Developmental changes in brain activation during novel grammar learning in 8-25-year-olds.

While it is well established that grammar learning success varies with age, the cause of this developmental change is largely unknown. This study examined functional MRI activation across a broad developmental sample of 165 Dutch-speaking individuals (8-25 years) as they were implicitly learning a new grammatical system. This approach allowed us to assess the direct effects of age on grammar learning ability while exploring its neural correlates. In contrast to the alleged advantage of children language learners over adults, we found that adults outperformed children. Moreover, our behavioral data showed a sharp discontinuity in the relationship between age and grammar learning performance: there was a strong positive linear correlation between 8 and 15.4 years of age, after which age had no further effect. Neurally, our data indicate two important findings: (i) during grammar learning, adults and children activate similar brain regions, suggesting continuity in the neural networks that support initial grammar learning; and (ii) activation level is age-dependent, with children showing less activation than older participants. We suggest that these age-dependent processes may constrain developmental effects in grammar learning. The present study provides new insights into the neural basis of age-related differences in grammar learning in second language acquisition.

18S-NemaBase: Curated 18S rRNA Database of Nematode Sequences.

Nematodes are the most abundant and diverse animals on the planet but lack representation in biodiversity research. This presents a problem for studying nematode diversity, particularly when molecular tools (i.e., barcoding and metabarcoding) rely on well-populated and curated reference databases, which are absent for nematodes. To improve molecular identification and the assessment of nematode diversity, we created and curated an 18S rRNA database specific to nematodes (18S-NemaBase) using sequences sourced from the most recent publicly available 18S rRNA SILVA v138 database. As part of the curation process, taxonomic strings were standardized to contain a fixed number of taxonomic ranks relevant to nematology and updated for the most recent accepted nematode classifications. In addition, apparent erroneous sequences were removed. To test the efficacy and accuracy of 18S-NemaBase, we compared it to an older but also curated SILVA v111 and the newest SILVA v138 by assigning taxonomies and analyzing the diversity of a nematode dataset from the Western Nebraska Sandhills. We showed that 18S-NemaBase provided more accurate taxonomic assignments and diversity assessments than either version of SILVA, with a much easier workflow and no need for manual corrections. Additionally, observed diversity further improved when 18S-NemaBase was supplemented with reference sequences from nematodes present in the study site. Although the 18S-NemaBase is a step in the right direction, a concerted effort to increase the number of high-quality, accessible, full-length nematode reference sequences is more important now than ever.

External and Internal Microbiomes of Antarctic Nematodes are Distinct, but More Similar to each other than the Surrounding Environment.

Host-associated microbiomes have primarily been examined in the context of their internal microbial communities, but many animal species also contain microorganisms on external host surfaces that are important to host physiology. For nematodes, single strains of bacteria are known to adhere to the cuticle (e.g., Pasteuria penetrans), but the structure of a full external microbial community is uncertain. In prior research, we showed that internal gut microbiomes of nematodes (Plectus murrayi, Eudorylaimus antarcticus) and tardigrades from Antarctica's McMurdo Dry Valleys were distinct from the surrounding environment and primarily driven by host identity. Building on this work, we extracted an additional set of individuals containing intact external microbiomes and amplified them for 16S and 18S rRNA metabarcoding. Our results showed that external bacterial microbiomes were more diverse than internal microbiomes, but less diverse than the surrounding environment. Host-specific bacterial compositional patterns were observed, and external microbiomes were most similar to their respective internal microbiomes. However, external microbiomes were more influenced by the environment than the internal microbiomes were. Non-host eukaryotic communities were similar in diversity to internal eukaryotic communities, but exhibited more stochastic patterns of assembly compared to bacterial communities, suggesting the lack of a structured external eukaryotic microbiome. Altogether, we provide evidence that nematode and tardigrade cuticles are inhabited by robust bacterial communities that are substantially influenced by the host, albeit less so than internal microbiomes are.

Host identity is the dominant factor in the assembly of nematode and tardigrade gut microbiomes in Antarctic Dry Valley streams.

