bluuebunny/crossref_metadata_2025 huggingface dataset:
Transitions to adulthood in first‐episode psychosis: a comparative study
Authors: Roy Laurence , Rousseau Jacqueline , Fortier Pierre , Mottard Jean‐Pierre
Published: July 2012

Aim

The first aim of this study is to compare attainment of five markers of transition to adulthood between young adults with first‐episode psychosis and young adults without any psychopathology. The second aim is to examine if the association between age group and transition to adulthood is similar for individuals who experience first‐episode psychosis versus those who do not.

Methods

Participants were 50 young adults with first‐episode schizophrenia aged between 18 and 30 years old, and 50 volunteers without any psychopathology matched for sex and age. Participants were assessed with the Quality of Life Scale and a questionnaire on markers of transition to adulthood.

Results

Significant differences appear between the groups for three of the five markers of transition to adulthood, namely: residential/financial independence, educational attainment and involvement in a romantic relationship. The effect of age on several markers is significant for the comparison group only.

Conclusion

Rehabilitation interventions should be informed by a developmental perspective on community functioning for young adults with first‐episode schizophrenia. Vocational rehabilitation should be extended to focus more extensively on supported education and not only on supported employment, and interventions targeting residential independence should be granted more attention.
Not all first‐episode psychosis is the same: preliminary evidence of greater basic self‐disturbance in schizophrenia spectrum cases
Authors: Nelson Barnaby , Thompson Andrew , Yung Alison R.
Published: July 2012

Aim

Disturbance in the basic sense of self has previously been found to characterize schizophrenia spectrum disorders and to predict onset of psychosis in the ultra‐high‐risk population. The current study examined basic self‐disturbance in a first‐episode psychosis (FEP) population. We hypothesized that basic self‐disturbance would be more prominent in cases with a schizophrenia spectrum disorder compared to those with other psychoses.

Method

Sixteen FEP patients from Orygen Youth Health, Melbourne, were recruited to the study. Participants were assessed using the Examination of Anomalous Self‐Experience and the Structured Clinical Interview for DSM‐IV.

Results

Basic self‐disturbance scores were significantly higher in patients with a schizophrenia spectrum diagnosis (n = 8) compared to patients with other psychotic diagnoses (n = 8).

Conclusions

The findings are consistent with previous work indicating that the disturbance of the basic sense of self is more characteristic of schizophrenia spectrum psychosis than other psychoses. This may have implications for early diagnosis, clinical formulation and intervention.
Pilot study of a mindfulness‐based, multi‐component, in‐school group sleep intervention in adolescent girls
Authors: Bei Bei , Byrne Michelle L. , Ivens Clare , Waloszek Joanna , Woods Michael J. , Dudgeon Paul , Murray Greg , Nicholas Christian L. , Trinder John , Allen Nicholas B.
Published: July 2012

Aim

Existing literature links poor sleep and anxiety symptoms in adolescents. This pilot study aimed to develop a practical method through which a program to improve sleep could reach adolescents in need and to examine the feasibility of a mindfulness‐based, multi‐component group sleep intervention using sleep and anxiety as outcome measures.

Methods

Sixty‐two grade 9 students (aged 13–15) at a girls’ school were screened with the Pittsburgh Sleep Quality Index (PSQI) and Spence Children's Anxiety Scale (SCAS). Ten participants with self‐reported poor sleep were enrolled into a six‐session program based on Bootzin & Stevens, with added stress/anxiety‐specific components. Sessions covered key aspects of basic mindfulness concepts and practice, sleep hygiene, sleep scheduling, evening/daytime habits, stimulus control, skills for bedtime worries and healthy attitudes to sleep. Treatment changes were measured by pre‐post scores on the PSQI, SCAS and 7‐day actigraphy‐measured sleep.

Results

The program demonstrated high acceptability, with a completion rate of 90%. Based on effect‐size analysis, participants showed significant improvement on objective sleep onset latency (SOL), sleep efficiency and total sleep time; actigraphy data also showed significantly earlier bedtime, rise time and smaller day‐to‐day bedtime variation. Post‐intervention global PSQI scores were significantly lower than that of pre‐intervention, with significant improvement in subjective SOL, sleep quality and sleep‐related daytime dysfunction. There were small improvements on some subscales of the SCAS, but change on its total score was minimal.

Conclusions

A mindfulness‐based, multi‐component, in‐school group sleep intervention following brief screening is feasible, and has the potential to improve sleep. Its impact on anxiety needs further investigation.
Predictive utility of blood pressure, waist circumference and body mass index for metabolic syndrome in patients with schizophrenia in Singapore
Authors: Nurjono Milawaty , Lee Jimmy
Published: July 2012

Aims

This study aims to examine and compare the predictive utility of blood pressure (BP), waist circumference (WC) and body mass index (BMI), and to determine optimal cut‐off values in prediction of metabolic syndrome (MetS) in patients with chronic schizophrenia.

Methods

About 100 patients with chronic schizophrenia were recruited. BMI and BP were measured and laboratory tests to evaluate patients’ high‐density lipoprotein cholesterol, triglycerides and glucose levels were performed. Presence of MetS was examined according to AHA/NHLBI guidelines. Predictive utility of BP, WC and BMI was examined using receiver operating curve and discriminant indices were determined accordingly.

Results

Forty‐six (46%) patients were identified to have MetS. BMI of ≥23 kg m−2 was most accurate (AUC = 0.83, P < 0.001), with sensitivity of 93.5%, specificity of 48.1%, positive predictive value of 60.6% and negative predictive value of 92.9% in identifying MetS.

