bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraindividual variability of the modified Schwartz and novel CKiD GFR equations in pediatric renal transplant patients
Authors: Tsampalieros Anne , Lepage Nathalie , Feber Janusz
Published: August 2011

Tsampalieros A, Lepage N, Feber J. Intraindividual variability of the modified Schwartz and novel CKiD GFR equations in pediatric renal transplant patients. Pediatr Transplantation 2011: 15: 760–765. © 2011 John Wiley & Sons A/S.

Abstract:  GFR in children can be obtained from a formula using SCr and height or various formulas including serum CysC. Recently, two new GFR formulas have been developed: (i) height and SCr—mSchwartz GFR and (ii) height, SCr, CysC, and serum urea (CKiD GFR). While these formulas proved to be accurate when compared to the gold standard, their use in children post‐kidney Tx is yet to be assessed. A total of 1174 blood samples (urea, SCr and CysC) were analyzed from the post‐Tx period in 24 Tx children (12 boys, median age = 8.6 yr) currently followed at our institution. CKiD GFR and mSchwartz GFR were compared using Bland–Altman analysis and the CV. The mSchwartz GFR overestimated the CKiD GFR (mean bias = 1.09 ± 0.14; 95% limits of agreements from 0.82 to 1.36). Median CV of CKiD GFR (10.3%) was significantly lower than that of mSchwartz GFR (15.0%), p = 0.04, and negatively correlated with the slope of GFR (r2 = 0.34, p = 0.0026). In conclusion, CKiD GFR has a significantly lower intraindividual variation than mSchwartz GFR and may be better suited for longitudinal follow‐up of patients post‐Tx.
Effect of initial combination therapy with sitagliptin and metformin on β‐cell function in patients with type 2 diabetes
Authors: Williams‐Herman D. , Xu L. , Teng R. , Golm G. T. , Johnson J. , Davies M. J. , Kaufman K. D. , Goldstein B. J.
Published: August 2011

Aim: To examine the effect of sitagliptin and metformin, alone and in combination, on modelled parameters of β‐cell function in patients with type 2 diabetes.

Methods: The data used in the present analyses are from a 104‐week study, which included a 24‐week, placebo‐ and active controlled phase followed by a 30‐week, active controlled, continuation phase and an additional 50‐week, active controlled extension phase. Patients were randomised to one of six blinded treatments: sitagliptin 50 mg + metformin 1000 mg b.i.d., sitagliptin 50 mg + metformin 500 mg b.i.d., metformin 1000 mg b.i.d., metformin 500 mg b.i.d., sitagliptin 100 mg q.d. or placebo. Patients on placebo were switched in a blinded manner to metformin 1000 mg b.i.d. at week 24. Subsets of patients volunteered to undergo frequently sampled meal tolerance tests at baseline and at weeks 24, 54 and 104. β‐cell responsivity was assessed with the C‐peptide minimal model. The static component (Φs) estimates the rate of insulin secretion related to above‐basal glucose concentration. The dynamic component (Φd) is related to the rate of change in glucose. The total index (Φtotal) represents the overall response to a glycaemic stimulus and is calculated as a function of Φs and Φd. Insulin sensitivity was estimated with the Matsuda index (ISI). The disposition index, which assesses insulin secretion relative to the prevailing insulin sensitivity, was calculated based on the Φtotal and ISI.

Results: At week 24, substantial reductions in postmeal glucose were observed with all active treatment groups relative to the placebo group. Φs, Φtotal and the disposition index were significantly improved from baseline at week 24 with all active treatments relative to placebo. Generally larger effects were observed with the initial combination of sitagliptin and metformin relative to the monotherapy groups. When expressed as median percent change from baseline, Φs increased from baseline by 137 and 177% in the low‐ and high‐dose combination groups and by 85, 54, 73 and −9% in the high‐dose metformin, low‐dose metformin, sitagliptin monotherapy and placebo groups, respectively. At weeks 54 and 104, the combination treatment groups continued to demonstrate greater improvements in β‐cell function relative to their respective monotherapy groups.

Conclusions: After 24 weeks of therapy, relative to placebo, initial treatment with sitagliptin or metformin monotherapy improved β‐cell function; moreover, initial combination therapy demonstrated larger improvements than the individual monotherapies. Improvements in β‐cell function were found with treatments for up to 2 years.
Cost‐effectiveness analysis of degarelix for advanced hormone‐dependent prostate cancer
Authors: Lu Lanting , Peters Jaime , Roome Chris , Stein Ken
Published: August 2011

Study Type – Therapy (cost‐effectiveness analysis)

Level of Evidence 2b

What's known on the subject? and What does the study add?

The European Medicines Evaluation Agency recognised that the principal advantage of degarelix is the avoidance of the transient rise in testosterone. This paper compares the cost‐effectiveness of degarelix with the most common treatment in the UK (LHRHa plus short‐term anti‐androgen) for the management of prostate cancer, focusing on the costs and clinical consequences that might be associated by the avoidance of the transient rise in testosterone. Our analysis suggests that, at the current UK list price, degarelix would not represent good value for money for the NHS.

OBJECTIVE

To evaluate the cost‐effectiveness of degarelix vs luteinizing hormone‐releasing hormone analogue (triptorelin) plus short‐term antiandrogen treatment for advanced prostate cancer.

METHODS

We developed a decision analytic model based on a clinical trial and literature review. The two interventions evaluated were: (i) monthly injection of degarelix and (ii) 3‐monthly triptorelin therapy plus short‐term flutamide, cyproterone or bicalutamide treatment.