Recent work examining nematode and tardigrade gut microbiomes has identified species-specific relationships between host and gut community composition. However, only a handful of species from either phylum have been examined. How microbiomes differ among species and what factors contribute to their assembly remains unexplored. Cyanobacterial mats within Antarctic Dry Valley streams host a simple and tractable natural ecosystem of identifiable microinvertebrates to address these questions. We sampled 2 types of coexisting mats (i.e., black and orange) across four spatially isolated streams, hand-picked single individuals of two nematode species (i.e., Eudorylaimus antarcticus and Plectus murrayi) and tardigrades, to examine their gut microbiomes using 16S and 18S rRNA metabarcoding. All gut microbiomes (bacterial and eukaryotic) were significantly less diverse than the mats they were isolated from. In contrast to mats, microinvertebrates' guts were depleted of Cyanobacteria and differentially enriched in taxa of Bacteroidetes, Proteobacteria, and Fungi. Among factors investigated, gut microbiome composition was most influenced by host identity while environmental factors (e.g., mats and streams) were less important. The importance of host identity in predicting gut microbiome composition suggests functional value to the host, similar to other organisms with strong host selected microbiomes.

Study protocol: a comprehensive multi-method neuroimaging approach to disentangle developmental effects and individual differences in second language learning.

BACKGROUND: While it is well established that second language (L2) learning success changes with age and across individuals, the underlying neural mechanisms responsible for this developmental shift and these individual differences are largely unknown. We will study the behavioral and neural factors that subserve new grammar and word learning in a large cross-sectional developmental sample. This study falls under the NWO (Nederlandse Organisatie voor Wetenschappelijk Onderzoek [Dutch Research Council]) Language in Interaction consortium (website: https://www.languageininteraction.nl/ ). METHODS: We will sample 360 healthy individuals across a broad age range between 8 and 25 years. In this paper, we describe the study design and protocol, which involves multiple study visits covering a comprehensive behavioral battery and extensive magnetic resonance imaging (MRI) protocols. On the basis of these measures, we will create behavioral and neural fingerprints that capture age-based and individual variability in new language learning. The behavioral fingerprint will be based on first and second language proficiency, memory systems, and executive functioning. We will map the neural fingerprint for each participant using the following MRI modalities: T1-weighted, diffusion-weighted, resting-state functional MRI, and multiple functional-MRI paradigms. With respect to the functional MRI measures, half of the sample will learn grammatical features and half will learn words of a new language. Combining all individual fingerprints allows us to explore the neural maturation effects on grammar and word learning. DISCUSSION: This will be one of the largest neuroimaging studies to date that investigates the developmental shift in L2 learning covering preadolescence to adulthood. Our comprehensive approach of combining behavioral and neuroimaging data will contribute to the understanding of the mechanisms influencing this developmental shift and individual differences in new language learning. We aim to answer: (I) do these fingerprints differ according to age and can these explain the age-related differences observed in new language learning? And (II) which aspects of the behavioral and neural fingerprints explain individual differences (across and within ages) in grammar and word learning? The results of this study provide a unique opportunity to understand how the development of brain structure and function influence new language learning success.

Context-dependent role of abiotic and biotic factors structuring nematode communities along two environmental gradients.

Although abiotic environmental factors have been historically regarded as the dominant deterministic process in microbial community assembly, recent studies indicate that biotic interactions may be equally significant. However, the extent to which both processes are important in assembly of belowground communities is unknown. Along two environmental gradients: alkalinity (ranging from pH ~7 to ~11) and habitat type (lakes, shorelines, and prairies around lakes) present in the Western Nebraska Sandhills, we used 18S rRNA gene marker metabarcoding and statistical analyses, including generalized dissimilarity modelling (GDM), to evaluate the dynamics between abiotic and biotic factors that might play a role in nematode community assembly. Lakes supported the least diverse and prairies the most diverse communities with completely distinct compositions. We also observed a potential role of alkalinity in shaping these communities but only in lakes. Generally, GDMs indicated the influence of both abiotic and biotic factors. However, their relative importance in explaining community variability was dependent on the habitat. Biotic factors influenced the lake communities most, followed by shorelines and prairies, explaining ~47%, 27% and 8% of the variation, respectively. In contrast, the role of abiotic factors was relatively similar in lakes, shorelines and prairies (~15%, 18% and 14% of the variation, respectively). Most variation in the shorelines (62%) and prairies (82%) remained unexplained, suggesting the potential importance of factors associated with specific traits or a stronger role of stochastic processes. Nevertheless, our findings suggest both deterministic processes are important in nematode community assembly, but their specific contributions are context-dependent.

