bluuebunny/crossref_metadata_2025 huggingface dataset:
Salt transport in the near‐surface layer in the monsoon‐influenced Indian Ocean using HYCOM
Authors: Nyadjro Ebenezer S. , Subrahmanyam Bulusu , Murty V. S. N. , Shriver Jay F.
Published: August 2010

Salt advection in the top 5 m layer of the monsoon‐influenced Indian Ocean has been studied with high resolution HYbrid Coordinate Ocean Model (HYCOM) simulated sea surface salinity (SSS) during 2003‐06. The effect of monsoon reversals and roles of Ekman drift and geostrophic currents are emphasized. The Ekman drift component is found to be more important than the geostrophic component in exchange of salt in the basins; an indication of the influence of winds and the associated surface currents. The strongest differences in the salt advection terms occurred in the Bay of Bengal (BoB), an indication of the significant role of advection for the distribution of freshwater and the Ekman processes. The Inter‐Tropical Convergence Zone (ITCZ) is seen to influence advection patterns via Ekman drift along the equatorial region. This results in the creation of two salt advection bands whose positions vary seasonally. This study will help to interpret data from the recently launched Soil Moisture Ocean Salinity (SMOS) and future Aquarius salinity missions for the Indian Ocean.
Expression of chemokine decoy receptors and their ligands at the porcine maternal–fetal interface
Authors: Wessels Jocelyn M , Linton Nicola F , van den Heuvel Marianne J , Cnossen Sonya A , Edwards Andrew K , Croy Barbara Anne , Tayade Chandrakant
Published: August 2010

Successful pregnancy requires coordinated maternal–fetal cross‐talk to establish vascular connections that support conceptus growth. In pigs, two waves of spontaneous fetal loss occur and 30–40% of conceptuses are lost before parturition. Previous studies associated these losses with decreased angiogenic and increased inflammatory cytokines. Chemokines, a sub‐category of cytokines, and decoy receptors control leukocyte trafficking, angiogenesis and development. The availability of chemokines is regulated by three non‐signalling decoy receptors: chemokine decoy receptor (D6), Duffy antigen receptor for chemokines (DARC) and Chemocentryx decoy receptor (CCX CKR). We hypothesized that the expression of these receptors and their chemokine ligands regulate the porcine pregnancy success or failure. Here, we describe for the first time the transcription and translation of all three decoy receptors and several chemokine ligands in endometrium and trophoblast associated with healthy and arresting conceptuses at gestation day (gd) 20 and gd50. Among decoy receptors, transcripts for DARC were significantly reduced in endometrium, whereas that for CCX CKR were significantly increased in endometrium and trophoblast at gd50 arresting compared with healthy sites. However, western blot analysis revealed no differences in decoy receptor expression between healthy and arresting tissues. Transcripts for decoy receptor ligands CCL2, CCL3, CCL4, CCL5, CCL11, CCL19, CCL21, CXCL2 and CXCL8 were stable between healthy and arresting littermates. Quantification by SearchLight chemiluminescent protein array confirmed ligand expression at the protein level. These data indicate that decoy receptors and ligands are expressed at the porcine maternal–fetal interface and dysregulation of decoy receptor (DARC and CCX CKR) transcripts occurs at sites of fetal arrest.
Molecular determination of selectivity of the site 3 modulator (BmK I) to sodium channels in the CNS: a clue to the importance of Nav1.6 in BmK I-induced neuronal hyperexcitability
Authors: He Huiqiong , Liu ZhiRui , Dong Bangqian , Zhou Jingjing , Zhu Hongyan , Ji Yonghua
Published: August 2010

BmK I, a site-3-specific modulator of VGSCs (voltage-gated sodium channels) from the Chinese scorpion Buthus martensi Karsch, can induce spontaneous nociception and hyperalgesia and generate epileptiform responses in rats, which is attributed to the modulation of VGSCs in the neural system. However, which VGSC subtype is targeted by BmK I remains to be identified. Using two-electrode voltage-clamp recording, we studied the efficacy and selectivity of BmK I to three neuronal VGSCs co-expressed with the auxiliary β1 subunit in Xenopus oocytes. Results revealed that BmK I induced a large increase in both transient and persistent currents in mNav1.6α/β1 (where m indicates mouse), which correlated with a prominent reduction in the fast component of inactivating current. In comparison, BmK I-increased currents of rNav1.2α/β1 (where r indicates rat) and rNav1.3α/β1 were much smaller. The EC50 values of BmK I for rNav1.2α/β1 (252±60 nM) and mNav1.6α/β1 (214±30 nM) were similar and roughly half of that for rNav1.3α/β1 (565±16 nM). Moreover, BmK I only accelerated the slow inactivation development and delay recovery of mNav1.6α/β1 through binding to the channel in the open state. Residue-swap analysis verified that an acidic residue (e.g. Asp1602 in mNav1.6) within the domain IV S3–S4 extracellular loop of VGSCs was crucial for the selectivity and modulation pattern of BmK I. Our findings thus provide the molecular determinant explaining the divergent and intriguing behaviour of neuronal VGSCs in response to site-3-specific modulators, indicating that these subtypes play different roles in BmK I-induced hyperexcitablity in rat models.
Vaccination with cell immunoglobulin mucin-1 antibodies and inactivated influenza enhances vaccine-specific lymphocyte proliferation, interferon-γ production and cross-strain reactivity
Authors: Soo Hoo W , Jensen E R , Saadat A , Nieto D , Moss R B , Carlo D J , Moll T
Published: August 2010