The model consisted of a decision tree monitoring a hypothetical cohort of patients aged 70 years from the start of hormonal treatment to the end of the first month, and a Markov model monitoring patients from the end of month 1 for a time horizon of 10 years (i.e. when 96% of patients are assumed to have died).

The base‐case analysis assumed patients present with asymptomatic metastatic prostate cancer. Costs and outcomes were collected over the model time horizon. Outcome measures were quality‐adjusted life years (QALYs), lifetime costs and incremental cost‐effectiveness ratios.

Sensitivity analyses (one‐way and multi‐way) and probabilistic sensitivity analyses were conducted to explore the uncertainties around the assumptions.

RESULTS

In the base‐case analysis, the incremental cost‐effectiveness ratio (ICER) for degarelix vs triptorelin plus antiandrogen was £59 000 per QALY gained.

The model was most sensitive to the rate of significant adverse events in the triptorelin plus antiandrogen group. The model was also sensitive to the assumed survival of patients with metastatic prostate cancer and the price of degarelix.

The results of the probabilistic sensitivity analyses suggested that there was a low probability (9.6%) of degarelix being the most cost‐effective treatment option when a willingness‐to‐pay threshold of £30 000 per QALY gained is assumed.

CONCLUSION

Degarelix is unlikely to be cost‐effective compared to triptorelin plus short‐term antiandrogen in the management of advanced prostate cancer with respect to the usual thresholds of cost‐effectiveness used in the UK: £20 000–30 000 per QALY gained (used by the National Institute for Health and Clinical Excellence).
‘Delegated’ Legislation in the (new) European Union: A Constitutional Analysis
Authors: Schütze Robert
Published: August 2011

This article brings classic constitutionalism to an analysis of delegated legislation in the European Union. To facilitate such a constitutional analysis, it starts with a comparative excursion introducing the judicial and political safeguards on executive legislation in American constitutionalism. In the European legal order, similar constitutional safeguards emerged in the last fifty years. First, the Court of Justice developed judicial safeguards in the form of a European non‐delegation doctrine. Second, the European legislator has also insisted on political safeguards within delegated legislation. Under the Rome Treaty, ‘comitology’ was the defining characteristic of executive legislation. The Lisbon Treaty represents a revolutionary restructuring of the regulatory process. The (old) Community regime for delegated legislation is split into two halves. Article 290 of the Treaty on the Functioning of the European Union (TFEU) henceforth governs delegations of legislative power, while Article 291 TFEU establishes the constitutional regime for delegations of executive power.
Targeted disruption of neuronal 19S proteasome subunits induces the formation of ubiquitinated inclusions in the absence of cell death
Authors: Droggiti Anna , Ho Cherry Chen‐Ying , Stefanis Leonidas , Dauer William T. , Rideout Hardy J.
Published: August 2011

J. Neurochem. (2011) 119, 630–643.

Proteasome‐mediated proteolysis is a major protein degradation mechanism in cells and its dysfunction has been implicated in the pathogenesis of several neurodegenerative diseases, each with the common features of neuronal death and formation of ubiquitinated inclusions found within neurites, the cell body, or nucleus. Previous models of proteasome dysfunction have employed pharmacological inhibition of the catalytic subunits of the 20S proteasome core, or the genetic manipulation of specific subunits resulting in altered proteasome assembly. In this study, we report the use of dominant negative subunits of the 19S regulatory proteasome complex that mediate the recognition of ubiquitinated substrates as well as the removal of the poly‐ubiquitin chain. Interestingly, while each mutant subunit‐induced inclusion formation, like that seen with pharmacological inhibition of the 20S proteasome, none was able to induce apoptotic death, or trigger activation of macroautophagy, in either dopaminergic cell lines or primary cortical neurons. This finding highlights the dissociation between the mechanisms of neuronal inclusion formation and the induction of cell death, and represents a novel cellular model for Lewy body‐like inclusion formation in neurons.
Racial disparities in being recommended to surgery for oral and oropharyngeal cancer in the United States
Authors: Weng Yanqiu , Korte Jeffrey E.
Published: August 2011

Weng Y, Korte JE. Racial disparities in being recommended to surgery for oral and oropharyngeal cancer in the United States. Community Dent Oral Epidemiol 2012; 40: 80–88. © 2011 John Wiley & Sons A/S

Abstract –  Objectives:  To investigate the impact of race on the likelihood of patients being recommended for surgery after a diagnosis of oral and oropharyngeal cancer.

Methods:  A total of 68 445 cases of oral and oropharyngeal cancer were extracted from the 1988 to 2005 Surveillance, Epidemiology, and End Results (SEER) database. County‐level rurality data and income data were merged using the US Department of Agriculture Rural‐Urban Continuum Codes dataset and US Census Bureau Small Area Income & Poverty Estimates dataset. We used logistic regression analyses to investigate the impact of race on being recommended to surgery for oral and oropharyngeal cancer, adjusting for demographic, socioeconomic, and clinical factors. Stratified analyses were further conducted by tumor site and rural/urban status.

Results:  Recommendation to surgery varied significantly by race, with black patients less likely than white patients to be recommended to surgery for their oral and oropharyngeal cancer. The racial difference in recommendation to surgery varied significantly by age, geography, and tumor subsite. Racial disparities are most evident in lip and buccal cancer from rural areas (OR, 4.4; 95% CI, 2.6–7.5); and least evident in oropharyngeal cancer from urban areas (OR, 1.2; 95% CI, 1.1–1.3). The magnitude of the racial disparity is attenuated with increasing age.