The effect of gabapentin and ketorolac on allodynia and conditioned place preference in antibody-induced inflammation.

BACKGROUND: Glucose-6-phosphate isomerase and collagen type II antibody-induced arthritis models (K/BxN and CAIA, respectively) have an inflammatory and a post-inflammatory phase. Both phases display robust tactile allodynia. In previous work, inflammatory phase allodynia was reversed by gabapentin and ketorolac, whereas in late phase only gabapentin was effective. Here, we sought to determine if the effects of these two drugs during the early and late phases of the two arthritis models were observed in the conditioned place preference (CPP) paradigm, indicating a differential drug effect on the aversive state. METHODS: Male C57BL/6 mice received K/BxN serum intraperitoneally, while male BALB/c mice received collagen type II antibody cocktail intravenously. After onset of inflammation and allodynia, we assessed effects of i.p. gabapentin (100 mg/kg) or ketorolac (15 mg/kg) using a CPP paradigm: 2 days adaptation, 2 days conditioning (vehicle in morning and drug in afternoon), preference testing on day 5. RESULTS: Consistent with the effects upon allodynia, both gabapentin and ketorolac produced a preference for the drug-paired compartment in the early phase of the K/BxN model, while gabapentin, but not ketorolac, resulted in a place preference during late phase. In the CAIA model, consistent with differential effects upon allodynia, gabapentin produced a preference in the early phase and a trend in the late phase, whereas ketorolac was ineffective at either time. CONCLUSIONS: CPP validated the aversive state in the inflammatory and post-inflammatory phases of the K/BxN and CAIA arthritis models and correspondence between the anti-hyperpathic pharmacology as defined by thresholds and CPP.

Synthesis and characterization of trans-[Os(en)2py(H)]2+ and related studies.

trans-[Os(en)(2)pyH](Otf)(2), 2, is recovered from an acidic solution of trans-[Os(en)(2)py(H(2))](OTf)(2), 1, which has been subjected to one electron oxidation. The structures of both 1 and 2 have been determined by single crystal X-ray analysis. In cyclic voltammetry, 2 shows a one electron oxidation wave at 0.95 V and a one electron reduction wave at -1.2 V, neither accompanied by a signal for the reverse process. Reduction of 2 by Zn/Hg in methanol solution leads to quantitative formation of [Os(en)(2)(py)H(2))](2+), predominantly in the trans-form. In aqueous solution, species 2 reacts rapidly with N-methylacridium ion, [MAH](+), by hydride transfer. One electron chemical oxidation of 2 to the corresponding Os(IV) is slower than that of 1 to 2 owing to the increase in coordination number when Os(IV) is produced. Treatment of 1, or the cis-form, 1', in DMSO by sodium t-butoxide produces mainly the corresponding isomers of the monohydrides of Os(II), that derived from 1' is deep red in color while the trans-monohydride is colorless. Both react with [MAH](+) to form [MAH](2), and both disappear rapidly in acetone or acetonitrile, presumably by reducing the solvents. Reaction of trans-[Os(NH(3))(4)(H(2))H(2)O](BPh(4))(2), 4, in acetone-d(6) as solvent with either CH(3)CHO or styrene leads to hydrogenation of the substrate. Reactions which compete with trans-[Os(en)(2)(eta(2)-H(2))(CF(3)SO)(3)]CF(3)SO(3) release of substrate from the trans-complex before isomerization to the cis-form, required for hydrogenation to occur, result in the trans-derivative of the added solute. When H(2)C=CH-CH(2)-SCH(3) is the substrate, binding takes place at sulfur. Complete conversion to the cis-substrate isomer is observed, without hydrogenation occurring even though contact between dihydrogen and the double bond is possible.

The time-limited influence of sentential context on function word identification.

Sentential context effects on the identification of the Dutch function words te (to) and de (the) were examined. In Experiment 1, listeners labeled words on a [t inverted e]-[d inverted e] continuum more often as te when the context waste biased (Ik probeer [? inverted e] schieten [I try to/the shoot]) than when it was de biased (Ik probeer [? inverted e] schoenen [I try to/the shoes]). The effect was weaker in slower responses. In Experiment 2, disambiguation began later, in the second word after [? inverted e]. There was a weak context effect only in the slower responses. In Experiments 3 and 4, disambiguation occurred on the word before [? inverted e]: There was no context effect when one set of sentences was used, but there was an effect (larger in the faster responses) when more sentences were used. Syntactic processing affects word identification only within a limited time frame. It appears to do so not by influencing lexical access processes through feedback but, instead, by biasing decision making.