Influenza virus causes a contagious and potentially serious infection of the upper respiratory tract. While neutralizing antibodies are protective against infection, the problem of antigenic drift remains, requiring the constant monitoring and development of new vaccines. The magnitude of this situation is underscored by the emergence of new potentially human pathogenic influenza strains, avian H5N1 being the most recent example. We present evidence that antibodies against T cell immunoglobulin mucin-1 (TIM-1), a recently identified immunomodulatory molecule, stimulate cellular immunity against influenza viruses and cross-strain immune reactivity. To determine potential immunostimulatory properties of anti-TIM-1, mice were vaccinated with inactivated influenza virus in the presence or absence of TIM-1-specific monoclonal antibodies. Development of cellular immunity against both the influenza strain used for immunization and serotypically distinct virus strains was monitored 3 weeks after vaccination by determining antigen-specific lymphocyte proliferation and cytokine production. Results show that TIM-1 antibodies enhance antigen-specific cellular proliferation (P < 0·05) and interferon (IFN)-γ production (P < 0·01). Using blocking anti-CD4 and CD8 antibodies, it was observed that antigen-specific cellular proliferation is CD4-dependent and that the majority of proliferating cells are CD4+. Finally, vaccination with inactivated influenza virus with TIM-1 antibody results in the significant (P < 0·001) induction of proliferation and IFN-γ production upon stimulation with one of three serologically distinct strains. TIM-1 antibodies demonstrate an adjuvant effect promoting antigen-specific cellular proliferation and IFN-γ production, which are important for the promotion of cell-mediated immunity. These results are the first to suggest that TIM-1 antibody may serve as a potent adjuvant in the development of new influenza virus vaccines.
Substrate-driven gene expression in
Roseburia inulinivorans
: Importance of inducible enzymes in the utilization of inulin and starch
Authors: Scott Karen P. , Martin Jenny C. , Chassard Christophe , Clerget Marlene , Potrykus Joanna , Campbell Gill , Mayer Claus-Dieter , Young Pauline , Rucklidge Garry , Ramsay Alan G. , Flint Harry J.
Published: August 2010

Roseburia inulinivorans
is a recently identified motile representative of the Firmicutes that contributes to butyrate formation from a variety of dietary polysaccharide substrates in the human large intestine. Microarray analysis was used here to investigate substrate-driven gene-expression changes in
R. inulinivorans
A2-194. A cluster of fructo-oligosaccharide/inulin utilization genes induced during growth on inulin included one encoding a β-fructofuranosidase protein that was prominent in the proteome of inulin-grown cells. This cluster also included a 6-phosphofructokinase and an ABC transport system, whereas a distinct inulin-induced 1-phosphofructokinase was linked to a fructose-specific phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS II transport enzyme). Real-time PCR analysis showed that the β-fructofuranosidase and adjacent ABC transport protein showed greatest induction during growth on inulin, whereas the 1-phosphofructokinase enzyme and linked sugar phosphotransferase transport system were most strongly up-regulated during growth on fructose, indicating that these two clusters play distinct roles in the use of inulin. The
R. inulinivorans
β-fructofuranosidase was overexpressed in
Escherichia coli
and shown to hydrolyze fructans ranging from inulin down to sucrose, with greatest activity on fructo-oligosaccharides. Genes induced on starch included the major extracellular α-amylase and two distinct α-glucanotransferases together with a gene encoding a flagellin protein. The latter response may be concerned with improving bacterial access to insoluble starch particles.
Discovery of drug mode of action and drug repositioning from transcriptional responses
Authors: Iorio Francesco , Bosotti Roberta , Scacheri Emanuela , Belcastro Vincenzo , Mithbaokar Pratibha , Ferriero Rosa , Murino Loredana , Tagliaferri Roberto , Brunetti-Pierri Nicola , Isacchi Antonella , di Bernardo Diego
Published: August 2010

A bottleneck in drug discovery is the identification of the molecular targets of a compound (mode of action, MoA) and of its off-target effects. Previous approaches to elucidate drug MoA include analysis of chemical structures, transcriptional responses following treatment, and text mining. Methods based on transcriptional responses require the least amount of information and can be quickly applied to new compounds. Available methods are inefficient and are not able to support network pharmacology. We developed an automatic and robust approach that exploits similarity in gene expression profiles following drug treatment, across multiple cell lines and dosages, to predict similarities in drug effect and MoA. We constructed a “drug network” of 1,302 nodes (drugs) and 41,047 edges (indicating similarities between pair of drugs). We applied network theory, partitioning drugs into groups of densely interconnected nodes (i.e., communities). These communities are significantly enriched for compounds with similar MoA, or acting on the same pathway, and can be used to identify the compound-targeted biological pathways. New compounds can be integrated into the network to predict their therapeutic and off-target effects. Using this network, we correctly predicted the MoA for nine anticancer compounds, and we were able to discover an unreported effect for a well-known drug. We verified an unexpected similarity between cyclin-dependent kinase 2 inhibitors and Topoisomerase inhibitors. We discovered thatFasudil(a Rho-kinase inhibitor) might be “repositioned” as an enhancer of cellular autophagy, potentially applicable to several neurodegenerative disorders. Our approach was implemented in a tool (Mode of Action by NeTwoRk Analysis, MANTRA,http://mantra.tigem.it).
Alarm pheromone habituation inMyzus persicaehas fitness consequences and causes extensive gene expression changes
Authors: de Vos Martin , Cheng Wing Yin , Summers Holly E. , Raguso Robert A. , Jander Georg
Published: August 2010

