it occurred. We measured regional cerebral blood flow by positron emission tomography during initial encoding and subsequent retrieval of item, location, and time information. Multivariate image analysis showed that left frontal brain regions were always activated during encoding, and right superior frontal regions were always activated at retrieval. Pairwise image subtraction analyses revealed information-specific activations at (i) encoding, item information in left hippocampal, location information in right parietal, and time information in left fusiform regions; and (ii) retrieval, item in right inferior frontal and temporal, location in left frontal, and time in anterior cingulate cortices. These results point to the existence of general encoding and retrieval networks of episodic memory whose operations are augmented by unique brain areas recruited for processing specific aspects of remembered events.

Short-term and long-term verbal memory: a positron emission tomography study.

Short-term and long-term retention of experimentally presented words were compared in a sample of 33 healthy normal volunteers by the [15O]H2O method with positron emission tomography (PET). The design included three conditions. For the long-term condition, subjects thoroughly studied 18 words 1 week before the PET study. For the short-term condition, subjects were shown another set of 18 words 60 sec before imaging, with instructions to remember them. For the baseline condition, subtracted from the two memory conditions, subjects read a third set of words that they had not previously seen in the experiment. Similar regions were activated in both short-term and long-term conditions: large right frontal areas, biparietal areas, and the left cerebellum. In addition, the short-term condition also activated a relatively large region in the left prefrontal region. These complex distributed circuits appear to represent the neural substrates for aspects of memory such as encoding, retrieval, and storage. They indicate that circuitry involved in episodic memory has much larger cortical and cerebellar components than has been emphasized in earlier lesion studies.

Distinct neural correlates of visual long-term memory for spatial location and object identity: a positron emission tomography study in humans.

The purpose of the present study was to investigate by using positron emission tomography (PET) whether the cortical pathways that are involved in visual perception of spatial location and object identity are also differentially implicated in retrieval of these types of information from episodic long-term memory. Subjects studied a set of displays consisting of three unique representational line drawings arranged in different spatial configurations. Later, while undergoing PET scanning, subjects' memory for spatial location and identity of the objects in the displays was tested and compared to a perceptual baseline task involving the same displays. In comparison to the baseline task, each of the memory tasks activated both the dorsal and the ventral pathways in the right hemisphere but not to an equal extent. There was also activation of the right prefrontal cortex. When PET scans of the memory tasks were compared to each other, areas of activation were very circumscribed and restricted to the right hemisphere: For retrieval of object identity, the area was in the inferior temporal cortex in the region of the fusiform gyrus (area 37), whereas for retrieval of spatial location, it was in the inferior parietal lobule in the region of the supramarginal gyrus (area 40). Thus, our study shows that distinct neural pathways are activated during retrieval of information about spatial location and object identity from long-term memory.

Teste anti-HIV entre homens que fazem sexo com homens em São Paulo: busca espontânea rotineira e episódica

Introdução No contexto da valorização crescente do teste anti-HIV como estratégia de prevenção programática, a promoção do teste anti-HIV como estratégia de prevenção entre homens que fazem sexo com homens (HSH) é fundamental. Objetivo - Analisar os fatores associados tanto ao uso rotineiro como episódico do teste anti-HIV. Métodos - Os participantes foram 946 HSH entrevistados pelo Projeto SampaCentro em locais de sociabilidade HSH da região central de São Paulo entre novembro de 2011 e janeiro de 2012, nunca testados ou que procuraram o teste espontaneamente. A metodologia de amostragem foi a time-space-sampling e foram utilizados protocolos do Stata 12.0 para análise de amostras complexas. Os homens que se testaram por rotina ou episodicamente foram comparados aos nunca testados. As variáveis analisadas nos dois modelos de regressão de Poisson foram divididas em três níveis: características sociodemográficas (primeiro nível); socialização na comunidade gay e exposição da orientação sexual, discriminação e opiniões e atitudes em relação ao HIV/Aids e ao teste (segundo nível); percepção de risco, estratégias de prevenção e práticas e parcerias sexuais (terceiro nível). Resultados Os homens que se testaram rotineiramente eram mais velhos e moradores no Centro de SP. Além disso, tinham exposto a orientação sexual para profissional de saúde, sido discriminados em serviços de saúde mas não por amigos e/ou vizinhos (em razão da sexualidade) e não mencionaram medo do resultado do teste como motivo para HSH não se testarem. Também tinham maior probabilidade de conhecer pessoa soropositiva e de ter parcerias estáveis sem sexo anal desprotegido nas casuais (comparado a ter apenas parcerias casuais protegidas). Os homens que se testaram episodicamente eram mais velhos, residentes do Centro de SP, não moravam com parentes, expuseram sua orientação sexual para profissional de saúde, não reportaram medo do resultado do teste como barreira, conheciam pessoa soropositiva e mencionaram parceria estável sem sexo desprotegido com parceiro casual ou então sexo desprotegido em parcerias casuais (comparado a ter apenas parcerias casuais protegidas). Conclusões Os mais jovens, os que moram fora do centro de São Paulo, e os que expões menos sua orientação sexual são os segmentos que menos se testam rotineira ou episodicamente. Assim, dependem de ações para que seu direito seja protegido e assegurado. A estigmatização e a discriminação da homossexualidade deve ser combatida para que não impeça o acesso ao teste e a outros serviços de saúde. Disseminar informações e socializar os mais jovens para o diálogo sobre as estratégias de prevenção biomédicas e estratégias comunitárias de prevenção é necessário. Para ampliar o acesso e qualidade da testagem como recurso fundamental de programas de prevenção permanece o desafio de sustentar o debate sobre sexualidade e prevenção a cada geração, assim como nos programas de formação de educadores e de profissionais de saúde de todas as áreas.