Conclusion

This finding has immediate and significant clinical implications in the local population with schizophrenia.
Biogeographic patterns and conservation priorities for the dung beetle tribePhanaeini (Coleoptera:Scarabaeidae:Scarabaeinae) inBolivia
Authors: Hamel‐Leigue A. Caroli , Herzog Sebastian K. , Larsen Trond H. , Mann Darren J. , Gill Bruce D. , Edmonds W. D. , Spector Sacha
Published: July 2012

The New World Phanaeini are the best known Neotropical dung beetle tribe and a conservation priority among the Scarabaeinae, an ideal focal taxon for biodiversity research and conservation.

We compiled a comprehensive distributional database for 39 phanaeine species in Bolivia and assessed patterns of species richness, body size and endemism in relation to abiotic variables and species richness and body mass of medium to large mammals across nine ecoregions.

Pair‐wise linear regressions indicated that phanaeine richness, mean size and endemism are determined by different factors. In all cases mammal body mass had greater explanatory power than abiotic variables or mammal richness. Phanaeine richness was greater in ecoregions with on average smaller mammals and greater mammal richness. Mean phanaeine size increased with mean body mass of the largest herbivorous and omnivorous mammals. Endemism was greater in ecoregions with on average smaller herbivorous and omnivorous mammals. On average, smaller phanaeines had more restricted distributions than larger species; ecoregional endemism and mean body size were negatively correlated.

Large phanaeines probably depend on large mammals to provide adequate food resources. Greater richness of smaller mammal species may allow for greater temporal and spatial resource partitioning and therefore greater phanaeine species richness. Low numbers of large mammal species may favour the persistence of geographically restricted phanaeine species by reducing interspecific competition with larger, more geographically widespread and presumably dominant phanaeines.

Cerrado, Southwest Amazonia and Yungas are priority ecoregions for phanaeine conservation due to high total and endemic species richness.
Stability in forest lepidopteran communities: how sensitive are pest species to experimental forest management?
Authors: Summerville Keith S. , Lane Jamie , Courard‐Hauri David
Published: July 2012

We tested how abundance shifts in lepidopteran species might impact two different aspects of moth community structure within managed forest stands of Morgan‐Monroe State Forest, Indiana.

Significant changes in species abundance and species richness were observed post‐harvest. Sudden eruptions in abundance, however, were not observed at the scale of the regional forest moth metacommunity. The form of the species‐abundance distribution within most forest stands did not deviate from the best‐fit log‐normal model across all three sampling years. Abundance shifts thus appeared to be spatially extensive, low density events.

Frequency of stands occupied by early seral moths increased significantly post‐harvest. Several species with larvae known to be row crop or forage pests were widespread throughout Morgan‐Monroe State Forest (Ostrinia nubilialis,Hypsopygia costalis,Noctua pronuba,Helicoverpa zea) 2 years post‐logging. Potential canopy defoliators were negatively affected by time since harvest even in unmanaged stands suggesting that outbreaks may not be expected as a consequence of harvest disturbance.

This suggests that pre‐harvest abundance is not a good predictor of a species' resilience to forest management. Importantly, weather‐related stochastic changes in abundance might obscure forestry effects.
Blood Pressure in Renal Disease: How to Accomplish the Goal?
Authors: Robles Nicolás R. , Hernandez‐Gallego Roman
Published: July 2012

The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial showed that initial antihypertensive therapy with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing progression of chronic kidney disease as well as cardiovascular morbidity and mortality in renal patients. The renal results of the ACCOMPLISH trial strongly support the recommendation of using calcium channel blockers as second antihypertensive agent added to renin–angiotensin axis‐blocking drugs. This review discusses the validity of these data and their relationship with the cumulative evidence on the effects of calcium antagonists on renal disease progression.
Hoya somadeeae sp. nov. (Apocynaceae, Asclepiadoideae) Thailand and lectotypification of Hoya wrayi
Authors: Rodda Michele , Juhonewe Nadhanielle Simonsson
Published: July 2012

A new species from evergreen montane forests of Thailand, Hoya somadeeae Rodda & Simonsson is here described and illustrated. The new species may be superficially confused with the Peninsular Malaysia endemic H. wrayi King & Gamble, but is clearly separated from it by the very elongated peduncles, up to 20 cm long, the revolute corollas, and outer processes of corona lobes with a membranaceous basal appendage. Morphological affinities between the new species and other Hoya species from Thailand and neighbouring Myanmar and Peninsular Malaysia are discussed.
Dichomitus hubeiensis sp. nov. and a new record of Dichomitus (Basidiomycota) from China
Authors: Li Hai‐Jiao , Cui Bao‐Kai
Published: July 2012

Dichomitus hubeiensis Hai J. Li & B. K. Cui sp. nov. is described from the Hubei province, central China. It is distinct in the genus by its cream to straw‐yellow pore surface and large pores (1–2 per mm), both inamyloid and indextrinoid skeletal hyphae, presence of cystidioles and dendrohyphidia in the hymenium, more or less ellipsoid basidiospores (10–14 × 5.6–7.0 µm). Dichomitus kirkii originally described from Zimbabwe was found in the Yunan province, it is new to the Chinese fungal flora, and is characterized by its buff‐yellow to cinnamon‐buff pore surface, entire to lacerate pores (1–2 per mm) and large cylindrical basidiospores (20.8–25.0 × 6.8–8.0 µm).
The identity of the genus Metaeritrichium in Boraginaceae
Authors: Han Bao‐Cai , Zhang Ming‐Li , Goyder David J.
Published: July 2012