Conclusions:  We observed substantial racial disparities in surgery recommendation for oral and oropharyngeal cancer in the United States. Our results suggest the need to improve accessibility to better health care in racial minority groups, particularly in rural areas, and call for individual and institutional efforts to avoid physician bias related to the patient’s sociodemographic characteristics in healthcare service.
Catecholamines are the key for explaining the biological relevance of insulin–melatonin antagonisms in type 1 and type 2 diabetes
Authors: Peschke E. , Hofmann K. , Pönicke K. , Wedekind D. , Mühlbauer E.
Published: August 2011

Abstract: In this paper, we analyze the biological relevance of melatonin in diabetogenesis. As has recently been demonstrated, melatonin decreases insulin secretion via specific melatonin receptor isoforms (MT1 and MT2) in the pancreatic β‐cells. In addition, type 2 diabetic rats, as well as patients, exhibit decreased melatonin levels, whereas the levels in type 1 diabetic rats are increased. The latter effects were normalized by insulin substitution, which signifies that a specific receptor‐mediated insulin–melatonin antagonism exists. These results are in agreement with several recent genome‐wide association studies, which have identified a number of single nucleotide polymorphisms in theMTNR1Bgene, encoding the MT2 receptor, that were closely associated with a higher prognostic risk of developing type 2 diabetes. We hypothesize that catecholamines, which decrease insulin levels and stimulate melatonin synthesis, control insulin–melatonin interactions. The present results support this assertion as we show that catecholamines are increased in type 1 but are diminished in type 2 diabetes. Another important line of inquiry involves the fact that melatonin protects the β‐cells against functional overcharge and, consequently, hinders the development of type 2 diabetes. In this context, it is striking that at advanced ages, melatonin levels are reduced and the incidence of type 2 diabetes is increased. Thus, melatonin appears to have a protective biological role. Here, we strongly repudiate misconceptions, resulting from observations that melatonin reduces the plasma insulin level, that the blockage of melatonin receptors would be of benefit in the treatment of type 2 diabetes.
Impact of tooth loss on the quality of life
Authors: Saintrain Maria Vieira de Lima , de Souza Eliane Helena Alvim
Published: August 2011

doi: 10.1111/j.1741‐2358.2011.00535.x
 
Impact of tooth loss on the quality of life of elderly people

Introduction:  There is scientific evidence that shows health contributes to the quality of life. These measurements have not been well guided towards the free response of oral health in people’s lives.

Objective:  This study aimed to investigate the impact of tooth loss on the quality of life of elderly people.

Material and methods:  Qualitative investigation with descriptive features – which used a random sample out of the total edentulous elderly people, who lived in an institution in Fortaleza, Brazil – was carried out. From 250 residents screened, 72 completely edentulous elderly, with ages from 60 to 79 years were selected. A semi‐structured questionnaire was used with closed and opened questions in which the last one was used for the free flow of the interviewee’s responses. The content was analysed and codified according to Bardin.

Results:  In total, 84.7% had attended the dentist to have exodontia. Of them, 81.9% reported difficulties after losing their teeth. Physical dimensions, characterised by the difficulties in eating and social dimensions, because of interference in communication with other people were obtained.

Conclusion:  Tooth loss causes disorder in the individual’s quality of life, mainly when it affects their well‐being and appearance.
Exploratory analysis of cardiac biomarkers in women with normal cardiac function receiving trastuzumab for breast cancer
Authors: Goel Shom , Simes R John , Beith Jane M
Published: August 2011

Aim:  As there is no method to detect trastuzumab‐related cardiotoxicity (TRC) preclinically, patients are monitored with serial assessments of left ventricular ejection fraction (LVEF) with instigation of cardiac therapy and possible interruption of trastuzumab therapy if TRC develops. Serum cardiac biomarkers, including troponins and natriuretic peptides, represent possible tools to detect cardiotoxicity at a preclinical level.

Methods:  We sought biochemical evidence of cardiac damage or strain in a cohort of women already receiving trastuzumab by performing a cross‐sectional study of serum cardiac biomarkers. All patients had a normal LVEF and no clinical evidence of cardiac failure. Serum troponin I and N‐terminal pro‐B type natriuretic peptide (NT pro‐BNP) were assayed immediately prior to trastuzumab infusion (t0; n = 36) and 24 hours later (t24; n = 31).

Results:  Troponin I was not elevated in any patient at t0 or t24. Overall 14/36 (39%) patients had at least one NT pro‐BNP level above the upper limit of normal (ULN) and both levels were above the ULN in 8/31 (26%) patients. There was no significant change in NT pro‐BNP from t0 to t24.

Conclusion:  NT pro‐BNP levels are elevated in a significant proportion of patients with normal LVEF receiving trastuzumab. Troponin I levels are not raised in this group, perhaps reflecting the mechanism of cardiotoxicity. The data provide biochemical evidence of subclinical cardiac strain in women receiving trastuzumab. Results are exploratory and have informed the design of a larger study examining the predictive utility of serial serum NT pro‐BNP levels for TRC in the adjuvant setting.
The results of a pilot time‐and‐motion study in three Australian hospitals: Where do we spend our time?
Authors: MILOSAVLJEVIC Marianna , WILLIAMS Peter , PEREZ Geraldine , DALLA Tegan
Published: August 2011

Aim:  To quantify the time nine dietitians spend on different tasks in the inpatient setting and to describe the main dietetic goals for the patients managed.

Methods:  We used a direct non‐participatory observational method and observed hospital dietitians during a typical work shift. The data were then sorted into six categories.

Results:  A total of 286 hours and 45 minutes was observed across two collection time periods. On average the dietitians spent 18.3% in direct patient contact, 40.4% in indirect patient support activities, 13.5% in administrative tasks, 4.5% in research and education and 3.8% in travel and miscellaneous tasks. Dietetic goals of patients seen during this time, as identified by the dietitians were; to increase energy intake (48%), decrease energy intake (3%), improve dietary knowledge(15%), to improve or manage clinical symptoms (7%) and to meet enteral or parental requirements(11%).