In most aphid species, facultative parthenogenetic reproduction allows rapid growth and formation of large single-genotype colonies. Upon predator attack, individual aphids emit an alarm pheromone to warn the colony of this danger. (E)-β-farnesene (EBF) is the predominant constituent of the alarm pheromone inMyzus persicae(green peach aphid) and many other aphid species. Continuous exposure to alarm pheromone in aphid colonies raised on transgenicArabidopsis thalianaplants that produce EBF leads to habituation within three generations. Whereas naive aphids are repelled by EBF, habituated aphids show no avoidance response. Similarly, individual aphids from the habituated colony can revert back to being EBF-sensitive in three generations, indicating that this behavioral change is not caused by a genetic mutation. Instead, DNA microarray experiments comparing gene expression in naive and habituated aphids treated with EBF demonstrate an almost complete desensitization in the transcriptional response to EBF. Furthermore, EBF-habituated aphids show increased progeny production relative to EBF-responsive aphids, with or without EBF treatment. Although both naive and habituated aphids emit EBF upon damage, EBF-responsive aphids have a higher survival rate in the presence of a coccinellid predator (Hippodamia convergens), and thus outperform habituated aphids that do not show an avoidance response. These results provide evidence that aphid perception of conspecific alarm pheromone aids in predator avoidance and thereby bestows fitness benefits in survivorship and fecundity. Therefore, although habituatedM. persicaeproduce more progeny, EBF-emitting transgenic plants may have practical applications in agriculture as a result of increased predation of habituated aphids.
Intermolecular associations determine the dynamics of the circadian KaiABC oscillator
Authors: Qin Ximing , Byrne Mark , Mori Tetsuya , Zou Ping , Williams Dewight R. , Mchaourab Hassane , Johnson Carl Hirschie
Published: August 2010

Three proteins from cyanobacteria (KaiA, KaiB, and KaiC) can reconstitute circadian oscillations in vitro. At least three molecular properties oscillate during this reaction, namely rhythmic phosphorylation of KaiC, ATP hydrolytic activity of KaiC, and assembly/disassembly of intermolecular complexes among KaiA, KaiB, and KaiC. We found that the intermolecular associations determine key dynamic properties of this in vitro oscillator. For example, mutations within KaiB that alter the rates of binding of KaiB to KaiC also predictably modulate the period of the oscillator. Moreover, we show that KaiA can bind stably to complexes of KaiB and hyperphosphorylated KaiC. Modeling simulations indicate that the function of this binding of KaiA to the KaiB•KaiC complex is to inactivate KaiA's activity, thereby promoting the dephosphorylation phase of the reaction. Therefore, we report here dynamics of interaction of KaiA and KaiB with KaiC that determine the period and amplitude of this in vitro oscillator.
Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment
Authors: Nistala Kiran , Adams Stuart , Cambrook Helen , Ursu Simona , Olivito Biagio , de Jager Wilco , Evans Jamie G. , Cimaz Rolando , Bajaj-Elliott Mona , Wedderburn Lucy R.
Published: August 2010

In several murine models of autoimmune arthritis, Th17 cells are the dominant initiators of inflammation. In human arthritis the majority of IL-17–secreting cells within the joint express a cytokine phenotype intermediate between Th17 and Th1. Here we show that Th17/1 cells from the joints of children with inflammatory arthritis express high levels of both Th17 and Th1 lineage-specific transcription factors, RORC2 and T-bet. Modeling the generation of Th17/1 in vitro, we show that Th17 cells “convert” to Th17/1 under conditions that mimic the disease site, namely low TGFβ and high IL-12 levels, whereas Th1 cells cannot convert to Th17. Th17/1 cells from the inflamed joint share T-cell receptor (TCR) clonality with Th17 cells, suggesting a shared clonal origin between Th17 and Th17/1 cells in arthritis. Using CD161, a lectin-like receptor that is a marker of human Th17, we show synovial Th17 and Th17/1 cells, and unexpectedly, a large proportion of Th1 cells express CD161. We provide evidence to support a Th17 origin for Th1 cells expressing CD161.In vitro,Th17 cells that convert to a Th1 phenotype maintain CD161 expression. In the joint CD161+ Th1 cells share features with Th17 cells, with shared TCR clonality, expression of RORC2 and CCR6 and response to IL-23, although they are IL-17 negative. We propose that the Th17 phenotype may be unstable and that Th17 cells may convert to Th17/1 and Th1 cells in human arthritis. Therefore therapies targeting the induction of Th17 cells could also attenuate Th17/1 and Th1 effector populations within the inflamed joint.
Nonmuscle myosin II isoform and domain specificity during early mouse development
Authors: Wang Aibing , Ma Xuefei , Conti Mary Anne , Liu Chengyu , Kawamoto Sachiyo , Adelstein Robert S.
Published: August 2010