Metaeritrichium has been considered monotypic and endemic to China in traditional taxonomic treatments. However, our examinations of specimens and bibliography, combined with field observations, reveal that Metaeritrichium microuloides is conspecific with Actinocarya acaulis. Metaeritrichium is therefore treated as a synonym of Actinocarya. We also clarify the typification of Actinocarya acaulis.
Cognition and the Evolution of Music: Pitfalls and Prospects
Authors: Honing Henkjan , Ploeger Annemie
Published: July 2012

What was the role of music in the evolutionary history of human beings? We address this question from the point of view that musicality can be defined as a cognitive trait. Although it has been argued that we will never know how cognitive traits evolved (Lewontin, 1998), we argue that we may know the evolution of music by investigating the fundamental cognitive mechanisms of musicality, for example, relative pitch, tonal encoding of pitch, and beat induction. In addition, we show that a nomological network of evidence (Schmitt & Pilcher, 2004) can be built around the hypothesis that musicality is a cognitive adaptation. Within this network, different modes of evidence are gathered to support a specific evolutionary hypothesis. We show that the combination of psychological, medical, physiological, genetic, phylogenetic, hunter–gatherer, and cross‐cultural evidence indicates that musicality is a cognitive adaptation.
A note on gene pleiotropy estimation from phylogenetic analysis of protein sequences
Authors: CHEN Wen‐Hai , SU Zhi‐Xi , GU Xun
Published: July 2012

Recently, several statistical methods have been independently proposed for estimating the degree (n) of gene pleiotropy (i.e. the capacity of a gene to affect many phenotypes) without knowing measurable phenotypic traits. However, the theoretical limitation of these approaches has not been well demonstrated. In this short note, we show that our previous method based on the phylogeny of protein sequences is, in fact, an effective estimate of a parameter that can be written symbolically as K = min(n,r), where r is the rank of mutations at an amino acid site. Hence, understanding of r is crucial for appropriate interpretation of the estimated K, denoted by Ke (the effective gene pleiotropy). Indeed, when protein sequence alignment is used to estimate effective gene pleiotropy (Ke) by this method, Ke can be interpreted as an effective estimate of n when n ≤ 20, as long as the phylogeny is sufficiently large. If n > 20, Ke → 20, although the true n could be much higher.
Structured elicitation of expert judgments for threatened species assessment: a case study on a continental scale using email
Authors: McBride Marissa F. , Garnett Stephen T. , Szabo Judit K. , Burbidge Allan H. , Butchart Stuart H. M. , Christidis Les , Dutson Guy , Ford Hugh A. , Loyn Richard H. , Watson David M. , Burgman Mark A.
Published: July 2012

1. Expert knowledge is used routinely to inform listing decisions under the IUCN Red List criteria. Differences in opinion arise between experts in the presence of epistemic uncertainty, as a result of different interpretations of incomplete information and differences in individual beliefs, values and experiences. Structured expert elicitation aims to anticipate and account for such differences to increase the accuracy of final estimates.

2. A diverse panel of 16 experts independently evaluated up to 125 parameters per taxon to assess the IUCN Red List category of extinction risk for nine Australian bird taxa. Each panellist was provided with the same baseline data. Additional judgments and advice were sought from taxon specialists outside the panel. One question set elicited lowest and highest plausible estimates, best estimates and probabilities that the true values were contained within the upper and lower bounds. A second question set elicited yes/no answers and a degree of credibility in the answer provided.

3. Once initial estimates were obtained, all panellists were shown each others’ values. They discussed differences and reassessed their original values. Most communication was carried out by email.

4. The process took nearly 6 months overall to complete, and required an average of 1 h and up to 13 h per taxon for a panellist to complete the initial assessment.

5. Panellists were mostly in agreement with one another about IUCN categorisations for each taxon. Where they differed, there was some evidence of convergence in the second round of assessments, although there was persistent non‐overlap for about 2% of estimates. The method exposed evidence of common subjective biases including overconfidence, anchoring to available data, definitional ambiguity and the conceptual difficulty of estimating percentages rather than natural numbers.

6. This study demonstrates the value of structured elicitation techniques to identify and to reduce potential sources of bias and error among experts. The formal nature of the process meant that the consensus position reached carried greater weight in subsequent deliberations on status. The structured process is worthwhile for high profile or contentious taxa, but may be too time intensive for less divisive cases.
Cyclothiazide‐induced persistent increase in respiratory‐related activity in vitro
Authors: Babiec Walter E. , Faull Kym F. , Feldman Jack L.
Published: July 2012

Key points

Hypoglossal (XII) motoneurons (MNs) innervate the genioglossus muscle of the tongue, which plays an important role in maintaining upper airway patency and modulating upper airway resistance.

Cyclothiazide (CTZ) is a diuretic, anti‐hypertensive, AMPA receptor modulator.

We show that CTZ induces a profound and long‐lasting increase in the amplitude of respiratory‐related XII nerve activity in rhythmically active neonatal rat medullary slices, with integrated XII nerve burst amplitude rising to 262 ± 23% of pre‐treatment control at 1 h post‐treatment and much of this increase lasting at least 12 h.

This phenomenon is not plasticity and does not depend on AMPA or NMDA receptor activation or on coincident protein kinase A or C activity for its induction.

Electrophysiological and mass spectrometric analyses indicate that the cause is prolonged bioavailability of CTZ.

Discovering methods for inducing long‐term increases in genioglossal motoneuronal excitability to AMPA‐mediated drive may help in the development of therapeutics for upper airway motor disorders such as obstructive sleep apnoea (OSA). These results illustrate a latent residual capacity for potentiating AMPA‐mediated inspiratory drive to XII MNs that might be applied to the treatment of upper airway motor deficits such as OSA.