Conclusion:  Knowing how the dietitians in the present study spend their time affords an opportunity to reflect on how these tasks contribute to the overall goals of the department. Furthermore, it provides baseline data for additional research into the area of dietetic work activities, which could be evaluated across a wider range of services and hospitals.
Interspecific hybridization transfers a previously unknown glyphosate resistance mechanism in Amaranthus species
Authors: Gaines Todd A. , Ward Sarah M. , Bukun Bekir , Preston Christopher , Leach Jan E. , Westra Philip
Published: August 2011

A previously unknown glyphosate resistance mechanism, amplification of the 5‐enolpyruvyl shikimate‐3‐phosphate synthase gene, was recently reported in Amaranthus palmeri. This evolved mechanism could introgress to other weedy Amaranthus species through interspecific hybridization, representing an avenue for acquisition of a novel adaptive trait. The objective of this study was to evaluate the potential for this glyphosate resistance trait to transfer via pollen from A. palmeri to five other weedy Amaranthus species (Amaranthus hybridus, Amaranthus powellii, Amaranthus retroflexus, Amaranthus spinosus, and Amaranthus tuberculatus). Field and greenhouse crosses were conducted using glyphosate‐resistant male A. palmeri as pollen donors and the other Amaranthus species as pollen recipients. Hybridization between A. palmeri and A. spinosus occurred with frequencies in the field studies ranging from <0.01% to 0.4%, and 1.4% in greenhouse crosses. A majority of the A. spinosus × A. palmeri hybrids grown to flowering were monoecious and produced viable seed. Hybridization occurred in the field study between A. palmeri and A. tuberculatus (<0.2%), and between A. palmeri and A. hybridus (<0.01%). This is the first documentation of hybridization between A. palmeri and both A. spinosus and A. hybridus.
A retrospective study of pemetrexed combined with oxaliplatin as second‐line treatment for advanced non‐small‐cell lung cancer: Comparable toxicity, better outcome
Authors: Zhang Xin‐xing , Huang Mei‐juan , Gong You‐ling , Zhou Lin , Liu Yong‐mei , Zhu Jiang
Published: August 2011

Background:  The outcomes of single‐agent regimens as second‐line chemotherapy for metastatic non‐small‐cell lung cancer (NSCLC) are poor. Pemetrexed combined with oxaliplatin has been reportedly well‐tolerated and active in chemotherapy‐naïve NSCLC. The current study aimed to evaluate the therapeutic effect and toxicity of the regimen of pemetrexed plus oxaliplatin for pretreated advanced NSCLC.

Patients and methods:  The clinical records of consecutive patients with metastatic NSCLC who received pemetrexed after failed first‐line chemotherapy were reviewed.

Results:  The medical records of 79 eligible patients were examined. Thirty‐four of them were treated with a regimen of pemetrexed plus oxaliplatin (PEMOX). Another 45 patients were administered pemetrexed alone (PEM). Both regimens were well‐tolerated and there was no therapy‐related death. Comparable response rates (15.2% vs. 11.1%) and tumor control rates (63.6% vs. 47.5%) were observed between the two groups. Median time to progression and overall survival of the PEMOX and PEM groups were 18 weeks (95% confidence interval (CI): 13.72–22.28 weeks) versus 13 weeks (95%CI: 12.28–13.72 weeks; P= 0.002), and 31 weeks (95%CI: 15.56–46.44 weeks) versus 21 weeks (95%CI: 18.37–23.63 weeks; P= 0.006), respectively.

Conclusions:  The current retrospective study suggests that pemetrexed combined with oxaliplatin as second‐line treatment for advanced NSCLC has comparable safety and response with a pemetrexed alone regimen, but better survival.
Inhaled methoxyflurane (Penthrox®) sedation for third molar extraction: a comparison to nitrous oxide sedation
Authors: Abdullah WA , Sheta SA , Nooh NS
Published: August 2011

Background:  The aim of this study was to evaluate the use of inhaled methoxyflurane (Penthrox®) in the reduction of dental anxiety in patients undergoing mandibular third molar removal in a specialist surgical suite and compare it to the conventional nitrous oxide sedation.

Methods:  A prospective randomized, non‐blinded crossover design study of 20 patients receiving two types of sedation for their third molar extraction who participated in 40 treatment sessions. At first appointment, a patient was randomly assigned to receive either nitrous oxide sedation or intermittent Penthrox® inhaler sedation, with the alternate regimen administered during the second appointment. Peri‐procedural vital signs (heart rate and blood pressure) were recorded and any deviations from 20% from the baseline values, as well as any drop in oxygen saturation below 92% were documented. The Ramsay Sedation Scale (RSS) score was recorded every five minutes. Patient cooperation during the procedure, patients’ general opinion about the sedation technique, surgeon satisfaction and the occurrence of side effects were all recorded. After the second procedure, the patient was also asked if he or she had any preference of one sedation technique over the other.