Evolução do veneno em cnidários baseada em dados de genomas e proteomas

A evolução do veneno, uma das misturas mais complexas da natureza, tem sustentado o sucesso da diversificação de inúmeras linhagens de animais. Serpentes deslizantes ou medusas flutuantes utilizam o veneno, um coquetel de peptídeos farmacologicamente ativos, sais e moléculas orgânicas. Esses animais surpreendentes têm provocado grande fascínio ao longo da história humana. Nesta dissertação propomos um estudo da evolução dos venenos no filo Cnidaria, englobando dados proteômicos e genômicos. Este projeto teve como objetivos: (1) caracterizar e elucidar a evolução da composição do veneno em Cnidaria por meio da comparação de listas de proteínas; (2) testar a hipótese de que a variação na família de toxinas específica de cnidários tem sido o resultado de um regime de seleção positiva; e (3) determinar a extensão em que a duplicação de genes pode ser considerada como a principal razão para a diversificação de toxinas em Cnidaria. O capítulo \"Comparative proteomics reveals common components of a powerful arsenal in the earliest animal venomous lineage, the cnidarians\" propõe o estudo comparado mais completo sobre a composição do veneno de cnidários e uma hipótese sobre a montagem evolutiva do complexo arsenal bioquímico de cnidários e do veneno ancestral desse grupo basal. Vinte e oito famílias de proteínas foram identificadas. Destas, 13 famílias foram registradas pela primeira vez no proteoma de Cnidaria. Pelo menos 15 famílias de toxinas foram recrutadas no proteoma de veneno de cnidários antes da diversificação dos grupos Anthozoa e Medusozoa. Nos capítulos \"Evidence of episodic positive selection in the evolution of jellyfish toxins of the cnidarian venom\" e \"Gene duplications are extensive and contribute significantly to the toxic proteome of nematocysts isolated from Acropora digitifera (Cnidaria: Anthozoa: Scleractinia)\", nossas análises demonstram que as famílias de toxinas nos cnidários se diversificam amplamente mediante a duplicação de genes. Além disso, em contraste com as famílias de toxinas do veneno na maioria das linhagens animais; nós identificamos um padrão diferente na família de toxinas específica de cnidários, em que há uma seleção purificadora por longos períodos seguindo longos tempos de diversificação ou vice-versa

Risk for engagement in nonsuicidal self-injury in children and adolescents

Although NSSI engagement is a growing public health concern, little research has documented the developmental precursors to NSSI in longitudinal studies using youth samples. This study aimed to expand upon previous research on groups of NSSI engagement in a population-based sample of youth using multi-wave data. Moreover, this study examined whether chronic peer and romantic stress, the serotonin transporter gene (5-HTTLPR), parenting behaviors, and negative attributional style predicted the NSSI group membership as well as the role of sex and grade. Participants were 549 youth in beginning in the 3rd, 6th, and 9th grades at the baseline assessment. NSSI was assessed across 7 waves of data. Chronic peer and romantic stress, 5-HTTLPR, parenting behaviors, and negative attributional style were assessed at baseline. Growth mixture models, conducted to test the latent trajectory of NSSI groups did not converge. Three NSSI groups were manually created according to classifications that were determined a priori. NSSI groups included: no NSSI (85.1%), episodic NSSI (8.5%), and repeated NSSI (6.4%). Chronic peer and romantic stress, sex, and grade differentiated the no NSSI vs. repeated NSSI groups and the episodic NSSI vs. repeated NSSI groups. Specifically, higher levels of stress, being female, and being in higher grades related to repeated NSSI. 5-HTTLPR differentiated the no NSSI vs. repeated NSSI groups, such that carrying the short allele of 5-HTTLPR related to repeated NSSI. Exploratory analyses revealed that the relationship between attributional style and NSSI group was moderated by grade. This study suggests chronic interpersonal peer and romantic stress is an important factor placing youth at greater risk for repeatedly engaging in NSSI.