Abstract  Hypoglossal (XII) motoneurons (MNs) innervate the genioglossus muscle of the tongue, which plays an important role in maintaining upper airway patency, particularly during sleep, and modulating upper airway resistance. Discovering methods for inducing long‐term increases in genioglossal motoneuronal excitability to AMPA‐mediated drive may help in the development of therapeutics for upper airway motor disorders such as obstructive sleep apnoea. We show that the diuretic, anti‐hypertensive, AMPA receptor modulator cyclothiazide (CTZ) induces a profound and long‐lasting increase in the amplitude of respiratory‐related XII nerve activity in rhythmically active neonatal rat medullary slices. Treatment of the slice with CTZ (90 μm) for 1 h increased the integrated XII (∫XII) nerve burst amplitude to 262 ± 23% of pre‐treatment control at 1 h post‐treatment; much of this increase lasted at least 12 h. The amount of CTZ‐induced facilitation (CIF) was dependent upon both CTZ dose and exposure time and was accompanied by a long‐lasting increase in endogenous AMPA‐mediated drive currents to XII MNs. CIF, however, is not a form of plasticity and does not depend on AMPA or NMDA receptor activation for its induction. Nor does it depend on coincident protein kinase A or C activity. Rather, measurement of mEPSCs along with mass spectrometric analysis of CTZ‐treated slices indicates that the cause is prolonged bioavailability of CTZ. These results illustrate a latent residual capacity for potentiating AMPA‐mediated inspiratory drive to XII MNs that might be applied to the treatment of upper airway motor deficits.
Sequential interaction of chloride and proton ions with the fast gate steer the voltage‐dependent gating in ClC‐2 chloride channels
Authors: Sánchez‐Rodríguez Jorge E. , De Santiago‐Castillo José A. , Contreras‐Vite Juan Antonio , Nieto‐Delgado Pablo G. , Castro‐Chong Alejandra , Arreola Jorge
Published: July 2012

Key points

Plasma membrane ClC‐2 chloride channels are widely distributed in our body and are important for vision and fertility.

ClC‐2 channels are gated by changes in transmembrane voltage despite of lacking a voltage sensor device. It has been hypothesized that the interaction of an external proton with the gating machinery is responsible for voltage‐dependent gating.

Here we used electrophysiological recordings and quantitative analysis under different external proton and internal chloride concentrations and found that the voltage dependence of gating is due to interaction between the passing chloride ion and the permeation pathway, with the external proton stabilizing the open state of the channel.

Abstract  The interaction of either H+ or Cl− ions with the fast gate is the major source of voltage (Vm) dependence in ClC Cl− channels. However, the mechanism by which these ions confer Vm dependence to the ClC‐2 Cl− channel remains unclear. By determining the Vm dependence of normalized conductance (Gnorm(Vm)), an index of open probability, ClC‐2 gating was studied at different [H+]i, [H+]o and [Cl−]i. Changing [H+]i by five orders of magnitude whilst [Cl−]i/[Cl−]o= 140/140 or 10/140 mm slightly shifted Gnorm(Vm) to negative Vm without altering the onset kinetics; however, channel closing was slower at acidic pHi. A similar change in [H+]o with [Cl−]i/[Cl−]o= 140/140 mm enhanced Gnorm in a bell‐shaped manner and shifted Gnorm(Vm) curves to positive Vm. Importantly, Gnorm was >0 with [H+]o= 10−10 m but channel closing was slower when [H+]o or [Cl−]i increased implying that ClC‐2 was opened without protonation and that external H+ and/or internal Cl− ions stabilized the open conformation. The analysis of kinetics and steady‐state properties at different [H+]o and [Cl−]i was carried out using a gating Scheme coupled to Cl− permeation. Unlike previous results showing Vm‐dependent protonation, our analysis revealed that fast gate protonation was Vm and Cl− independent and the equilibrium constant for closed–open transition of unprotonated channels was facilitated by elevated [Cl−]i in a Vm‐dependent manner. Hence a Vm dependence of pore occupancy by Cl− induces a conformational change in unprotonated closed channels, before the pore opens, and the open conformation is stabilized by Cl− occupancy and Vm‐independent protonation.
Human phase response curve to intermittent blue light using a commercially available device
Authors: Revell Victoria L. , Molina Thomas A. , Eastman Charmane I.
Published: July 2012

Key points

Misalignment between the internal circadian clock driving daily rhythms in physiology and behaviour, such as sleepiness, performance and metabolism, and the sleep–wake schedule, as occurs in jet lag and night shift work, can have profound, harmful consequences for health, performance and safety.

Light applied at specific times of day can be used to shift the timing of the clock and reduce this circadian misalignment.

We show for the first time that a small, commercially available, portable blue light device is capable of shifting the clock when it is administered daily over a 2 h window (90 min blue light as 30 min pulses with 15 min breaks).

The direction and amount that the clock is shifted depends on the time of day that the light is administered.

The results of this work provide a practical, effective light treatment that can be used in the real world.