Nonmuscle myosins (NMs) II-A and II-B are essential for embryonic mouse development, but their specific roles are not completely defined. Here we examine the isoforms and their domain specifically in vivo and in vitro by studying mice and cells in which nonmuscle myosin heavy chain (NMHC) II-A is genetically replaced by NMHC II-B or chimeric NMHC IIs that exchange the rod and head domains of NM II-A and II-B. In contrast with the failure of visceral endoderm formation resulting in embryonic day (E)6.5 lethality of A
−
/A
−
mice, replacement with NM II-B or chimeric NM IIs restores a normal visceral endoderm. This finding is consistent with NM II's role in cell adhesion and also confirms an essential, isoform-independent requirement for NM II in visceral endoderm function. The knock-in mice die between E9.5 and 12.5 because of defects in placenta formation associated with abnormal angiogenesis and cell migration, revealing a unique function for NM II-A in placenta development. In vitro results further support a requirement for NM II-A in directed cell migration and focal adhesion formation. These findings demonstrate an isoform-specific role for NM II-A during these processes, making replacement by another isoform, or chimeric NM II isoforms, less successful. The failure of these substitutions is not only related to the different kinetic properties of NM II-A and II-B, but also to their subcellular localization determined by the C-terminal domain. These results highlight the functions of the N-terminal motor and C-terminal rod domains of NM II and their different roles in cell-cell and cell-matrix adhesion.
Roles of familiarity and novelty in visual preference judgments are segregated across object categories
Authors: Park Junghyun , Shimojo Eiko , Shimojo Shinsuke
Published: August 2010

Understanding preference decision making is a challenging problem because the underlying process is often implicit and dependent on context, including past experience. There is evidence for both familiarity and novelty as critical factors for preference in adults and infants. To resolve this puzzling contradiction, we examined the cumulative effects of visual exposure in different object categories, including faces, natural scenes, and geometric figures, in a two-alternative preference task. The results show a clear segregation of preference across object categories, with familiarity preference dominant in faces and novelty preference dominant in natural scenes. No strong bias was observed in geometric figures. The effects were replicated even when images were converted to line drawings, inverted, or presented only briefly, and also when spatial frequency and contour distribution were controlled. The effects of exposure were reset by a blank of 1 wk or 3 wk. Thus, the category-specific segregation of familiarity and novelty preferences is based on quick visual categorization and cannot be caused by the difference in low-level visual features between object categories. Instead, it could be due either to different biological significances/attractiveness criteria across these categories, or to some other factors, such as differences in within-category variance and adaptive tuning of the perceptual system.
Combinatorial homophilic interaction between γ-protocadherin multimers greatly expands the molecular diversity of cell adhesion
Authors: Schreiner Dietmar , Weiner Joshua A.
Published: August 2010

The specificity of interactions between neurons is believed to be mediated by diverse cell adhesion molecules, including members of the cadherin superfamily. Whereas mechanisms of classical cadherin adhesion have been studied extensively, much less is known about the related protocadherins (Pcdhs), which together make up the majority of the superfamily. Here we use quantitative cell aggregation assays and biochemical analyses to characterize
cis
and
trans
interactions among the 22-member γ-Pcdh family, which have been shown to be critical for the control of synaptogenesis and neuronal survival. We show that γ-Pcdh isoforms engage in
trans
interactions that are strictly homophilic. In contrast to classical cadherins, γ-Pcdh interactions are only partially Ca
2+
-dependent, and their specificity is mediated through the second and third extracellular cadherin (EC) domains (EC2 and EC3), rather than through EC1. The γ-Pcdhs also interact both covalently and noncovalently in the
cis
-orientation to form multimers both in vitro and in vivo. In contrast to γ-Pcdh
trans
interactions,
cis
interactions are highly promiscuous, with no isoform specificity. We present data supporting a model in which γ-Pcdh
cis
-tetramers represent the unit of their adhesive
trans
interactions. Unrestricted tetramerization in
cis
, coupled with strictly homophilic interactions in
trans,
predicts that the 22 γ-Pcdhs could form 234,256 distinct adhesive interfaces. Given the demonstrated role of the γ-Pcdhs in synaptogenesis, our data have important implications for the molecular control of neuronal specificity.
A mammalian neural tissue opsin (Opsin 5) is a deep brain photoreceptor in birds
Authors: Nakane Yusuke , Ikegami Keisuke , Ono Hiroko , Yamamoto Naoyuki , Yoshida Shosei , Hirunagi Kanjun , Ebihara Shizufumi , Kubo Yoshihiro , Yoshimura Takashi
Published: August 2010

It has been known for many decades that nonmammalian vertebrates detect light by deep brain photoreceptors that lie outside the retina and pineal organ to regulate seasonal cycle of reproduction. However, the identity of these photoreceptors has so far remained unclear. Here we report that Opsin 5 is a deep brain photoreceptive molecule in the quail brain. Expression analysis of members of the opsin superfamily identified as Opsin 5 (
OPN5
; also known as Gpr136, Neuropsin, PGR12, and TMEM13) mRNA in the paraventricular organ (PVO), an area long believed to be capable of phototransduction. Immunohistochemistry identified Opsin 5 in neurons that contact the cerebrospinal fluid in the PVO, as well as fibers extending to the external zone of the median eminence adjacent to the pars tuberalis of the pituitary gland, which translates photoperiodic information into neuroendocrine responses. Heterologous expression of Opsin 5 in
Xenopus
oocytes resulted in light-dependent activation of membrane currents, the action spectrum of which showed peak sensitivity (λ
max
) at ∼420 nm. We also found that short-wavelength light, i.e., between UV-B and blue light, induced photoperiodic responses in eye-patched, pinealectomized quail. Thus, Opsin 5 appears to be one of the deep brain photoreceptive molecules that regulates seasonal reproduction in birds.
Polo-like kinase 1 phosphorylation of p150
Glued
facilitates nuclear envelope breakdown during prophase
Authors: Li Hongchang , Liu X. Shawn , Yang Xiaoming , Song Bing , Wang Yun , Liu Xiaoqi
Published: August 2010