Radar interferometry techniques for the study of ground subsidence phenomena: a review of practical issues through cases in Spain

Subsidence related to multiple natural and human-induced processes affects an increasing number of areas worldwide. Although this phenomenon may involve surface deformation with 3D displacement components, negative vertical movement, either progressive or episodic, tends to dominate. Over the last decades, differential SAR interferometry (DInSAR) has become a very useful remote sensing tool for accurately measuring the spatial and temporal evolution of surface displacements over broad areas. This work discusses the main advantages and limitations of addressing active subsidence phenomena by means of DInSAR techniques from an end-user point of view. Special attention is paid to the spatial and temporal resolution, the precision of the measurements, and the usefulness of the data. The presented analysis is focused on DInSAR results exploitation of various ground subsidence phenomena (groundwater withdrawal, soil compaction, mining subsidence, evaporite dissolution subsidence, and volcanic deformation) with different displacement patterns in a selection of subsidence areas in Spain. Finally, a cost comparative study is performed for the different techniques applied.

Evaluating Taphonomic Bias in a Storm-Disturbed Carbonate Platform: Effects of Compositional and Environmental Factors in Lower Jurassic Brachiopod Accumulations (Eastern Subbetic Basin, Spain)

In order to evaluate taxonomic and environmental control on the preservation pattern of brachiopod accumulations, sedimentologic and taphonomic data have been integrated with those inferred from the structure of brachiopod accumulations from the easternmost Lower Jurassic Subbetic deposits in Spain. Two brachiopod communities (Praesphaeroidothyris and Securina communities) were distinguished showing a mainly free-lying way of life in soft-bottom habitats. Three taphofacies are discriminated based on proportion of disarticulation, fragmentation, packing, and shell filling. Taphofacies 1 is represented by thinly fragmented, dispersed brachiopod shells in wackestone beds. Taphofacies 2 is spatially restricted to small lenses where shells are poorly fragmented, rarely disarticulated, usually void filled, and highly packed. Taphofacies 3 is represented by mud or cement filled, loosely packed, articulated brachiopods forming large pocket-like structures. Temporal and spatial averaging were minimally involved in taphofacies 2 and 3. It is interpreted that patchy preservation implies preservation of primary original patchiness of brachiopod communities on the seafloor. The origin of shell-rich taphofacies (2 and 3) is related to rapid burial due to episodic storm activity, while shell-poor taphofacies 1 records background conditions. The nature and comparative diversity of these taphofacies underscores the importance of rapid burial for shell beds preservation. Differences in preservation between taphofacies 2 and 3 are mainly related to environmental criteria, most importantly storm energy and water depth. In contrast, the taxonomic-specific pattern of the communities is a subordinate element of control, controlling only minor within-taphofacies differences in preservation.