Abstract  Light shifts the timing of the circadian clock according to a phase response curve (PRC). To date, all human light PRCs have been to long durations of bright white light. However, melanopsin, the primary photopigment for the circadian system, is most sensitive to short wavelength blue light. Therefore, to optimise light treatment it is important to generate a blue light PRC. We used a small, commercially available blue LED light box, screen size 11.2 × 6.6 cm at ∼50 cm, ∼200 μW cm−2, ∼185 lux. Subjects participated in two 5 day laboratory sessions 1 week apart. Each session consisted of circadian phase assessments to obtain melatonin profiles before and after 3 days of free‐running through an ultradian light–dark cycle (2.5 h wake in dim light, 1.5 h sleep in the dark), forced desynchrony protocol. During one session subjects received intermittent blue light (three 30 min pulses over 2 h) once a day for the 3 days of free‐running, and in the other session (control) they remained in dim room light, counterbalanced. The time of blue light was varied among subjects to cover the entire 24 h day. For each individual, the phase shift to blue light was corrected for the free‐run determined during the control session. The blue light PRC had a broad advance region starting in the morning and extending through the afternoon. The delay region started a few hours before bedtime and extended through the night. This is the first PRC to be constructed to blue light and to a stimulus that could be used in the real world.
Hypoxic regulation of cardiac Ca2+ channel: possible role of haem oxygenase
Authors: Rosa Angelo O. , Movafagh Shahrzad , Cleemann Lars , Morad Martin
Published: July 2012

Key points

Lack of oxygen to the heart, hypoxia, triggers a cascade of events that within minutes leads to irreversible tissue damage.

One of the initial steps at the onset of hypoxia is suppression of the cellular calcium channels that control the strength of the heartbeat.

The role of oxygen in energy production is well known, but it is not known how lack of oxygen within seconds may suppress the calcium channels.

We tested the involvement of different regulatory pathways that are known to modulate the calcium channel in response to various stimuli, and succeeded to link it to a haem oxygenase protein that may act as the primary oxygen sensor.

Our findings provide a better understanding of the initial events that occur during episodes of acute hypoxia induced by coronary thrombosis and bring into focus a new set of therapeutic considerations.

Abstract  Acute and chronic hypoxias are common cardiac diseases that lead often to arrhythmia and impaired contractility. At the cellular level it is unclear whether the suppression of cardiac Ca2+ channels (CaV1.2) results directly from oxygen deprivation on the channel protein or is mediated by intermediary proteins affecting the channel. To address this question we measured the early effects of hypoxia (5–60 s, ) on Ca2+ current (ICa) and tested the involvement of protein kinase A (PKA) phosphorylation, Ca2+/calmodulin‐mediated signalling and the haem oxygenase (HO) pathway in the hypoxic regulation of CaV1.2 in rat and cat ventricular myocytes and HEK‐293 cells. Hypoxic suppression of ICa and Ca2+ transients was significant within 5 s and intensified in the following 50 s, and was reversible. Phosphorylation by cAMP or the phosphatase inhibitor okadaic acid desensitized ICa to hypoxia, while PKA inhibition by H‐89 restored the sensitivity of ICa to hypoxia. This phosphorylation effect was specific to Ca2+, but not Ba2+ or Na+, permeating through the channel. CaMKII inhibitory peptide and Bay K8644 reversed the phosphorylation‐induced desensitization to hypoxia. Mutation of CAM/CaMKII‐binding motifs of the α1c subunit of CaV1.2 fully desensitized the Ca2+ channel to hypoxia. Rapid application of HO inhibitors (zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP)) suppressed the channel in a manner similar to acute hypoxia such that: (1) ICa and IBa were suppressed within 5 s of ZnPP application; (2) PKA activation and CaMKII inhibitors desensitized ICa, but not IBa, to ZnPP; and (3) hypoxia failed to further suppress ICa and IBa in ZnPP‐treated myocytes. We propose that the binding of HO to the CaM/CaMKII‐specific motifs on Ca2+ channel may mediate the rapid response of the channel to hypoxia.
Expression and properties of hyperpolarization‐activated current in rat dorsal root ganglion neurons with known sensory function
Authors: Gao L. L. , McMullan S. , Djouhri L. , Acosta C. , Harper A. A. , Lawson S. N.
Published: July 2012

Key point

I
h is a hyperpolarisation‐activated current that influences neuronal excitability and is present in some sensory neurons.

The magnitude and properties of Ih in different groups of sensory neurons that respond to painful stimuli (nociceptors) or to non‐painful stimuli, such as low threshold mechanoreceptors (LTMs), were unknown.

We found that neurons with the greatest Ih were the nociceptors and LTMs with the fastest conducting fibres. The highest Ih of all was present in LTM neurons that sense muscle stretch and length (muscle spindle afferents).

The high levels of Ih could fundamentally influence excitability of fast conducting sensory neurons which detect muscle stretch/length, touch and pressure, and painful stimuli. Ih could thus influence sensations associated with all these.

The properties of Ih are similar to those of HCN1‐ and HCN2‐related Ih, suggesting that these channels underlie the current.