Results:  Levels of sedation were comparable in nitrous oxide and Penthrox® sedation sessions. However, at 15 minutes of sedation it was significantly lighter (p < 0.05) in Penthrox®. No patient in both regimens reached a RSS deeper than a score of 4. Parameters measured for assessment of sedation (patient cooperation, surgeon satisfaction and patient general opinion about sedation technique) were all similarly comparable for both nitrous oxide and Penthrox®. In both sedation sessions, the odour of the inhalational agent was accepted by the patients; half of the patients (10 patients) who received methoxyflurane thought its odour was pleasant. Patients preferred methoxyflurane (Penthrox®) inhalation over nitrous oxide sedation (Fisher’s Exact test, p < 0.05). Adverse events were minimal. No patient was either deeply sedated or agitated. Blood pressure was within ± 20% from the baseline values. No patient had oxygen saturation less than 92%. Dizziness was the most frequently encountered side effect in both regimens (four patients each). Two patients had bradycardia (HR < 60 beats/minute) when nitrous oxide was used in comparison to one patient with Penthrox® sedation. Paraesthesia of fingers and heaviness of the chest was encountered only with nitrous oxide sedation (four patients). Mild self‐limited shivering occurred in one patient with Penthrox® sedation.

Conclusions:  The Penthrox® Inhaler can produce a comparable sedation to that of nitrous oxide for the surgical extraction of third molars under local anaesthesia.
Does Better Local Governance Improve District Growth Performance in Indonesia?
Authors: McCulloch Neil , Malesky Edmund
Published: August 2011

A large literature suggests that countries with better governance have higher growth rates. We explore whether this is also true at the sub‐national level in Indonesia. We exploit a new dataset of firm perceptions of the quality of economic governance in 243 districts across Indonesia to estimate the impact of nine different dimensions of governance on district growth. Surprisingly, we find relatively little evidence of a robust relationship between the quality of governance and economic performance. However, we do find support for the idea that structural variables, such as economic size, natural resource endowments and population, have a direct influence on the quality of local governance as well as on economic growth. This suggests that efforts to improve local governance should pay greater attention to understanding how such structural characteristics shape the local political economy and how this in turn influences economic performance.
A cue‐based approach to ‘theory of mind’: Re‐examining the notion of automaticity
Authors: German Tamsin C. , Cohen Adam S.
Published: August 2011

The potential utility of a distinction between ‘automatic (or spontaneous) and implicit’ versus ‘controlled and explicit’ processes in theory of mind (ToM) is undercut by the fact that the terms can be employed to describe different but related distinctions within cognitive systems serving that function. These include distinctions in the underlying cognitive systems, processes, or representations involved in ToM, distinctions among methodologies or task procedures used to measure ToM, and distinctions among behavioural signatures evaluated as evidence for the engagement of ToM. We propose an approach in which rather than continued dispute over whether or not ToM ‘is’ or ‘is not’ automatic, researchers focus instead on discovering what the range of stimulus conditions and task contexts are that give rise to various signatures of the ToM system. These input–output relations will constrain theorizing about the kinds of representations employed, the types of processing operating over those representations, and the overall architecture of ToM mechanisms.
Transient expression of functional serotonin 5‐HT3 receptors by glutamatergic granule cells in the early postnatal mouse cerebellum
Authors: Oostland Marlies , Sellmeijer Jim , van Hooft Johannes A.
Published: August 2011

Non‐Technical Summary  The serotonin 3 receptor is a ligand‐gated ion channel which is activated by the neurotransmitter serotonin. This receptor is present in many parts of the brain, yet there is hardly any information on its function in the cerebellum. In this study, we use transgenic mice to show that the serotonin 3 receptor is localised in the cerebellum during the first three weeks after birth. We found that during this period, the serotonin 3 receptor regulates communication between two major types of neurons in the cerebellum, the granule cells and the Purkinje cells. In the absence of this receptor during early postnatal development, synaptic transmission between those neurons is disturbed. Taken together, these findings can help us understand the way serotonin affects the function of the cerebellum, and may provide insight into pathophysiological conditions in which the serotonergic system is compromised.
Two Novel Alkane Hydroxylase-Rubredoxin Fusion Genes Isolated from a Dietzia Bacterium and the Functions of Fused Rubredoxin Domains in Long-Chain
n
-Alkane Degradation
Authors: Nie Yong , Liang Jieliang , Fang Hui , Tang Yue-Qin , Wu Xiao-Lei
Published: August 2011

Two alkane hydroxylase-rubredoxin fusion gene homologs (
alkW1
and
alkW2
) were cloned from a
Dietzia
strain, designated DQ12-45-1b, which can grow on crude oil and
n
-alkanes ranging in length from 6 to 40 carbon atoms as sole carbon sources. Both AlkW1 and AlkW2 have an integral-membrane alkane monooxygenase (AlkB) conserved domain and a rubredoxin (Rd) conserved domain which are fused together. Phylogenetic analysis showed that these two AlkB-fused Rd domains formed a novel third cluster with all the Rds from the alkane hydroxylase-rubredoxin fusion gene clusters in Gram-positive bacteria and that this third cluster was distant from the known AlkG1- and AlkG2-type Rds. Expression of the
alkW1
gene in DQ12-45-1b was induced when cells were grown on C
8
to C
32
n
-alkanes as sole carbon sources, but expression of the
alkW2
gene was not detected. Functional heterologous expression in an
alkB
deletion mutant of
Pseudomonas fluorescens
KOB2Δ1 suggested the
alkW1
could restore the growth of KOB2Δ1 on C
14
and C
16
n
-alkanes and induce faster growth on C
18
to C
32
n
-alkanes than
alkW1
ΔRd, the Rd domain deletion mutant gene of
alkW1
, which also caused faster growth than KOB2Δ1 itself. In addition, the artificial fusion of AlkB from the Gram-negative
P. fluorescens
CHA0 and the Rds from both Gram-negative
P. fluorescens
CHA0 and Gram-positive
Dietzia
sp. DQ12-45-1b significantly increased the degradation of C
32
alkane compared to that seen with AlkB itself. In conclusion, the
alkW1
gene cloned from
Dietzia
species encoded an alkane hydroxylase which increased growth on and degradation of
n
-alkanes up to C
32
in length, with its fused rubredoxin domain being necessary to maintain the functions. In addition, the fusion of alkane hydroxylase and rubredoxin genes from both Gram-positive and -negative bacteria can increase the degradation of long-chain
n
-alkanes (such as C
32
) in the Gram-negative bacterium.
Niche Partitioning of Marine Group I Crenarchaeota in the Euphotic and Upper Mesopelagic Zones of the East China Sea
Authors: Hu Anyi , Jiao Nianzhi , Zhang Rui , Yang Zao
Published: August 2011