Structural features in ODP Holes 128-794D and 128-799B

Numerous structural features occur in the Leg 128 cores from the Japan Sea. They include (1) gravity-induced structures such as slump folds, (2) dewatering structures comprising several sets of veins, and (3) larger faults and veins developed in the volcanic basement of the Yamato Basin as well as in the sedimentary rocks of the Oki Ridge and Kita-Yamato Trough. Gravity-induced structures, mainly slumps and associated faults, suggest the existence of paleoslopes and the dominance of gravitational tectonics during the early and middle Miocene, at the Pliocene/Pleistocene boundary, and during the Quaternary. Several types of mud-filled veins having various shapes were observed. These are especially abundant in the middle Miocene siliceous claystones and porcellanites from the Kita-Yamato Trough. They have been interpreted as dewatering conduits that formed preferentially in highly porous, water-saturated diatomaceous muds on a slope, because of episodic loss of sediment strength, collapse of the sediment framework, and consequent fluid migration. The central part of the vein serves once as a fluid conduit, whereas the transition between conduit-controlled and intergranular flow occurs at the branching extremities, with concentration of fines. The likely trigger responsible for the strength loss is seismic activity. Development of these veins, spatially and chronologically linked to small normal microfaults, implies an extensional regime having layer-parallel extension and a local bedding-parallel shear couple, probably the result of gravitational gliding. The brittle fractures found in Yamato Basin basement Hole 794D cores comprise joints, faults, and veins filled with chlorite-saponite, saponite, and calcite. They suggest a likely transpressive to transtensional regime around the early Miocene/ middle Miocene boundary, with a north-northeast-south-southwest compression alternating with a west-northwest-eastsoutheast extension. The faults from Site 799 cores on the Yamato Rise exhibit a prominent early Miocene-middle Miocene extensional environment, a late Miocene-early Pliocene phase of normal and strike-slip faulting, and a final phase that began during the latest Pliocene. Site 798, on the Oki Ridge, reveals faults that recorded a consistent extensional tectonic regime from Pliocene to the Holocene. These data support the pull-apart kinematic model for early Miocene-middle Miocene time, as regarding the stress regime deduced from the Yamato Basin basement fractures. The recent compression known in the eastern margin of the Japan Sea was not documented by compressive structures at any site. The late Miocene-early Pliocene faulting phase corresponds to a major and general reorganization of the stress distribution in the arc area. Evidence for rapid and main subsidence and synsedimentary extension of the Yamato Basin and Yamato Rise areas between 20 and 15 Ma, and the concomitant rotation of southwest Japan, raise the question of links between this opening and the Shimanto Belt collision in southwest Japan, between the arc and the Philippine Sea Plate.

Nitrogen isotope ratios of Cretaceous Atlantic sedimentary sequences

At two locations in the Atlantic Ocean (DSDP Sites 367 and 530) early to middle Cretaceous organic-carbon-rich beds (black shales) were found to have significantly lower delta15N values (lower 15N/14N ratios) than adjacent organic-carbon-poor beds (white limestones or green claystones). While these lithologies are of marine origin, the black strata in particular have delta15N values that are significantly lower than those previously found in the marine sediment record and most contemporary marine nitrogen pools. In contrast, black, organic-carbon-rich beds at a third site (DSDP Site 603) contain predominantly terrestrial organic matter and have C- and N-isotopic compositions similar to organic matter of modern terrestrial origin. The recurring 15N depletion in the marine-derived Cretaceous sequences prove that the nitrogen they contain is the end result of an episodic and atypical biogeochemistry. Existing isotopic and other data indicate that the low 15N relative abundance is the consequence of pelagic rather than post-depositional processes. Reduced ocean circulation, increased denitrification, and, hence, reduced euphoric zone nitrate availability may have led to Cretaceous phytoplankton assemblages that were periodically dominated by N2-fixing blue-green algae, a possible source of this sediment 15N-depletion. Lack of parallel isotopic shifts in Cretaceous terrestrially-derived nitrogen (Site 603) argues that the above change in nitrogen cycling during this period did not extend beyond the marine environment.

Stable isotope record, Mg/Ca ratios and sea surface reconstruction for sediment core MD06-3067

We present sea surface, upper thermocline, and benthic d18O data, as well as temperature and paleoproductivity proxy data, from the International Marine Global Change Study Program (IMAGES) Core MD06-3067 (6°31'N, 126°30'E, 1575 m water depth), located in the western equatorial Pacific Ocean within the flow path of the Mindanao Current. Our records reveal considerable glacial-interglacial and suborbital variability in the Mindanao Dome upwelling over the last 160 kyr. Dome activity generally intensified during glacial intervals resulting in cooler thermocline waters, whereas it substantially declined during interglacials, in particular in the early Holocene and early marine oxygen isotope stage (MIS) 5e, when upwelling waters did not reach the thermocline. During MIS 3 and MIS 2, enhanced surface productivity together with remarkably low SST and low upper ocean thermal contrast provide evidence for episodic glacial upwelling to the surface, whereas transient surface warming marks periodic collapses of the Mindanao Dome upwelling during Heinrich events. We attribute the high variability during MIS 3 and MIS 2 to changes in the El Niño Southern Oscillation state that affected boreal winter monsoonal winds and upper ocean circulation. Glacial upwelling intensified when a strong cyclonic gyre became established, whereas El Niño-like conditions during Heinrich events tended to suppress the cyclonic circulation, reducing Ekman transport. Thus, our findings demonstrate that variations in the Mindanao Dome upwelling are closely linked to the position and intensity of the tropical convection and also reflect far-field influences from the high latitudes.