Abstract  The hyperpolarization‐activated current (Ih) has been implicated in nociception/pain, but its expression levels in nociceptors remained unknown. We recorded Ih magnitude and properties by voltage clamp from dorsal root ganglion (DRG) neurons in vivo, after classifying them as nociceptive or low‐threshold‐mechanoreceptors (LTMs) and as having C‐, Aδ‐ or Aα/β‐conduction velocities (CVs). For both nociceptors and LTMs, Ih amplitude and Ih density (at −100 mV) were significantly positively correlated with CV. Median Ih magnitudes and Ih density in neuronal subgroups were respectively: muscle spindle afferents (MSAs): −4.6 nA, −33 pA pF−1; cutaneous Aα/β LTMs: −2.2 nA, −20 pA pF−1; Aβ‐nociceptors: −2.6 nA, −21 pA pF−1; both Aδ‐LTMs and nociceptors: −1.3 nA, ∼−14 pA pF−1; C‐LTMs: −0.4 nA, −7.6 pA pF−1; and C‐nociceptors: −0.26 nA, −5 pA pF−1. Ih activation slow time constants (slow τ values) were strongly correlated with fast τ values; both were shortest in MSAs. Most neurons had τ values consistent with HCN1‐related Ih; others had τ values closer to HCN1+HCN2 channels, or HCN2 in the presence of cAMP. In contrast, median half‐activation voltages (V0.5) of −80 to −86 mV for neuronal subgroups suggest contributions of HCN2 to Ih. τ values were unrelated to CV but were inversely correlated with Ih and Ih density for all non‐MSA LTMs, and for Aδ‐nociceptors. From activation curves ∼2–7% of Ih would be activated at normal membrane potentials. The high Ih may be important for excitability of A‐nociceptors (responsible for sharp/pricking‐type pain) and Aα/β‐LTMs (tactile sensations and proprioception). Underlying HCN expression in these subgroups therefore needs to be determined. Altered Ih expression and/or properties (e.g. in chronic/pathological pain states) may influence both nociceptor and LTM excitability.
Science Signaling
Podcast: 3 July 2012
Authors: Garcia K. Christopher , VanHook Annalisa M.
Published: July 2012

Structural analysis reveals how a Wnt binds to its receptor.
PINning a Tumor Suppressor
Authors: Wong Wei
Published: July 2012

Prolyl isomerization reduces the abundance of the tumor suppressor Fbw7 by triggering its self-ubiquitination.
Antibacterial Properties of an Oligo-Acyl-Lysyl Hexamer Targeting Gram-Negative Species
Authors: Zaknoon Fadia , Goldberg Keren , Sarig Hadar , Epand Raquel F. , Epand Richard M. , Mor Amram
Published: July 2012

Toward developing new tools for fighting resistance to antibiotics, we investigated the antibacterial properties of a new decanoyl-based oligo-acyl-lysyl (OAK) hexamer, aminododecanoyl-lysyl-[aminodecanoyl-lysyl]
5
(α
12
-5α
10
). The OAK exhibited preferential activity against Gram-negative bacteria (GNB), as determined using 36 strains, including diverse species, with an MIC
90
of 6.2 μM. The OAK's bactericidal mode of action was associated with rapid membrane depolarization and cell permeabilization, suggesting that the inner membrane was the primary target, whereas the observed binding affinity to lipoteichoic acid suggested that inefficacy against Gram-positive species resulted from a cell wall interaction preventing α
12
-5α
10
from reaching internal targets. Interestingly, perturbation of the inner membrane structure and function was preserved at sub-MIC values. This prompted us to assess the OAK's effect on the proton motive force-dependent efflux pump AcrAB-TolC, implicated in the low sensitivity of GNB to various antibiotics, including erythromycin. We found that under sub-MIC conditions, wild-type
Escherichia coli
was significantly more sensitive to erythromycin (the MIC dropped by >10-fold), unlike its
acr
-deletion mutant. Collectively, the data suggest a useful approach for treating GNB infections through overcoming antibiotic efflux.
Serotype and Clonal Evolution of Penicillin-Nonsusceptible Invasive Streptococcus pneumoniae in the 7-Valent Pneumococcal Conjugate Vaccine Era in Italy
Authors: Gherardi Giovanni , D'Ambrosio Fabio , Visaggio Daniela , Dicuonzo Giordano , Del Grosso Maria , Pantosti Annalisa
Published: July 2012

The percentage of invasive penicillin-nonsusceptible pneumococci (PNSSP) isolated in Italy in the seven-valent pneumococcal conjugate vaccine (PCV7) era moderately increased in comparison to the pre-PCV7 era. Increase of nonvaccine serotypes was observed among PNSSP. The most frequent PNSSP clones were the same as those identified in the pre-PCV7 era, although they were present in different proportions. Clonal expansion, emergence of new clones, and acquisition of penicillin resistance by established clones contributed to the maintenance of penicillin resistance.
The Antibiotic Resistance Arrow of Time: Efflux Pump Induction Is a General First Step in the Evolution of Mycobacterial Drug Resistance
Authors: Schmalstieg Aurelia M. , Srivastava Shashikant , Belkaya Serkan , Deshpande Devyani , Meek Claudia , Leff Richard , van Oers Nicolai S. C. , Gumbo Tawanda
Published: July 2012

We hypothesize that low-level efflux pump expression is the first step in the development of high-level drug resistance in mycobacteria. We performed 28-day azithromycin dose-effect and dose-scheduling studies in our hollow-fiber model of disseminated
Mycobacterium avium-M. intracellulare
complex. Both microbial kill and resistance emergence were most closely linked to the within-macrophage area under the concentration-time curve (AUC)/MIC ratio. Quantitative PCR revealed that subtherapeutic azithromycin exposures over 3 days led to a 56-fold increase in expression of MAV_3306, which encodes a putative ABC transporter, and MAV_1406, which encodes a putative major facilitator superfamily pump, in
M. avium
. By day 7, a subpopulation of
M. avium
with low-level resistance was encountered and exhibited the classic inverted U curve versus AUC/MIC ratios. The resistance was abolished by an efflux pump inhibitor. While the maximal microbial kill started to decrease after day 7, a population with high-level azithromycin resistance appeared at day 28. This resistance could not be reversed by efflux pump inhibitors. Orthologs of pumps encoded by MAV_3306 and MAV_1406 were identified in
Mycobacterium tuberculosis
,
Mycobacterium leprae
,
Mycobacterium marinum
,
Mycobacterium abscessus
, and
Mycobacterium ulcerans
. All had highly conserved protein secondary structures. We propose that induction of several efflux pumps is the first step in a general pathway to drug resistance that eventually leads to high-level chromosomal-mutation-related resistance in mycobacteria as ordered events in an “antibiotic resistance arrow of time.”
Novel Dehalogenase Mechanism for 2,3-Dichloro-1-Propanol Utilization in Pseudomonas putida Strain MC4
Authors: Arif Muhammad Irfan , Samin Ghufrana , van Leeuwen Jan G. E. , Oppentocht Jantien , Janssen Dick B.
Published: June 2012