Nuclear envelope breakdown (NEBD) is an essential step during the G2/M transition in higher eukaryotic cells. Increasing evidence supports the notion that both microtubules and microtubule-associated motor proteins are critical regulators of NEBD. Although it has been described that p150
Glued
, the major component of the dynein/dynactin complex, localizes in the nuclear envelope during prophase, the exact role of p150
Glued
and its regulation during NEBD are largely elusive. Polo-like kinase 1 (Plk1), the best characterized Ser/Thr kinase, is involved in mitotic entry in several systems; however, the targets of Plk1 during NEBD are unknown. Herein, we show that in mammalian cells both Plk1 and p150
Glued
regulate NEBD and that Plk1 interacts with and phosphoryates p150
Glued
during NEBD at prophase. Using various approaches, we showed that Plk1 phosphorylates p150
Glued
at Ser-179 and that the pS179 epitope is generated at the nuclear envelope of prophase cells. Significantly, Plk1-mediated phosphorylation of p150
Glued
at Ser-179 positively regulates its accumulation at the nuclear envelope during prophase. Finally, we found that cells expressing the Plk1-unphosphorylatable mutant (p150
Glued
-S179A) arrest at G2, as indicated by reduced NEBD, increased levels of cyclin B and phospho-H3, but a decreased level of Cdc2 kinase activity. Taking these data together, we conclude that Plk1 phosphorylation of p150
Glued
might be one major pathway of NEBD regulation.
Fluid intelligence loss linked to restricted regions of damage within frontal and parietal cortex
Authors: Woolgar Alexandra , Parr Alice , Cusack Rhodri , Thompson Russell , Nimmo-Smith Ian , Torralva Teresa , Roca Maria , Antoun Nagui , Manes Facundo , Duncan John
Published: August 2010

Tests of fluid intelligence predict success in a wide range of cognitive activities. Much uncertainty has surrounded brain lesions producing deficits in these tests, with standard group comparisons delivering no clear result. Based on findings from functional imaging, we propose that the uncertainty of lesion data may arise from the specificity and complexity of the relevant neural circuit. Fluid intelligence tests give a characteristic pattern of activity in posterolateral frontal, dorsomedial frontal, and midparietal cortex. To test the causal role of these regions, we examined fluid intelligence in 80 patients with focal cortical lesions. Damage to each of the proposed regions predicted fluid intelligence loss, whereas damage outside these regions was not predictive. The results suggest that coarse group comparisons (e.g., frontal vs. posterior) cannot show the neural underpinnings of fluid intelligence tests. Instead, deficits reflect the extent of damage to a restricted but complex brain circuit comprising specific regions within both frontal and posterior cortex.
Interaction of JMJD6 with single-stranded RNA
Authors: Hong Xia , Zang Jianye , White Janice , Wang Chao , Pan Cheol-Ho , Zhao Rui , Murphy Robert C. , Dai Shaodong , Henson Peter , Kappler John W. , Hagman James , Zhang Gongyi
Published: August 2010

JMJD6 is a Jumonji C domain-containing hydroxylase. JMJD6 binds α-ketoglutarate and iron and has been characterized as either a histone arginine demethylase or U2AF65 lysyl hydroxylase. Here, we describe the structures of JMJD6 with and without α-ketoglutarate, which revealed a novel substrate binding groove and two positively charged surfaces. The structures also contain a stack of aromatic residues located near the active center. The side chain of one residue within this stack assumed different conformations in the two structures. Interestingly, JMJD6 bound efficiently to single-stranded RNA, but not to single-stranded DNA, double-stranded RNA, or double-stranded DNA. These structural features and truncation analysis of JMJD6 suggest that JMJD6 may bind and modify single-stand RNA rather than the previously reported peptide substrates.
Successive-signal biasing for a learned sound sequence
Authors: Zhou Xiaoming , de Villers-Sidani Étienne , Panizzutti Rogerio , Merzenich Michael M.
Published: August 2010

Adult rats were trained to detect the occurrence of a two-element sound sequence in a background of nine other nontarget sound pairs. Training resulted in a modest, enduring, static expansion of the cortical areas of representation of both target stimulus sounds. More importantly, once the initial stimulus A in the target A-B sequence was presented, the cortical “map” changed dynamically, specifically to exaggerate further the representation of the “anticipated” stimulus B. If B occurred, it was represented over a larger cortical area by more strongly excited, more coordinated, and more selectively responding neurons. This biasing peaked at the expected time of B onset with respect to A onset. No dynamic biasing of responses was recorded for any sound presented in a nontarget pair. Responses to nontarget frequencies flanking the representation of B were reduced in area and in response strength only after the presentation of A at the expected time of B onset. This study shows that cortical areas are not representationally static but, to the contrary, can be biased moment by moment in time as a function of behavioral context.
S-glutathionylation activates STIM1 and alters mitochondrial homeostasis
Authors: Hawkins Brian J. , Irrinki Krishna M. , Mallilankaraman Karthik , Lien Yu-Chin , Wang Youjun , Bhanumathy Cunnigaiper D. , Subbiah Ramasamy , Ritchie Michael F. , Soboloff Jonathan , Baba Yoshihiro , Kurosaki Tomohiro , Joseph Suresh K. , Gill Donald L. , Madesh Muniswamy
Published: August 2010