Different forms of LTD in the CA1 region of the hippocampus: role of age and stimulus protocol.

In this study, we have investigated the developmental range over which different stimulus protocols induce long-term depression (LTD). Low-frequency stimulation (LFS; 900 stimuli, 1 Hz) produced LTD in hippocampal slices from rats younger than approximately 40 days old, but not in animals aged between approximately 40 days and 16 weeks. We demonstrate, however, that different stimulus protocols can result in LTD in the adult hippocampus. Whilst one paired-pulse low-frequency stimulus protocol [PP-LFS; 50 ms paired-pulse interval (PPI), 900 pairs of stimuli] produced N-methyl-D-aspartate (NMDA) receptor-independent LTD, another PP-LFS protocol (200 ms PPI; 900 pairs) produced NMDA receptor-dependent LTD. Furthermore, the saturation of NMDA receptor-dependent LTD did not prevent the induction of further NMDA receptor-independent LTD. This lack of occlusion suggests that different mechanisms of expression may underlie each of the above forms of LTD in the adult hippocampus. In contrast to the adult hippocampus, NMDA receptor-dependent LTD was induced by both LFS and PP-LFS (50 ms PPI) in slices from young animals (12-20 days). Although they share a common induction mechanism, LTD induced by PP-LFS may be expressed through other mechanisms in addition to those underlying LFS-induced LTD in the young hippocampus. In conclusion, the results in this study demonstrate that mechanisms of long-term synaptic depression within the hippocampus can alter radically with development of the central nervous system and with the use of different induction protocols.

Merging information in speech recognition: feedback is never necessary.

Top-down feedback does not benefit speech recognition; on the contrary, it can hinder it. No experimental data imply that feedback loops are required for speech recognition. Feedback is accordingly unnecessary and spoken word recognition is modular. To defend this thesis, we analyse lexical involvement in phonemic decision making. TRACE (McClelland & Elman 1986), a model with feedback from the lexicon to prelexical processes, is unable to account for all the available data on phonemic decision making. The modular Race model (Cutler & Norris 1979) is likewise challenged by some recent results, however. We therefore present a new modular model of phonemic decision making, the Merge model. In Merge, information flows from prelexical processes to the lexicon without feedback. Because phonemic decisions are based on the merging of prelexical and lexical information, Merge correctly predicts lexical involvement in phonemic decisions in both words and nonwords. Computer simulations show how Merge is able to account for the data through a process of competition between lexical hypotheses. We discuss the issue of feedback in other areas of language processing and conclude that modular models are particularly well suited to the problems and constraints of speech recognition.

Androgen actions on central serotonin neurotransmission: relevance for mood, mental state and memory.

Sex steroids exert potent effects on mood and mental state in the human. Our previous experimental findings in female rats suggest that these effects may be mediated, in part, by the action of estrogen on the 5-hydroxytryptamine2A receptor (5-HT(2A)R) and serotonin transporter (SERT) in brain. Here we review our recent findings on the effect of acute (approximately 32 h) testosterone manipulation on central 5-HT(2A)R and SERT in male rats. Castration decreased while testosterone or estrogen, but not 5alpha-dihydrotestosterone (5alpha-DHT), increased significantly the content of 5-HT(2A)R mRNA and SERT mRNA in the dorsal raphe nucleus (DR) and the density of 5-HT(2A)R and SERT binding sites in higher centers of the brain. The lack of effect of 5alpha-DHT, a potent androgen which cannot be converted to estrogen, suggests that the action of testosterone depends upon its conversion to estrogen by aromatase. This may also explain why estrogen, but not testosterone or 5alpha-DHT, increased the density of 5-HT(2A)R binding sites in the caudate-putamen, a brain region where aromatase is scarce. The estrogen induction of SERT mRNA is most prominent in the rostral DR and this together with the correlation between sensitivity of DR serotonin neurons to estrogen and neurotoxic amphetamine derivatives provides a potential topochemical handle with which to investigate testosterone/estrogen regulation of SERT gene expression. These findings are discussed in relation to the possible role of interactions between sex steroids and serotonin mechanisms in mood disorders, schizophrenia and Alzheimer's disease.