Marine group I
Crenarchaeota
(MGI) represents a ubiquitous and numerically predominant microbial population in marine environments. An understanding of the spatial dynamics of MGI and its controlling mechanisms is essential for an understanding of the role of MGI in energy and element cycling in the ocean. In the present study, we investigated the diversity and abundance of MGI in the East China Sea (ECS) by analysis of crenarchaeal 16S rRNA gene, the ammonia monooxygenase gene
amoA
, and the biotin carboxylase gene
accA
. Quantitative PCR analyses revealed that these genes were higher in abundance in the mesopelagic than in the euphotic zone. In addition, the crenarchaeal
amoA
gene was positively correlated with the copy number of the MGI 16S rRNA gene, suggesting that most of the MGI in the ECS are nitrifiers. Furthermore, the ratios of crenarchaeal
accA
to
amoA
or to MGI 16S rRNA genes increased from the euphotic to the mesopelagic zone, suggesting that the role of MGI in carbon cycling may change from the epipelagic to the mesopelagic zones. Denaturing gradient gel electrophoretic profiling of the 16S rRNA genes revealed depth partitioning in MGI community structures. Clone libraries of the crenarchaeal
amoA
and
accA
genes showed both “shallow” and “deep” groups, and their relative abundances varied in the water column. Ecotype simulation analysis revealed that MGI in the upper ocean could diverge into special ecotypes associated with depth to adapt to the light gradient across the water column. Overall, our results showed niche partitioning of the MGI population and suggested a shift in their ecological functions between the euphotic and mesopelagic zones of the ECS.
Merging Taxonomy with Ecological Population Prediction in a Case Study of Vibrionaceae
Authors: Preheim Sarah P. , Timberlake Sonia , Polz Martin F.
Published: August 2011

We synthesized population structure data from three studies that assessed the fine-scale distribution of
Vibrionaceae
among temporally and spatially distinct environmental categories in coastal seawater and animals. All studies used a dynamic model (AdaptML) to identify phylogenetically cohesive and ecologically distinct bacterial populations and their predicted habitats without relying on a predefined genetic cutoff or relationships to previously named species. Across the three studies, populations were highly overlapping, displaying similar phylogenetic characteristics (identity and diversity), and were predominantly congruent with taxonomic
Vibrio
species previously characterized as genotypic clusters by multilocus sequence analysis (MLSA). The environmental fidelity of these populations appears high, with 9 out of 12 reproducibly associating with the same predicted (micro)habitats when similar environmental categories were sampled. Overall, this meta-analysis provides information on the habitat predictability and structure of previously described species, demonstrating that MLSA-based taxonomy can, at least in some cases, serve to approximate ecologically cohesive populations.
Alga-Derived Substrates Select for Distinct Betaproteobacterial Lineages and Contribute to Niche Separation in Limnohabitans Strains
Authors: Šimek Karel , Kasalický Vojtěch , Zapomělová Eliška , Horňák Karel
Published: August 2011

We examined the proportions of major Betaproteobacteria subgroups within bacterial communities in diverse nonaxenic, monospecific cultures of algae or cyanobacteria: four species of cryptophyta (genera
Cryptomonas
and
Rhodomonas
), four species of chlorophyta (genera
Pediastrum
,
Staurastrum
, and
Chlamydomonas
), and two species of cyanobacteria (genera
Dolichospermum
and
Aphanizomenon
). In the cryptophyta cultures,
Betaproteobacteria
represented 48 to 71% of total bacteria, the genus
Limnohabitans
represented 18 to 26%, and the
Polynucleobacter
B subcluster represented 5 to 16%. In the taxonomically diverse chlorophyta group, the genus
Limnohabitans
accounted for 7 to 45% of total bacteria. In contrast, cyanobacterial cultures contained significantly lower proportions of the
Limnohabitans
bacteria (1 to 3% of the total) than the cryptophyta and chlorophyta cultures. Notably, largely absent in all of the cultures was
Polynucleobacter necessarius
(
Polynucleobacter
C subcluster). Subsequently, we examined the growth of
Limnohabitans
strains in the presence of different algae or their extracellular products (EPP). Two strains, affiliated with
Limnohabitans
planktonicus
and
Limnohabitans
parvus
, were separately inoculated into axenic cultures of three algal species growing in an inorganic medium:
Cryptomonas
sp.,
Chlamydomonas noctigama
, and
Pediastrum boryanum
. The
Limnohabitans
strains cocultured with these algae or inoculated into their EPP consistently showed (i) pronounced population growth compared to the control without the algae or EPP and (ii) stronger growth stimulation of
L. planktonicus
than of
L. parvus.
Overall, growth responses of the
Limnohabitans
strains cultured with algae were highly species specific, which suggests a pronounced niche separation between two closely related
Limnohabitans
species likely mediated by different abilities to utilize the substrates produced by different algal species.
Comparison of the Gut Microbiotas of Healthy Adult Twins Living in South Korea and the United States
Authors: Lee Sunghee , Sung Joohon , Lee JungEun , Ko GwangPyo
Published: August 2011