Oxidant stress influences many cellular processes, including cell growth, differentiation, and cell death. A well-recognized link between these processes and oxidant stress is via alterations in Ca2+ signaling. However, precisely how oxidants influence Ca2+ signaling remains unclear. Oxidant stress led to a phenotypic shift in Ca2+ mobilization from an oscillatory to a sustained elevated pattern via calcium release–activated calcium (CRAC)–mediated capacitive Ca2+ entry, and stromal interaction molecule 1 (STIM1)– and Orai1-deficient cells are resistant to oxidant stress. Functionally, oxidant-induced Ca2+ entry alters mitochondrial Ca2+ handling and bioenergetics and triggers cell death. STIM1 is S-glutathionylated at cysteine 56 in response to oxidant stress and evokes constitutive Ca2+ entry independent of intracellular Ca2+ stores. These experiments reveal that cysteine 56 is a sensor for oxidant-dependent activation of STIM1 and demonstrate a molecular link between oxidant stress and Ca2+ signaling via the CRAC channel.
The inositol 5-phosphatase SHIP2 regulates endocytic clathrin-coated pit dynamics
Authors: Nakatsu Fubito , Perera Rushika M. , Lucast Louise , Zoncu Roberto , Domin Jan , Gertler Frank B. , Toomre Derek , De Camilli Pietro
Published: August 2010

Phosphatidylinositol (PI) 4,5-bisphosphate (PI(4,5)P2) and its phosphorylated product PI 3,4,5-triphosphate (PI(3,4,5)P3) are two major phosphoinositides concentrated at the plasma membrane. Their levels, which are tightly controlled by kinases, phospholipases, and phosphatases, regulate a variety of cellular functions, including clathrin-mediated endocytosis and receptor signaling. In this study, we show that the inositol 5-phosphatase SHIP2, a negative regulator of PI(3,4,5)P3-dependent signaling, also negatively regulates PI(4,5)P2 levels and is concentrated at endocytic clathrin-coated pits (CCPs) via interactions with the scaffold protein intersectin. SHIP2 is recruited early at the pits and dissociates before fission. Both knockdown of SHIP2 expression and acute production of PI(3,4,5)P3 shorten CCP lifetime by enhancing the rate of pit maturation, which is consistent with a positive role of both SHIP2 substrates, PI(4,5)P2 and PI(3,4,5)P3, on coat assembly. Because SHIP2 is a negative regulator of insulin signaling, our findings suggest the importance of the phosphoinositide metabolism at CCPs in the regulation of insulin signal output.
Double affine Hecke algebras at roots of unity
Authors: Varagnolo M. , Vasserot E.
Published: August 2010

We study double affine Hecke algebras at roots of unity and their relations with deformed Hilbert schemes. In particular their categories of finitely generated modules are derived equivalent to some category of coherent sheaves.
ISA software suite: supporting standards-compliant experimental annotation and enabling curation at the community level
Authors: Rocca-Serra Philippe , Brandizi Marco , Maguire Eamonn , Sklyar Nataliya , Taylor Chris , Begley Kimberly , Field Dawn , Harris Stephen , Hide Winston , Hofmann Oliver , Neumann Steffen , Sterk Peter , Tong Weida , Sansone Susanna-Assunta
Published: August 2010

Summary: The first open source software suite for experimentalists and curators that (i) assists in the annotation and local management of experimental metadata from high-throughput studies employing one or a combination of omics and other technologies; (ii) empowers users to uptake community-defined checklists and ontologies; and (iii) facilitates submission to international public repositories.

Availability and Implementation: Software, documentation, case studies and implementations at http://www.isa-tools.org

Contact:  isatools@googlegroups.com
An integrated treatment approach to child sexual abuse in the family
Authors: FURNISS TILMAN H.
Published: August 2010

SUMMARY. In responding to the increasing professional recognition of child sexual abuse within the family, this paper, relating data from a clinical sample to epidemiological studies, is the first of a number devoted to experimental approaches being taken to identify and treat this problem. The author goes on to describe the multi‐disciplinary approach taken at the Tavistock Clinic and other treatment centres. The need for close cooperation and coordination of all professionals concerned and for the involvement of all family members in different forms of treatment is particularly emphasised. This paper was given at the 11th International Congress of the International Association for Child and Adolescent Psychiatry and Allied Professions, Paris, July 1986
Children's experience of divorce
Authors: MITCHELL ANN
Published: August 2010

SUMMARY. Until very recently, little has been known about children's personal experiences of parental separation and divorce. Interviews with children from a representative sample of divorced families showed that they lacked information, that they suffered more distress than their parents realised, that their satisfaction with access was directly related to the speed with which it was arranged, and that relationships with custodial parents' new partners were similar to their relationships with absent parents
New directions in child care
Authors: KAHAN BARBARA
Published: August 2010