A
Pseudomonas putida
strain (MC4) that can utilize 2,3-dichloro-1-propanol (DCP) and several aliphatic haloacids and haloalcohols as sole carbon and energy source for growth was isolated from contaminated soil. Degradation of DCP was found to start with oxidation and concomitant dehalogenation catalyzed by a 72-kDa monomeric protein (DppA) that was isolated from cell lysate. The
dppA
gene was cloned from a cosmid library and appeared to encode a protein equipped with a signal peptide and that possessed high similarity to quinohemoprotein alcohol dehydrogenases (ADHs), particularly ADH IIB and ADH IIG from
Pseudomonas putida
HK. This novel dehalogenating dehydrogenase has a broad substrate range, encompassing a number of nonhalogenated alcohols and haloalcohols. With DCP, DppA exhibited a
k
cat
of 17 s
−1
.
1
H nuclear magnetic resonance experiments indicated that DCP oxidation by DppA in the presence of 2,6-dichlorophenolindophenol (DCPIP) and potassium ferricyanide [K
3
Fe(CN)
6
] yielded 2-chloroacrolein, which was oxidized to 2-chloroacrylic acid.
Distance-Decay Relationships Partially Determine Diversity Patterns of Phyllosphere Bacteria on Tamrix Trees across the Sonoran Desert
Authors: Finkel Omri M. , Burch Adrien Y. , Elad Tal , Huse Susan M. , Lindow Steven E. , Post Anton F. , Belkin Shimshon
Published: June 2012

Dispersal limitation in phyllosphere communities was measured on the leaf surfaces of salt-excreting
Tamarix
trees, which offer unique, discrete habitats for microbial assemblages. We employed 16S rRNA gene pyrosequencing to measure bacterial community dissimilarity on leaves of spatially dispersed
Tamarix
specimens in sites with uniform climatic conditions across the Sonoran Desert in the Southwestern United States. Our analyses revealed diverse bacterial communities with four dominant phyla that exhibited differential effects of environmental and geographic variables. Geographical distance was the most important parameter that affected community composition, particularly that of betaproteobacteria, which displayed a statistically significant, distance-decay relationship.
Production of Aromatic Compounds by Metabolically Engineered Escherichia coli with an Expanded Shikimate Pathway
Authors: Koma Daisuke , Yamanaka Hayato , Moriyoshi Kunihiko , Ohmoto Takashi , Sakai Kiyofumi
Published: June 2012

Escherichia coli
was metabolically engineered by expanding the shikimate pathway to generate strains capable of producing six kinds of aromatic compounds, phenyllactic acid, 4-hydroxyphenyllactic acid, phenylacetic acid, 4-hydroxyphenylacetic acid, 2-phenylethanol, and 2-(4-hydroxyphenyl)ethanol, which are used in several fields of industries including pharmaceutical, agrochemical, antibiotic, flavor industries, etc. To generate strains that produce phenyllactic acid and 4-hydroxyphenyllactic acid, the lactate dehydrogenase gene (
ldhA
) from
Cupriavidus necator
was introduced into the chromosomes of phenylalanine and tyrosine overproducers, respectively. Both the phenylpyruvate decarboxylase gene (
ipdC
) from
Azospirillum brasilense
and the phenylacetaldehyde dehydrogenase gene (
feaB
) from
E. coli
were introduced into the chromosomes of phenylalanine and tyrosine overproducers to generate phenylacetic acid and 4-hydroxyphenylacetic acid producers, respectively, whereas
ipdC
and the alcohol dehydrogenase gene (
adhC
) from
Lactobacillus brevis
were introduced to generate 2-phenylethanol and 2-(4-hydroxyphenyl)ethanol producers, respectively. Expression of the respective introduced genes was controlled by the T7 promoter. While generating the 2-phenylethanol and 2-(4-hydroxyphenyl)ethanol producers, we found that produced phenylacetaldehyde and 4-hydroxyphenylacetaldehyde were automatically reduced to 2-phenylethanol and 2-(4-hydroxyphenyl)ethanol by endogenous aldehyde reductases in
E. coli
encoded by the
yqhD
,
yjgB
, and
yahK
genes. Cointroduction and cooverexpression of each gene with
ipdC
in the phenylalanine and tyrosine overproducers enhanced the production of 2-phenylethanol and 2-(4-hydroxyphenyl)ethanol from glucose. Introduction of the
yahK
gene yielded the most efficient production of both aromatic alcohols. During the production of 2-phenylethanol, 2-(4-hydroxyphenyl)ethanol, phenylacetic acid, and 4-hydroxyphenylacetic acid, accumulation of some by-products were observed. Deletion of
feaB
,
pheA
, and/or
tyrA
genes from the chromosomes of the constructed strains resulted in increased desired aromatic compounds with decreased by-products. Finally, each of the six constructed strains was able to successfully produce a different aromatic compound as a major product. We show here that six aromatic compounds are able to be produced from renewable resources without supplementing with expensive precursors.
Host Preferences of Arbuscular Mycorrhizal Fungi Colonizing Annual Herbaceous Plant Species in Semiarid Mediterranean Prairies
Authors: Torrecillas E. , Alguacil M. M. , Roldán A.
Published: June 2012