Intrauterine growth restriction is associated with persistent juxtamedullary expression of renin in the fetal kidney.

BACKGROUND: Intrauterine growth restriction (IUGR) has been linked to impaired renal function and hypertension, suggesting that an adverse prenatal environment could alter kidney development and renin production. METHODS: Immunohistochemistry and in situ hybridization were employed to localize renin-containing cells (RCCs) in the deep, middle, and superficial zones of autopsy kidney sections, in parallel with histologic maturation, from unexplained stillborn fetuses of normal weight (N = 26) and stillborn fetuses with IUGR (N = 17). RESULTS: In the control group, the number of RCC per 100 glomeruli in the deep zone decreased with advancing gestation from 40 at 20 weeks gestation to five at term (P < 0.001), whereas the opposite change was found in the superficial zone (increase from 5 per 100 to 55 per 100; P < 0.001). In the IUGR group, the density of RCCs in both the superficial and deep zones was similar to the control group at 20 weeks, and no shift in renin gene expression was observed as gestation advanced. Histologic maturation was unaltered. CONCLUSIONS: Renin gene expression persists and predominates in the deep renal cortex of the stillborn IUGR fetus, and could contribute to the pathogenesis of neonatal oliguria and/or hypertension during postnatal life.

Serotonin transporter (SERT) mRNA and binding site densities in male rat brain affected by sex steroids.

Estrogen increases serotonin transporter (SERT) mRNA and binding sites in female rat brain. In order to determine whether changes in SERT are gender- and steroid-specific we have now carried out studies on adult male Wistar rats which were either intact or castrated (under halothane anesthesia) and injected with arachis oil, estradiol benzoate (EB), testosterone propionate (TP) or the non-aromatizable androgen, 5alpha-dihydrotestosterone (5alpha-DHT). The number of SERT mRNA-expressing cells in the dorsal raphe (DR) nucleus was decreased by castration and increased by treatment (for approximately 32 h) with EB or TP, but not 5alpha-DHT. Sex steroids had no effect on the number of SERT mRNA-expressing cells in the median raphe nucleus. The density of SERT sites, assessed by autoradiography of [3H]paroxetine binding, was significantly reduced in arcuate nucleus and median raphe after castration, and increased in arcuate, basolateral amygdala and ventromedial hypothalamic nucleus by treatment with EB or TP, but not 5alpha-DHT. Estradiol, but not testosterone or 5alpha-DHT reduced the density of SERT sites in midbrain central grey. These data show that testosterone as well as estrogen affects SERT expression in male brain, and that the action of testosterone probably depends upon its enzymatic conversion, by aromatase, to estradiol. Our findings may have implications for sex steroid control of mood and behavior, and the action of neurotoxic derivatives of amphetamine, such as 3, 4-methylenedioxymethamphetamine, in the human.

Serotonergic 5-HT2A receptors important for the oestradiol-induced surge of luteinising hormone-releasing hormone in the rat.

Serotonin (5-HT) plays a role in mediating the oestradiol-induced surge of luteinising hormone (LH), but so far the 5-HT receptor subtype involved has not been identified. Our previous in-situ hybridization and pharmacological studies suggest that the action of 5-HT involves the 5-HT2A receptor. The aim of the present study was to investigate this possibility by the direct approach of determining whether 5-HT2A receptor antagonists block the oestradiol-induced surge of luteinising hormone releasing hormone (LHRH). Adult female Wistar rats, which had shown at least two consecutive 4-day oestrous cycles, were ovariectomised under halothane anaesthesia in the morning of dioestrus and injected with vehicle (arachis oil) alone or oestradiol benzoate (OB). At 12.00 h of the next day, presumptive pro-oestrus, the animals were injected intraperitoneally with one of three 5-HT2A antagonists, a selective 5-HT reuptake inhibitor (fluoxetine), or the appropriate vehicles; hypophysial portal blood was then collected under alphaxalone anaesthesia between 15.00 and 19.00 h. The amount of LHRH released into hypophysial portal blood during consecutive 30-min periods was determined by radioimmunoassay. As expected, oestradiol, but not oil, triggered a surge of LHRH in hypophysial portal blood with a peak at about 16.00 h of presumptive pro-oestrus. This oestradiol-induced surge of LHRH was blocked by ketanserin, ritanserin and the highly selective 5-HT2A receptor antagonist, RP62203, but not by fluoxetine. These results provide the first direct evidence that the 5-HT2A receptor plays an important role in the oestradiol-induced surge of LHRH.