SUMMARY. This article examines through examples of child care services the gaps between research findings, child care policies and good practice. Links are made between research studies and Parliamentary enquiries, and the White Paper on Child Care law, concerning Children's Homes, fostering, education and health in care and leaving care

The writer proposes that agencies should consider setting up internal means of keeping up to date with and disseminating research into policy and practice, and monitoring performance in relation to research findings, guidelines, legal requirements and inspectorial findings, Linked with internal training and staff development the article concludes that quality services might thus he more readily achieved than at present

This article is based on a presentation to the joint Association of Metropolitan Authorities/Association of County Councils/National Children's bureau Child Care Conference on 26 January 1988
Children's rights after Cleveland
Authors: NEWELL PETER
Published: August 2010

SUMMARY. The Cleveland Inquiry Report rightly emphasises that children should be treated as people, not objects of concern. The ‘best interests’ justification for intervention in children's lives can be inadequate and add professional abuse to the abuse already suffered. Child abuse must be seen as an issue of children's rights. The recommendations of the Inquiry Report are seen as a good basis for action but it fails to draw the logical conclusions in some areas, including children's rights to confidentiality and attendance at case conferences and court hearings
The role of social networks in the care of young children
Authors: HILL MALCOLM
Published: August 2010

SUMMARY. From birth, children develop, play and work within extensive social networks; yet little systematic research has been carried out to examine these relationships. This article summarises findings about the network relationships of young children from a study undertaken to explore the diverse ways in which their parents made childcare and babysitting arrangements. The different experiences of the children were found to be closely linked to parental beliefs and values, as well as the nature of the local neighbourhoods and network patterns. They were also associated with varied evolutionary sequences in the social relationships of both adults and children
Giving children a voice in divorce: the role of family conciliation
Authors: SIMPSON BOB
Published: August 2010

SUMMARY. The last ten yean have seen a rapid development of conciliation in matters relating to divorce and separation, both in the accessibility of services and in the styles of conciliation practice. Throughout this period the vexed question of the involvement of children in conciliaion has persisted. Should children be involved at all and, if so, how? This paper outlines these debates, in the light of data collected during the study of conciliation commissioned by the Lord Chancellor's department between 1985 and 1988 (Ogus et al., 1989). It is the first of two papers on this subject in this issue and a third., by Fiona Garwood, will appear in the next issue
HIV and AIDS: unexpected lessons for Save the Children
Authors: EISENSTADT NAOMI , WILSON JANIE
Published: August 2010

SUMMARY. HIV and AIDS training is a sensitive area in which experience is all recent. Previous articles in Children & Society (issues 1. 1, 1.2 and 2.4) have looked at major concerns for children's services. This paper reports on an imaginative approach to staff training in one child care agency — Save the Children Fund. The authors' frankness about problems as well as benefits will help others to identify lessons for their organisations., particularly for those in management
The best interests of the child? The role of the court welfare officer
Authors: KINGSLEY JAMES R.K.
Published: August 2010

SUMMARY. The current developments in practice, where children are involved with the courts, will form a fundamental part of work with children under the 1989 Children Act. One of the key actors will be the Court Welfare Officer, part of the Probation Service. This article reviews the role as it has developed in recent years, pointing out the different practices which coexist, even in the same area. Using evidence from a small scale research study in one Service, the article argues for a clearer and more consistent role, which can only really develop under a Family Court Welfare Service
A bereavement model for working with families of handicapped children
Authors: STEWART JUNE , POLLACK GLORIA
Published: August 2010

SUMMARY. This paper presents a model for counselling families of young handicapped children. It is argued that the process that parents go through following the birth of a handicapped child is akin to bereavement following loss. Therefore, professionals on a wide range of disciplines should be sensitive to the grief that parents are experiencing. The authors have used Le Poidevin s theory of adjustment to loss to structure their own theories and to devise a checklist to aid other professionals. Their experience indicates that the birth of the handicapped child may act as a catalyst for psychological growth in parents—mast particularly mothers.
The recent history of Scottish child welfare
Authors: MURRAY KATHLEEN , HILL MALCOLM
Published: August 2010

SUMMARY. During this century, the main features of child care policy in Britain have been the creation of a separate system of juvenile justice, the extension of state responsibilities for child protection and substitute care, a growing emphasis on foster care in preference to residential care, and increased professionalism and co‐ordination of services. This article, the second in a two‐part series, begun in issue 5(2) looks particularly at differences in child care policy between Scotland and England, the most striking of which has been in the juvenile justice arrangements. The Scottish children's hearings are fully committed to welfare principles, keeping young offenders and children in need of care and protection within a single system of decision‐making.
Parents and Educators: Dialogue and Development Through Partnership
Authors: Easen Patrick , Kendall Pippa , Shaw Janet
Published: August 2010

SUMMARY. This paper describes an approach to working with parents which emphasises the parents' own learning process and which might be termed ‘developmental partnership’. By this is meant a relationship in which not only are the parents explicitly acknowledged as the primary educators of their own children but also that, through a process of mutual enquiry into the activities and development of these children, parents, educator and children learn and work together. A number of issues are raised about working in ‘developmental partnership’ with parents, including the role of the unconscious in relationships focused upon learning.
Trends in Child Health
Authors: Woodroffe Caroline , Glickman Myer
Published: August 2010