We compared the composition of the fecal microbiotas of Korean and U.S. adult twins. Our data indicated that the gut microbiota shows some signature of biogeography, potentially mediated by differences in diet and/or other environmental factors; however, these regional differences may be masked by other phenotypic variations, such as obesity.
Relationships between Free-Living Protozoa, Cultivable Legionella spp., and Water Quality Characteristics in Three Drinking Water Supplies in the Caribbean
Authors: Valster Rinske M. , Wullings Bart A. , van den Berg Riemsdijk , van der Kooij Dick
Published: August 2011

The study whose results are presented here aimed at identifying free-living protozoa (FLP) and conditions favoring the growth of these organisms and cultivable
Legionella
spp. in drinking water supplies in a tropical region. Treated and distributed water (±30°C) of the water supplies of three Caribbean islands were sampled and investigated with molecular techniques, based on the 18S rRNA gene. The protozoan host
Hartmannella vermiformis
and cultivable
Legionella pneumophila
were observed in all three supplies. Operational taxonomic units (OTUs) with the highest similarity to the potential or candidate hosts
Acanthamoeba
spp.,
Echinamoeba exundans
,
E. thermarum
, and an
Neoparamoeba
sp. were detected as well. In total, 59 OTUs of FLP were identified. The estimated protozoan richness did not differ significantly between the three supplies. In supply CA-1, the concentration of
H. vermiformis
correlated with the concentration of
Legionella
spp. and clones related to Amoebozoa predominated (82%) in the protozoan community. These observations, the low turbidity (<0.2 nephelometric turbidity units [NTU]), and the varying ATP concentrations (1 to 12 ng liter
−1
) suggest that biofilms promoted protozoan growth in this supply. Ciliophora represented 25% of the protozoan OTUs in supply CA-2 with elevated ATP concentrations (maximum, 55 ng liter
−1
) correlating with turbidity (maximum, 62 NTU) caused by corroding iron pipes. Cercozoan types represented 70% of the protozoan clones in supply CA-3 with ATP concentrations of <1 ng liter
−1
and turbidity of <0.5 NTU in most samples of distributed water. The absence of
H. vermiformis
in most samples from supply CA-3 suggests that growth of this protozoan is limited at ATP concentrations of <1 ng liter
−1
.
Identification and Targeted Cultivation of Abundant Novel Freshwater Sphingomonads and Analysis of Their Population Substructure
Authors: Jogler Mareike , Siemens Helge , Chen Hong , Bunk Boyke , Sikorski Johannes , Overmann Jörg
Published: August 2011

Little is known with respect to bacterial population structures in freshwater environments. Using complementary culture-based, cloning, and high-throughput Illumina sequencing approaches, we investigated microdiverse clusters of bacteria that comprise members with identical or very similar 16S rRNA gene sequences. Two 16S rRNA phylotypes could be recovered by cultivation in low-nutrient-strength liquid media from two lakes of different trophic status. Both phylotypes were found to be physiologically activein situthroughout most of the year, as indicated by the presence of their rRNA sequences in the samples. Analyses of internal transcribed spacer (ITS1) sequences revealed the presence of seven different sequence types among cultured representatives and the clonedrrnfragments. Illumina sequencing yielded 8,576 ITS1 sequences that encompassed 15 major and numerous rare sequence types. The major ITS1 types exhibited distinct temporal patterns, suggesting that the correspondingSphingomonadaceaelineages occupy different ecological niches. However, since strains of the same ITS1 type showed highly variable substrate utilization patterns, the potential mechanism of niche separation inSphingomonadaceaecannot be explained by substrate utilization alone and may be related to other traits.
Anatoxin-a Synthetase Gene Cluster of the Cyanobacterium Anabaena sp. Strain 37 and Molecular Methods To Detect Potential Producers
Authors: Rantala-Ylinen Anne , Känä Suvi , Wang Hao , Rouhiainen Leo , Wahlsten Matti , Rizzi Ermanno , Berg Katri , Gugger Muriel , Sivonen Kaarina
Published: August 2011

Cyanobacterial mass occurrences are common in fresh and brackish waters. They pose a threat to water users due to toxins frequently produced by the cyanobacterial species present. Anatoxin-a and homoanatoxin-a are neurotoxins synthesized by various cyanobacteria, e.g.,
Anabaena
,
Oscillatoria
, and
Aphanizomenon
. The biosynthesis of these toxins and the genes involved in anatoxin production were recently described for
Oscillatoria
sp. strain PCC 6506 (A. Méjean et al., J. Am. Chem. Soc.
131:
7512-7513, 2009). In this study, we identified the anatoxin synthetase gene cluster (
anaA
to
anaG
and
orf1
; 29 kb) in
Anabaena
sp. strain 37. The gene (81.6% to 89.2%) and amino acid (78.8% to 86.9%) sequences were highly similar to those of
Oscillatoria
sp. PCC 6506, while the organization of the genes differed. Molecular detection methods for potential anatoxin-a and homoanatoxin-a producers of the genera
Anabaena
,
Aphanizomenon
, and
Oscillatoria
were developed by designing primers to recognize the
anaC
gene.
Anabaena
and
Oscillatoria anaC
genes were specifically identified in several cyanobacterial strains by PCR. Restriction fragment length polymorphism (RFLP) analysis of the
anaC
amplicons enabled simultaneous identification of three producer genera:
Anabaena
,
Oscillatoria
, and
Aphanizomenon
. The molecular methods developed in this study revealed the presence of both
Anabaena
and
Oscillatoria
as potential anatoxin producers in Finnish fresh waters and the Baltic Sea; they could be applied for surveys of these neurotoxin producers in other aquatic environments.
Directed Chromosomal Integration and Expression of the Reporter Gene
gusA3
in Lactobacillus acidophilus NCFM
Authors: Douglas Grace L. , Klaenhammer Todd R.
Published: August 2011