Care of the woman with hypertension in pregnancy: the viewpoint of the midwife.

Key principles underpin good midwifery care of every pregnant woman, including a sound knowledge base, meeting the woman's needs and enhancing care. Normal antenatal care, with regular measurement of blood pressure, remains the mainstay of screening for hypertension in pregnancy. The midwife's role is that of accurate assessment and communication when detecting the first signs of hypertension. The midwife will then play a major role in the ongoing monitoring of the condition, liaison with the medical team and education of the woman and her family. Continuity of care is an important principle in avoiding errors in recording blood pressure between care givers; familiarity of a known midwife may reduce the likelihood of white coat hypertension. Advocacy should be employed by the midwife as a key link between the woman, her family and the obstetric team. Every woman who has experienced pre-eclampsia should be given the opportunity to talk through her care at a later date. This may be at the postnatal appointment or through a debriefing service.

Sex steroid control of mood, mental state and memory.

1. Sex steroid hormones exert profound effects on mood and mental state. Thus, in women, oestrogen is thought to protect against depression and delay the onset of schizophrenia and Alzheimer's disease. 2. Our studies in the female rat show that oestradiol, in its positive feedback mode for gonadotrophin release, increases the expression of genes for the 5-hydroxytryptamine 5-HT2A receptor and the serotonin transporter (SERT) in the dorsal raphe nucleus and the density of 5-HT2A receptor and SERT sites in regions of the forebrain that, in the human, are concerned with cognition, mental state, emotion and memory. 3. In the male rat, castration decreases while oestrogen and testosterone, but not 5 alpha-dihydrotestosterone (5 alpha-DHT), increase the density of 5-HT2A receptors in forebrain. The fact that 5 alpha-DHT has no effect suggests that the action of testosterone depends on its conversion to oestradiol by aromatase. 4. In intact rats, the density of 5-HT2A receptors in cerebral cortex is significantly higher in pro-oestrous female than in male and dioestrous female rats, showing that the spontaneous, preovulatory surge of oestradiol that reaches a peak at 12.00 h of pro-oestrus also increases the density of 5-HT2A receptors in cortex. 5. Oestrogen and testosterone (by way of its conversion to oestrogen) also stimulate the expression of the arginine vasopressin gene in the bed nucleus of the stria terminalis of the rodent, a mechanism that plays a key role in olfactory memory. 6. These actions of sex steroid hormones are discussed in the context of genomic versus non-genomic mechanisms, the recent discovery that there are two oestradiol receptors with different distributions in brain, the significance of our findings for our understanding of the control of mood, mental state and memory and the mechanism by which oestrogen stimulation of the 5-HT2A receptor could delay the onset of Alzheimer's disease.

Estradiol-17 beta increases serotonin transporter (SERT) mRNA levels and the density of SERT-binding sites in female rat brain.

The aim of the present study was to determine the effect of estradiol-17 beta (E2), in its positive feedback mode for gonadotropin release, on the serotonin transporter (SERT) in female rat brain. Levels of SERT mRNA were determined by in situ hybridization and SERT-binding sites were measured by quantitative [3H]paroxetine receptor autoradiography. The injection of estradiol benzoate (EB) in acutely ovariectomized rats increased significantly (approximately 50%) the numbers of cells that expressed SERT mRNA in the dorsal raphe nucleus and the density of SERT-binding sites in lateral septum (90%), basolateral amygdala (20%), ventral nucleus of thalamus (250%) and ventromedial hypothalamic nucleus (250%). SERT-binding sites in EB-treated rats were significantly lower in periaqueductal central grey (15%). These findings indicate that effects on SERT gene expression may be involved in the E2-induction of the gonadotropin surge. Together with our previous findings, they also suggest that the sex differences in depression and the apparent psychotropic effect of E2 may be due to the action of E2 on the serotonin transporter as well as 5-HT2A receptors.