SUMMARY: In the lifetime of the National Children's Bureau childhood death and serious infection have become increasingly rare. Chronic disease and disability may have become more common, partly as a result of the increased number of survivors of once fatal conditions. Income and social class are strongly associated with health, children in unskilled manual households being twice as likely to die before the age of 15 years as children in the professional social class. The proportion of children living in poverty doubled in the last decade. The rational allocation of resources to improve the health of children and teenagers is discussed.
Punishing Children for Caring: The Hidden Cost of Young Carers
Authors: Aldridge Jo , Becker Saul
Published: August 2010

SUMMARY. This paper examines the lives, experiences and needs of children who care ‐ those children under the age of 18 who provide primary care for a sick, disabled or elderly adult in the home. It presents data from a recent study into the lives of these children, their responsibilities, their commitments, their pain and their fears. It paints a picture of neglect both by professionals paid to care as well as by other family members. It suggests that child carers are effectively punished for caring. The paper goes on to examine the implications for child carers of the Community Care Act, finally implemented on 1 April 1993, to raise a number of critical questions about the rights of children who care, and to suggest a number of innovative ways forward, based upon the expressed needs of young carers.
Understanding Adolescence Today: A Review
Authors: Coleman John C.
Published: August 2010

SUMMARY. Much has changed in our understanding of adolescence over the last three decades. In the first place the very definition of this stage has become more uncertain, both at the point where childhood ceases, and at the time when it merges into adulthood. Second, there has been an enormous increase in the amount of empirical research available. This has had the effect of modifying ‐ even transforming ‐ some traditional notions of adolescence. Thirdly, a greater awareness of gender and race has enabled us to move beyond the white male dominated views of the teenage years which went unchallenged for some considerable time. Lastly, changes in legislation and youth policy in the United Kingdom have had a major impact on practice, and on the way professionals work with young people. This article reviews some of these changes, and attempts to reflect on our understanding of adolescence in the 1990s.
What Role Has the Law Played in Getting Rid of Racism in the Lives of Children?
Authors: Lane Jane
Published: August 2010

SUMMARY. It is only relatively recently that a detailed knowledge of how the Race Relations Act 1976 works in practice has made it possible to use it more effectively ‐ to eliminate that element of racism ‐ discrimination. The later Children Act 1989 and its accompanying Guidance, in requiring a heal authority, (when making a decision about a child for whom it is responsible), to take account of the child's religious persuasion, racial origin and cultural and linguistic background establishes a framework to promote equality of opportunity and to counter the learning of racist attitudes. This paper attempts to identify the role of these two Acts in getting rid of racism in children's lives. Knowledge of both Acts will empower parents and professionals' to be able to challenge discrimination and identify anti‐racist practice.
Bridge Arts Education Centre ‘A Real Chance for the Arts’
Authors: Perring Lizzie
Published: August 2010

SUMMARY: Bridge Arts Education is a centre for troubled children, part of Warwickshire Education Support Service. In this article, I explore its history and some of the strategies employed to work effectively with what can be a highly stressed group of children. At Bridge, the education department employs artists to work with children who have serious emotional and behavioural problems. I explain our use of creative themes and mention some of the practicalities of getting disillusioned children down to work. I discuss the value of this arts approach in meeting our National Curriculum and GCSE obligations. I also mention our approach to behavioural problems. We attracted the interest of West Midlands Arts and the article ends with a look at a Trainee Artist Placement which they funded at Bridge.
From Sickly Survival to the Realisation of Potential: Child Health as a Social Project in Twentieth Century England
Authors: Baistow Karen
Published: August 2010

SUMMARY: During the last century the improvement of child health has become an important matter of public concern, reflecting preoccupations with the quality of the future adult population as well as with the current welfare of children. This paper traces some of the changing ideas and practices associated with this social project, from the late nineteenth century to the postwar years of the twentieth. From a period when survival beyond birth and infancy was the critical area of social concern to one when psychological adjustment and behaviour emerged as the essential indices of children's present and future health status.
Family Support and the Health of Children
Authors: Roberts Ian
Published: August 2010

This paper examines the relationship between family support and the health of children. The impact of the decline in the structural support for child rearing is considered first, followed by an examination of the health effects of support provided in home visitation programmes. Finally, the health and welfare effects of the provision of day‐care services for children are considered. Because the validity of evidence from properly conducted randomised controlled trials is more readily assured than with other study designs, particular emphasis has been given to the results of experimental evaluations.
Some Australian Children's Perceptions of Physical Punishment in Childhood
Authors: Saunders Bernadette J. , Goddard Chris
Published: August 2010

Despite ratification of the United Nations Convention on the Rights of the Child, children remain the only people in Australia against whom violence may be justified as discipline. This article presents findings from qualitative research conducted in the State of Victoria, in which children were invited to contextualise incidents of physical punishment by describing the experience from different standpoints and reflecting on the feelings and motivations of victims and perpetrators. The research provides new insights into children's experiences of childhood ‘discipline’, as children reveal the physical and emotional impact of being hit by a parent, the futility of ‘physical punishment’, parents’ confusing reactions and children's awareness of double standards. Children suggest more positive ways to communicate and to resolve conflict, and provide insightful comments that have the potential to enlighten adults’ thinking about the issue.