Lactobacillus acidophilus
NCFM is a probiotic microbe that survives passage through the human gastrointestinal tract and interacts with the host epithelium and mucosal immune cells. The potential for
L. acidophilus
to express antigens at mucosal surfaces has been investigated with various antigens and plasmid expression vectors. Plasmid instability and antibiotic selection complicate the possibility of testing these constructs in human clinical trials. Integrating antigen encoding genes into the chromosome for expression is expected to eliminate selection requirements and provide genetic stability. In this work, a reporter gene encoding a β-glucuronidase (GusA3) was integrated into four intergenic chromosomal locations. The integrants were tested for genetic stability and GusA3 activity. Two locations were selected for insertion downstream of constitutively highly expressed genes, one downstream of
slpA
(LBA0169), encoding a highly expressed surface-layer protein, and one downstream of phosphopyruvate hydratase (LBA0889), a highly expressed gene with homologs in other lactic acid bacteria. An inducible location was selected downstream of
lacZ
(LBA1462), encoding a β-galactosidase. A fourth location was selected in a low-expression region. The expression of
gusA3
was evaluated from each location by measuring GusA3 activity on 4-methyl-umbelliferyl-β-
d
-glucuronide (MUG). GusA3 activity from both highly expressed loci was more than three logs higher than the
gusA3
-negative parent,
L. acidophilus
NCK1909. GusA3 activity from the
lacZ
locus was one log higher in cells grown in lactose than in glucose. The differences in expression levels between integration locations highlights the importance of rational targeting with gene cassettes intended for chromosomal expression.
Occurrence of Intestinal and Extraintestinal Virulence Genes in Escherichia coli Isolates from Rainwater Tanks in Southeast Queensland, Australia
Authors: Ahmed W. , Hodgers L. , Masters N. , Sidhu J. P. S. , Katouli M. , Toze S.
Published: August 2011

In this study, 200
Escherichia coli
isolates from 22 rainwater tank samples in Southeast Queensland, Australia, were tested for the presence of 20 virulence genes (VGs) associated with intestinal and extraintestinal pathotypes. In addition,
E. coli
isolates were also classified into phylogenetic groups based on the detection of the
chuA
,
yjaA
, and TSPE4.C2 genes. Of the 22 rainwater tanks, 8 (36%) and 5 (23%) were positive for the
eaeA
(belonging to enteropathogenic
E. coli
[EPEC] and Shiga-toxigenic
E. coli
[STEC]) and ST1 (belonging to enterotoxigenic
E. coli
[ETEC]) genes, respectively. VGs (
cdtB
,
cvaC
,
ibeA
,
kpsMT
allele III, PAI,
papAH
, and
traT
) belonging to extraintestinal pathogenic
E. coli
(ExPEC) were detected in 15 (68%) of the 22 rainwater tanks. Of the 22 samples, 17 (77%) and 11 (50%) contained
E. coli
belonging to phylogenetic groups A and B1, respectively. Similarly, 10 (45%) and 16 (72%) contained
E. coli
belonging to phylogenetic groups B2 and D, respectively. Of the 96 of the 200 strains from 22 tanks that were VG positive, 40 (42%) were carrying a single VG, 36 (37.5%) were carrying two VGs, 17 (18%) were carrying three VGs, and 3 (3%) had four or more VGs. This study reports the presence of multiple VGs in
E. coli
strains belonging to the STEC, EPEC, ETEC, and ExPEC pathotypes in rainwater tanks. The public health risks associated with potentially clinically significant
E. coli
in rainwater tanks should be assessed, as the water is used for drinking and other, nonpotable purposes. It is recommended that rainwater be disinfected using effective treatment procedures such as filtration, UV disinfection, or simply boiling prior to drinking.
The Paf1 Complex Represses
SER3
Transcription in Saccharomyces cerevisiae by Facilitating Intergenic Transcription-Dependent Nucleosome Occupancy of the
SER3
Promoter
Authors: Pruneski Justin A. , Hainer Sarah J. , Petrov Kostadin O. , Martens Joseph A.
Published: August 2011

Previous studies have shown that repression of the
Saccharomyces cerevisiae
SER3
gene is dependent on transcription of
SRG1
from noncoding DNA initiating within the intergenic region 5′ of
SER3
and extending across the
SER3
promoter region. By a mechanism dependent on the activities of the Swi/Snf chromatin remodeling factor, the HMG-like factor Spt2, and the Spt6 and Spt16 histone chaperones,
SRG1
transcription deposits nucleosomes over the
SER3
promoter to prevent transcription factors from binding and activating
SER3
. In this study, we uncover a role for the Paf1 transcription elongation complex in
SER3
repression. We find that
SER3
repression is primarily dependent on the Paf1 and Ctr9 subunits of this complex, with minor contributions by the Rtf1, Cdc73, and Leo1 subunits. We show that the Paf1 complex localizes to the
SRG1
transcribed region under conditions that repress
SER3
, consistent with it having a direct role in mediating
SRG1
transcription-dependent
SER3
repression. Importantly, we show that the defect in
SER3
repression in strains lacking Paf1 subunits is not a result of reduced
SRG1
transcription or reduced levels of known Paf1 complex-dependent histone modifications. Rather, we find that strains lacking subunits of the Paf1 complex exhibit reduced nucleosome occupancy and reduced recruitment of Spt16 and, to a lesser extent, Spt6 at the
SER3
promoter. Taken together, our results suggest that Paf1 and Ctr9 repress
SER3
by maintaining
SRG1
transcription-dependent nucleosome occupancy.