In this study, we have analyzed and compared the diversities of the arbuscular mycorrhizal fungi (AMF) colonizing the roots of five annual herbaceous species (
Hieracium vulgare
,
Stipa capensis
,
Anagallis arvensis
,
Carduus tenuiflorus
, and
Avena barbata
) and a perennial herbaceous species (
Brachypodium retusum
). Our goal was to determine the differences in the communities of the AMF among these six plant species belonging to different families, using
B. retusum
as a reference. The AMF small-subunit rRNA genes (SSU) were subjected to nested PCR, cloning, sequencing, and phylogenetic analysis. Thirty-six AMF phylotypes, belonging to
Glomus
group A,
Glomus
group B,
Diversispora
,
Paraglomus
, and
Ambispora
, were identified. Five sequence groups identified in this study clustered to known glomalean species or isolates: group
Glomus
G27 to
Glomus intraradices
, group
Glomus
G19 to
Glomus iranicum
, group
Glomus
G10 to
Glomus mosseae
, group
Glomus
G1 to
Glomus lamellosum/etunicatum/luteum
, and group
Ambispora
1 to
Ambispora fennica
. The six plant species studied hosted different AMF communities. A certain trend of AMF specificity was observed when grouping plant species by taxonomic families, highlighting the importance of protecting and even promoting the native annual vegetation in order to maintain the biodiversity and productivity of these extreme ecosystems.
Serratia marcescens Quinoprotein Glucose Dehydrogenase Activity Mediates Medium Acidification and Inhibition of Prodigiosin Production by Glucose
Authors: Fender James E. , Bender Cody M. , Stella Nicholas A. , Lahr Roni M. , Kalivoda Eric J. , Shanks Robert M. Q.
Published: June 2012

Serratia marcescens
is a model organism for the study of secondary metabolites. The biologically active pigment prodigiosin (2-methyl-3-pentyl-6-methoxyprodiginine), like many other secondary metabolites, is inhibited by growth in glucose-rich medium. Whereas previous studies indicated that this inhibitory effect was pH dependent and did not require cyclic AMP (cAMP), there is no information on the genes involved in mediating this phenomenon. Here we used transposon mutagenesis to identify genes involved in the inhibition of prodigiosin by glucose. Multiple genetic loci involved in quinoprotein glucose dehydrogenase (GDH) activity were found to be required for glucose inhibition of prodigiosin production, including pyrroloquinoline quinone and ubiquinone biosynthetic genes. Upon assessing whether the enzymatic products of GDH activity were involved in the inhibitory effect, we observed that
d
-glucono-1,5-lactone and
d
-gluconic acid, but not
d
-gluconate, were able to inhibit prodigiosin production. These data support a model in which the oxidation of
d
-glucose by quinoprotein GDH initiates a reduction in pH that inhibits prodigiosin production through transcriptional control of the prodigiosin biosynthetic operon, providing new insight into the genetic pathways that control prodigiosin production. Strains generated in this report may be useful in large-scale production of secondary metabolites.
Enhanced Basophil Reactivities during Severe Malaria and Their Relationship with the Plasmodium falciparum Histamine-Releasing Factor Translationally Controlled Tumor Protein
Authors: Pelleau Stéphane , Diop Sylvie , Dia Badiane Méry , Vitte Joana , Beguin Pierre , Nato Farida , Diop Bernard M. , Bongrand Pierre , Parzy Daniel , Jambou Ronan
Published: July 2012

Recent studies suggest shared pathogenic pathways during malaria and allergy. Indeed, IgE, histamine, and the parasite-derived
Plasmodium falciparum
histamine-releasing factor translationally controlled tumor protein (PfTCTP) can be found at high levels in serum from patients experiencing malaria, but their relationship with basophil activation remains unknown. We recruited
P. falciparum
-infected patients in Senegal with mild malaria (MM;
n
= 19) or severe malaria (SM;
n
= 9) symptoms and healthy controls (HC;
n
= 38). Levels of serum IgE, PfTCTP, and IgG antibodies against PfTCTP were determined by enzyme-linked immunosorbent assays (ELISA). Basophil reactivities to IgE-dependent and -independent stimulations were measured
ex vivo
using fresh blood by looking at the expression level of the basophil activation marker CD203c with flow cytometry. Unstimulated basophils from MM had significantly lower levels of CD203c expression compared to those from HC and SM. After normalization on this baseline level, basophils from SM showed an enhanced reactivity to calcimycin (A23187) and hemozoin. Although SM reached higher median levels of activation after anti-IgE stimulation, great interindividual differences did not allow the results to reach statistical significance. When primed with recombinant TCTP before anti-IgE, qualitative differences in terms of a better ability to control excessive activation could be described for SM. IgE levels were very high in malaria patients, but concentrations in MM and SM were similar and were not associated with basophil responses, which demonstrates that the presence of IgE alone cannot explain the various basophil reactivities. Indeed, PfTCTP could be detected in 32% of patients, with higher concentrations for SM. These PfTCTP-positive patients displayed significantly higher basophil reactivities to any stimulus. Moreover, the absence of anti-PfTCTP IgG was associated with higher responses in SM but not MM. Our results show an association between basophil reactivity and malaria severity and suggest a pathogenic role for plasmodial PfTCTP in the induction of this allergy-like mechanism.